UEG Week 2016 Oral Presentations United European Gastroenterology Journal

4(5S) A1–A156
! Author(s) 2016
MONDAY, OCTOBER 17, 2016 08:00–10:00 Reprints and permissions:
OPENING SESSION: PART 1 – ROOM A_____________________ sagepub.co.uk/journalsPermissions.nav
DOI: 10.1177/2050640616663688
OP001 LAPAROSCOPIC ILEOCECAL RESECTION VERSUS ueg.sagepub.com
INFLIXIMAB TREATMENT OF TERMINAL ILEITIS IN CROHN’S
DISEASE: THE LIR!C TRIAL
J. De Groof1, W. A. Bemelman2, E. Eshuis3, T. Gardenbroek4, P.M. Bossuyt5,
B. Van Wagensveld6, M.A. Brink7, E. Consten8, C.J. Buskens4, G.
R.A.M. D’Haens3, P. Stokkers9, C.Y. Ponsioen3
1
Surgery and Gastroenterology & Hepatology, AMC, Amsterdam/Netherlands
2
Department of Surgery, Academic Medical Center, Amsterdam/Netherlands OP002 CELL AUTONOMOUS AND NON-CELL AUTONOMOUS
3
Gastroenterology & Hepatology, Academic Medical Center, Amsterdam/ RESCUE OF NNOS DEFICIENT MOUSE COLON FOLLOWING IN
Netherlands VIVO ENTERIC NERVOUS SYSTEM STEM CELL
4
Surgery, Academic Medical Center, Amsterdam/Netherlands TRANSPLANTATION
5
Clinical Epidemiology, Biostatistics and Bioinformatics, Academic Medical C. J. Mccann, J. Cooper, D. Natarajan, B. S. Jevans, A. J. Burns, N. Thapar
Centre, Amsterdam/Netherlands Stem Cells and Regenerative Medicine, University College London Institute of
6
Surgery, OLVG West, Amsterdam/Netherlands Child Health, London/United Kingdom
7
Gastroenterology & Hepatology, Meander Medisch Centrum MDL, Amersfoort/
Netherlands Contact E-mail Address: [email protected]
8
Surgery, Meander Medisch Centrum, Amersfoort/Netherlands Introduction: Enteric neural stem cells (ENSC) have been identified as a possible
9
Gastroenterology & Hepatology, OLVG West, Amsterdam/Netherlands treatment for enteric neuropathies following successful colonization of recipient
gut after transplantation. However, the ability of ENSC to rescue pathophysio-
Contact E-mail Address: [email protected] logical conditions remains unclear. Loss of neuronal subtypes, including neuro-
Introduction: The optimal therapeutic approach to ileocecal Crohn’s disease (CD) nal nitric oxide synthase (nNOS), has been implicated in many enteric
remains unclear. neuropathies. nNOS-/- mice display slow colonic transit providing a model to
Aims & Methods: The objective of this study was to compare infliximab with test ENSC rescue in a pathological setting.
laparoscopic ileocecal resection in patients with thiopurine or steroid refractory Aims & Methods: Our aim was to assess the functional integration of trans-
recurrent CD of the terminal ileum, with respect to quality of life (QoL) and planted ENSC within recipient nNOS-/- colon. Initially, donor ENSC were
costs. A multicentre randomised controlled, open-label trial was performed in 33 obtained from Wnt1-cre;YFP transgenic mice allowing specific fluorescent label-
centres in the Netherlands and the UK. Adult patients with CD of the terminal ing, FACS selection and fate mapping of cells. YFPþ ENSC were transplanted
ileum who failed 4 3 months of thiopurine treatment or steroids without signs of to nNOS-/-distal colon at post natal day (P)14. Subsequently, integration and
a critical stricture were randomised to infliximab or laparoscopic ileocecal resec- functionality were assessed using immunolabelling and organ bath physiology
tion. Patients with a prior ileocecal resection, a diseased length 4 40 cm, abdom- after 4 weeks.
inal abscesses or fluid collections or an American Society of Anaesthesiologists Results: After 1 month, YFPþ/nNOSþ neurons were identified and transcrip-
(ASA) score of III or IV were excluded. The primary endpoint was QoL mea- tional analysis showed specific expression of nNOS in recipient nNOS-/- colon. In
sured by the Inflammatory Bowel Disease Questionnaire (IBDQ) at one year NANC (non-adrenergic non-cholinergic) conditions, organ bath physiology
follow-up. Furthermore, the mean direct costs per individual patient were pro- revealed significant increases in electrical field stimulation (EFS)-induced relaxa-
spectively documented and analysed according to intention-to-treat until one tion (Area under curve;AUC) in transplanted nNOS-/- (1.13  0.16 g.s, n ¼ 5)
year after start of treatment. Dutch Trial Registry NTR1150. compared with non-transplanted nNOS-/- (0.31  0.0.08 g.s, n ¼ 5; P ¼ 0.0016).
Results: Between May 2008 and October 2015, 143 patients were randomised In transplanted colonic segments, addition of the nitric oxide synthase blocker L-
(32.9% male) with a median age of 27.0 years (interquartile range (IQR) 22.0– NAME resulted in significant reductions in the observed EFS-induced relaxation
40.0). Eventually, 65 patients started with infliximab treatment and 70 patients (0.74  0.17 g.s vs 0.12  0.16 g.s, n ¼ 4; P ¼ 0.0389) demonstrating restora-
were operated. On April 28th 2016, 96.5% of the patients have completed follow- tion of nitrergic responses after transplantation. Interestingly, significant
up. At baseline, the mean difference (MD) in IBDQ score was 4.9 points in increases in basal contractile amplitude were also observed in transplanted
favour of the resection group. After correction for the baseline difference, the nNOS-/- colonic segments (0.30  0.06 g, n ¼ 5) compared with both C57BL/6J
MD at one year follow-up was 5.8 points in favour of resection (95% confidence (0.10  0.01 g, n ¼ 5; P ¼ 0.0093) and non-transplanted nNOS-/- mice
interval (CI) 4.7 to 16.3, p ¼ 0.28). The mean direct total costs per patient at (0.05  0.008 g, n ¼ 5; P ¼ 0.0025). These high-amplitude contractions were unaf-
one year were E14,589 in the infliximab group and E10,318 in the resection fected by application of tetrodotoxin, suggesting that transplantation of ENSC
group (MD 04,270, 95% CI 01,325 – 07,126, p ¼ 0.005). Infliximab was stopped can also lead to changes in underlying myogenic motility patterns. To assess the
in 21 patients (30.0%) due to intolerance or insufficient response, 13 of whom mechanisms involved in these non-cell autonomous phenomena we sought to
underwent an ileocecal resection after a median time of 27.0 weeks (IQR 11.0– investigate potential changes in gut morphology. No significant change was
33.5) after start of infliximab treatment. CD related serious adverse events in observed in the diameter of the distal colon between transplanted nNOS-/-
terms of Clavien Dindo IIIb complications occurred in three patients (4.1%) in mice (1.04  0.13 mm; n ¼ 3) compared to either non-transplanted nNOS-/-
the laparoscopic ileocecal resection group and in one patient allocated to inflix- (1.12  0.68 mm; n ¼ 3; P ¼ 0.609) or sham-operated nNOS-/- (1.05  0.02 mm;
imab eventually going for surgery. Three patients (4.1%) in the resection group n ¼ 3; P ¼ 0.947). In addition, no change in muscle thickness was observed
were started on infliximab within one year. Readmissions (for flares or additional between transplanted nNOS-/- mice (55.33  8.67 mm; n ¼ 3) compared to either
surgery or dilatation) during follow-up were comparable (21.4% of patients in non-transplanted nNOS-/- (54.0  8.0 mm; n ¼ 3; P ¼ 0.915) or sham-operated
the infliximab versus 17.8% in the resection group). nNOS-/- (54.33  2.96 mm; n ¼ 3; P ¼ 0.918). Ongoing work is targeting other
Conclusion: QoL at one year was not significantly different between the laparo- potential processes such as modification of cell types involved in neuromuscular
scopic ileocecal resection and infliximab group. Given the lower bound of the signaling, including interstitial cells of Cajal within the transplanted
95% CI, laparoscopic ileocecal resection can be considered a non-inferior alter- microenvironment.
native for infliximab treatment at significantly lower cost. Conclusion: Here we demonstrate, for the first time, that transplanted ENSC
Disclosure of Interest: All authors have declared no conflicts of interest. integrate and effect restoration of function, at the organ level, in a pathological
GI disease model potentially via both ENSC-specific and non ENSC-specific
processes.
Disclosure of Interest: All authors have declared no conflicts of interest.
A2 United European Gastroenterology Journal 4(5S)

MONDAY, OCTOBER 17, 2016 10:30–12:00 Results: A total of 98 patients were enrolled in 19 Dutch hospitals. The primary
OPENING SESSION: PART 2 – ROOM A_____________________ endpoint occurred in 10 of 51 patients (20%) in the endoscopic group and in 13
of 49 patients (28%) in the surgical group (risk ratio 0.75; 95% CI 0.37 to 1.52,
OP003 MULTIVARIATE MODELLING OF GUT MICROBIAL PROFILES P ¼ 0.35). There were no significant differences in the individual components of
PREDICTS RESPONSIVENESS TO A DIET LOW IN FODMAPS the primary endpoint (e.g. death 18% versus 13%; P ¼ 0.50). In the endoscopic
S. M.P. Bennet1, L. Böhn2, S. Störsrud2, T. Liljebo3, L. Collin4, P. Lindfors2, group, 21 patients (41%) as compared with 23 patients (49%) in de surgical
H. Törnblom2, L. Öhman5, M. Simrén2 group did not need necrosectomy after drainage as first step of treatment (risk
1
Dept. Of Internal Medicine and Clinical Nutritio, Sahlgrenska University ratio 0.84; 95% CI 0.54 to 1.31, P ¼ 0.43). There was a lower incidence of pan-
Hospital, Gothenburg/Sweden creatic fistula (5% versus 32%; P ¼ 0.001) and length of hospital stay was shorter
2
Dept. Of Internal Medicine & Clinical Nutrition, Institute Of Medicine, (median 36 days versus 69 days; P ¼ 0.03) in the endoscopic group. Furthermore,
Sahlgrenska Academy. University of Gothenburg, Gothenburg/Sweden the difference in total mean costs was 013655 (19%, BCa 95% CI -10836–35782)
3
Karolinska Institute, Stockholm/Sweden in favour of the endoscopic group.
4
Sabbatsbergs Hospital, Stockholm/Sweden Conclusion: The TENSION trial did not show superiority of the endoscopic step-
5
Dept. Of Internal Medicine and Clinical Nutrition, University of Gothenburg, up approach, as compared with a surgical step-up approach, in reducing major
Gothenburg/Sweden complications or death in patients with infected necrotizing pancreatitis.
However, the rate of pancreatic fistula, length of hospital stay and costs were
Contact E-mail Address: [email protected] significantly reduced in the endoscopic group.
Introduction: Dietary interventions may be recommended to IBS patients yet Disclosure of Interest: All authors have declared no conflicts of interest.
effects on gut microbiota and factors predicting response are largely unknown.
Aims & Methods: We aimed to determine how two different diets affect gut
microbiota and if bacterial profiles and modelling thereof can be used to predict MONDAY, OCTOBER 17, 2016 10:30–12:00
patient intervention response in a secondary analysis of a previously published ESTABLISHED AND NEW DRUGS IN IBD – ROOM B_____________________
intervention study (Böhn et.al 2015). After a 10 day screening period 61 IBS
patients with at least moderately severe IBS symptoms according to IBS OP005 EFFICACY AND SAFETY OF DOSE ADJUSTMENT
Symptom Severity Score (IBS-SSS) followed either a traditional IBS (n ¼ 30) or AND DELAYED RESPONSE TO USTEKINUMAB IN MODERATE–
low-FODMAP (n ¼ 31) diet for 4 weeks. Faecal samples were collected and IBS- SEVERE CROHN’S DISEASE PATIENTS: RESULTS FROM THE
SSS were completed before and after the intervention. Food intake was recorded IM-UNITI MAINTENANCE STUDY
in 4-days food diaries before (baseline) and during the interventions. Responders B. E. Sands1, C. Gasink2, D. Jacobstein3, L.L. Gao4, J. Johanns5, P. Szapary5,
were defined as having a reduction of IBS-SSS 50 after the intervention. Faecal J. Colombel6, S. Targan7, S. Ghosh8, W. Sandborn9
bacterial composition was evaluated by GA-mapTM Dysbiosis Test which mea- 1
Icahn School of Medicine at Mt Sinai, New York/United States of America/NY
sures probe signal intensity (PSI) of 54 DNA probes targeting 300 bacteria on 2
Janssen Research and Development, LLC, Spring House/United States of
different taxonomic levels. Bacterial profiles created for each patient were evalu- America/PA
ated by multivariate discrimination analysis and graded from 1–5, relative to a 3
Janssen Research and Development, LLC, Spring House/United States of
healthy reference group. A dysbiosis index (DI) 2 signify normal microbiota America
composition and 3 signify altered microbiota composition (dysbiosis). For all 4
Janssen Research & Development, LLC, Spring House/United States of America
models, both strong and moderate outliers were sequentially excluded. 5
Janssen Research & Development, LLC, Spring House/United States of America/
Results: At baseline, 45 patients (25 randomized to traditional diet and 20 to low- PA
FODMAP) had a DI 3, i.e. dysbiosis; of these, 10 patients following the tradi- 6
Icahn School of Medicine at Mount Sinai, New York/United States of America
tional IBS diet and 3 following the low-FODMAP diet experienced an improve- 7
Cedars-Sinai Medical Center, Los Angeles/United States of America
ment in DI, while 6 following the traditional diet and 11 on the low-FODMAP diet 8
Division Of Gastroenterology, University of Calgary, Calgary/Canada
had worsening of their dysbiosis; the rest experienced no change. In the low- 9
UCSD, La Jolla/United States of America
FODMAP group, but not traditional diet group, non-responders (n ¼ 19) had
more severe dysbioisis than responders (n ¼ 12) ((3 (3–4) DI; 2 (2–3) DI; Contact E-mail Address: [email protected]
p ¼ 0.007) at baseline. Although patients on a traditional diet consumed signifi- Introduction: Ustekinumab (UST) has been shown to induce and maintain clin-
cantly less protein, fat and alcohol, they experienced no change in overall bacterial ical response and remission in moderate to severe Crohn’s disease (CD) in 2
composition after the intervention. Patients on a low-FODMAP diet ate signifi- induction (UNITI-1 and 2) and 1 maintenance (IM-UNITI) randomized, pla-
cantly less carbohydrates, fibre, monosaccharides, fructose and total FODMAPS, cebo controlled Phase 3 trials. We evaluated the efficacy of UST in 2 additional
and had significant reduction in potentially beneficial Bifidobacterium after the groups in IM-UNITI: patients who underwent dose adjustment following loss of
intervention (33 (25.4–122.4) PSI) compared to before (152 (45.7–70) PSI, response (LOR) and patients who did not have a clinical response to IV UST
p ¼ 0.0005) which was even more prominent in non-responders. An OPLS-DA during induction and had an additional subcutaneous (SC) dose.
model of before the low-FODMAP intervention demonstrated satisfactory mod- Aims & Methods: Patients achieving clinical response after single dose IV induc-
elling and predictive abilities (R2Ycum 0.652, Q2 cum 0.541), showing that bac- tion were randomized to SC placebo (PBO), UST 90 mg every 12 weeks (q12w)
terial profiles differed between responders and non-responders. An OPLS-DA or every 8 weeks (q8w). Patients who met LOR criteria, defined as a CDAI score
model of the traditional diet group was inadequate, showing good model fit but of  220 and a  100 point increase from the maintenance baseline CDAI score,
poor predictability (R2Ycum 0.742, Q2 cum 0.004), demonstrating that bacterial between weeks 8 and 32 of the maintenance trial could undergo a single dose
profiles did not differ between responders and non-responders. adjustment as follows: PBO!q8w, q12w!q8w, and q8w!q8w (no dose adjust-
Conclusion: Faecal bacterial profiles predict patient responsiveness to a low- ment) and were assessed for clinical response ( 100 point decrease in CDAI) and
FODMAP dietary intervention. Thus, before considering dietary interventions, clinical remission (CDAI 5 150) 16 weeks later. Separately, UST patients not in
bacterial profiles could be determined in order to identify patients whom are clinical response 8 weeks after the IV induction dose were given SC UST 90 mg
likely to respond favourably. and if in clinical response 8 weeks later were continued on q8w dosing.
Disclosure of Interest: L. Öhman: Unrestricted research grants from AstraZeneca; Results: 51 (39%), 29 (23%), and 28 (22%) patients in the PBO, q12w and q8w
Consultant/ Advisory Board member for Genetic Analysis; Speaker for Genetic groups, respectively, underwent dose adjustment after meeting LOR criteria.
Analysis, Takeda and Abbot. Among these patients, clinical remission and clinical response were observed in
All other authors have declared no conflicts of interest. 39% and 71% of patients adjusting PBO!q8w (a situation similar to a drug
holiday), 41% and 55% in the q12w!q8w group, and 32% and 46% in the
q8w!q8w group when assessed 16 weeks later (Table 1). Median change in
CDAI after adjustment was 121, 141 and 78.5 in the PBO!q8w,
OP004 ENDOSCOPIC OR SURGICAL STEP-UP APPROACH FOR q12w!q8w and q8w!q8w groups, respectively. Of 467 patients not in response
NECROTIZING PANCREATITIS, A MULTI-CENTER to UST following IV induction in UNITI1&2, 50.5% and 28.9% were in clinical
RANDOMIZED CONTROLLED TRIAL response and remission 8 weeks after one additional UST dose (90 mg SC). Among
S. Van Brunschot the 251 of these patients continuing dosing at week 8 of maintenance, 68.1% were
Gastroenterology and Hepatology, Academic Medical Center, Amsterdam/ in response and 50.2% were in remission at Week 44. No increases or changes in
Netherlands patterns of adverse events were seen among patients who dose adjusted.
Conclusion: In patients who met LOR criteria, dose adjustment from UST 90 mg
Contact E-mail Address: [email protected] q12w to 90 mg q8w provided some additional clinical benefit compared to
Introduction: Infected necrotizing pancreatitis is a potentially lethal disease that patients who remained on UST 90 mg q8w. Additionally, patients who were
almost always requires an invasive intervention. In recent years, the surgical step- initial induction non-responders can benefit from continued treatment with at
up approach has become standard of care replacing primary open necrosectomy. least 1 SC UST dose 8 weeks after IV induction.
A promising minimally invasive alternative is the endoscopic step-up approach. We
conducted a multicenter randomized trial (TENSION trial) comparing a endoscopic
Table 1: Proportion of subjects achieving clinical response and remission 16
and surgical step-up approach in patients with infected necrotizing pancreatitis.
weeks after dose adjustment
Aims & Methods: Patients with infected necrotizing pancreatitis were randomly
assigned to the endoscopic or surgical step-up approach. The endoscopic step-up Clinical Response Clinical Remission
approach consisted of endoscopic transluminal drainage followed, if necessary,
by endoscopic necrosectomy. The surgical step-up approach consisted of percu- PBO!UST q8w 71% 39%
taneous catheter drainage followed, if necessary, by video-assisted retroperito-
neal debridement (VARD). The primary endpoint was a composite of major UST q12w!UST q8w 55% 41%
complications (i.e. new onset organ failure, bleeding, perforation of a visceral UST q8w ! UST q8w 46% 32%
organ, enterocutaneous fistula and incisional hernia) or death during 6 months of
follow-up. Secondary endpoints included, among other, pancreatic fistula, length
of hospital stay and costs.
United European Gastroenterology Journal 4(5S) A3
Conclusion: This is the first real-life experience with VDZ that shows substantial
Disclosure of Interest: B.E. Sands: Investigator for Janssen Research & variability in exposure to VDZ between patients. A clear exposure-response
Development, LLC correlation was observed as early as w2 and w6, with significant impact of
C. Gasink: Employee of Janssen Research & Development, LLC higher VDZ TC on meaningful outcomes as biological response, remission and
D. Jacobstein: Employee of Janssen Research & Development, LLC endoscopic healing. Our data support a potentially important role for early
L.L. Gao: Employee of Janssen Research & Development, LLC therapeutic drug monitoring also with VDZ.
J. Johanns: Employee of Janssen Research & Development, LLC Disclosure of Interest: A. Gils: Lecture fee(s): MSD, Janssen Biologicals, Abbvie,
P. Szapary: Employee of Janssen Research & Development, LLC Pfizer, Takeda. Consultancy: UCB. Conflict with: license of infliximab, anti-
J. Colombel: Investigator for Janssen Research & Development, LLC infliximab and adalimumab ELISA from Institution to apDia and with lateral
S. Targan: Investigator for Janssen Research & Development, LLC flow infliximab to R-Biopharm AG.
S. Ghosh: Investigator for Janssen Research & Development, LLC M. Ferrante: Financial support: research from Janssen Takeda, Lecture fees:
W. Sandborn: Investigator for Janssen Research & Development, LLC Tillotts, Ferring, Boehringer-Ingelheim, Janssen, Chiesi, Falk, Zeria,
Mitsubishi Tanabe, MSD, Takeda, and Abbie Consultancy: Abbvie, Ferring,
MSD, Boehringer-Ingelheim and Janssen.
G. Van Assche: Gert Van Assche receives financial support for research from
OP006 VEDOLIZUMAB EXPOSURE CORRELATES WITH CLINICAL, Abbvie and MSD, lecture fees from Janssen, Takeda, Ferring, MSD, and Abbvie
BIOLOGICAL AND ENDOSCOPIC OUTCOME IN PATIENTS WITH and does consultancy for Abbvie, MSD, and Takeda.
INFLAMMATORY BOWEL DISEASE S. Vermeire: Grant/research support Takeda, MSD, Abbvie Consultancy/speak-
A. Gils1, E. Dreesen1, G. Compernolle1, M. Peeters1, E. Brouwers1, V. Ballet2, er’s fees from Abbvie, MSD, Takeda, Pfizer, Galapagos, Genentech/Roche,
M. Noman2, M. Ferrante2, G. Van Assche2, S. Vermeire2 Mundipharma, Celgene, Hospira, Second Genome
1
Department Of Pharmaceutical and Pharmacological Sciences, KU Leuven, All other authors have declared no conflicts of interest.
Leuven/Belgium
2
Department Of Gastroenterology and Hepatology, University Hospitals Leuven,
Leuven/Belgium
OP007 EARLY VEDOLIZUMAB DRUG LEVELS AND INDUCTION
Contact E-mail Address: [email protected] SUCCESS IN PATIENTS WITH INFLAMMATORY BOWEL DISEASE
Introduction: Vedolizumab (VDZ) specifically targets the 4b7 integrin on gut- B. Ungar1, U. Kopylov1, M. Waterman2, O. Haj-Natour1, M. Yavzori1,
homing lymphocytes and has been approved for the treatment of patients with O. Picard1, E. Fudim1, Y. Chowers3, R. Eliakim1, S. Ben-Horin1
moderate to severe Crohn’s disease (CD) and ulcerative colitis (UC). We studied 1
Gastroenterology Institute, Sheba medical center, Ramat Gan/Israel
the relation between serum VDZ trough concentrations (TC) and clinical, biolo- 2
Dept. Of Gastroenterology, Rambam Health Care Campus, Haifa/Israel
gical and endoscopic outcomes in real-life practice. 3
Gastroenterology, Ramabm Medical Center, haifa/Israel
Aims & Methods: The first 75 patients (49 CD, 26 UC) who initiated VDZ
therapy (300 mg IV administered) in our tertiary referral center were sampled Contact E-mail Address: [email protected]
at trough during induction (w2 and w6) and early maintenance (w10, w14 and Introduction: Vedolizumab is an anti-4b7 monoclonal antibody effective in
w22) treatment. Clinical response (clinical symptoms and physician global assess- ulcerative colitis (UC) and Crohn’s disease (CD). Data regarding pharmacoki-
ment) was correlated to VDZ TC. All patients with UC received sigmoidoscopy netics/ pharmacodynamics of vedolizumab are still scarce.
at baseline and w10 and mucosal healing was defined as a Mayo endoscopic sub- Aims & Methods: Aim: To assess whether early vedolizumab trough levels (weeks
score of 0 or 1. Biological response (CRP decrease 50% from baseline) and 2, 6) correlate with response to vedolizumab induction therapy. Methods: A
remission (CRP5 mg/L) were assessed at w6 and w22 in patients with CD. An novel ELISA-based assay was developed for measuring vedolizumab levels,
ELISA for measuring serum VDZ TC was developed in house. TC are shown as and employed in prospectively-followed IBD patients receiving vedolizumab
median [IQR]. induction therapy. Drug levels were assessed for association with clinical remis-
Results: A substantial interindividual variability in VDZ TC was observed at w2 sion, defined by HBI55 and SCCAI53 for CD and UC, respectively. The
(27.8 mg/mL [21.5–35.9]), w6 (25.5 mg/mL [16.4–36.3]), w10 (23.6 mg/mL [12.0– primary outcome was the comparison of week 6 levels in patients with or without
37.7]) and w22 (11.3 mg/mL [4.4–17.5]). VDZ TC at w14 are about twice as high clinical remission at the same time-point. Association of week 2 and week 6 levels
in patients receiving an additional infusion at w10 (23.7 mg/mL [17.1–36.6], with week 14 clinical remission was also sought, as well as association of trough
n ¼ 42) compared to patients who did not receive a w10 infusion (13.1 mg/mL levels with inflammatory markers (Albumin and C-reactive protein, CRP).
[6.6–19.3], n ¼ 28) (p 5 .0001). Biological response and remission were achieved Results: Seventy-two patients were included (47 CD, 25 UC), of whom 14 (30%)
in 52% (14/27) and 30% (8/27) of patients with CD. Significantly higher VDZ and 15 (32%) of CD patients and 6(25%) and 8 (32%) of UC patients reached
TC were observed at w6 in case of biological response (23.8 mg/mL [16.1–33.8]), clinical remission by weeks 6 and 14, respectively. The median level of vedolizu-
compared to non-response (11.8 mg/mL [7.2–18.2]) (p ¼ .004) and when biological mab at week 6 was not different between patients who achieved remission by
remission was achieved (25.4 mg/mL [23.7–35.5]), compared to when no remission week 6 and those who did not (37.3 vs. 29.4 mg/ml respectively, p ¼ 0.85). Clinical
was achieved (13.0 mg/mL [9.8–19.8]) (p ¼ .0004). At w22, 59% (16/27) of remission rates at week 6 were also not associated with drug level quartiles at
patients with CD were in biological remission. Patients who were in biological week 6. Similarly, neither week 2 or 6 levels were predictive of clinical remission
remission at w22 had significantly higher VDZ TC throughout w2 to w22, com- at week 14 (35.4 vs. 44.8 mg/ml, p ¼ 0.75, 33.9 vs. 25.5 mg/ml, p ¼ 1, respectively).
pared to patients who were not in biological remission at w22 (table 1). Vedolizumab levels were also not associated with steroid free remission (p ¼ 0.1,
p ¼ 0.57) or with CRP normalization (p ¼ 0.26, p ¼ 0.73) at weeks 6 and 14,
respectively. Among UC patients separately analyzed, week 2 levels were asso-
Table 1: Vedolizumab trough concentrations, in mg/mL, median [IQR] (n),
ciated with clinical remission at week 14 (p ¼ 0.04). However, statistical signifi-
during induction (w2 and w6) and early maintenance (w10, w14 and w22)
cance for this difference was not retained after Bonferroni correction for multiple
treatment correlate with biological remission (CRP 5 mg/L) at w22 in patients
testing. Finally, multivariable analysis for clinical remission at week 6 has been
with CD.
performed including baseline albumin level and patient weight. When adjusting
Biological remission at w22 No biological remission at w22 for these co-variates, week 6 vedolizumab levels were not associated with clinical
remission at week 6 (p ¼ 0.56).
w2* 31.8 [23.9–38.9] (23) 23.6 [18.4–31.9] (17) Conclusion: In this real-life cohort of consecutive IBD patients receiving vedoli-
zumab, drug levels during induction were not associated with or predictive of
w6** 33.5 [22.1–38.5] (23) 16.6 [9.0–31.4] (17) clinical response to induction therapy and were not associated with CRP normal-
w10*** 37.9 [24.4–45.1] (15) 12.8 [7.5–19.3] (10) ization or steroid-free clinical remission. Future studies are pertinent in order to
w14** 25.8 [16.1–39.4] (22) 14.0 [9.7–18.6] (17) elucidate the role of therapeutic drug monitoring of vedolizumab during induc-
w22*** 16.1 [9.5–25.2] (23) 6.3 [2.8–11.2] (17) tion and maintenance.
Disclosure of Interest: U. Kopylov: Dr. Kopylov recieved consultancy fees from
*p 5 .05; ** p 5 .01; *** p 5 .001 Endoscopic healing was achieved in 65% (13/ Jannsen, research support from Jannsen and Takeda and lecture fees from
20) of patients with UC. Patients with endoscopic healing had significantly higher Jannsen, Takeda, Abbvie and CTS.
VDZ TC at w6 (30.5 mg/mL [18.6–38.0]), compared to patients who did not Y. Chowers: Prof. Chowers recieved consulting and lecture fees as well as grant
achieve endoscopic healing (16.6 mg/mL [11.0–29.3]) (p ¼ .02). Clinical response support from Takeda, Abbvie, Janssen, Pfizer, Ferring and Protalix.
was achieved in 69% (47/68) of the patients. Only in patients with UC, clinical R. Eliakim: Prof. Eliakim has received consulting and lecture fees from Takeda.
response was associated with higher VDZ TC at w2 (27.8 mg/mL [22.3–37.1], S. Ben-Horin: Prof. Ben-Horin has received consulting and/or advisory board
n ¼ 16) and w6 (32.0 mg/mL [17.8–37.7], n ¼ 16) compared to absence of clinical fees from Janssen, Takeda, Celltrion, Abbvie, & Schering-Plough and research
response (21.6 mg/mL [16.0–25.2] and 16.6 mg/mL [11.0–20.6], resp., n ¼ 7) support from Celltrion and Abbvie
(p ¼ .03 and p ¼ .02). All other authors have declared no conflicts of interest.
A4 United European Gastroenterology Journal 4(5S)
OP008 PREDICTORS OF NON-RESPONSE OR LOSS OF RESPONSE TO soft stools per day. These predictors should be considered when evaluating treat-
TUMOUR NECROSIS FACTOR ANTAGONIST THERAPIES IN ment options for patients.
INFLAMMATORY BOWEL DISEASE Disclosure of Interest: L. Peyrin-Biroulet: Consulting fees from Merck, Abbvie,
L. Peyrin-Biroulet1, A. Armuzzi2, J. P. Gisbert3, G.C. Nguyen4, B. Bokemeyer5, Janssen, Genentech, Mitsubishi, Ferring, Norgine, Tillots, Vifor, Therakos,
J. Lindsay6, M. Smyth7, M. Munsaka8, S. Ramagopalan9, J.M. Khalid10 BMS, UCB-pharma, Hospira, Celltrion, Takeda, Biogaran, Boerhinger-
1
Department Of Gastroenterology, Nancy University Hospital, Vandoeuvre les Ingelheim, Lilly, Pfizer, Amgen, Sandoz, Celgene, Biogen, Lycera, Bioepis.
Nancy/France A. Armuzzi: Grant/research support from: MSD, Consultant for: Abbvie,
2
Complesso Integrato Columbus, Internal Medicine and Gastroenterology - Celltrion, Hospira, Janssen, Lilly, MSD, Mundipharma, Pfizer, Sofar,
Complesso Integrato Columbus Catholic University, Rome/Italy Samsung, Takeda, Speaker bureau with: Abbvie, Astra-Zeneca, Chiesi,
3
Digestive Services, Hospital Universitario de La Princesa, Instituto de Ferring, Hospira, MSD, Mundipharma, Otsuka, Takeda, Zambon
Investigación Sanitaria Princesa (IP) and Centro, Madrid/Spain J.P. Gisbert: Grant/research support from and is on speaker bureau with MSD,
4
Mount Sinai Hospital Toronto, Toronto/Canada Abbvie, Hospira, Kern Pharma, Takeda, Janssen, Pfizer, Ferring, Faes Farma,
5
Gastroenterology Practice Minden, Minden/Germany Shire Pharmaceuticals, Dr. Falk Pharma, Chiesi, Casen Fleet, Gebro Pharma,
6
Dept. Of Digestive Diseases, Digestive Disorders Clinical Academic Unit, Barts & Otsuka Pharmaceutical, Vifor Pharma.
The London School of Medicine &, London/United Kingdom G.C. Nguyen: Consultant for: Janssen, Abbvie, and Takeda.
7
Global Medical Affairs, Takeda Pharmaceutical Global Medical Affairs, London/ B. Bokemeyer: Grant/research support from: Abbvie, Ferring, UCB, Consultant
United Kingdom for: Abbvie, MSD, Shire, Ferring, UCB, Hospira, Takeda, Movetis, Speaker
8
Safety Statistics & Observational Research Analytics, Takeda Development bureau with: Abbvie, Ferring, MSD, Merckle, Falk, HLR, UCB.
Center Americas Ltd, Deerfield/United States of America/IL J. Lindsay: Grant/research support from and is on speaker bureau with: MSD,
9
Evidera Real-world Evidence, London/United Kingdom Abbvie, Hospira, Takeda, Janssen, Ferring, Shire Pharmaceuticals, Vifor
10
Global Outcomes Research, Takeda Development Centre Europe Ltd, London/ Pharma, Atlantic Health care, Actavis (Warner Chilcott), and Tillotts.
United Kingdom M. Smyth: Employee of Takeda Development Centre Europe Ltd, London,
United Kingdom.
Contact E-mail Address: [email protected] M. Munsaka: Employee of Takeda Development Center Americas Ltd,
Introduction: Tumour necrosis factor antagonists (anti-TNFs) are effective at Deerfield, Illinois, USA.
inducing and maintenance disease remission in patients with moderate to S. Ramagopalan: Employee of Evidera and was commissioned by Takeda
severe ulcerative colitis (UC) or Crohn’s disease (CD). However, considerable Development Centre Europe Ltd. to conduct the study
proportions of patients do not respond to therapy or lose response over time. J.M. Khalid: Employee of Takeda Development Centre Europe Ltd, London,
Aims & Methods: This study uses real-world data to identify predictors of non- or United Kingdom.
loss of response to anti-TNF therapy. The study recruited UC and CD patients
from 6 countries [Canada, France, Germany, Italy, Spain, and the United
Kingdom (UK)] aged 18 years who initiated anti-TNFs (infliximab/adalimu-
mab) during June 2009 to June 2011 (CD) or June 2009 to June 2013 (UC). Data OP009 INFLAMMATORY BOWEL DISEASE COURSE AND
were collected on patient demographics, clinical characteristics and healthcare THERAPEUTIC MANAGEMENT IN REAL LIFE PRACTICE IN THE
resource use. Patients were classified as having non- or loss of response if they: CURRENT ERA OF ANTI-TNFS: ANALYSIS OF THE FRENCH
were hospitalized or required UC/CD surgery whilst on therapy, discontinued ADMINISTRATIVE HEALTH DATABASES 2009–2014
due to UC or CD flare, required dose-escalation or augmentation with steroids/ J. Kirchgesner1, M. Lemaitre2, A. Racine3, M. Zureik2, F. Carbonnel3, R. Dray-
immunosuppressants 4 months after therapy initiation, or disease severity Spira2
became worse after therapy initiation. Multilevel multivariate logistic regression 1
Institut Pierre Louis D’Épide´miologie Et De Sante´ Publique (unite´ Mixte De
was used to identify predictors of non- or loss of response. Recherche En Sante´ 1136), INSERM, Paris/France
Results: The study included 1195 patients (45% UC, 55% CD; 9.6% Canada, 2
Department Of Epidemiology Of Health Products, French National Agency for
13% France, 22% Germany, 23% Italy, 19% Spain and 14% UK). Mean age: Medicines and Health Products Safety (ANSM), Saint-Denis/France
40.3 (SD ¼ 13.7); 51%: male. Most patients had a Charlson comorbidity index 3
Gastroenterology Unit, CHU de Biceˆtre, APHP-Universite´ Paris Sud, Le Kremlin
(CCI) score of 0–1 (83%), 16% were current smokers, mean BMI was 24.8 Biceˆtre/France
(SD ¼ 7.18) and mean disease duration was 8 years (SD ¼ 8.07). Most patients
had a physician global assessment of moderate (45%) at study entry. Mean Contact E-mail Address: [email protected]
follow up was 3.4 years (UC) and 4.4 years (CD). Overall, 22% of patients Introduction: Management of inflammatory bowel disease (IBD) has evolved in
had a primary non-response and 71% were classified as having non- or loss of the last decade. Clinical trials have shown that the combination of anti-TNFs and
response to anti-TNF therapy in the maintenance period (4 months after initiat- thiopurines is more efficient than monotherapy with either of these. The impact
ing anti-TNF) over a mean follow up period of 32 months (SD ¼ 20.4). of these results in real-life practice is unknown. Moreover, the frequency of
Significant predictors of non-/loss of response are shown in the Table 1. treatment withdrawal has never been assessed in population-based cohort
studies.
Aims & Methods: Our aim was to assess IBD course and therapeutic management
Table 1: Predictors of non-response or loss of response among patients with
including treatment withdrawal, surgery rates and hospital stays in the current
ulcerative colitis and Crohn’s disease
era of anti-TNFs. Every patient affiliated to the French national health insurance
Odds Ratio with a diagnosis of IBD based on listed long-term diseases and/or hospital dis-
Baseline Variables (95% Confidence Interval) P-value charge diagnosis was included from 2009 to 2013, and followed up until 31
December 2014. Cumulative incidence rates were used to estimate the cumulative
Patients with probabilities of medication use, surgery and hospitalization among prevalent and
Ulcerative Colitis incident patients. Treatment sequences including treatment withdrawal after
introduction of thiopurines, anti-TNFs and combotherapy were assessed for
Rectal Bleeding (Reference: None) - 0.04 incident patients included between 2009 and 2012.
- Passing blood alone 0.24 (0.06–0.97) Results: 195,834 individuals were diagnosed with IBD (Crohn’s disease (CD), 106
- Passing blood with stool 50% of time 0.35 (0.10–1.19) 436 (31,353 incident patients); ulcerative colitis (UC), 89,398 (27,578 incident
- Passing blood with stool 550% of time 0.17 (0.05–0.62) patients)). Among incident patients treated with thiopurines or anti-TNFs (17
566 CD and 8035 UC patients), the first treatment was thiopurines, anti-TNFs
Endoscopic Findings - 0.02 monotherapy, and combotherapy in 69.1%, 24.8% and 6.1% of CD patients and
(Reference: Inactive/Mild) 78.2%, 17.7% and 4.1% of UC patients, respectively. Subsequently, 36.8% and
- Moderate 3.19 (1.14–8.97) 20% of CD patients were exposed to anti-TNFs monotherapy and combother-
- Severe 4.86 (1.61–14.7) apy, respectively, 5 years after diagnosis. More than 25% of CD and UC incident
Patients with Crohn’s Disease patients included between 2009 and 2012 withdrew thiopurines or anti-TNFs,
during more than three months after a first treatment course. Drug withdrawal
Number of Liquid or Soft Stools per Day1 1.12 (1.00–1.24) 0.04 was related to hospitalization or surgical procedures in less than 30% of these
C-reactive Protein (CRP)1,2 1.02 (1.00–1.03) 0.03 patients. Nearly 50% of CD patients and 40% of UC patients went back to their
initial treatment after withdrawal. Around 5% of CD patients and 4% of UC
Note: Only the significant predictors are included in the table above. Other non- patients stopped all IBD therapy during follow-up. Five years after diagnosis, the
significant variables included age, gender, body mass index, disease duration, cumulative risks of first intestinal resection in CD, and colectomy in UC were
Charlson comorbidity index score, and use of corticosteroids or immunomodu- 12.8% and 3.5%, respectively.
lators. 1Both were analyzed as continuous variables. 2Highest CRP values during Conclusion: The step-up approach remains the dominant strategy in IBD,
the baseline period were used. whereas exposure to anti-TNFs is high and surgery rates are low. Treatment
withdrawal in IBD is more common than expected. This study emphasizes the
growing need of studying de-escalation strategy in IBD.
Disclosure of Interest: F. Carbonnel: Franck Carbonnel had consulting fees for
Conclusion: In this cohort the majority of patients did not respond or lost Genentech, Otsuka, Vifor, and lecture fees for Hospira.
response to anti-TNF therapy over time. Predictors for patients with UC All other authors have declared no conflicts of interest.
included the absence of rectal bleeding and moderate/severe endoscopic scores,
and for patients with CD included higher CRP and higher number of liquid or
United European Gastroenterology Journal 4(5S) A5
OP010 CHARACTERISTICS OF CHILDREN WITH CROHN’S DISEASE J. Rahier: Advisory board and consultancy: abbvie, msd, GSK, hospira, jansens,
FAILING SUSTAINED REMISSION DESPITE ANTI-TNF EXPOSURE takeda. Speaker fee: abbvie, msd. Grant: abbvie, msd, takeda.
L.I. Wauters1, F. Smets2, I. Hoffman3, E. De Greef4, P. Bontems5, P. Alliet6, T. Moreels: None communicated
W. Arts7, B. Hauser8, S. Van Biervliet9, E. Van De Vijver10, I. Paquot11, O. Dewit: None communicated
H. Peeters12, P. Bossuyt13, J. Rahier14, T. Moreels15, O. Dewit15, D. Franchimont: None communicated
D. Franchimont16, V. Muls16, F. Fontaine17, E. J. Louis17, J. Coche18, M. De V. Muls: None communicated
Vos9, F. Baert19, J. Paul20, S. Vermeire21, G. Veereman4 F. Fontaine: None communicated
1
Gastroenterology and Hepatology, UZ Leuven, Leuven/Belgium E.J. Louis: Fees for: Educational Grant: MSD, Abbvie. Speaker Fees: Abbvie,
2
Pediatric Gastroenterology, UCL St Luc, Brussels/Belgium Ferring, MSD, Chiesi, Mitsubishi Pharma, Hospira, Janssen, Takeda. Advisory
3
Pediatric Gastroenterology, UZ Leuven, Leuven/Belgium Board: Abbvie, Ferring, MSD, Takeda, Mitsubishi Pharma, Celltrion,
4
Pediatric Gastroenterology, UZ Brussels, Brussels/Belgium Prometheus.
5
Pediatric Gastroenterology, HUDERF, Brussels/Belgium J. Coche: None communicated
6
Jessa Ziekenhuis, Hasselt/Belgium M. De Vos: None communicated
7
ZOL, Genk/Belgium F. Baert: None communicated
8
UZ Brussel, Brussels/Belgium S. Vermeire: Grant/research support Takeda, MSD, Abbvie. Consultancy/speak-
9
UZ Gent, Gent/Belgium er’s fees from Abbvie, MSD, Takeda, Pfizer, Galapagos, Genentech/Roche,
10
UZ Antwerpen, Antwerpen/Belgium Mundipharma, Celgene, Hospira, Second Genome.
11
CHC Liege, Liege/Belgium G. Veereman: Grant from MSD to Bespghan. Advisory board Janssen and
12
St Lucas, Gent/Belgium Boehringer Ingeleheim. Consulting Mead Johnson.
13
Imelda ziekenhuis, Bonheiden/Belgium All other authors have declared no conflicts of interest.
14
UCL Mont Godinne, Namur/Belgium
15
UCL St Luc, Brussels/Belgium MONDAY, OCTOBER 17, 2016 10:30–12:00
16
ULB Erasme, Brussels/Belgium IS MASS ERADICATION OF H. PYLORI RATIONAL? – ROOM C_____________________
17
CHU Liege, Liege/Belgium
18
St Pierre, Ottignies/Belgium
19
Heilig Hart, Roeselaere/Belgium OP011 IS HELICOBACTER PYLORI ERADICATION ABLE TO
20
DNAlytics, Brussels/Belgium IMPROVE THE SCORES OF ATROPHIC GASTRITIS AND
21
UZ Leuven, Leuven/Belgium INTESTINAL METAPLASIA? – LONG-TERM FOLLOW-UP STUDY
IN HIGH RISK POPULATION OF GASTRIC CANCER
Contact E-mail Address: [email protected] Y.J. Hwang1, N. Kim2, Y.J. Choi1, H. Yoon2, C. M. Shin2, Y.S. Park2,
Introduction: The identification of chidren at risk for failure to reach sustained D.H. Lee2
remission despite exposure to anti-TNF remains challenging in Crohn’s disease 1
Internal Medicine, Seoul National University Bundang Hospital, Seongnam/
(CD). Korea, Republic of
Aims & Methods: Data from BELCRO (Belgian observational prospective cohort 2
Department Of Internal Medicine, Seoul National University Bundang Hospital,
of paediatric CD) were analysed after 5 yrs follow-up. Disease severity was Seongnam/Korea, Republic of
scored at diagnosis and yearly thereafter as inactive, mild and moderate-to-
severe on a 3-point scale based on PCDAI/PGA scores. Sustained remission Contact E-mail Address: [email protected]
was defined as inactive disease for  2 yrs follow-up. Univariate analyses were Introduction: Helicobacter pylori (H. pylori) is a risk factor of atrophic gastritis
performed between anti-TNF exposed patients with or without sustained remis- (AG) and intestinal metaplasia (IM) which can undergo to gastric cancer.
sion and correlations assessed between variables and the outcomes average dis- However, the reversibility of AG and IM by H. pylori eradication is controver-
ease severity and sustained remission. sial, so far.
Results: Of 66 anti-TNF exposed patients (median (IQR) age 13.1 (11.5–15.2) yrs, Aims & Methods: This study was performed to evaluate the reversibility of AG and
50% male), 17% failed to reach sustained remission. Disease location was similar IM by anti-H. pylori therapy in large number of patients for a long period in South
in both groups and mild disease at diagnosis (45% vs. 16%; p ¼ .03) more frequent Korea. A total of 810 patients with follow-up at least 1 year were enrolled from
in the group failing sustained remission. There were no differences between age, January, 2006 to September, 2014. On the basis of H. pylori infection status and
gender, WBC or CRP at diagnosis and treatment between both groups. eradication, the subjects were divided into three groups, as follows: Group A
Percentages of infliximab and adalimumab use were similar in both groups, includ- (n ¼ 214) included those patients who were H. pylori negative. Group B (n ¼ 580)
ing drug switching and dose or interval adjustments. When stratified by follow-up had successful eradication result for H. pylori. Group C (n ¼ 116) had not received
clinic, infliximab in paediatric follow-up was less frequently associated with failure eradication therapy or showed eradication failure. The histological features of the
to reach sustained remission compared to sustained remission. AG and IM in the antrum and body were measured, respectively, using Sydney
system scores. All of three groups were followed at 1, 2, 4 and 5 or more years.
Results: In patients with successful eradication (Group B), grades of AG and IM
Univariate analyses of the type of follow-up clinic and anti-TNF treatment in both antrum and body significantly decreased at 1, 2, 4 and 5 or more years
between patients with or without sustained remission (more than one anti- (p 5 0.001) (Table). In contrast, in the H. pylori negative group (Group A), no
TNF possible). significant change was documented for grades of AG and IM in either antrum or
body except for grades of IM in body at 2 years and AG in body at 4 years
No sustained Sustained (Table). Similarly, in Group C, no significant change was documented for grades
remission remission of AG and IM in either antrum or body except for scores of AG in body at 5 or
Variable, number (%) (n ¼ 11) (n ¼ 55) P value more years (Table).

Paediatric follow-up and infliximab 3 (27) 37 (67) .01 Table: Histological changes in atrophic gastritis and intestinal metaplasia at 1, 2,
Paediatric follow-up and adalimumab 1 (9) 8 (15) .63 4 and 5 or more years after eradication therapy.
Adult clinic follow-up and infliximab 6 (55) 14 (25) .05 group n baseline 1 year 2 years 4 years 45 years
Adult clinic follow-up and adalimumab 2 (18) 4 (7) .25
Paediatric follow-up and adjustments 1 (9) 8 (15) .63 AG in antrum A 110 1.46  0.66 1.35  1.04 1.19  1.06 1.03  1.01 1.45  0.89
a a a a
AG in antrum B 282 1.49  0.62 0.87  0.86 0.86  0.90 0.76  0.88 0.56  0.89
Adult follow-up and adjustments 1 (9) 3 (11) .65
AG in antrum C 52 1.46  0.70 1.24  0.95 0.80  1.10 1.17  1.17 0.43  0.79
a
AG in body A 66 1.71  0.72 1.38  1.07 1.12  1.12 1.04  0.91 1.82  1.01
Higher average disease severity (2.1 (2.0–2.3) vs. 1.6 (1.3–1.8); p 5 .001), adult a a a a
AG in body B 195 1.62  0.65 0.77  0.92 0.78  0.95 0.75  0.98 0.25  0.68
clinic follow-up (73% vs. 27%; p 5 .01), surgery for CD (1 (0–3) vs. 0 (0–3); a
p 5 .01) and active disease after 5 yrs (91% vs. 24%; p 5 .05) were associated AG in body C 34 1.85  0.74 1.08  1.14 1.50  1.05 0.67  1.03 0.14  0.38
with failure to reach sustained remission. Both colonic disease and adult follow- IM in antrum A 117 1.81  0.68 1.61  0.86 1.56  0.87 1.63  0.96 1.54  0.89
a a a a
up (AUC ¼ .66; both p ¼ .04) correlated with average disease severity (no correc- IM in antrum B 369 1.65  0.66 1.37  0.83 1.28  0.94 1.11  0.92 0.66  0.88
tion for multiple testing). No other correlations were found. IM in antrum C 69 1.67  0.66 1.68  0.98 1.71  0.85 1.06  0.99 1.33  1.00
a
IM in body A 85 1.78  0.70 1.52  1.04 1.25  1.15 1.41  1.06 1.54  1.07
Conclusion: Patient phenotype at diagnosis does not predict failure to reach IM in body B 247 1.64  0.67 1.24  0.84 a
1.00  0.94 a
0.92  0.94 a
0.73  0.94 a
sustained remission despite anti-TNF exposure. Mild disease may not trigger
IM in body C 48 1.71  0.62 1.57  0.95 1.20  0.63 1.00  1.00 1.00  1.10
appropriate treatment and lead to active and complicated disease course.
Sustained remission occurred most with infliximab in paediatric follow-up.
: p 5 0.001. Group A included those patients who were H. pylori negative.
Information on serum levels is lacking.
Group B had successful eradication result for H. pylori. Group C had not
Disclosure of Interest: F. Smets: None communicated
received eradication therapy or showed eradication failure. AG, atrophic gastri-
I. Hoffman: None communicated
tis; IM, intestinal metaplasia.
P. Alliet: None communicated
W. Arts: None communicated Conclusion: This study shows improvement of AG and IM in both antrum and
B. Hauser: None communicated body by H. pylori eradication, which could be underlying mechanism of the
S. Van Biervliet: None communicated prevention of gastric cancer by H. pylori eradication.
E. Van de Vijver: None communicated Disclosure of Interest: All authors have declared no conflicts of interest.
H. Peeters: None communicated
P. Bossuyt: Advisory baord: Mundipharma, Dr Falk Benelux, MSD, Janssens-
Cilag. Lecturing fee: Abbvie, Takeda, Vifor Pharma. Educational grant: Abbvie
A6 United European Gastroenterology Journal 4(5S)
pathway. Higher expression of APLN is correlated with a more advanced clinical
stage and worse prognosis in HCC patients.
OP012 THE EFFECT OF CURRENT HELICOBACTER PYLORI Disclosure of Interest: All authors have declared no conflicts of interest.
INFECTION ON GASTRIC CANCER IN A LARGE POPULATION
BASED STUDY
S. Nam1, B.J. Park2, J.H. Nam3
1
Gastroenterology, Kyungpook National University Medical Center, Daegu/Korea, OP014 TUMORS SKEW THE CCR2-DEPENDENT ANTI-TUMOR
Republic of IMMUNE RESPONSE INITIATED BY ONCOGENE-INDUCED
2
Gastroenterology, National Cancer Center, Seoul/Korea, Republic of SENESCENCE TOWARDS TUMOR GROWTH PROMOTION
3
National Cancer center, Seoul/Korea, Republic of T. Eggert1, M. Heikenwälder2, X. W. Wang3, L. Zender4, T. Greten5
1
Thoracic and Gastrointestinal Oncology Branch, National Cancer Institute,
Contact E-mail Address: [email protected] Bethesda/United States of America/MD
Introduction: Although the association between risk of gastric cancer and 2
Chronic Inflammation and Cancer, German Cancer Research Center, Heidelberg/
Helicobacter pylori (H. pylori) in case-control study have evaluated, the effect Germany
of current H. pylori infection on the risk of gastric cancer has not been studied in 3
Laboratory Of Human Carcinogenesis, National Cancer Institute, Bethesda/
a large general population. United States of America/MD
Aims & Methods: Their first Health check-up persons, who underwent compre- 4
Dept. Of Internal Medicine I, University Hospital Tübingen, Tuebingen/Germany
hensive screening including endoscopy and H. pylori test from 2003 to 2013, were 5
Thoracic and Gastrointestinal Oncology Branch, National Cancer Institute,
enrolled. Current infection of H. pylori was defined as positive rapid urease test. Bethesda/United States of America
Negative current infection was defined as negative rapid urease test and absence
of previous H. pylori eradication. Adjusted regression analysis was performed Contact E-mail Address: [email protected]
and estimated odds ratio (OR) and 95% confidence interval (CI). Introduction: Oncogene-induced senescence induces the immune-mediated clear-
Results: Among 35519 persons with 19396 men, 113 gastric cancers and 158 ance of these precancerous senescent hepatocytes, preventing malignant transfor-
gastric adenomas were detected. In adjusted analysis, age (OR 1.06, 95% CI mation and tumor initiation; a process termed ‘senescence surveillance’ (1).
1.04–1.08), current infection of H. pylori (OR 2.39, 95% CI 1.53–3.74), first However, senescent hepatocytes can give rise to hepatocellular carcinomas
degree relatives with gastric cancer (OR 2.08, 95% CI 1.30–3.32), and high (HCC), if the senescence program is abrogated and/or senescent cells are not
glucose (OR 1.66, 95% CI 1.04–2.65) increased the risk of gastric cancer, whereas cleared (1). We set out to identify the mechanism of recruitment of senescent cell-
high HDL (60 mg/dL) reduced the risk of gastric cancer (OR 0.49, 95% CI clearing macrophages. Furthermore, we studied the effect of senescence-asso-
0.22–0.94). In sub-analysis by H. pylori, age was a common risk factor of gastric. ciated immune responses on neighboring full-blown tumor cells in the liver.
First degree relatives (OR 3.23, 95% CI 1.39–7.50) increased gastric cancer risk in Aims & Methods: To induce senescence in mouse livers, either oncogenic Nras
the absence of H. pylori, whereas high glucose (OR 1.98, 95% CI 1.16–3.39) (NrasG12V) or an effector loop mutant (NrasG12V/D38A), which is incapable
increased gastric cancer risk in the presence of H. pylori. of downstream signaling and senescence induction, were hydrodynamically deliv-
Conclusion: Current infection of H. pylori increased the risk of gastric cancer ered into C57BL/6, CCR2 KO and p19 KO mice. To achieve tumor development
about 2.4-fold in a large general population. in senescent livers, luciferase-expressing hepatocellular carcinoma cells were
Disclosure of Interest: All authors have declared no conflicts of interest. intrasplenically injected into mice after hydrodynamic gene delivery. Tumor
growth was assessed using weight and bioluminescence measurements as well
as quantification of macroscopic tumors. Senescent livers with or without
MONDAY, OCTOBER 17, 2016 08:00–12:00 tumors were analyzed using flow cytometry and immunohistochemistry.
AN UPDATE ON THE MANAGEMENT OF HEPATOCULLULAR CARCINOMA Furthermore, peritumoral tissue of 226 HCC patients was hierarchical clustered
– ROOM G_____________________ based on the expression of 35 senescence-associated genes (2). Senescence-asso-
ciated gene signature expression was then compared with chemokine expression
OP013 APLN PROMOTES TUMORIGENICITY IN HEPATOCELLULAR and survival. In addition, human peritumoral tissue was analyzed by immuno-
CARCINOMA THROUGH ACTIVATING PI3K-AKT PATHWAY AND histochemistry for the presence of senescence and myeloid cell markers.
ITS EXPRESSION IS ASSOCIATED WITH POOR SURVIVAL IN Results: In tumor-free livers, senescent hepatocytes induced CCR2þ immature
PATIENTS myeloid cell (iMC) accumulation, followed by iMC maturation into macro-
H. Chen, Q. Liang, J. Shen, J.J.Y. Sung, J. Yu phages, which clear senescent hepatocytes. In CCR2 KO mice, iMC recruitment
Medicine and Therapeutics, The Chinese University Of Hong Kong, Institute of and macrophage accumulation was impaired, causing persistence of oncogenic
Digestive Disease, Hong Kong/Hong Kong Prc Nras-expressing hepatocytes and ultimately HCC development. In contrast, how-
ever, tumor cells in senescent livers blocked the maturation of CCR2þ iMC into
Contact E-mail Address: [email protected] macrophages, which lead to an accumulation of iMC. These iMC inhibited NK
Introduction: We have recently identified that Apelin (APLN) was highly cell cytotoxicity against tumor cells, as demonstrated by reduced NK cell degra-
expressed in 18 paired hepatocellular carcinoma (HCC) tumor tissues compared nulation in vivo. NK cell inhibition through senescence-recruited iMC lead to
to adjacent normal liver specimen by transcriptome sequencing. APLN is an accelerated tumor growth. Accordingly, in CCR2 KO mice or C57BL/6 wild type
endogenous ligand for the G-protein-coupled APJ receptor. In this study, we mice depleted of iMC, senescence-induced tumor growth promotion was abro-
aim to investigate its function, mechanism of action and clinical implication in gated. Finally, gene expression and immunohistochemistry analyses in peritu-
HCC. moral tissue of patients with hepatocellular carcinoma confirmed the
Aims & Methods: APLN expression was examined in paired human HCC tissues, association of senescence-induced CCL2 expression, myeloid cell accumulation,
HCC cell lines, and mouse models of liver cancer. Biological function of APLN NK cell inhibition and poor prognosis.
was determined using cell viability, colony formation, cell cycle, apoptosis and Conclusion: Senescence-induced CCL2-CCR2 signaling and the ensuing myeloid
murine xenograft assays. Downstream effectors and pathways were identified by cell accumulation harbor context dependent functions in preventing HCC initia-
promoter luciferase reporter assay and western blot. Clinical implication of tion, but also promoting progression of established HCC. These findings hold
APLN was assessed in two human HCC cohorts. important translational significance for clinical practice: 1. CCR2 antagonists
Results: Liver cancer was induced in genetically obese mice (db/db, deficient in may fuel liver cancer growth in patients with chronic liver disease, in which
leptin receptor) and wild-type mice with diethylnitrosamine. mRNA analysis of senescent hepatocytes accumulate. 2. In patients with HCC, CCR2 antagonists
mice HCC tissues and adjacent non-HCC livers revealed that APLN was a top may reduce senescence-augmented immunosuppression induced by liver tumors.
candidate gene consistently up-regulated in HCC tumor tissues compared to Disclosure of Interest: All authors have declared no conflicts of interest.
adjacent non-tumor tissues. APLN was also overexpressed in human HCC tis-
sues as compared with adjacent normal tissues at mRNA level (28 pairs of non- References
alcoholic steatohepatitis (NASH) -HCC and 26 pairs of HBV-HCC patients) and
protein level (9 pairs of NASH-HCC patients). APLN was ubiquitously 1. Kang T. W., Yevsa T., Woller N., Hoenicke L., Wuestefeld T., Dauch D.,
expressed in eight HCC cell lines (7404, HepG2, Huh6, Huh7, PLC5, SKHEP1 Hohmeyer A., Gereke M., Rudalska R., Potapova A., et al. Senescence
and two NASH-HCC cell lines HKCI-2 and HKCI-10), whilst no or very low surveillance of pre-malignant hepatocytes limits liver cancer development.
expression was observed in a normal liver cell line (MIHA) and human normal Nature 2011; 479: 547–551.
liver tissues. Ectopic expression of APLN (in Huh7, Miha, HKCI-2 and HKCI- 2. Yildiz G., Arslan-Ergul A., Bagislar S., Konu O., Yuzugullu H., Gursoy-
10) was found to promote cell proliferation, accelerate G1/S phase progression Yuzugullu O., Ozturk N., Ozen C., Ozdag H., Erdal E., et al. Genome-wide
by increasing cyclin D1 expression, and render cells more resistant to MG132 or transcriptional reorganization associated with senescence-to-immortality
staurosporine induced apoptosis. Silencing of APLN by shAPLN transfection switch during human hepatocellular carcinogenesis. PLoS One 2013; 8:
(HepG2 and SK-Hep1) had the opposite effects in vitro and significantly inhib- e64016.
ited xenograft tumor growth in vivo. Promoter luciferase reporter assays revealed
that APLN promoted the PI3K/AKT pathway. Ectopic expression of APLN or
exogenous addition of APLN peptide induced the phosphorylation of AKT and
glycogen synthase kinase-3beta. Conversely, silencing of APLN or administra-
tion of ML221, an antagonist of APLN receptor, inactivated PI3K-AKT signal-
ing. APLN expression was significantly higher in late stage HCC (II-IV) than
early stage HCC (I) (P 5 0.05 for our cohort, and P 5 0.01 for TCGA cohort).
Kaplan–Meier curves showed that higher APLN expression was significantly
associated with shortened survival in patients with HCC (N ¼ 43 for our
cohort, and N ¼ 328 for TCGA cohort; both P 5 0.05).
Conclusion: APLN is commonly up-regulated in HCC. APLN plays an important
ocogenic role in promoting liver tumor growth via activation of PI3K-AKT
United European Gastroenterology Journal 4(5S) A7

MONDAY, OCTOBER 17, 2016 10:30–12:00 versus 33.9%, p ¼ .003) than standard LSL. NNL (n ¼ 50) were also more likely
IMPROVEMENTS OF ENDOSCOPIC RESECTION TECHNIQUES IN THE COLON to be non-granular (46 versus 33.9%, p ¼ .12) and were associated with previous
– ROOM K_____________________ biopsy (32 vs 13.8%, p ¼ .001) and carbon particle suspension injection within
10 mm of the lesion (26 vs 3.8%, p 5 .001). Neither intra-procedural bleeding nor
OP015 COLD FORCEPS AVULSION (CFA) WITH ADJUVANT SNARE deep injury were more common in NL-LSL treated with CFA and STSC. The
TIP SOFT COAGULATION (STSC) IS AN EFFECTIVE AND SAFE technique was technically successful in all cases. One perforation was recognised
STRATEGY FOR THE MANAGEMENT OF NON-LIFTING LARGE secondary to CFA in a previously attempted lesion and was successfully closed
LATERALLY SPREADING COLORECTAL LESIONS (NL-LSLS) with endoscopic clips with no sequelae. Endoscopic recurrence at SC1 was not
D. J. Tate, F. Bahin, L. Desomer, V. Gupta, M. Sidhu, M. J. Bourke significantly different for PANL-LSL treated with CFA and STSC than LSLs
Gastroenterology and Hepatology, Westmead Hospital, Sydney/Australia treated with complete snare excision, whereas NNL-LSL recurred more fre-
quently (16.0 vs 12.2%, p ¼ .578 and 28.2 vs 12.2%, p ¼ .005 respectively).
Contact E-mail Address: [email protected] Conclusion: CFA and adjuvant STSC is a safe, effective and surgery-sparing
Introduction: Non-lifting (NL) large laterally spreading and colorectal lesions therapy for the majority of NL-LSL. It is easy to use, inexpensive and does
(NL-LSL) are challenging to resect endoscopically and often necessitate surgery. not require additional equipment. Early recurrence rates at SC1 are comparable
Previously attempted endoscopic resection, pre-resection biopsy and sub-lesion between PANL-LSL and standard LSL. NNL-LSL recur more frequently. Non-
carbon particle suspension are common reasons for NL. Conventional endo- granular LSLs were over-represented in both groups. They may be more suscep-
scopic mucosal resection (EMR) techniques are often ineffective due to extensive tible to developing fibrosis after biopsy and therefore care should be taken to
submucosal fibrosis. Simple methods for safe and effective endoscopic manage- avoid significant tampering with these lesions prior to referral for definitive
ment of NL-LSL have not been described. endoscopic treatment.
Aims & Methods: The study aimed to evaluate the characteristics of NL-LSL and Disclosure of Interest: All authors have declared no conflicts of interest.
the safety and efficacy of endoscopic treatment by Cold Forceps Avulsion (CFA)
followed by thermal ablation of the avulsion site by Snare Tip Soft Coagulation
(STSC). Amongst a prospective observational study of patients referred for wide
field EMR of LSL 420 mm, LSLs which could not be completely resected by OP016 SCISSORS TYPE KNIFE SIGNIFICANTLY IMPROVED SELF-
snare due to NL were labelled NL-LSL. These were divided into previously COMPLETION RATE OF COLORECTAL ENDOSCOPIC
attempted non-lifting LSLs (PANL-LSL) and naı̈ve, non-lifting LSLs (NNL- SUBMUCOSAL DISSECTION PERFORMED BY SUPERVISED
LSL). [MB1] Such lesions had completion of resection using a standardized RESIDENTS: A PROSPECTIVE RANDOMIZED TRIAL
approach with CFA and STSC. The NL area was isolated by circumferential T. Yamashina1, Y. Takeuchi2, N. Uedo2
snare excision of all adjacent tissue including adenoma and/or normal mucosa to 1
Cancer and Cardiovascular Diseases, Osaka Medical Center for, Osaka/Japan
free the lateral margins. This then allowed effective CFA of NL adenoma. 2
Department Of Gastrointestinal Oncology, Osaka Medical Center for Cancer and
Systematic CFA was then performed to remove all visible NL adenoma. The Cardiovascular Diseases, Osaka/Japan
exposed submucosa of the avulsion site and its margins were treated with con-
trolled thermal ablation using STSC (ERBE effect 4, 80W). Scheduled surveil- Contact E-mail Address: [email protected]
lance colonoscopy was performed at 5 months (SC1) and 18 months (SC2) post Introduction: Colorectal endoscopic submucosal dissection (ESD) is currently not
the index procedure. The primary outcome was endoscopic and histological a common treatment for unskilled endoscopists because of technical difficulties.
evidence of adenoma clearance. The secondary outcome was safety. Standard Recently, the scissors-type knife, SB knife Jr type (SB Jr), was launched to reduce
statistical analyses were performed to compare standard LSL with NL-LSL. the difficulty of colorectal ESD, although it can be a time-consuming procedure.
Results: From January 2012 to April 2016, 677 patients (mean age 69 years, Aims & Methods: The aim of the present study was to evaluate the efficacy and
50.6% male) with 780 lesions (median size 35 mm (IQR 25–45 mm), 65.4% safety of the combined SB Jr and Flushknife for colorectal ESD compared with
proximal colon) were referred for WF-EMR. 33 lesions were excluded due to using the Flushknife alone performed by supervised residents. This was a pro-
suspicion for submucosal invasive cancer and the patients referred for surgery. spective randomized controlled trial in a cancer referral center. Eighty-five
EMR was performed on 83 NL-LSL and 664 standard LSL. 14 lesions were patients, with the same number of superficial colorectal neoplasms, were enrolled
excluded at initial EMR as a two-stage procedure was required for their resec- and randomly assigned to undergo ESD using the Flushknife alone (Flush group)
tion. Key comparisons between NL-LSL and standard LSL are presented in table or the SB Jr supported Flushknife (SB Jr group). The procedures were conducted
1. PANL-LSL (n ¼ 33) were smaller and more likely to be non-granular (62.5 by two residents. Primary endpoint was self-completion rate by the residents.

Abstract No: OP015

Table 1: lesions where cold forceps avulsion and snare tip soft coagulation (CFA and STSC) was used in the resection of PANL or NNL; p values represent
comparison to LSL. Two stage procedures were excluded. SD – standard deviation, IQR – interquartile range, SC1 – surveillance colonoscopy 1, ICV – ileocaecal
valve, PANL – previously attempted non lifting lesion, NNL – naı̈ve non lifting lesion.

PANL n ¼ 33 p NNL n ¼ 50 p LSL n ¼ 650

Patient

Age, mean (SD) 70.2 (8.6) .121 73.0 (9.5) 5.001 66.9 (12.1)
Male, (%) 18 (54.5) .598 29 (58.0) .266 324 (49.8)
Lesion
Median size (IQR) 25 (20–30) 5 .001 37.5 (25–50) .424 35 (25–45)
Morphology (%)
Granular 8 (25.0) .003 22 (44.0) .012 323 (52.4)
Non granular 20 (62.5) 23 (46.0) 209 (33.9)
Unclassified 4 (12.5) 5 (10.0) 85 (13.8%)
Location (%)
Rectum 11 (34.4) .121 6 (13.0) .091 121 (18.8)
Splenic to sigmoid 6 (18.8) 11 (23.9) 98 (15.2)
Transverse 5 (15.6) 14 (30.4) 132 (20.5)
Ascending and caecum (þICV) 10 (31.3) 15 (32.6) 294 (45.6)
Submucosal fibrosis 33 (100) 5 .001 50 (100) 5.001 179 (27.6)
Previous attempt at resection (%) 33 (100) 5 .001 0 (0) 5 .030 56 (8.7)
Previous biopsy (%) na 16 (32.0) .001 90 (13.8)
SPOT mark within 10 mm of lesion (%) na 13 (26) 5 .001 25 (3.8)
Histopathology (%)
Conventional adenoma 25 (92.6) .324 44 (90.0) .147 482 (77.5)
Serrated adenoma 2 (7.4) 4 (10.0) 135 (21.7)
Cancer 0 (0) 0 (0) 4 (0.6)
Other 0 (0) 0 (0) 1 (0.2)
Procedure
Duration, minutes, median (IQ range) 35 (18–45) .004 25 (15–40) .003 20 (10–30)
Intraprocedural bleeding requiring endoscopic control (%) 2 (7.7) .078 11 (22.4) .966 144 (22.2)
Deep injury (%) 6 (18.2) .181 1 (2.0) .049 66 (10.7)
Outcomes
Endoscopic Recurrence at SC1 (%) 4 (16.0) .578 11 (28.2) .005 59 (12.2)
A8 United European Gastroenterology Journal 4(5S)
Results: Self-completion rate was 66.7% in the SB Jr group, which was signifi-
cantly higher than that in the Flush group (39%, P ¼ 0.01). Even after exclusion
of four patients in the SB Jr group in whom ESD was completed using the OP018 THERMAL ABLATION OF THE MARGIN OF THE POST
Flushknife alone, the self-completion rate was significantly higher (62.8% vs. ENDOSCOPIC MUCOSAL RESECTION (EMR) MUCOSAL DEFECT
39%; P ¼ 0.03). The median procedure time among the self-completion cases IS HIGHLY EFFECTIVE IN THE PREVENTION OF ADENOMA
did not differ significantly between the two groups (58.5 vs. 50.5 min; RECURRENCE FOLLOWING EMR. THE ‘‘SCAR’’ STUDY
P ¼ 0.14). No severe adverse events were observed in either group. A. Klein1, V. Jayasekeran1, L. Hourigan2, D. J. Tate1, R. Singh3, G. Brown4,
Conclusion: SB Jr supported Flushknife significantly improved residents’ self- F. Bahin1, N. Burgess5, S. J. Williams1, E. Lee1, M. J. Bourke5
completion rate for colorectal ESD compared with the Flushknife alone, with 1
Gastroenterology and Hepatology, Westmead Hospital, Sydney/Australia/NSW
no increase in procedure time or adverse events. (University hospital Medical 2
Gastroenterology, Princess Alexandra Hospital, Brisbane/Australia/QLD
Information Network Clinical Trials Registry number UMIN000009497). 3
Gastroenterology, Lyell McEwin hospital, Adelaide/Australia/SA
Disclosure of Interest: All authors have declared no conflicts of interest. 4
Alfred Hospital, Melbourne/Australia/VIC
5
Gastroenterology and Hepatology, Westmead Hospital, Westmead/Australia/
NSW
OP017 FEASIBILITY, SAFETY AND EFFICACY OF KNIFE ASSISTED Contact E-mail Address: [email protected]
RESECTION (KAR) OF RECTAL POLYPS EXTENDING TO THE Introduction: Endoscopic mucosal resection (EMR) of large sessile and lateral
DENTATE LINE: HOW LOW CAN YOU GO? spreading colonic lesions 20 mm (LSLs) is safe and effective. The main limita-
K. Kandiah1, F.J.q. J. Chedgy2, S. Thayalasekaran1, S. Subramaniam1, tion is adenoma recurrence, which occurs in up to 20% at first surveillance
R. Bhattacharyya3, F. Thursby-Pelham1, P. Bhandari1 colonoscopy (SC1), mandating a structured surveillance program. Surveillance
1
Gastroenterology, Queen Alexandra Hospital, Portsmouth/United Kingdom procedures create compliance burdens, additional costs and potential patient
2
Endoscopy, Queen Alexandra Hospital, Portsmouth/United Kingdom morbidity. Endoscopically invisible micro-adenoma present at the margin of
3
Dept. Of Gastroenterology, Queen Alexandra Hospital Dept. of Gastroenterology, the resected LSL may account for adenoma recurrence. Adjuvant thermal abla-
Portsmouth/United Kingdom tion of the EMR defect margin may reduce adenoma recurrence rates.
Aims & Methods: A prospective multi-center randomized control study was per-
Contact E-mail Address: [email protected] formed (NCT01789749). The primary end-point was endoscopic and histological
Introduction: Rectal polyps extending to the dentate line (RPDL) pose a technical recurrence at SC1. Standard inject and resect EMR technique was used for all
challenge to endoscopic resection due to the narrow lumen, rich venous/haemor- lesions. Exclusion criteria included previously attempted lesions, incomplete
rhoidal plexus and proximity to the skin. Conventional snare EMR is challenging snare excision or involvement of the ileocaecal valve. After successful complete
due to the restrcited space and lack of precision with the snare. This has led to the LSL excision by EMR and careful inspection of the defect to ensure no residual
use of surgical techniques like TEMS and TAR for resection of RPDLs. Knife adenoma, mucosal defects were randomized 1:1 to either thermal ablation of the
Assisted snare Resection (KAR) allows for precise mucosal incision at the dentate defect edges using snare tip soft coagulation (STSC) at 80w effect 4, or no
line and the dissection of the polyp from the anorectal junction. additional treatment. SC1 was performed at 5–6 months, with standardized
Aims & Methods: We aim to assess the feasibility, safety and efficacy of KAR for photo documentation and biopsies of the scar.
RPDLs. This is a prospective observational study of patients who underwent Results: Over 32 months to January 2015, 768 lesions  20 mm were referred for
KAR with a mean follow-up of 32 months (range 1–83 months). All procedures EMR at 4 centers (407 were enrolled, 48 were later excluded, 359 were rando-
were done on a day case basis and were carried out under sedation by two mized (null arm n ¼ 178, active arm n ¼ 181)). Patient, procedure and lesion
endoscopists using high-definition gastroscopes with a distal transparent cap. characteristics were similar between the two groups. 267 (74.3%) patients have
The polyp margin on the anal side was injected with lifting solution consisting completed SC1. Endoscopic, and histologic recurrences at SC1 were significantly
of gelofusin, indigo carmine, 1% lignocaine and adrenaline. Haemostasis was lower in the active arm (8/138 (5.8%) versus 26/129 (20.2%), p 5 .001, relative
maintained using a combination of the endoscopic knife and coag-grasper risk (RR) ¼ 0.29 (95% CI 0.14–0.61) and 6/104 (5.8%) versus 20/97 (20.6%),
(Olympus Medical). A mucosal incision was extended around the margins of p ¼ 0.002, RR ¼ 0.28 (95% CI 0.12–0.67) respectively) (Table 1). Endoscopic
the polyp, followed by submucosal dissection to facilitate snare deployment to assessment of the post EMR scar had a sensitivity of 100%, a specificity of
achieve complete polyp resection. Post-procedural antibiotics were not routinely 98% and a negative predictive value of 100% for correctly identifying recurrence
given. when compared to histology results. There was no difference in the rate
Results: A total of forty patients (20 female, median age 69 years) underwent of delayed bleeding between the active and null groups (8/124 (6.5%) versus
KAR for RPDLs over the study period. The polyp characteristics and histology 9/136 (6.6%), p ¼ .957) and no difference in delayed perforation (0/124 (0%)
are described in Table 1. The curative resection after a single KAR was achieved vs 1/136 (0.7%), p ¼ .341).
in 33 (82.5%) patients. 7 of the 40 patients required further KARs, leading to a
total curative resection rate to 97%. The risk factors for multiple resections are
Table 1: Endoscopic and histological recurrence in patients randomised to null
polyps measuring 4 60 mm and encompassing 4 50% of the circumference
versus active arm of the SCAR study. Relative risk (RR); Confidence interval
(p 5 0.01). Overall, there was one complication where the patient had delayed
(CI)
bleeding which was managed conservatively. None of the patients experienced
perforation, or post-procedural sepsis. Null arm Active arm RR (95% CI) P value

Table 1: Lesion characteristics and histology Endoscopic 26/129 20.2% 8/138 5.8% 0.29 5 .001
recurrence (95% CI) (14.1–27.9%) (2.9–11.0%) (0.14–0.61)
Lesion size, median (range), mm 50 (12–150) Histological 20/97 20.6% 6/104 5.8 0.28 0.002
recurrence (13.8–29.7%) (2.7–12.0%) (0.12–0.67)
Morphology, n (%) LST – G, 29 (72.5) 2 (5) 2 (5) 7 (17.5) (95% CI)
nodular mixed LST – G,
homogenous LST – NG Is
Scarring, n (%) 13 (32.5)
Histology, n (%) 30 (75) 6 (15) 3 (7.5) 1 (2.5)
Adenoma with LGD Adenoma with HGD Conclusion: Thermal ablation of the margin of the post EMR mucosal defect with
Cancer Other – Condyloma acuminatum STSC, results in significantly lower adenoma recurrence rates at first surveillance
colonoscopy. Routine implementation of this simple and safe technique may
enhance EMR efficacy and reduce surveillance requirements with fewer proce-
dures and extended intervals.
Disclosure of Interest: All authors have declared no conflicts of interest.
Conclusion: This is the largest reported series of KAR for RPDLs. Our data
demonstrates that for Western endoscopists, KAR is a very safe and effective
technique in the treatment of RPDLs. As KAR is a viable alternative to full ESD,
TEMS and TAR, it will play an increasingly significant role in the management
of RPDLs.
Disclosure of Interest: All authors have declared no conflicts of interest.
United European Gastroenterology Journal 4(5S) A9
The results between hemoclip group and twin-grasper group

OP019 EVALUATION OF THE LONG-TERM OUTCOMES OF Number of Procedure Complete closure Endoscopical
ENDOSCOPIC SUBMUCOSAL DISSECTION PERFORMED WITH A Groups endoclips time(min) in water leak fail
SCISSORS-TYPE KNIFE FOR EARLY COLORECTAL NEOPLASMS
2.0 cm hemoclip 4.8  0.8 7.6  0.5 60% 0%
T. Kuwai, T. Yamaguchi, H. Imagawa, Y. Sumida, T. Takasago, Y. Miyasako,
T. Nishimura, S. Iio, A. Yamaguchi, H. Kouno, H. Kohno 2.0 cm twin-grasper 4.0  1.0 7.7  0.6 80% 0%
Gastroenterology, Kure Medical Center and Chugoku Cancer Center, Kure/Japan p-value 0.207 0.776 0.545
Contact E-mail Address: [email protected] 2.5 cm hemoclip 6.0  1.6 9.9  3.3 60% 0%
Introduction: Endoscopic submucosal dissection (ESD) is one of the most useful 2.5 cm twin-grasper 5.0  0.7 8.3  1.9 60% 0%
methods for treating early colorectal neoplasms, and an insulation-tipped knife, p-value 0.233 0.384
hook knife, or needle knife are conventionally used to perform ESD. However, 3.0 cm hemoclip 8.4  2.1 13.9  4.1 40% 20%
because these devices are used without fixation of target tissue, there is the
potential risk of complications due to an unexpected incision. To reduce the 3.0 cm twin-grasper 5.4  1.1 9.1  2.7 60% 0%
risk of complications associated with using a conventional knife to perform p-value 0.022 0.06 0.58
ESD, we used a scissors-type knife (stag beetle [SB] knife Jr, Akita Sumitomo
Bakelite Co.) that maintains an adequate dissection layer and prevents an unex-
pected muscular layer injury. We previously reported that performing colorectal Conclusion: The twin grasper-clips technique seems to reduce the use of hemo-
ESD with an SB knife Jr is an easy, safe, and technically efficient method. clips and to result in more effective and rapid closure than does the conventional
However, the long-term outcomes of this method are unknown. technique in large perforations of the sigmoid colon.
Aims & Methods: We aimed to evaluate the feasibility and long-term outcomes of Disclosure of Interest: All authors have declared no conflicts of interest.
ESD performed with an SB knife Jr for treating early colorectal neoplasms. ESD References
was performed for 227 lesions in 211 patients (male:female ratio ¼ 116:95; mean
age ¼ 69.1 years) between October 2010 and March 2016. We evaluated the 1. Anderson M, Pasha T and Leighton J. Endoscopic perforation of the colon:
patients’ clinicopathological characteristics, en bloc resection rate, histological lessons from a 10-year study. Am J Gastroenterol 2000 Dec; 95(12): 3418–22.
complete resection rate, R0 resection rate, tumor size, procedure time, complica- 2. Yoshikane H, Hidano H, Sakakibara A, Ayakawa T, Mori S, Kawashima H,
tions, and long-term outcomes, including local recurrence, and the survival rate. et al. Endoscopic repair by clipping of iatrogenic colonic perforation.
Results: The sites of the neoplasms were as follows: right colon, 94 lesions Gastrointest Endosc 1997; 46: 464–6.
(41.4%); left colon, 58 (25.6%), and rectum, 75 (33.0%). Regarding the macro- 3. Mana F, De Vogelaere K and Urban D. Iatrogenic perforation of the colon
scopic type of lesions, there were 95 (41.9%) laterally spreading tumors (LSTs) of during diagnostic colonoscopy: endoscopic treatment with clips. Gastrointest
the granular type, 79 (34.8%) LSTs of the nongranular type, and 48 (21.1%) Endosc 2001 Aug; 54(2): 258–9.
polypoid lesions. Histological examination findings showed that 102 lesions 4. Jovanovic I, Zimmermann L, Fry LC and Mönkemüller K. Feasibility of
(44.9%) were intramucosal carcinomas, 22 (9.7%) were shallow submucosal endoscopic closure of an iatrogenic colon perforation occurring during colo-
invasive carcinomas (51,000 mm), 25 (11.0%) were deep submucosal invasive noscopy. Gastrointestinal Endoscopy 2011; 73: 550–5.
carcinomas (41,000 mm), and 78 (34.4%) were tubular adenomas. The mean size 5. Matthes K, Jung Y, Kato M, Gromski M and Chuttani R. Efficacy of full-
of the resected tumors was 32.0  14.9 mm, and the median procedure time was thickness GI perforation closure with a novel over-the-scope clip application
76.5 minutes (range, 10–420 minutes). The rates of en bloc resection, histological device: an animal study. Gastrointest Endosc 2011 Dec; 74: 1369–75.
complete resection, and R0 resection were 98.2% (223/227 lesions), 93.8% (213/ 6. Renteln Dv, Schmidt A, Vassiliou M, Rudolph HU, Gieselmann M and
227), and 85.0% (193/227), respectively. All lesions were treated easily and safely Caca K. Endoscopic closure of large colonic perforations using an over-
without an unexpected incision, and no perforations occurred during the proce- the-scope clip: a randomized controlled porcine study. Endoscopy 2009; 41:
dure. Delayed bleeding, delayed perforation, and rectal stricture occurred in 481–6.
3.8% (6/227), 0.4% (1/227), and 0.4% (1/227) of the lesions, respectively, and
all of these complications were cured conservatively. The median follow-up time
MONDAY, OCTOBER 17, 2016 10:30–12:00
was 558 days (range, 18–1,976 days). Local recurrence was observed in only 0.8%
of the lesions (2/227). One patient (0.5%) died of colorectal cancer, and 5 patients HOT TOPICS FROM LATIN AMERICA – ROOM M_____________________
(2.3%) died of other diseases. The 5-year overall survival rate and disease-specific OP021 ENDOSCOPIC TREATMENT OF COMPLEX BILIARY STONES:
survival rate were 94.8% and 98.7%, respectively. SPYGLASS þ ELECTROHYDRAULIC LITHOTRIPSY X BALLOON
Conclusion: ESD performed with an SB knife Jr is a technically efficient and safe DILATION OF THE MAJOR PAPILLA - PRELIMINARY RESULTS
method that is associated with favorable long-term outcomes in cases of early OF A RANDOMIZED CONTROLLED TRIAL
colorectal neoplasms. T. Franzini, R. N. Moura, G. O. Luz, M. E.L. Dos Santos, T. F. De Souza, G.
Disclosure of Interest: All authors have declared no conflicts of interest. L.R. Silva, S. E. Matuguma, S. Cheng, P. C. Bonifacio, L. A.C. D’Albuquerque,
P. Sakai, E. G.H. De Moura
Department Of Gastroenterology, University of Sao Paulo Medical School, Sao
Paulo/Brazil
OP020 THE EFFICACY OF THE NOVEL TISSUE GRASPER-CLIPS
TECHNIQUE FOR LARGE SIGMOID COLON PERFORATIONS IN Contact E-mail Address: [email protected]
EXPERIMENTAL SIMULATION MODEL Introduction: Endoscopic technique is the first choice for the treatment of bile
S.J. Han1, Y. Jung2, I. Chung1, Y.S. Cho1, T.H. Lee1, S. Park1, S. Kim1 duct stones, with success rates, ranging from 85% to 95%, and relatively low
1
Internal Medicine, Soonchunhyang University Hospital, Cheonan/Korea, Republic complication rate. However, some stones can become a great challenge for endos-
of copists. Complementary methods are available as mechanical lithotripsy and
2
Internal Medicine, Soonchunhyang university hospital, cheonan/Korea, Republic papillary balloon dilation after sphincterotomy. Single operator cholangioscopy
of combined with electrohydraulic lithotripsy (EHL) is emergent in this scenario.
Aims & Methods: We compare the success between two methods in the endo-
Contact E-mail Address: [email protected] scopic removal of difficult bile duct stones: Spyglass associated with EHL X
Introduction: The incidence of iatrogenic colonic perforation has been gradually Balloon dilation of the major duodenal papilla. 100 patients were randomized
increasing. An effective method of treating iatrogenic perforations including into two groups. Group one was Spyglass þ EHL and group 2 balloon dilation.
visual recognition followed by immediate closure during colonoscopy reduces From april of 2014 to present date (March 2016) we have enrolled 82 patients.
the incidence of sequelae and the morbidity and mortality. Perforations in the Include criteria were: Over 18 years, difficult biliary stones, signed term of con-
sigmoid colon are more frequent and more difficult to close due to the narrow sent. All patients receive antibiotic prophylaxis with 400 mg of Ciprofloxacin IV.
lumen and considerable mobility. Failures in both groups were submitted to plastic stenting. To compare the
Aims & Methods: This study was to evaluate the efficacy of combined use of methods we use the student t-test and Mann-Whitney Rank Sum test.
endoclip and a novel tissue grasper closure technique using double channel endo- Complications were analyzed by the Fisher test and Q squared.
scope for large colon perforation in sigmoid colon model. This study was Results: The average age was 55.1 þ/ 16.9 years. Women corresponded to
designed as a prospective, randomized, experimental study using ex vivo porcine 76.54% of the patients. Success rate reached 77.77% in group 1 and 72.22% in
colorectal specimens. Thirty-five standardized and variable artificial perforations group 2 (P ¼ 0.568). Median procedure time was 71.08 minutes (17–150) in group
were closed in the hemoclip group (hemoclips) and twin-grasper group (hemo- 1 and 49.81 (17–180) in group 2 (P ¼ 0.021). X-ray time was 10.89 minutes in
clips with a novel tissue grasper). We counted the number of hemoclips used per group 1 and 10.16 in group 2 (P ¼ 0.052). Median number of stones per patient
case to assess the cost and efficacy of the procedure. was 2.31 (1–8) in group 1 and 2.22 (1–15) in group 2 (P ¼ 0.605). Size of the
Results: In the hemoclip group (n ¼ 20), among the 1.5, 2.0, 2.5, and 3.0 cm stones in group 1 was 1.88 (1–3.5) and 2.09 (1–3.5) in group 2 (P ¼ 0.015). Minor
defects, the mean number of clips (3.8  0.8, 4.8  0.8, 6.0  1.6, and 8.4  2.1, adverse event occurred in one patient of each group. There was one death not
respectively, p ¼ 0.001) and closure time (5.3  1.8, 7.6  0.5, 9.9  3.3, and related to procedure (cardiologic cause).
13.9  4.1 min, respectively, p ¼ 0.001) differed significantly. In the twin-grasper Conclusion: To our knowledge this is the largest randomized controlled trial
group (n ¼ 15), among the 2.0, 2.5, and 3.0 cm defects, the mean number of clips comparing this two techniques. We found so far an overall success rate of
(4.0  1.0, 5.0  0.7, and 5.4  1.1, respectively, p ¼ 0.101) and closure time 77.77% in Spyglass þ EHL procedure and 72.22% in balloon dilation group.
(7.7  0.6, 8.3  1.9, and 9.1  2.7 min, respectively, p ¼ 0.506) did not differ
significantly. In 3 cm defects, the mean number of hemoclips used per case and
total closure time were significantly lower in the twin-grasper group than the
hemoclip group.
A10 United European Gastroenterology Journal 4(5S)

Abstract No: OP022

Characteristics of procedures, patients and outcome

NUMBER NUMBER POST
OF OF POST HYBRYDKNIFE
PACKED HYBRID PRE HYBRIDKNIFE HYDRIBKNIFE HB
AGE/ CLINICAL NAIVE VS RBC APC GAVE HB HB AT 1M AT 6M
PATIENT GENDER PICTURE REFRACTORY TRANSFUSED TREATMENTS/ TIME TYPE COMPLICATIONS (GR/DL) (GR/DL) (GR/DL)

1 58/F Anemia Naive 2 1 Watermelon None 8 13.6 14.2

2 60/F Melena Refractory 10 1 Watermelon Mild 3.5 6.6 13.3
(4 APC) abdominal pain
3 61/F Melena Refractory 15 1 Punctate None 6.1 9.2 12.9
(9 APC)
4 79/F Melena Refractory 9 1 Watermelon None 4.2 10.8 13.4
(3 BL)
5 67/F Anemia Refractory 12 2 Watermelon None 6.3 8.4 13.1
(4 APC/4 BL)
6 55/F Anemia Naive 2 1 Punctate None 7.2 10.1 14.5
7 67/F Anemia Naive 8 1 Watermelon Mild abdominal pain 6.5 11.4 14.1
8 48/M Melena Naive 6 1 Watermelon None 7.2 10.2 15.1
9 89/F Melena Refractory 14 1 Punctate None 4.9 9.3 13
(5 APC)
Total Mean 44.4% 44.4% Naive Median 9 88.8% 66.6% 77.8% 5.98  1.49 9.95  1.96 13.7  0.76
64.7  12.5 Anemia 55.6% Refractory (2–15) 1 Treatment Watermelon No complications
8F/ 1M 55.6% Melena 21.2% 33.4% 22.2% Mild
2 Treatments Punctate abdominal pain

previous treatments in refractory patients were 4 (3–9). All patients reached

normal Hb levels after 6months. The mean difference between prehybrid-APC
It is important highlight that only one session of Spyglass þ EHL was performed (5.98  1.49gr/dl) and 6m after hybrid-APC (13.7  0.76gr/dl) was þ7.74 gr/dl
in each patient of our protocol. Better success rates can be achieved with two or (p 5 0.000/CI 95% 6.84–8.64) student T-test. 8 patients received 1 session and 1
more sessions and increase up to 90%. Cross-over of the failure cases in both required 2. No major complications were observed (Table 1).
groups is bringing us a very interesting result and suggests that in some cases the Conclusion: Based on these preliminary results, Hybrid-APC is safe and effective
methods can be complementary. There was no statistical difference between the for the treatment of GAVE (nave or refractory) with the advantage of needing
groups, although spyglass group had numerically a little higher success rate. The only 1 or maximum 2 applications and with excellent results at medium term.
study provides us an evidence-based algorithm of difficult stones endoscopic Disclosure of Interest: All authors have declared no conflicts of interest.
treatments. In addition, we observed potential advantages when we associate References
the methods, providing one step more before declaring endoscopic failure in
treating a difficult biliary stone. 1. Fuccio Lorenzo, Mussetto Alessandro, Laterza Liboria. et al. Diagnosis and
Disclosure of Interest: All authors have declared no conflicts of interest. managment of gastric antral vascular ectasia. World J Gastrointest Endosc
2013; 5(1): 6–13.
2. Sebastian S., McLoughlin R, Qasim A., et al. Endoscopic argón plasma
coagulation for the treatment of gastric antral vascular ectasia (watermelon
OP022 SAFETY AND EFFICACY OF HYBRID-APC IN GASTRIC stomach): long-term results. Digestive and Liver Disease 2004; 36: 212–217.
ANTRAL VASCULAR ECTASIA (GAVE): A PILOT STUDY 3. Zepeda Gómez Sergio, Sultanian Richard, Teshima Christopher, et al.
Gastric antral vascular ectasia: a prospective study of treatment with band
O.V.V. Hernandez Mondragon, G. Blanco Velasco, J. M. Blancas Valencia
ligation endoscopic. Endoscopy 2015; 47: 538–540.
Endoscopy, IMSS, Mexico city/Mexico
4. Naidu Harini, Huang Qin, Mashimo Hiroshi. Gastric antral vascular ectasia:
Contact E-mail Address: [email protected] the evoltion of therapeutic modalities. Endoscopy International Open 2014;
Introduction: Antral vascular ectasia (GAVE) is a capillary-like vascular malfor- 02: 67–73.
mation usually located in gastric antrum. Liver cirrhosis, autoimmune, cardiac 5. Manner Hendrik, Neugebauer Alexander, Scharpf Marcus, et al. The tissue
and chronic renal disease are ussualy concomitant. Patients often require high effect of argón-plasma coagulation with prior submucosal injection (Hybrid-
number of RBC transfusions because of anemia or melena. Treatment includes APC) versus standard APC: a randomized exvivo study. United European
argon plasma coagulation (APC), Band ligation (BL) and radiofrequency abla- Gastroenterology Journal 2014; 2(5): 383–390.
tion (RFA). Patients usually respond to 3 to 5 APC, or 2 to 3 band ligation (BL) 6. Fujishiro Mitsuhiro, Kodashima Shinya, Ono Satoshi, et al. Submucosal
sessions, if not, refractory GAVE is considered and other treatments should be injection of normal saline can prevent unexpected deep termal injury of
offered. RFA is effective but expensive and requires at least two sessions. Hybrid- argón plasma coagulation in the in vivo porcine stomach. Gut and Liver
APC is new technique that combines submucosal injection of saline solution to 2008; 2(2): 95–98.
create a ‘‘safety cushion’’ with the use of APC, this could have the advantage of a
deeper and safer treatment compared with other endoscopic modalities.
MONDAY, OCTOBER 17, 2016 10:30–12:00
Aims & Methods: We aimed to evaluate the safety and efficacy of hybrid-APC in
naı̈ve or refractory GAVE patients. Methods: This is a prospective, longitudinal PREVENTION OF GI CANCERS: NUTRITION AND CHEMOPREVENTION – ROOM 1.61/
and comparative (before and after) pilot study that includes symptomatic 1.62_____________________
patients with GAVE (endoscopic and histologic diagnosis). Naı̈ve or refractory
patients (defined as more than 5 previous APC or 3 BL without endoscopic, OP023 CD24 INDUCES THE ACTIVATION OF B-CATENIN IN
clinical and laboratorial response) between 18 and 90 years old were included. INTESTINAL TUMORIGENESIS
We excluded patients with GAVE without clinical manifestations or anemia of A. Fokra1, S. Shapira2, D. Kazanov2, F. Bedny3, E. Brazowski3, C. Varol4,
other GI source. After a creation of a ‘‘saline cushion’’ with the APC catheter in S. Kraus2, N. Arber2
the GAVE zone, all received APC with forced coagulation at 80w effect 2 in a 1
Faculty Of Medicine, Tel Aviv University, Tel Aviv/Israel
single session and then they were followed at 1,3 and 6 months. New session was 2
The Integrated Cancer Prevention Center, Tel Aviv Sourasky Medical Center, Tel
applied if anemia and endoscopic picture of GAVE were documented. Aviv/Israel
Characteristics of the patients were described and expressed in means and SD 3
Pathology Institute, Tel Aviv Sourasky Medical Center, Tel Aviv/Israel
or median and IQR and percentages as appropriate. Comparisons between quan- 4
Research Center For Digestive Tract and Liver Diseases, Tel Aviv Sourasky
titative variables was done using paired T-test and considering p 5 0.05 as sta- Medical Center, Tel Aviv/Israel
tically significant.
Results. Between July 2015 and March 2016 9 patients were included, 8 women Contact E-mail Address: [email protected]
and 1 men. Mean age was 64.7  12.5yo. 44.4% presented anemia and 55.6% Introduction: CD24 is a GPI-linked protein that functions as an adhesion mole-
melena. Median number of transfusions was 9 (2–15). 3 had liver cirrhosis, 2 cule and is overexpressed at an early stage of CRC.The Wnt/b-catenin signaling
chronic renal failure, 1 cardiac disease and 3 without any association. GAVE pathway plays an important role in CRC carcinogenesis process. We had shown
type was ‘‘watermelon’’ in 6 and ‘‘punctate’’ in 3. 44.4% were naı̈ve and 55.6% that CD24 could affect the tumorigenesis process in Apc Min mice
refractories to previous treatment (3 in APC and 2 with BL). The median Aims & Methods: Aim to study the cellular interactions between CD24 and b-
catenin, and their effects on intestinal tumorigenesis Methods CD24-inducible
293T-Rex cells previously developed in our lab and SW480 CRC cells stably
transfected with CD24were used to study this interaction in vitro. Apc Min
and CD24 knockout (KO) mice, both on a C57BL/6J genetic background,
were crossed to generate double KO transgenic mice. Genotypes were routinely
verified by analysis ofDNA extracted from tail biopsies. Small and large bowel
polyps were counted macroscopically following methylene blue staining and his-
tology was verified microscopically. Colonic polyps were measured and counted
United European Gastroenterology Journal 4(5S) A11
using mice colonoscopy. Histology confirmed by an experienced pathologist was MONDAY, OCTOBER 17, 2016 10:30–12:00
used to study this interaction in vitro. NEW PERSPECTIVES IN DIAGNOSTIC AND THERAPEUTIC EUS – ROOM
Results: In vitro Western blotting analyses showed that expression of CD24 in N2_____________________
293T-Rex cells induced the activation of b-catenin and co-immunoprecipitation
studies of CD24 and b-catenin indicated that these two proteins might beinter- OP025 LOW PROCUREMENT YIELD AND DIAGNOSTIC ACCURACY
acting, while down-regulation of CD24 in SW480 cells caused a decrease in the OF EUS-GUIDED FINE NEEDLE BIOPSY OF TRANSDUODENAL
levels of active b-catenin and cytoplasmic/nuclear fractionation showed that LESIONS USING THE 19-GAUGE FLEXIBLE NEEDLE: A LARGE
more active b-catenin enters the nucleus in cells thatexpress CD24 (clone1) com- MULTICENTER PROSPECTIVE STUDY
pared to control cells (clone 4). In addition, in both cell lines, TOP/FOPluciferase M. Rimbas1, F. Attili2, C. Fabbri3, I. Yasuda4, L. Fuccio5, L. Palazzo6,
reporter assay showed a significant increase in Luciferase activity upon CD24 I. Tarantino7, J. Dewitt8, L. Frazzoni9, A. Larghi2
expression induction Depletion of CD24 alleles in Apc Min mice led to a sig- 1
Gastroenterology Department, Colentina Clinical Hospital, Carol Davila
nificant reduction in the number of polyps in the intestine.C57BL6/J mice carry- University of Medicine, Bucharest/Romania
ing the Apc Min mutation develop 24.3  3.7 adenomas and several 2
Digestive Endoscopy Unit, Catholic University, Rome/Italy
carcinomas in the smallintestine by the age of 16 weeks. The ApcMin/CD24 3
Unit Of Gastroenterology and Digestive Endoscopy, AUSL Bologna, Bellaria-
þ/- mice developed 8  1.4 polyps and ApcMin/CD24 -/- (doubleKO) mice Maggiore Hospital, Bologna/Italy
developed 7  1.7 polyps (p ¼ 0.006). Colonoscopy showed a significant reduc- 4
Department Of Gastroenterology, Teikyo University Mizonokuchi Hospital,
tion in thenumber and size of polyps upon depletion of CD24 alleles. The Kawasaki/Japan
ApcMin displayed severe splenomegaly (355  68 mg)compared to (205  51 5
Department Of Medical and Surgical Sciences, S.Orsola-Malpighi University
mg) in ApcMin/CD24 þ/- mice and (141  49 mg) in double KO mice similar Hospital, Bologna/Italy
to WT mice (p ¼ 0.006). Hb level was 3.8  2.5 in the ApcMin significantly lower 6
Department Of Endoscopy, Trocadero Clinic, Paris/France
than in the double KO mice (8.2  0.9) and the WT (p ¼ 0.0009) 7
Endoscopy Service, Department Of Diagnostic and Therapeutic Services, IRCCS-
Conclusion: 1. CD24 plays a major role in intestinal tumorigenesis 2. Knocking ISMETT (Istituto Mediterraneo per i Trapianti e Terapie ad alta specializza-
down even one copy of CD24 almost completelyabolished formation in vivo, and zione), Palermo/Italy
prevent anemia and splenomegaly the whole mark of intestinal blood loss seeing 8
Department Of Gastroenterology, Indiana University Health Medical Center,
inthe ApcMin 3. CD24 interacts with the Wnt pathway by activating b-catenin 4. Indianapolis/United States of America/IN
Down regulation of CD24 maybe animportant aim in the therapy of CRC 9
Gastroenterology Unit, Department Of Medical and Surgical Sciences, University
Disclosure of Interest: N. Arber: Consultation Fee: Bio-View, Check-Cap, Bayer of Bologna, Bologna/Italy
Stock Shareholder: Micromedic, Gi-VieW
All other authors have declared no conflicts of interest. Contact E-mail Address: [email protected]
Introduction: Endoscopic ultrasound-guided fine needle aspiration (EUS-FNA) is
the procedure of choice to obtain samples for reaching the definitive diagnosis of
lesions of the gastrointestinal (GI) tract and of adjacent organs (1). The proce-
OP024 LOSS OF PTPN2 IN MACROPHAGES AGGRAVATES COLITIS dure is safe and very accurate, especially when rapid on-site evaluation (ROSE)
BUT PROTECTS FROM COLORECTAL TUMOUR FORMATION of the adequacy of the collected specimens is performed. However, in centers
M. R. Spalinger1, S. H. Kasper1, S. Bengs2, C. Gottier1, K. Atrott1, T. Raselli1, where ROSE is not available, it has been suggested that the performance of EUS-
G. Rogler3, M. Scharl4 fine needle biopsy (EUS-FNB) can result in a greater chance to reach a diagnosis
1
Gastroenterology and Hepatology, University Hospital Zurich, Zurich/ than a typical EUS-FNA sample. Based on a previous study (2), which reported a
Switzerland 19-gauge flexible needle to be able to sample transduodenal lesions and be diag-
2
, Department Of Gastroenterology and Hepatology, Usz, Zurich/Switzerland nostic in all 32 included patients, an algorithm for EUS-tissue acquisition (EUS-
3
Division Of Gastroenterology and Hepatology, University Hospital Zurich, TA) of solid lesions from the duodenum depending on the availability of ROSE
Zürich/Switzerland has been proposed. Thus, in institutions with no availability of ROSE, for lesions
4
Klinik Für Gastroenterologie Und Hepatologie, Universitätsspital Zürich, Zürich/ accessed from the duodenum, which represent the most difficult sampling posi-
Switzerland tion because of the stiffness induced by the needle assembly on the echoendo-
scope shaft, the authors recommended the use of a 19-gauge needle made of
Contact E-mail Address: [email protected] nitinol with increased flexibility (3).
Introduction: Variants in the gene locus encoding protein tyrosine phosphatase Aims & Methods: To test the validity of this recommendation we performed a
non-receptor type 2 (PTPN2) are associated with Crohn’s disease (CD) and prospective multicenter study aimed at evaluating the technical feasibility, pro-
ulcerative colitis (UC). We have previously shown that loss of PTPN2 in T curement yield, and diagnostic accuracy of this newly developed 19-gauge nitinol
cells results in enhanced colitis and signs of autoimmunity. Inflammasomes flexible needle in patients with solid lesions or enlarged lymph nodes that could
form upon cytosolic presence of danger molecules and induce the cleavage of be punctured only from the duodenum. Consecutive patients with solid lesions
pro-IL-1b and pro-IL-18 into their active forms. Secretion of IL-1b is an impor- who needed to undergo EUS sampling from the duodenum were prospectively
tant activator of innate and adaptive immune functions, while IL-18 is involved enrolled in 6 tertiary care referral centers. Puncture of the lesion was performed
in epithelial cell protection. with the 19-gauge flexible needle (ExpectTM 19 Flex and Slimeline ExpectTM 19
Aims & Methods: In this study, we aimed to address whether loss of PTPN2 in Flex) and at least 3 needle passes were performed in each case. The feasibility,
macrophages affects inflammasome activation and whether this affects colitis procurement yield, and diagnostic accuracy were evaluated.
severity and susceptibility for colorectal cancer. To specifically delete PTPN2 Results: 246 patients (144 males, mean age 65.1  12.7 years) with solid lesions
in macrophages, mice with a floxed PTPN2 gene were crossed with mice expres- (203 cases, 82.5%) or enlarged lymph nodes (43 cases, 17.5%) were enrolled. The
sing Cre-recombinase under the Lysozyme promoter (PTPN2-LysMCre mice). mean size of the target lesion was 32.6  12.2 mm. The procedure was technically
Acute colitis was induced in 10–12 week old female mice by administration of 2% feasible in 228 (92.7%) patients, with an overall procurement yield of 76.8%.
DSS for 7 days, chronic colitis by administration of four cycles of 1.5% DSS for Two centers had suboptimal procurement yields of 66.7% and 64.2% (table).
7 days, followed by 10 days normal drinking water each. For tumour induction, Major complications occurred in six patients (2.4%): two cases of bleeding, two
mice were injected with AOM at day 1 and day 10 of each DSS cycle during of mild acute pancreatitis, one perforation that required surgery and one duo-
chronic colitis induction. denal hematoma that resolved spontaneously. Considering malignant vs. non-
Results: PTPN2-deficient macrophages show enhanced levels of cleaved caspase- malignant diseases, the sensitivity, specificity, positive likelihood ratio, negative
1 and IL-1b upon in vitro activation of the NOD-like receptor protein 3 (Nlrp3) likelihood ratio, and diagnostic accuracy were 70.7% (95% CI, 64.3–76.6), 100%
and absent in melanoma 2 (AIM2) inflammasomes, finally resulting in enhanced (95% CI, 79.6–100), 35.3 (95% CI. 2.3–549.8), 0.3 (95% CI, 0.2–0.4), and 73.6%
secretion of active IL-1b and IL-18. This effect was mediated by increased phos- (95% CI, 67.6–79), respectively. On multivariate analysis, the only determinant
phorylation of the inflammasome adaptor apoptosis associated speck-like pro- of successful EUS-FNB was the center in which the procedure was performed.
tein containing a CARD (ASC), a mechanism recently shown to promote
inflammasome activation. In vivo, PTPN2-LysMCre mice suffered from pro-
nounced acute colitis, accompanied with enhanced secretion of mature IL-1b
and IL-18, but concomitant decreased IL-10 production. On the other hand,
no differences were observed in T cell subsets or other T helper cell associated Study Center Technical success rates Procurement yield
cytokine expression/secretion. In chronic colitis, PTPN2-LysMCre mice again
showed enhanced inflammasome activation in the intestine, and further devel- A 64/67 (95.5) 43/67 (64.2)
oped metaplasia to squamous epithelium in the distal part of the colon epithe- B 44/45 (97.8) 38/45 (84.4)
lium, but there was no overt effect on colitis severity. Of interest, however, and in C 39/40 (97.5) 34/40 (85)
contrast to their WT littermates, PTPN2-LysMCre mice did not develop any D 37/39 (94.9) 32/39 (82.1)
tumours upon AOM-DSS treatment. Interestingly, when IL-1b was inhibited,
acute colitis severity in PTPN2-LysMCre mice did not differ from that observed E 20/30 (66.7) 20/30 (66.7)
in WT animals. Further, inhibition of IL-1b restored susceptibility to AOM-DSS F 24/25 (96) 22/25 (88)
induced tumours in PTPN2-LysMCre mice.
Conclusion: PTPN2 is an important regulator of inflammasome activation, and
loss of PTPN2 in macrophages enhances acute colitis. Further, during chronic Conclusion: The findings of our study, with a procurement yield and diagnostic
intestinal inflammation, macrophage-specific loss of PTPN2 promotes metapla- accuracy of only 76.8% and 73.6%, respectively, redefine the role of the 19-gauge
sia to squamous epithelium, but at the same time protects from tumour forma- flexible needle for transduodenal EUS-FNB. Thus, the correct diagnosis was
tion. This indicates an important, previously under-estimated macrophage- missed in about 1 every 4 patients. Since the prevalence of malignant disease
specific role for PTPN2 during intestinal inflammation and tumour induction. in our population was 86%, this finding cannot be considered negligible. The
Disclosure of Interest: All authors have declared no conflicts of interest. results of our study are of particular interest since we showed that the diagnostic
performance of the 19-gauge flexible needle has a wide intercenter variability, not
depending on the expertise of the endoscopist. In conclusion, our results suggest
A12 United European Gastroenterology Journal 4(5S)

Abstract No: OP026

Comparison of procedure outcomes according to needle size and use of suction

22G No Suction 22G Suction 25G No Suction 25G Suction

(n ¼ 88) (n ¼ 88) (n ¼ 85) (n ¼ 91) p-value

ROSE-Diagnostic adequacy: n (%) 88 (100) 86 (97.7) 85 (100) 91 (100) 0.182

Total no. of passes for onsite diganostic adequacy Mean (SD) 1.8 (1.9) 2.8 (2.7) 1.7 (1.5) 2.0 (2.2) 50.001
Median (IQR) 1 (1–2) 2 (1–3) 1 (1–1) 1 (1–2)
Specimen bloodiness: n (%) Mild 52 (59.1) 32 (36.4) 55 (64.7) 43 (47.3) 0.008
Moderate 20 (22.7) 34 (38.6) 20 (23.5) 30 (33.0)
Severe 16 (18.2) 22 (25.0) 10 (11.8) 18 (19.8)
ROSE-Diagnostic performance: % (95% CI) Accuracy 98.9 (93.8–100) 93.2 (85.7–97.5) 97.6 (91.8–99.7) 97.8 (92.3–99.7) 0.230
Sensitivity 100 (95.1–100) 92.6 (83.7–97.6) 97.1 (89.9–99.6) 98.8 (93.2–100) -
Specificity 93.3 (68.1–99.8) 95.0 (75.1–99.9) 100 (79.4–100) 90.9 (58.7–99.8) -
PPV 98.6 (92.7–100) 98.4 (91.6–100) 100 (94.6–100) 98.8 (93.2–100) -
NPV 100 (76.8–100) 79.2 (57.8–92.9) 88.9 (65.3–98.6) 90.9 (58.7–99.8) -
Diagnostic cell block: n (%) 71 (80.7) 63 (71.6) 56 (65.9) 67 (73.6) 0.177
EUS-FNA-Diagnostic performance: % (95% CI) Accuracy 98.9 (93.8–100) 93.2 (85.7–97.5) 98.8 (93.6–100) 98.9 (94.0–100) 0.060
Sensitivity 98.6 (92.6–100) 92.6 (83.7–97.6) 98.6 (92.2–100) 98.8 (93.2–100) -
Specificity 100 (78.2–100) 95.0 (75.1–99.9) 100 (79.4–100) 100 (71.5–100) -
PPV 100 (95.0–100) 98.4 (91.6–100) 100 (94.7–100) 100 (95.4–100) -
NPV 93.8 (69.8–99.8) 79.2 (57.8–92.9) 94.1 (71.3–99.9) 91.7 (61.5–99.8) -
Technical failure: n (%) 0 5 (5.7) 1 (1.2) 7 (7.7) 0.011
Adverse events: n (%) 4 (4.5) 3 (3.4) 7 (8.2) 10 (11.0) 0.179

that the use of the 19-gauge flexible needle for transduodenal FNB cannot be S. Varadarajulu: Consultant for Boston Scientific Corporation and Olympus
widely suggested and its implementation should receive a local validation, with America Inc.
careful evaluation of both the local technical success rates and diagnostic yields. All other authors have declared no conflicts of interest.
Disclosure of Interest: L. Palazzo: Laurent Palazzo has received educational funds
from Boston Scientific Corp.
A. Larghi: Alberto Larghi is a consultant for Boston Scientific Corp.
All other authors have declared no conflicts of interest. OP027 EUS-GUIDED BILIARY DRAINAGE VERSUS PERCUTANEOUS
References BILIARY DRAINAGE: RESULTS OF A MULTICENTER
RANDOMIZED PHASE II STUDY
1. Panic N and Larghi A. Techniques for endoscopic ultrasound-guided fine-
E. Bories1, J.P. Ratone1, F. Caillol1, C. Pesenti2, C. Zemmour3, J. Boher3,
needle biopsy. Gastrointest Endosc Clin N Am 2014; 24: 83–107.
D. Genre4, M. Barthet5, B. Napoléon6, M. Giovannini1
2. Varadarajulu S, et al. Assessment of the technical performance of the flexible 1
Endoscopy, Institut Paoli Calmette, marseille/France
19-gauge EUS-FNA needle. Gastrointest Endosc 2012; 76: 336–43. 2
Endoscopy, Paoli Calmettes Institute, Marseille/France
3. Varadarajulu S, et al. Endoscopic ultrasound-guided tissue acquisition. Dig 3
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Endosc 2014; 26(Suppl 162–9. 4
paoli calmettes institute, marseille/France
5
Hopital Nord, Hopital Nord, Marseille/France
6
69, Hôpital Prive´ Jean Mermoz, Lyon/France
OP026 RANDOMIZED TRIAL COMPARING THE 22 AND 25 GAUGE Contact E-mail Address: [email protected]
NEEDLES USING THE SUCTION-IN AND NO-SUCTION (SINS) Introduction: For 10 years, EUS-guided biliary drainage has been an option as
TECHNIQUES FOR EUS-GUIDED FNA OF PANCREATIC MASSES EUS guided choledoco-duodenostomy or hepatico-gastrostomy. Two small ran-
J.Y. Bang, S. Hebert-Magee, M. Hasan, U. Navaneethan, R. Hawes, domized studies showed no difference between EUS guided BD vs Percutaneous
S. Varadarajulu drainage. The aim of this work was to evaluate in a multicenter randomized study
Center For Interventional Endoscopy, Florida Hospital, Orlando/United States of the percutaneous biliary drainage (PBD) vs EUS-guided biliary drainage (EBD)
America/FL in patients with an obstructive jaundice when ERCP failed or impossible due do
duodenal involvement or previous Surgery as gastrectomy or Whipple resection.
Contact E-mail Address: [email protected] Aims & Methods: Inclusion criteria were: benign or malignant obstructive jaun-
Introduction: Prior studies comparing the 22 and 25G needles and utility of dice with failure of ERCP. Exclusion criteria were: ascites, blood coagulation
suction for EUS-FNA of pancreatic masses were indefinite due to patient hetero- disorders, stenosis of the right bile duct. Randomization ratio was 1: 1, with a
geneity and small sample size. Also, the optimal tissue acquisition technique for stratification by indication (benign vs malignant) and by centers (4 centers were
onsite and offsite specimen assessment is unclear. included). The route of the biliary drainage was randomized as PTB (arm A) and
Aims & Methods: We aimed to compare the 22 and 25G needles and evaluate the EGD (arm B). But the choice of the EGD technique was free for the operator as
role of suction in EUS-FNA of pancreatic masses. Methods: Consecutive (Anterograde transpapillary stenting, choledoco-duodenostomy, hepatico-gas-
patients with solid pancreatic masses were randomized to 1 of 4 cohorts: 22G trostomy). The main goal was to evaluate the specific morbidity and mortality
needle with suction, 22G needle without suction, 25G needle with suction and during the 30 days following the biliary drainage in each arm. To prove a
25G needle without suction. After two dedicated passes were performed for cell decrease of 50% of the morbidity rate in the EGD arm (A ¼ 30%, B ¼ 15%),
block (offsite) evaluation, an experienced pathologist rendered rapid onsite eva- 55 patients should be included in the EGD arm (B) as a Simon plan in 2 steps
luation (ROSE) for specimen adequacy. Cross-over to alternate arms was per- with an intermediate analysis to exclude severe adverse events in the EGD arm.
mitted if ROSE was indeterminate at 8 passes. Diagnostic accuracy of ROSE was Intermediate analysis was performed after inclusion of 47 patients and showed
confirmed by final pathology interpreted by a second independent pathologist. significantly higher morbidity rate in the PTB arm. Then, PTB arm was stopped
Final diagnosis was established by surgical histology or patient follow-up at 12 and inclusions were made only in the EGD arm.
months. Main outcome measures were to compare diagnostic adequacy and Results: Sixty-five patients from 4 centres were screened between 2011 to 2015.
accuracy of ROSE, number of passes to establish onsite diagnostic adequacy, Eight patients were excluded (ascites, ERCP finally feasible). Fifty-six patients
specimen bloodiness, diagnostic accuracy of cell block and operating character- were randomized (Arm A ¼ 21/ Arm B ¼ 35). The 2 groups were similar except
istics between cohorts. To detect a 15% difference in diagnostic accuracy and cell the sex ratio (Female: Arm A, n ¼ 11; Arm B, n ¼ 7; p ¼ 0.012). The biliary
block yield between the type of needles and use of suction at 80% power and type stenosis was malignant in 52 cases (Arm A ¼ 19; Arm B ¼ 33). Biliary access
1 error of 0.05, the total sample size was estimated at 352 patients. was successful in 100% in the Arm A and in 94% in the Arm B. However,
Results: The median age of 352 patients was 69 years, 54.3% male, median size of technical success was respectively 17/21 (85%) in the Arm A and 33/56 (94%)
mass was 3cm with vascular invasion in 55.4% and FNA passes were transduo- in the Arm B. No difference was showed regarding the decrease of the bilirubin
denal in 68.5%. The final diagnosis was adenocarcinoma or other malignancy in level after the drainage in the two arms. Median hospitalization duration was
290 (82.4%) and benign or chronic pancreatitis in 62 (17.6%) patients. Interim shorter in the Arm B (6 days range 3–30 days) than the Arm A (12 days range 2–
analysis pending completion of 12-month follow-up is shown in the Table. 32 days). Ten patients died 30 days following the biliary drainage, 7 deaths were
Conclusion: While there was no overall difference in operating characteristics reliable to biliary drainage procedure (Arm A ¼ 3, Arm B ¼ 4) p ¼ 1. Specific
between the 22 and 25G needles, the use of suction must be avoided in centers complication occurred in twelve patients (62%) in the Arm A vs 7 (31%) in
utilizing ROSE as it increases specimen bloodiness and number of passes needed the Arm B p ¼ 0,0276: Bleeding (A ¼ 5[24%], B ¼ 3[9%]; ns), Cholangitis
to achieve diagnostic adequacy, particularly with 22G needles. (A ¼ 3 [14%], B ¼ 1[3%]), Sepsis not related to cholangitis (A ¼ 7 [35%], B ¼ 5
Disclosure of Interest: R. Hawes: Consultant for Boston Scientific Corporation [25%]), Peritonitis (A ¼ 1[5%], B¼1[3%], ns), external biliary fistula (A ¼ 1[5%],
and Olympus America Inc. B ¼ 0[0%], ns).
United European Gastroenterology Journal 4(5S) A13
Conclusion: This randomized prospective study showed similar high technical and Results: A total of 205 patients (mean age 34.8  12.5 years, 181 males) under-
clinical success rates in PTB and EUS-guided biliary approach. Specific compli- went EUS-guided drainage with BFMS. Technical success was achieved in 203
cation rate was higher in the PTB arm than in the EUS-guided biliary drainage. patients (99%). Peri-procedure adverse events occured in 8 (3.9%) patients
EUS guided biliary drainage should be the first therapeutic approach after failure (bleeding in 6 and perforation in 2). WON resolved with BFMS in 158
of ERCP, in selected patients. (74.6%). Endoscopic re-intervention, required in 49 (23.9%) patients, for persis-
Disclosure of Interest: All authors have declared no conflicts of interest. tent or new onset symptoms, was approached in step-up manner. At first, de-
clogging of BFMS alone succeeded in 10 out of 21. Second step of naso-cystic
placement through BFMS followed by irrigation with saline and hydrogen per-
oxide improved 16 out of 39. At final step, DEN improved outcome in 19 out of
OP028 EUS-GUIDED GASTROENTEROSTOMY IS COMPARABLE TO 23. BFMS migrated in 5 (2.9%) patients (2 internal, 3 external). Four patients
ENTERAL STENTING IN TERMS OF TECHNICAL FEASIBILITY failed to achieve clinical success, requiring surgery (n ¼ 2) or additional percuta-
AND CLINICAL SUCCESS WITH LOWER RATES OF RE- neous drainage (n ¼ 2). Overall, clinical success was achieved in 198 (96.5%)
INTERVENTION: AN INTERNATIONAL MULTICENTER patients.
COMPARATIVE STUDY Conclusion: EUS-guided drainage with BFMS is safe and effective in WON.
Y. Chen1, T. Itoi2, T.H. Baron3, J. Nieto4, Y. Haito-Chavez1, I. S. Grimm5, BFMS substantially reduces the requirement of DEN. Success rate incrementally
S. Ngamruengphong1, M. Bukhari1, G. Hajiyeva1, A. Ismail1, A. Alawad1, improves with endoscopic step-up approach.
V. Kumbhari1, M. Khashab1 Disclosure of Interest: All authors have declared no conflicts of interest.
1
Gastroenterology and Hepatology, Johns Hopkins Medical Intitutions, Baltimore/ References
United States of America
2 1. Chandran S, Efthymiou M, Kaffes A, et al. Management of pancreatic
Department Of Gastroenterology and Hepatology, Tokyo Medical University,
collections with a novel endoscopically placed fully covered self-expandable
Tokyo/Japan
3 metal stent: a national experience (with videos). Gastrointest Endosc 2015
Gastroenterology & Hepatology, University of North Carolina, North Carolina/
Jan; 81(1): 127–35.
United States of America
4 2. Mukai S, Itoi T, Baron TH, et al. Endoscopic ultrasound-guided placement
Borland-Groover Clinic, Jacksonville/United States of America
5 of plastic vs. biflanged metal stents for therapy of walled-off necrosis: a
Gastroenterology and Hepatology, University of North Carolina, North Carolina/
retrospective single center series. Endoscopy 2015; 47: 47–55.
United States of America
3. Walter D, Will U, Sanchez-Yague A, et al. A novel lumen-apposing metal
Contact E-mail Address: [email protected] stent for endoscopic ultrasound-guided drainage of pancreatic fluid collec-
Introduction: Endoscopic enteral stenting (ES) in malignant gastric outlet tions: a prospective cohort study. Endoscopy 2015 Jan; 47(1): 63–7.
obstruction (GOO) is limited by high rates of stent obstruction. EUS-guided 4. Van Santvoort H. C., Besselink M. G., Bakker O. J., et al. A step-up
gastroenterostomy (EUS-GE) is a novel procedure that potentially offers sus- approach or open necrosectomy for necrotizing pancreatitis. N Engl J Med
tained patency without tumor ingrowth/overgrowth. 2010; 362: 1491–1502.
Aims & Methods: The aim of this study is to compare EUS-GE with ES in terms 5. Siddiqui Ali A., Adler Douglas G., Jose Nieto, et al. EUS-guided drainage of
of 1) need for re-intervention, 2) technical success (proper stent positioning as peripancreatic fluid collections and necrosis by using a novel lumen-apposing
determined via endoscopy and fluoroscopy), 3) clinical success (ability to tolerate stent: a large retrospective, multicenter U.S. experience (with videos).
oral intake without vomiting), and 4) procedure-related adverse events (AEs). Gastrointestinal Endoscopy 2016; 83: 699–707.
This is a multicenter retrospective study of all consecutive patients who under-
went either EUS-GE at 4 centers between 2013 and 2015 or ES at one center
between 2008 and 2010.
Results: A total of 82 patients (mean age 66-years  13.5 and 40.2% female) were OP030 CLINICAL OUTCOME AFTER BILIARY DRAINAGE FOR
identified: 30 in EUS-GE and 52 in ES. Technical and clinical success were not METASTATIC COLORECTAL CANCER: SURVIVAL ANALYSIS
significantly different 86.7% EUS-GE vs. 94.2% ES (p ¼ 0.2) and 83.3% EUS- AND PRONOSTIC FACTORS
GE vs. 69.2% ES (p ¼ 0.2) respectively. Need for re-intervention, however, was F. Sellier1, E. Bories2, C. Sibertin-Blanc3, K. Griffiths4, L. Dahan3,
significantly lower in EUS-GE 3.3% vs. 46.2% ES (p 5 0.001). Post-procedure M. Giovannini2, J. Gaudart4, J.F. Seitz3, R. Laugier1, P. Grandval1
mean length of hospitalization was comparable at 11.3 days  6.6 for EUS-GE 1
Dept. Of Gastroenterology, Timone Hospital, Assistance Publique Hôpitaux de
vs. 9.5 days  8.3 for ES (p ¼ 0.3). Rates and severity of AEs (as per the ASGE Marseille, Marseille Cedex/France
lexicon) were also similar occurring in 16.7% EUS-GE vs. 11.5% ES (p ¼ 0.5). 2
Dept. Of Endoscopy, Paoli-Calmettes Institute, Marseille Cedex/France
On multivariable analysis, EUS-GE was independently associated with fewer 3
Dept. Of Digestive Oncology, Timone Hospital, Assistance Publique Hôpitaux de
needs for re-intervention (OR 0.03, p ¼ 0.002). Marseille, Marseille Cedex/France
Conclusion: EUS-GE may be ideal for malignant GOO with comparable effec- 4
Dept. Of Public Health and Medical Information, Timone Hospital, Assistance
tiveness and safety to ES while being associated with fewer requirements for re- Publique Hôpitaux de Marseille, Marseille Cedex/France
intervention.
Disclosure of Interest: M. Khashab: Consultant for Boston Scientific Contact E-mail Address: [email protected]
All other authors have declared no conflicts of interest. Introduction: Biliary obstruction secondary to colorectal cancer liver metastases is
associated with a poor prognosis without drainage especially when chemotherapy
cannot be re started. However, little information is known about clinical benefits
of such endoscopical and radiological interventions, as well as the impact of
OP029 DEDICATED BI-FLANGED METAL STENT WITH ENDOSCOPIC chemotherapy achievement. The aim of this study was to determine survival
‘‘STEP-UP APPROACH’’ REDUCES THE NEED FOR DIRECT after biliary drainage and look for prognostic factors.
NECROSECTOMY IN WON - LARGE EXPERIENCE FROM A SINGLE Aims & Methods: This retrospective study analyzed patients from two expert
TERTIARY CARE CENTRE French centers between 2005 and 2014. Patients were included after first biliary
S. Lakhtakia, J. Basha, R. Talukdar, R. Gupta, M. K. Ramchandani, B. endoscopic retrograde cholangiopancreatography (ERCP) or percutaneous
K. Sureddi, P. Pal, Z. Nabi, R. Kalpala, P. M. Reddy, J. R. Singh, R. Pradeep, transhepatic cholangiography (PTC) drainage for biliary obstruction secondary
G. V. Rao, D.N. Reddy to liver metastases of colorectal cancer occurring during chemotherapy.
Gastroenterology, Asian Institute of Gastroenterology, Hyderabad/India Demographical, biochemical, and outcome data were registered. We used
Kaplan-Meyer analysis to assess survival after first biliary stenting and cox
Contact E-mail Address: [email protected] models for univariate and multivariate analysis.
Introduction: EUS-guided trans-mural drainage using plastic stents may be inade- Results: The final analysis included 69 patients. Sixty patients underwent ERCP,
quate for pancreatic fluid collections (PFC) having solid debris, i.e. ‘‘Walled Off 2 underwent PTC drainage, and 7 underwent both techniques. Overall median
Necrosis (WON)’’. Recent publications have reported variable outcome using survival was 115 days (5–1876). In univariate analysis, a previous liver surgery, a
covered metal stents for PFC drainage, using either conventional or dedicated technical and a functional success of drainage and restarted chemotherapy were
metal stents. There are few reports on dedicated metal stent for EUS guided significantly associated with an improved survival. Chemotherapy was restarted
drainage of only WON. Treatment strategy using a ‘‘step-up approach’’ by endo- after a median of 27 days. When drainage was efficient survival improved from
scopic methods has not been systematically addressed. 33 days to 262 days (p 5 0.001). In multivariate analysis, protective factors for
Aims & Methods: To evaluate the efficacy of a dedicated covered bi-flanged metal survival included a previous hepatectomy (hazard ratio (HR) 0.41, 95% CI [0.22–
stent (BFMS) using a ‘‘step-up approach’’ in drainage of symptomatic WON. 0.75], p ¼ 0.004), functional success drainage (HR 0.29, 95% CI [0.15–0.56],
Consecutive patients with symptomatic WON undergoing EUS-guided drainage p ¼ 0.0002). Predictive factors for death included increased lines of chemotherapy
using BFMS were included from January 2013 to December 2015. Patients were (HR 1.68, 95% CI [1.36–2.06], p 5 0.001), and fever before drainage (HR 2.97,
reassessed at 48–72 hours for symptom improvement and reduction in size of 95% CI [1.39–6.36], p ¼ 0.005).
collection. The endoscopic interventions were approached in a step-up manner to Conclusion: This the first study concerning benefits of biliary drainage during the
manage patients who did not have expected clinical improvement after index course of chemotherapy of colorectal cancer with malignant biliary obstruction.
drainage of WON with BFMS. Declogging of blocked lumen of BFMS was A successful biliary drainage leads to improved survival and allows achievement
the first step. Second step involved a naso-cystic catheter (NCT) placement of chemotherapy for 50% of patients.
through BFMS followed by intermittent irrigation with saline and hydrogen Disclosure of Interest: All authors have declared no conflicts of interest.
peroxide. Third step involved direct endoscopic necrosectomy (DEN), which
was performed through BFMS in patients with persistent symptoms. Patients
were reassessed between 4 to 8 weeks and BFMS were removed after document-
ing radiological resolution of collection. The main outcome measures studied
were technical success, clinical success, adverse events and the need for various
endoscopic reinterventions, using step-up approach.
A14 United European Gastroenterology Journal 4(5S)

MONDAY, OCTOBER 17, 2016 10:30–12:00 Disclosure of Interest: All authors have declared no conflicts of interest.
MECHANISMS OF PRIMARY SCLEROSING CHOLANGITIS – ROOM References
L7_____________________
1. Hirschfield GM, et al. Lancet. 2013;382:1587–99.
OP031 BILE DUCT INFLAMMATION ASSESSED BY BILIARY 2. Bergquist A, et al. J Hepatol. 2002; 36:321–327.
CALPROTECTIN AND NEUTROPHILS CORRELATES WITH RISK 3. Ananthakrishnan AN et al. JCC 2014;8:956–63.
OF BILIARY DYSPLASIA AND CHOLANGIOCARCINOMA 4. Manninen P, et al. Scand J Gastroenterol. 2015;50:423–8.
5. Boberg KM, et al. Scand J Gastroenterol 2002; 37: 1205–11.
M.A. Färkkila1, H. Mustonen2, K. Jokelainen1, J. Arola3, H. Alfthan4
1 6. de Valle MB, et al. Liver Int 2012; 32: 441–8.
Dept. Of Gastroenterology, Helsinki University Hospital, Helsinki/Finland
2 7. Claessen MM. J Hepatol. 2009;50:158–64.
Helsinki University, Biomedicum, Helsinki/Finland
3 8. Lewis JT, et al. Am J Surg Pathol. 2010;34:27–34.
Huslab, Helsinki University Hospital, Helsinki/Finland
4 9. Boyd S, et al. Endoscopy. 2016;48:432–439.
HUSLab, Helsinki University Hospital, Helsinki, Finland, Helsinki/Finland
Contact E-mail Address: [email protected]
Introduction: Primary sclerosing cholangitis (PSC) is a chronic inflammatory
disease of biliary epithelium leading to strictures intra- and extrahepatic bile OP032 TARGET-SPECIFIC ANTI-PANCREATIC ANTIBODIES ARE
ducts and finally to cholestasis and secondary biliary cirrhosis (1). The chronic FREQUENT IN PATIENTS WITH PRIMARY SCLEROSING
inflammation is associated with increased proliferation of biliary epithelial cells CHOLANGITIS AND ASSOCIATED WITH POOR DISEASE
and a markedly increased risk of biliary dysplasia and cholangiocarcinoma (2), OUTCOME
SIR ranging from 55 to 973 (3–4). The lifetime risk of CCA is around 10% (5). M. Papp1, T. Tornai1, N. Sipeki1, Z. Vitalis1, I. Tornai1, K. Fechner2,
CCA is the most common reason for death among PSC patients (6–7). CCA is D. Roggenbuck3, D. Tornai4, G. L. Norman5, Z. Shums5, G. Veres6, P. Orosz7,
thought to develop through metaplasia, low-grade dysplasia, and high-grade- B. Lombay8, J. Gervain9, G. Par10, A. Par10, P.L. Lakatos11, F. Szalay12,
dysplasia (8). Chronic inflammation has been regarded as risk factor for dyspla- P. Antal-Szalmas4
sia and malignancy. Because CCA is generally a contraindication for liver trans- 1
Department Of Internal Medicine, Division Of Gastroenterology, University of
plantation (LT) and the prognosis of CCA is dismal, it would be feasible to Debrecen, Faculty of Medicine, Debrecen/Hungary
screen the dysplastic changes of the biliary epithelium to treat patients with LT 2
Institute of Experimental Immunology, Euroimmun AG, Luebeck/Germany
before development of advanced malignancy, detected based on imaging methods 3
Faculty Of Natural Sciences, Brandenburg University of Technology Cottbus-
or symptoms. Senftenberg, Senftenberg/Germany
Aims & Methods: We aimed to evaluate the grade of bile duct inflammation as a 4
Department Of Laboratory Medicine, University of Debrecen, Faculty of
risk factor for dysplasia and cholangiocarcinoma in PSC patients. In total, 210 Medicine, Debrecen/Hungary
patients with confirmed PSC referred for ERC for disease surveillance were 5
Inova Diagnostics, Inc., San Diego/United States of America
included (121 females, 179 males). After cannulation of the common bile duct 6
1st Department Of Pediatrics, Semmelweis University, Budapest/Hungary
bile sample was aspirated using balloon catheter and immersed immediately in 7
Gastroenterology Department Of Medicine, Borsod-Abauj Zemplen County
liquid nitrogen (196oC) and then stored in 20oC. Brush cytology (BC) was Hospital, Miskolc/Hungary
collected both from extra- and intrahepatic bile ducts for Papanicolau staining 8
Department Of Medicine, Szent Ferenc Hospital, Miskolc/Hungary
for grading dysplasia and inflammation. Neutrophilic inflammation in BC was 9
Division Of Hepato-pancreatology and Molecular Diagnostics Laboratory, 1st
evaluated semiquantitatively (0 ¼ neutrophils/epithelial cells 50.05, Department Of Internal Medicine, Szent György Teaching Hospital of Fejer
1 ¼ neutrophils/epithelial cells 0.05–0.4, 2 ¼ neutrophils/epithelial cells 40.4). County, Sze´kesfehe´rvár/Hungary
Bile concentrations of calprotectin were analyzed using ELISA method. Liver 10
1st Department Of Medicine, University of Pecs, Pecs/Hungary
function tests were taken at the time of ERC. ERC findings were scored accord- 11
1st Department Of Medicine, Semmelweis University Faculty of Medicine 1st
ing to modified Amsterdam score, [Helsinki score] (9). Dept. of Medicine, Budapest/Hungary
Results: Bile duct inflammation assessed by biliary calprotectin correlated sig- 12
1st Department Of Medicine, Semmelweis University, Budapest/Hungary
nificantly with neurophils in BC, with S-CA19–9, S-ALP and S-AST levels and
interestingly with S-IgG. Patients with dysplasia or CCA had markedly elevated Contact E-mail Address: [email protected]
B-calprotectin, as compared to those without dysplasia (34.7 vs 4.0 mg/l, respec- Introduction: Glycoprotein 2 [GP2] and CUB zona pellucida-like domain 1
tively), see table. The risk of dysplasia was associated with advanced bile duct [CUZD1] belong to protein families involved in gut innate immunity processes
disease, (mERC score48 vs 54, OR 15.2 [95% 1.8–127.9], p ¼ 0.012), increased and have recently been identified as specific targets of anti-pancreatic autoanti-
bile duct inflammation based on BC-neutrophils (BC-Neurophil 1–2 vs 0, OR 8.2 bodies [PAbs] in Crohn’s disease [CD]. We aimed to determine the prevalence
[95%1.1–64.0], p ¼ 0.044), B-calprotectin higher than 45 mg/l (OR 3.3 [95%1.1– and prognostic potential of novel target-specific PAbs regarding long-term dis-
9.9], p ¼ 0.0032) and S-Ca19–9 426 kU/l vs526 kU/l (OR 7.4[95% 2.0–27.6], ease course in a cohort of a primary sclerosing cholangitis [PSC] patients.
P ¼ 0.003). Aims & Methods: Sera of 69 PSC patients (median age[range]: 32[5–79] years,
concomitant IBD:67% and cirrhosis:20%) were tested by indirect immunofluor-
escence test [IIFT] system with GP2 and CUZD1 expressing transfected HEK
Bile calprotectin in relation to variables of PSC activity
293 cells [anti-rPAg2 and rPAg1 IgA/IgG]. Classical serologic markers of IBD
were also assessed (pANCA and aLFS IgA/IgG by IIFT, while ASCA IgG/IgA
Variable N B-calpro, mg/l, median [25%–75%] p-value and anti-OMP PlusTM IgA by ELISA). A previously reported inflammatory
bowel disease [IBD] patient cohort (CD:264 and UC:179) were the controls.
ERC-score4 94 0.4 [0.1–3.9] 50.0001 Poor disease outcome was defined as orthotopic liver transplantation [OLTx]
ERC score44 116 13.8 [1.6–96.3] and/or liver-related death during the follow-up (median: 94 months].
Bil-Neutrophils Results: A total of 43.5% of PSC patients were positive for either of the two
-0 74 0.2 [0–1.1] 50.0001 target-specific anti-PABs, with a significant difference compared to patients with
CD [26.8%, p 5 0.01] or UC [7.6%, p 5 0.001]. Distribution of the two types of
-1 100 5.3 [0.9–22.9] PAbs was equal and one-third of the positive cases showed double positivity.
-2 36 172.8 [59.1–286.8] Anti-GP2 antibody positivity was exclusively IgA type, while anti-CUZD1 anti-
Dysplasia bodies were of both IgA and IgG isotypes. No difference was found in the
- No 203 4.0 [0.2–41.0] 0.023 frequency of PAbs according to the baseline disease characteristics. Positivity
for the IgA subtype of anti-GP2, but not for the classical serologic markers,
- Yes 14 34.7 [4.8–99.5] predicted a faster progression of the disease. In Kaplan-Meier analysis, anti-
S-CA19–9 kU/l GP2 IgA positivity was associated with shorter time to OLTx and/or liver-related
- 526 (UNL) 198 2.7 [0.2–28.5] 0.003 death [pLogRank50.01], and remained an independent predictor after adjusting
- 26 (UNL) 12 57.4 [19.4–179.3] for the presence of cirrhosis in Cox-regression analysis (HR: 4.31 [1.05–17.61]).
Conclusion: Our small-scale study has shown that occurrence of target-specific
S-ALP, U/l PAbs is common in PSC. Association of IgA type anti-GP2 antibody with faster
- 105 (UNL) 101 1.2 [0.2–9.6] 50.0001 disease progression serves as an additional hint towards the significance of gut-
- 4105 (UNL) 109 6.1 [0.5–81.9] liver interaction in the disease course of PSC.
S-AST, U/L Disclosure of Interest: All authors have declared no conflicts of interest.
- 40 (UNL) 141 1.4 [0.1–21.0] 50.0001
- 440 (UNL) 69 8.3 [1.0–89.6]
S-IgG, g/l
- 15 (UNL) 177 2.8 [0.2–27.0] 0.008
- 415 (UNL) 33 19.5 [1.3–112.1]

Conclusion: S-ALP, AST and IgG seem to be good surrogate markers for bile
duct inflammation compared to biliary calprotectin levels. Risk of dysplasia is
associated with bile duct inflammation assessed by brush cytology neutrophils,
B-calprotectin and S-Ca19–9 levels 426 kU/l. These variables seem be useful for
individual risk stratification for PSC patients for disease progression and
dysplasia.
United European Gastroenterology Journal 4(5S) A15
OP033 GUT BARRIER FAILURE BIOMARKERS ARE ASSOCIATED bile duct when the enhanced, biliary wall thickness was recognized at more than
WITH POOR DISEASE OUTCOME IN PATIENTS WITH PRIMARY 10 mm upstream of the stenosis.
SCLEROSING CHOLANGITIS Results: Autoimmune pancreatitis (AIP) was accompanied in 88% (42/48) of
T. Tornai1, G. Kovacs1, Z. Vitalis1, I. Tornai1, K. Fechner2, D. Roggenbuck3, IgG4-SC patients at the initial diagnosis. On MDCT imaging, the long thickened
D. Tornai4, G. L. Norman5, G. Veres6, Z. Shums5, P. Orosz7, B. Lombay8, bile duct rate was higher in IgG4-SC cases than in ECC cases (76% of IgG4-SC
J. Gervain9, G. Par10, A. Par10, P.L. Lakatos11, F. Szalay12, P. Antal-Szalmas4, and 32% of ECC, respectively). By IDUS, a continuous circular-symmetric wall
M. Papp1 thickness more than 10 mm upstream from stenosis was recognized in 84% of
1
Department Of Internal Medicine, Division Of Gastroenterology, University of IgG4-SC cases and in 36% of ECC cases. In IgG4-SC cases, biliary biopsy
Debrecen, Faculty of Medicine, Debrecen/Hungary revealed one or more positive pathological diagnostic items in only 13% of
2
Institute of Experimental Immunology, Euroimmun AG, Luebeck/Germany cases. In ECC cases, the sensitivity of biopsy was 92%, and brush cytology
3
Faculty Of Natural Sciences, Brandenburg University of Technology Cottbus- increased this by 6%. Among three out of six IgG4-SC patients without AIP,
Senftenberg, Senftenberg/Germany pancreatoduodenectomy was performed without careful examination. The
4
Department Of Laboratory Medicine, University of Debrecen, Faculty of remaining three underwent steroid trial after negative work up for malignancy.
Medicine, Debrecen/Hungary Conclusion: A longitudinal biliary wall-thickness, upstream of the stenosis, was
5
Inova Diagnostics, Inc., San Diego/United States of America characteristic for imaging of IgG4-SC. Endobiliary forceps biopsy is effective for
6
1st Department Of Pediatrics, Semmelweis University, Budapest/Hungary discriminating IgG4-SC from ECC.
7
Gastroenterology Department Of Medicine, Borsod-Abauj Zemplen County Disclosure of Interest: All authors have declared no conflicts of interest.
Hospital, Miskolc/Hungary References
8
Department Of Medicine, Szent Ferenc Hospital, Miskolc/Hungary
9 1. Nakazawa T, Naitoh I and Hayashi K. Usefulness of Intraductal
Division Of Hepato-pancreatology and Molecular Diagnostics Laboratory, 1st
Ultrasonography in the Diagnosis of Cholangiocarcinoma and IgG4-
Department Of Internal Medicine, Szent György Teaching Hospital of Fejer
Related Sclerosing Cholangitis. Clinical Endoscopy 2012; 45: 331–6.
County, Sze´kesfehe´rvár/Hungary
10 2. Okazaki K. Current concept, diagnosis and pathogenesis of autoimmune
1st Department Of Medicine, University of Pecs, Pecs/Hungary
11 pancreatitis as IgG4-related disease. Minerva Medica 2014; 105: 109–19.
1st Department Of Medicine, Semmelweis University Faculty of Medicine 1st
Dept. of Medicine, Budapest/Hungary
12
1st Department Of Medicine, Semmelweis University, Budapest/Hungary
Contact E-mail Address: [email protected] OP035 SELECTIVE TARGETING OF FXRA ISOFORMS BY NOVEL BILE
Introduction: Gut-liver interaction is a pathogenic feature of primary sclerosing ACID DERIVATIVES IS ASSOCIATED WITH INHIBITION OF
cholangitis (PSC), however the effect of this cross-talk on the disease course has LIPOTOXICITY IN LIVER CELLS
not been fully elucidated. A panel of serological markers that reflect either H.M.D.S. Brito1, S. Batista2, M. M.C. Silva3, J. Salvador2, R.E. Castro4,
mechanical or immunological gut barrier dysfunction were assessed in a cohort C.M.P. Rodrigues5
of patients with PSC. Association of these markers with disease specific charac- 1
Faculty Of Pharmacy, Universidade De Lisboa, Research Institute for Medicines
teristics and the long-term disease course was evaluated. iMed.ULisboa, Lisboa/Portugal
Aims & Methods: Sera of 69 PSC patients (median age[range]:32[5–79] years, 2
Faculdade de Farmácia Universidade de Coimbra, Coimbra/Portugal
concomitant IBD: 67% and cirrhosis: 20%) were assayed for intestinal fatty 3
Faculty of Pharmacy, University of Coimbra, Coimbra/Portugal
acid-binding protein(I-FABP) and various immunoglobulin A (IgA) molecules 4
iMed Research Institute For Medicines, Faculdade de Farmácia, Universidade de
(IgA1, IgA2 and secretory[s]IgA, anti-F-actin[AAA IgA] and anti-gliadin[AGA Lisboa, Lisboa/Portugal
IgA/IgG]) by ELISA. Poor disease outcome was defined as orthotopic liver 5
Faculty Of Pharmacy, Universidade De Lisboa, iMed Research Institute For
transplantation [OLTx] and/or liver-related death during the follow-up Medicines, Faculdade de Farmácia, Universidade de Lisboa, Lisboa/Portugal
(median: 94 months]. 155 healthy subjects (HCONT) and 179 ulcerative colitis
(UC) patients were the controls. Contact E-mail Address: [email protected]
Results: In PSC, median I-FABP level was similar to that in HCONT (216 vs. 244 Introduction: Farnesoid X receptor (FXR), a bile acid (BA)-activated nuclear
pg/mL) but higher than in UC (176 pg/mL, p 5 0.05). sIgA level (95.7 mg/ml) was receptor, plays a critical role in maintaining lipid, glucose and BA homeostasis.
two- and three-fold higher compared to either the HCONT or the UC FXR expression is significantly decreased in livers of non-alcoholic fatty liver
(p 5 0.001, for both). 28.4%, 9% and 20.9% of PSC patients were positive for disease (NAFLD) patients and genetic ablation leads to hepatic steatosis and
AAA IgA, AGA IgA and AGA IgG, respectively. Frequencies of AAA IgA hyperlipidaemia. The FXR gene expresses four biologically active variants
(p 5 0.001, for both) and AGA IgG (p ¼ 0.01, for both) but not AGA IgA (FXR1–4), which regulate hepatic and lipid metabolism in an isoform-depen-
were significantly higher compared to HCONT and UC. Regarding disease-spe- dent manner.
cific characteristics, sIgA level was significantly lower in PSC patients with con- Aims & Methods: Our aim was to screen potential BA-derived FXR agonists for
comitant IBD (80.7 vs. 160.4 mg/ml). In Kaplan-Meier analysis only target- their ability to selectively activate different FXR isoforms and protect liver cells
specific IgAs and sIgA (4175 mg/ml) were associated with a shorter time to against free fatty acid (FFA)-induced steatosis and cytotoxicity. Nineteen novel
OLTx and/or liver-related death, whereas total IgA or IgA2/IgA1 ratio and I- BA derivatives, synthesized based on the cholic (CA), deoxycholic (DCA), che-
FABP were not. All markers remained significant after adjusting for the presence nodeoxycholic (CDCA) and ursodeoxycolic (UDCA) acid scaffolds were incu-
of cirrhosis in Cox-regression analysis (HR[95%CI]: 3.67[1.05–12.82] for sIgA, bated in HepG2 cells transfected with a dual-luciferase reporter construct and
5.15[1.27–20.86] for AAA IgA and 5.07[1.25–20.54] for AGA IgA). Combining overexpression vector plasmids for FXR1–4 isoforms. Selected BA-derivatives
these markers further enhanced their predicative potential (HR[95%CI]: were then co-incubated in HepG2 cells treated with 200 and 500 mM oleic and
11.30[2.84–44.93] for 2 marker positivity). palmitic acid (2:1 ratio), for assessment of cellular cytotoxicity using the MTS,
Conclusion: In our small-scale study, gut-related IgA type antibodies identified LDH and ToxilightTM assays, as well as intracellular lipid accumulation, by oil
PSC patients with progressive disease, further highlighting the importance of the red O (ORO) staining. Additionally, mRNA levels of both direct and indirect key
gut-liver interaction in PSC. FXR-targets, namely SHP, SREBP1-c, PPAR-, CYP7a1 and VLDLR, were
Disclosure of Interest: All authors have declared no conflicts of interest. assessed after incubation of primary mouse hepatocytes with the select BA-
derivatives.
Results: As a result of the diverse structural modifications, BA derivatives
showed differential activation of the FXR1–4 isoforms, when compared to
OP034 COMPARISONS OF IMAGING AND BILIARY BIOPSY their precursor BAs. From the precursor BAs, only CDCA, a natural FXR
BETWEEN IGG4-RELATED SCLEROSING CHOLANGITIS AND ligand, significantly activated FXR1 and 2 isoforms, with CA and UDCA
EXTRAHEPATIC CHOLANGIOCARCINOMA displaying a modest activation of FXR1 isoform only. Interestingly, 2 novel
T. Matsui1, H. Matsubayashi1, H. Ishiwatari1, S. Ito1, N. Kawata1, K. Imai1, CA-, 1 DCA- and 4 UDCA-derivatives were stronger activators of both FXR1
M. Tanaka1, K. Takizawa1, N. Kakushima1, K. Hotta1, H. Ono2 and 2, comparing with their corresponding precursors. Further, 3 novel CA-, 2
1
, Shizuoka Cancer Center Division of Endoscopy, Shizuoka/Japan DCA-, 3 CDCA- and 4 UDCA-derivatives specifically and significantly activated
2
Division of Endoscopy, Shizuoka cancer center, Sunto-gun, Japan, Shizuoka/ FXR3 and 4. Incubation of HepG2 cells with the FFAs mixture led to a 5–
Japan 25% reduction in cell viability and a 10–35% increase in cell death, concomi-
tantly with a dose-dependent accumulation of lipid droplets. Pre-incubation of
Contact E-mail Address: [email protected] cells with CA-derivatives preferentially activating FXR2 over 1 isoform
Introduction: IgG4-related sclerosing cholangitis (IgG4-SC) often presents similar reverted most of the FFA-induced cell death and lipid accumulation. Of note,
medical images to extrahepatic cholangiocarcinoma (ECC). However, the differ- these derivatives were among the stronger inducers of SHP, VLDLR and PPAR-
entiation is crucial for further treatment.  mRNA expression in primary mouse hepatocytes.
Aims & Methods: To elucidate characteristics of medical images of IgG4-SC and Conclusion: Altogether, we describe a novel strategy to screen for selective ago-
ECC, we retrospectively analyzed images of multi-detector computed tomogra- nists of FXR1–4 isoforms and have identified new selective BA-derived FXR1
phy (MDCT) and intraductal ultrasonography (IDUS). Biopsy-based diagnoses through 4 agonists. In particular, derivatives with a higher FXR2 over 1
from stenotic bile ducts were also compared. From April 2005 to March 2013, 48 binding ratios appear to be more effective in affording cytoprotection against
IgG4-SC patients and 50 ECC patients who underwent an initial ERCP at our lipotoxicity in liver cells. The differential functional effect of these new molecules
institution were analyzed. Diagnosis of IgG4-SC was made based on the will undoubtedly contribute for a better understanding of pharmacological tar-
Japanese clinical diagnostic criteria (2012), and autoimmune pancreatitis (AIP) geting and therapeutic efficacy of FXR agonists in liver diseases such as
based on International Consensus Diagnostic Criteria (ICDC). The pathological NAFLD. (Supported by HMSP-ICT/0018/2011,SFRH/BD/110672/2015 and
criteria consist of four items: (1) marked lymphocytic and plasmacyte infiltration SFRH/BD/80975/2011 FCT, Portugal).
and fibrosis, (2) infiltration of IgG4-positive plasma cells: 410 IgG4-positive Disclosure of Interest: All authors have declared no conflicts of interest.
plasma cell/HPF, (3) storiform fibrosis, and (4) obliterative phlebitis. In all
cases of ECC, pathological evidence of carcinoma was obtained from biliary
biopsy, cytology or surgical material. On MDCT, we defined the long thickened
A16 United European Gastroenterology Journal 4(5S)
OP036 THE IMPACT OF PNPLA3 (RS738409 C4G P.I148M) ALLELE MONDAY, OCTOBER 17, 2016 10:30–12:00
DOSE ON DISEASE COURSE IN PRIMARY SCLEROSING BASIC MECHANISMS OF INTESTINAL CARCINOGENESIS – ROOM
CHOLANGITIS (PSC) L8_____________________
1 2 1 3 4
M.A. Färkkila , H. Kautiainen , K. Jokelainen , J. Arola , K. Kontula
1 OP037 TRANSGENIC EXPRESSION OF HUMAN LYSOPHOSPHATIDIC
Dept. Of Gastroenterology, Helsinki University Hospital, Helsinki/Finland
2 ACID RECEPTOR (LPA2) IN MOUSE INTESTINAL EPITHELIAL
Helsinki University, Helsinki/Finland CELLS INDUCES INTESTINAL DYSPLASIA
3
Huslab, Helsinki University Hospital, Helsinki/Finland
4
Depart. Of Medicine, Helsinki University Hospital, Helsinki/Finland M. Yoshida1, C. Yun2, K. Hayashi1, T. Ban1, I. Naitoh1, H. Kondo3, Y. Nishi1,
S. Umemura4, Y. Fujita1, M. Natsume1, A. Kato1, H. Ohara5, T. Joh1
1
Contact E-mail Address: [email protected] Gastroenterology and Metabolism, Nagoya City University Graduate School of
Introduction: PNPLA3 (patatin-like phospholipase domain containing 3) encodes Medical Sciences, Nagoya/Japan
2
carbohydrate-regulated lipogenic and/or lipolytic enzymes in liver. The mutation Division Of Digestive Diseases, Emory University School of Medicine, Atlanta/
of isoleucine to methionine at position 148 (I148M) causes a loss of function United States of America/GA
3
effect leading to increased triglyceride synthesis and accumulation in liver (1). Gastroenterology & Metabolism, Department of Gastroenterology and
The PNPLA3 rs738409 C4G p.I148M has been associated with steatosis and Metabolism, Nagoya City University Graduate School of Medical Sci, Nagoya/
fibrosis in various liver disease and increased risk for development of liver cir- Japan
4
rhosis and hepatocellular cancer (2). The impact of PNPLA3 rs738409 [G] on Department Of Gastroenterology and Metabolism, Nagoya City University
liver damage has a strong environmental interaction and is usually associated Graduate School of Medical Sciences, Nagoya/Japan
5
concomitant liver insult. PSC is a chronic inflammatory disease of bile duct Community-based Medical Education, Nagoya City University Graduate School
epithelium leading to strictures and may secondarily cause liver cirrhosis. PSC of Medical Sciences, Nagoya/Japan
is also associated with inflammatory bowel disease and markedly increased risk
Contact E-mail Address: [email protected]
of cholangiocarcinoma (3,4). PLPN3 variant has been associated with elevations
Introduction: Colorectal cancer (CRC) develops through a series of genetic mod-
of liver enzymes in IBD (5) and in increased risk of bile duct stenosis in male PSC
ifications that transform normal colonic epithelium to an adenoma and the
patients (6). Survival free of liver transplantation is reduced in male PSC patients
adenocarcinoma. In addition to the genetic instability, the activation of growth
with development of dominant strictures in carriers of PNPLA3 I148M variant
factor pathways (eg. The activation of Cox-2, EGF, and VEGF) is common in
(5).
the pathogenesis of CRC cells. Lysophosphatidic acid (LPA) acts on LPA2
Aims & Methods: To evaluate the allele dose effect of PNPLA3 variant on the receptor to mediate multiple pathological effects that are associated with tumor-
clinical manifestations, disease severity, progression and prognosis of PSC in a igenesis. LPA2 expression is increased in CRC patients and proportionally
large patient population from single center. increases with the size of adenomas in rodent models. The absence of LPA2
Results: Of the 563 patients 334 (59.3%) had the wild type (CC), 197 (35%) were attenuates tumor progression in rodent models of colorectal cancer, but whether
heterozygous (CG) and 32 (5.7%) were homozygous for the mutation (GG). A overexpression of LPA2 alone can lead to malignant transformation in the intest-
concomitant IBD was diagnosed in 80% of the males and 60% the females. inal tract has not been studied.
Summary of the results are presented in the table. Aims & Methods: The aim of this study is to determine whether increased LPA2
expression in intestinal epithelial cells (IECs) alone is sufficient to induce spon-
PNPLA3 rs738409 in PSC taneous transformation in the intestinal tract. In this study, we expressed human
LPA2 in IECs under control of the villin promoter. The transgene DNA was
CC, CG, GG, p for injected into the pronuclei of fertilized eggs of C57BL/6J mice. The transgenic
Variable, mean(SD) n ¼ 334 n ¼ 197 n ¼ 32 linearity mice were identified by PCR analysis of tail genomic DNA.
Results: Less than 4% of F1-generation mice had germline transmission of trans-
Males, n (%) 195(58) 124(63) 17(53) 0.75 genic (TG) human LPA2 as such only 3 F1 mice out of 72 genotyped had TG
expression. These TG mice appeared anemic with hematochezia and died shortly
Age at diagnosis of PSC,y 38(14) 36(13) 35(13) 0.10 after birth. TG mice were smaller in size compared with the wild type mouse of
Weight, kg, males 82(14) 80(15) 81(14) 0.37 the same age and sex. Morphological analysis showed that TG LPA2 colon had
Weight, kg, females 69(7) 70(17) 71(13) 0.62 hyper-proliferation of IECs resulting in increased colonic crypt depth.
IBD, n (%) 263(71) 152(77) 21(65) 0.49 Surprisingly, TG small intestine had villus blunting and decreased IEC prolifera-
tion and dysplasia. In both intestine and colon, TG immunohistochemical ana-
Age at dg of IBD 26(11) 26(11) 29(12) 0.74 lysis revealed that expression of LPA2 compromised the terminal epithelial
ERC-score (0–16) 5.8(3.5) 5.4(3.3) 5.7(3.7) 0.88 differentiation, consistent with epithelial dysplasia. Furthermore, we showed
Dominant strictures, n (%) 128(38) 61(31) 9(28) 0.061 that epithelial dysplasia was observed in founder mouse intestine, correlating
Progression of ERC score/month* 0.014 0.002 0.004 0.44 LPA2 overexpression with epithelial dysplasia.
Conclusion: We demonstrated that overexpression of LPA2 induces dysplasia in
Advanced fibrosis F3/4, (%)* 8.8 15.1 12.5 0.25 mouse intestine that alter IEC proliferation and differentiation. Our results rein-
S-ALP, U/l 5105 183(148) 194(170) 182(135) 0.60 force the importance of the LPA-LPA2 axis in homeostatic regulation of IECs
S-GT, U/l, 560 191(249) 236(269) 189(154) 0.94 and its potential contribution to carcinogenesis in the intestinal tract.
S-ALT, U/l, 550 74(125) 78(96) 61(50) 0.35 Disclosure of Interest: All authors have declared no conflicts of interest.
S-AST, U/l, 545 55(73) 54(63) 59(41) 0.68 References
1. Lin S, Wang D, Iyer S, Ghaleb AM, Shim H, Yang VW, et al. The absence of
*Adjusted for sex, age and IBD Cholangiocarcinoma was diagnosed in 12 (3.6%) LPA2 attenuates tumor formation in an experimental model of colitis-asso-
patients with CC, in 6 (3.1%) of CG an in none of GG, (p for linearity¼0.42; ciated cancer. Gastroenterology 2009; 136(5): 1711–20.
adjusted for sex, age and IBD). 49 patients underwent liver transplantation 2. Lin S, Lee SJ, Shim H, Chun J and Yun CC. The Absence of LPA receptor 2
during 5 years mean follow up: 2.5% (95% CI: 1.2 to 5.1) in CC, 3.1% (95% Reduces the Tumorigenesis by ApcMin Mutation in the Intestine. Am J
CI: 1.3 to 7.3) in CG and 7.1% (95% CI: 1.8 to 24.4) in GG, (p for linear- Physiol Gastrointest Liver Physiol 2010; 299(5): G1128–G38.
ity ¼ 0.12; adjusted for sex, age and IBD).

Conclusion: The PNPLA3 I148M variant did not have any significant impact on
clinical manifestation, disease progression, development of dominant strictures,
on risk of cholangiocarcinoma or liver transplantation in PSC.
Disclosure of Interest: All authors have declared no conflicts of interest.

References
1. Kumari M, et al. Cell Metab 2012;15: 691–702.
2. Trepo E et al. J Hepatol. 2016 Mar 30. pii: S0168–8278(16)30084–8.
3. Hirschfield GM, et al. Lancet. 2013;382:1587–99.
4. Bergquist A, et al. J Hepatol. 2002; 36:321–327.
5. Friedrich K, et al. PLoS ONE 8(3): e58734. doi:10.1371.
United European Gastroenterology Journal 4(5S) A17
OP038 CELL-SPECIFIC ROLES OF CALCINEURIN IN INTESTINAL OP039 ALIX POSITIVE EXOSOMES IN COLORECTAL ADENOMA-
TUMOR DEVELOPMENT CARCINOMA SEQUENCE
K. Peuker1, S. Muff2, J. Wang3, M. Basic4, A. Strigli1, A. Kaser5, A. Arlt6, G. Valcz1, O. Galamb1, T. Krenacs2, A.V. Patai3, S. Spisák4, A. Kalmár5,
G.R. Van Den Brink7, C. Schafmayer8, J. Egberts8, T. Becker8, A. Bleich4, B. Wichmann6, K. Dede7, Z. Tulassay8, B. Molnar9
C. Röcken9, J. Hampe10, S. Schreiber11, J. Baines12, R.S. Blumberg13, S. Zeissig1 1
Molecular Medicine Research Unit, Hungarian Academy of Sciences, Budapest/
1
Tu Dresden, Center for Regenerative Therapies, Dresden/Germany Hungary
2 2
Uksh Kiel, Innere Medizin I, Kiel/Germany 1st Department Of Pathology and Experimental Cancer Research, Semmelweis
3
Max Planck Institute for Evolutionary Biology, Plön/Germany University, Budapest/Hungary
4 3
Hannover Medical School, Institute for Laboratory Animal Science and Central 2nd Department Of Internal Medicine, Semmelweis University 2nd Dept. of
Animal Facility, Hannover/Germany Medicine, Budapest/Hungary
5 4
Dept. Of Medicine, University of Cambridge Gastroenterology and Hepatology, Department Of Medical Oncology, Dana-Farber Cancer Institute, Boston/United
Cambridge/United Kingdom States of America
6 5
Department Of Medicine, University Hospital of Schleswig-Holstein, Campus 2nd Dept. Of Internal Medicine, Semmelweis University, Budapest/Hungary
6
Kiel, Kiel/Germany Molecular Medicine Research Group, Hungarian Academy of Sciences, Budapest/
7
Dept. Of Gastroenterology, Academisch Medisch Centrum, Amsterdam/ Hungary
7
Netherlands Uzsoki utcai Kórház, Budapest/Hungary
8 8
Department Of General Surgery and Thoracic Surgery, University Hospital of 2nd Department Of Medicine, SE II. Belgy. Klinika Belgyogyaszat, Budapest/
Schleswig-Holstein, Kiel/Germany Hungary
9 9
University Medical Center Schleswig-holstein, Institute of Pathology, Kiel/ 2nd Dept. Of Internal Medicine, Semmelweis University 2nd Dept. of Internal
Germany Medicine, Budapest/Hungary
10
Department Of Medicine I, University Medical Center Dresden, Dresden/
Germany Contact E-mail Address: [email protected]
11
Department Of Medicine I, University Hospital of Schleswig-Holstein, Kiel/ Introduction: During colorectal carcinoma (CRC) formation exosomes play
Germany important roles as intercellular regulators in conveying complex signals between
12
Christian-albrechts University Of Kiel, Institute for Experimental Medicine, Kiel/ epithelial/carcinoma cells and their abnormal microenvironment.
Germany Aims & Methods: Our aim was to characterize changes in exosome-based com-
13
Brigham and Womens Hospital, Boston/United States of America munication in the colorectal adenoma-carcinoma sequence by determining ALG
2-interacting protein X (ALIX) exosome marker production on mRNA and
Contact E-mail Address: [email protected] protein level. mRNA expression was analyzed using Affymetrix HGU133
Introduction: Colorectal cancer (CRC) development is characterized by the Plus2.0 whole transcriptome data of healthy (n ¼ 49), adenoma (n ¼ 49) and
sequential accumulation of somatic mutations, which promotes epithelial prolif- CRC (n ¼ 49) samples. Immunohistochemistry was performed on healthy
eration and subsequently tumor invasion. Calcineurin is a phosphatase, which (n ¼ 27), adenoma (n ¼ 42), CRC (n ¼ 37) patients and stained for ALIX exo-
contributes to innate and adaptive immunity through the activation of transcrip- some, cytokeratin (CK) epithelial, podoplanin (PDPN) lymphatic vessel, Ki-67
tion factors of the family of nuclear factor of activated T cells (NFAT). Systemic proliferative and Musashi-1 (MSI1) stem cell markers. Slides were digitalized and
inhibition of calcineurin as applied in human immunosuppression is associated analyzed with digital microscopy.
with an increased incidence of CRC. However, calcineurin and NFAT are also Results: We found significantly decreased (p 5 0.05) ALIX mRNA expression
expressed in CRC cell lines and rather promote than inhibit epithelial prolifera- both in adenoma and CRC samples compared to normal samples. Similarly,
tion in vitro. These findings raise the question of whether calcineurin plays cell- significantly reduced (p 5 0.05) ALIX protein levels were detectable in adenoma
specific roles in CRC and, in particular, whether intestinal epithelial calcineurin and CRC samples compared to normal ones. The reduced protein expression was
promotes tumor development in a cell-intrinsic manner. accompanied by gradual transition from diffuse cytoplasmic (in normal epithe-
Aims & Methods: To investigate the role of calcineurin and NFAT in intestinal lium) expression to granular signals (in adenoma and CRC samples) with 0.6–
tumor development, we generated mice with intestinal epithelial cell (IEC)-spe- 2 mm diameter size range of multivesicular bodies. The granular ALIX expression
cific deletion of the regulatory B1 subunit of calcineurin and analyzed these mice was not limited to the proliferative and stem cells, but was also observed in
in the Apcfl/wt and ApcMin/þ models of genetically induced intestinal tumor budding CKþ and MSI1þ stromal cells, as well as in the lumen of PDPNþ
development as well as in the AOM/DSS model of colitis-associated cancer. lymphatic vessels in invasive CRCs.
For mechanistic studies, organoid cultures, immortalized IECs and CRC cell Conclusion: The altered ALIX expression pattern in pre-neoplastic lesions sug-
lines as well as samples of more than 700 CRC patients were studied. gests that abnormal exosome transport may play an important role in the ade-
Results: We demonstrate that systemic inhibition of calcineurin with cyclosporine noma to carcinoma transformation. Furthermore, the increased frequency of
leads to increased intestinal tumor growth in ApcMin/þ mice, which is consistent exosome marker expression in stromal and budding cancer cells, and also in
with an increased CRC incidence observed in patients receiving calcineurin inhi- the lumen of lymphatic vessels suggests that the exosome based information
bitors. In contrast, intestinal epithelial cell-specific deletion of calcineurin is flow may be fundamental in the development of local and distant pre-metastatic
associated with reduced intestinal tumor formation and growth in the Apcfl/wt microenvironments in CRC patients. This study was funded by the Research and
and ApcMin/þ model. Antibiotic treatment of mice as well as backcrossing to a Technology Innovation Fund, Hungary, KMR_12–1-2012–0216 and Hungarian
Myd88-deficient background revealed that the activation of oncogenic epithelial Scientific Research Fund (OTKA-K111743 grant).
calcineurin is dependent on the intestinal microbiota and results from tumor- Disclosure of Interest: All authors have declared no conflicts of interest.
associated alterations in microbial composition and stratification as well as from
increased tumor-associated toll-like receptor expression. Tumor-promoting
effects of epithelial calcineurin are elicited through NFAT-dependent transcrip-
tional regulation of Lgr5-positive tumor stem cells as shown by chromatin immu-
noprecipitation (ChIP), gene expression analysis and functional studies together
leading to control of tumor stem cell apoptosis and proliferation as shown by
FACS and immunofluorescence staining. Moreover, somatic mutations identi-
fied in human CRC are associated with constitutive activation of calcineurin,
while nuclear translocation of NFAT correlates with reduced survival in a large
cohort of CRC patients.
Conclusion: These results support the concept of cell-specific roles of calcineurin
in the regulation of colorectal carcinogenesis and reveal novel potential targets
for the prevention and treatment of CRC.
Disclosure of Interest: All authors have declared no conflicts of interest.
A18 United European Gastroenterology Journal 4(5S)
OP040 NHERF2 REGULATES COLON CANCER PROGRESS VIA STAT3 OP041 THE EXTRACELLULAR MATRIX PROTEIN EMILIN2 AS A
M. Yoshida1, C. Yun2, K. Hayashi1, T. Ban1, I. Naitoh1, H. Kondo1, Y. Nishi1, REGULATOR OF THE MYELOID RESPONSE IN A MODEL OF
S. Umemura1, Y. Fujita1, M. Natsume1, A. Kato1, H. Ohara3, T. Joh1 INFLAMMATION-INDUCED COLON CARCINOGENESIS
1
Gastroenterology and Metabolism, Nagoya City University Graduate School of E. Andreuzzi1, A. Paulitti1, G. Tarticchio1, E. Di Carlo2, R. Pellicani1,
Medical Sciences, Nagoya/Japan A. Colombatti1, R. Cannizzaro3, M. Mongiat1
2 1
Division Of Digestive Diseases, Emory University School of Medicine, Atlanta/ Translational Research, Experimental Oncology Ii, CRO-IRCCS, Aviano/Italy
2
United States of America/GA Department Of Oncology and Experimental Medicine, University of Chieti-
3
Community-based Medical Education, Nagoya City University Graduate School Pescara, Chieti/Italy
3
of Medical Sciences, Nagoya/Japan Oncological Gastroenterology, Centro di Riferimento Oncologico di Aviano
S.O.C. di Gastroenterologia, Aviano/Italy
Contact E-mail Address: [email protected]
Introduction: Scaffold proteins mediate protein-protein interaction to bring Contact E-mail Address: [email protected]
together key members of signaling pathways that drive cell division and Introduction: EMILIN2 is an extracellular matrix molecule belonging to the EMI
growth. The Naþ/Hþ exchanger regulatory factor (NHERF) family of proteins Domain ENdowed (EDEN) protein family that exerts pleiotropic effects in the
is scaffolds that orchestrate interaction of receptors and cellular proteins. Among tumor microenvironment overall functioning as a tumor suppressive molecule (1–
the NHERF proteins, NHERF1 and NHERF2 share most similarities with 3). EMILIN2 affects tumor cell viability and proliferation by activating apopto-
tandem PDZ domains and an ERM interacting motif in the carboxyl domain sis and functioning as a negative regulator of the Wnt/b-catenin axis.
that enables anchoring to the actin cytoskeleton. One major function of Interestingly EMILIN2 expression is down-modulated by methylation in a
NHERF1/2 is to recruit and spatially organize signaling proteins that either number of tumors including breast and colorectal cancer (4). Our preliminary
alters protein functions or downstream signaling pathways originating from results highlight a possible new function for E2 in the control of CRC incidence.
receptor. NHERF1 is reported to be a tumor suppressor. However, the role of In particular these findings indicate that E2 seems to modulate the myeloid
NHERF2 in cancer progress has not been reported. response and to profoundly affect the inflammatory microenvironment asso-
Aims & Methods: We investigated the role of NHERF2 in colon tumor progres- ciated with CRC.
sion. We first determined NHERF2 expression in human colorectal cancer Aims & Methods: Given its involvement in the regulation of Wnt signaling, a
(CRC) using a tissue microarray. Next, the role of NHERF2 on colon cancer crucial pathway in colon carcinogenesis, and its altered expression in colorectal
growth and invasion was assessed by a loss-of-function approach (shRNA) and a cancer, we took advantage of the EMILIN2 null mouse model to assess its role in
small peptide which blocked the PDZ domain of NHERF2 to bind using colon colorectal cancer (CRC) development, subjecting the mice to the inflammation-
cancer cell lines (HCT116, SW480, and HT-29). We validated tumor growth related AOM/DSS protocol. Colorectal tumors were induced subjecting the mice
change by xenograft model. Moreover, we used ApcMin/þ mouse model to to a AOM/DSS treatment. Tumor development was assessed by colonoscopy.
investigate the tumorigenesis in intestine with NHERF2 homozygous deletion Histopathological and IHC analyses were performed on colon samples from
mice. To investigate the molecular mechanism of NHERF2 in tumor growth, we treated mice. b-catenin activation was assessed by Western blot and qPCR.
performed the transcriptom analysis. Multiplex serum cytokine analyses from the two mouse models were performed
Results: We found that NHERF2 expression is elevated in advanced-stage CRC. through Luminex Screening and peripheral blood cells were counted. The inflam-
Knockdown of NHERF2 decreased cancer cell proliferation and invasion matory infiltrate was analysed by flow cytometry.
in vitro, and tumor growth in a mouse xenograft tumor model. Histologic ana- Results: The EMILIN2 KO mice developed a significantly higher number of
lysis confirmed the reduction of cell proliferation by Ki67 immunostaining. In tumors compared to wt mice. Tumors from EMILIN2 KO mice were more
addition, deletion of NHERF2 in ApcMin/þ (ApcMin/þ;Nherf2-/-) mice undifferentiated and at an advanced stage compared to the tumors from control
resulted in decreased tumor growth in ApcMin/þ mice and increased lifespan. mice. Surprisingly, and contrary to our expectations, tumors from EMILIN2 KO
Blocking NHERF2 interaction with a small peptide designed to bind the second mice did not display any changes in the activation of the Wnt/b-catenin pathway
PDZ domain of NHERF2 attenuated cancer cell proliferation. Although compared to the controls. Accordingly, the b-catenin target genes cyclin D1 and
NHERF2 is known to facilitate the effects of lysophosphatidic acid receptor 2 c-Myc were not altered in the tumors and in the normal mucosa of the two mouse
(LPA2), transcriptome analysis of xenograft tumors revealed that NHERF2- models. Histopathological and IHC analysis indicated that the tumors from
dependent genes largely differ from LPA2-regulated genes. b-catenin and EMILIN2 KO mice where characterized by a higher number of macrophages
ERK1/2 activation was mitigated in ApcMin/þ;Nherf2-/- adenomas. and granulocytes than those from WT mice. Similar alterations in the KO model
Moreover, Stat3 phosphorylation and CD24 expression levels were suppressed were found during the acute fase of inflammation: mice subjected to DSS treat-
in ApcMin/þ;Nherf2-/- adenomas. Consistently, NHERF2 knockdown attenu- ment alone developed a more severe colitis than WT mice. Accordingly, the
ated Stat3 activation and CD24 expression in colon cancer cells. Interestingly, infiltration of myeloid cells within the intestinal mucosa was altered and the
NHERF2-dependent increase in CD24 expression was blocked by inhibition of serum level of a number of cytokines, including IL-1b, INF-gamma, TNF-
Stat3, suggesting that NHERF2 regulates Stat3 phosphorylation followed by the and IL-10, was affected.
increase in CD24. Conclusion: Our results let us suggest that EMILIN2 may affect colon carcinog-
Conclusion: This study demonstrated NHERF2 stimulates colon cancer growth esis impinging on the recruitment and/or the activation of myeloid cells. By
by intersecting at multiple signaling nodes. NHERF2 potentiates the oncogenic altering the inflammatory microenvironment, EMILIN2 may significantly influ-
effects in part by regulation of Stat3 and CD24. This study provides NHERF2 as ence colon cancer development.
a new potential target for cancer treatment. Disclosure of Interest: All authors have declared no conflicts of interest.
Disclosure of Interest: All authors have declared no conflicts of interest. References
References
1. Mongiat M, Ligresti G, Marastoni S, Lorenzon E, Doliana R and
1. Pan Y, Wang L and Dai JL. Suppression of breast cancer cell growth by Colombatti A. Regulation of the extrinsic apoptotic pathway by the extra-
Naþ/Hþ exchanger regulatory factor 1 (NHERF1). Breast Cancer Res 2006; cellular matrix glycoprotein EMILIN2. Mol Cell Biol 2007; 27: 7176–87.
8: R63. 2. Mongiat M, Marastoni S, Ligresti G, Lorenzon E, Schiappacassi M, Perris
2. Hayashi Y, Molina JR, Hamilton SR, et al. NHERF1/EBP50 is a new R, et al. The extracellular matrix glycoprotein elastin microfibril interface
marker in colorectal cancer. Neoplasia 2010; 12: 1013–1022. located protein 2: a dual role in the tumor microenvironment. Neoplasia
3. Lin S, Wang D, Iyer S, et al. The absence of LPA2 attenuates tumor forma- 2010; 12: 294–304.
tion in an experimental model of colitis-associated cancer. Gastroenterology 3. Marastoni S, Andreuzzi E, Paulitti A, Colladel R, Pellicani R, Todaro F,
2009; 136: 1711–1720. et al. EMILIN2 down-modulates the Wnt signalling pathway and suppresses
4. Lin S, Lee SJ, Shim H, Chun J and Yun CC. The Absence of LPA receptor 2 breast cancer cell growth and migration. J Pathol 2014; 232: 391–404.
Reduces the Tumorigenesis by ApcMin Mutation in the Intestine. Am J 4. Hill VK, Hesson LB, Dansranjavin T, Dallol A, Bieche I, Vacher S, et al.
Physiol Gastrointest Liver Physiol 2010; 299: G1128–G1138. Identification of 5 novel genes methylated in breast and other epithelial
cancers. Mol Cancer 2010; 9: 51.
United European Gastroenterology Journal 4(5S) A19
OP042 THE ROLE OF MIRNA-145 IN COLON CANCER STEM CELL- recruiting investigators). A local coordinator was selected from each country.
LIKE CELLS Each coordinator selected a representative group of recruiting investigators
S.E. Gomes1, D. M. Pereira1, A. E. s. Simões1, R. E. Castro1, P. M. Borralho1, C. from his/her country. An electronic clinical research file (e-CRF) was created
M.P. Rodrigues2 on AEG-REDCap to systematically register all adult patients infected with H.
1
Faculty Of Pharmacy, iMed.ULisboa, Faculty of Pharmacy, University of Lisbon, pylori. Variables included: Patient’s demographics, previous eradication
Lisbon/Portugal attempts, prescribed eradication treatments, adverse events, and outcomes
2
iMed.ULisboa, Faculty of Pharmacy, Universidade de Lisboa, Lisbon/Portugal (cure rates, compliance, follow up, etc.). Patients with both eradication confir-
matory test and with less than one year follow-up have been considered ongoing
Contact E-mail Address: [email protected] and were excluded from the analysis.
Introduction: Cancer stem cells (CSCs) are thought to be responsible for tumour Results: Up to now, 16,025 patients have been included, and 12,921 have finished
initiation, metastasis and relapse through their unlimited self-renewal and differ- follow up (59% females, 87% Caucasian). Mean age was 55 years. The bismuth-
entiation potential. miRNAs have recently emerged as promising candidates to levofloxacin quadruple treatment was prescribed to 327 patients (2% of all treat-
target CSCs. miR-145 is a tumour suppressor miRNA, downregulated in colon ments registered): 7% in first-line, 76% in second, 12% in third, and 5% in
cancer adenomas and carcinomas. It has been shown to be involved in tumour following rescues. Overall efficacy was 84% (95%C.I. ¼ 75–93%) by ITT and
growth, metastasis and resistance to chemo/targeted agents, as well as in mod- 92% (89–95%) by PP. First-line data is insufficient for analysis. Second-line
ulation of CSC-like properties in prostate cancer and lung adenocarcinoma. In efficacy was 85% (80–91%) by ITT and 92% (89–94%) by PP. Treatment was
this context, we hypothesise that miR-145 may play a role in the ability of colon generally prescribed with esomeprazole (95%) and as a 14 day regimen (98%).
CSCs (CCSCs) to self-renew and differentiate. Compliance with treatment was 95%. Adverse events were reported in 38% of
Aims & Methods: We aimed to evaluate the effect of miR-145 overexpression in cases and caused treatment discontinuation in 7 (2.1%) patients.
maintaining CCSCs-like properties. We produced miR-145 overexpressing and Conclusion: A 14-day regimen combining bismuth salts with levofloxacin triple
empty vector control cells using HCT116, HT29, SW480 and SW620 colon therapy as second-line treatment for H. pylori eradication achieves near 90%
cancer cell lines, and examined their ability to form colon spheres in ultralow- eradication rates.
attachment plates and specific CCSC media. Colon spheres were dissociated to Disclosure of Interest: A.G. McNicholl: Speaker for allergan
single cells and reseeded to yield the second and third generation of colon M. Castro: Teaching activities for Allergan
spheres. The number of spheres and cells per sphere were counted over 3 gen- J. Molina Infante: Scientific Advisory for Casen Recordati Teaching activities for
erations. mRNA expression levels of stemness markers were evaluated by SYBR Allergan and Zambon
Real-Time PCR. CD44 and CD133 expression levels and aldehyde dehydrogen- J.P. Gisbert: Scientific advisory and teaching for Almirall, Allergan,
ase 1 (ALDH1) activity were evaluated by flow cytometry. AstraZeneca, Casen Recordati, Nycomed.
Results: Our results showed that forced miR-145 expression reduced colon sphere All other authors have declared no conflicts of interest.
diameter and number of cells per sphere in HCT116, HT29, SW480 and SW620
cells. Moreover, miR-145 overexpression had an impact on HT29 and SW620
sphere formation, reducing the number of colon spheres. Similar results were
observed with the second and third generation of cell line-derived colon spheres. OP044 ERADICATION RATES OF HELICOBACTER PYLORI USING A
mRNA expression levels of the stemness markers KLF4 and BMI1, were sig- NEW GASTRIC ACID SUPPRESSANT, VONOPRAZAN, COMPARED
nificantly reduced in colon spheres overexpressing miR-145 (p 5 0.01). In addi- WITH AN ESOMEPRAZOLE REGIMEN
tion, HT29 and SW480 cell line-derived colon spheres overexpressing miR-145 M. Tsujimae1, H. Yamashita2, A. Kanamori3, K. Matsumoto4, A. Koizumi5,
displayed reduced OCT4 mRNA levels. Furthermore, miR-145 overexpression T. Eguchi6, A. Okada7
significantly decreased the proportion of CD44/CD133þ cells and ALDH1 activ- 1
Gastroenterology, Osakafu Nakatsu Saiseikai Hospital, Osaka/Japan
ity (p 5 0.05). The mature colonocyte marker, CK20, was increased in HCT116 2
Gastroenterology, Nakatsu Saiseikai Hospital, Osaka/Japan
spheres overexpressing miR-145 (p 5 0.01). 3
Gastrointestinal Medicine, Osakafu Saiseikai Nakatsu Hospital, Osaka/Japan
Conclusion: miR-145 appears to be involved in colon sphere formation, self- 4
Osakafu Saiseikai Nakatsu Hospital, osaka, Japan, Osaka/Japan
renewal of colon spheres and differentiation ability of HCT116 colon spheres. 5
Gastroenterology and Hepatology, Osakafu Saiseikai Nakatsu Hospital, Osaka/
miR-145 may contribute to the induction of CCSC differentiation to cells that are Japan
sensitive to chemotherapy and targeted agents. 6
Osakafu Saiseikai Nakatsu Gastroenterology & Hepatology, Osaka/Japan
Disclosure of Interest: All authors have declared no conflicts of interest. 7
Gastroenterology & Hepatology, Osakafu Saiseikai Nakatsu Hospital, Osaka/
Japan
MONDAY, OCTOBER 17, 2016 10:30–12:00 Contact E-mail Address: [email protected]
GASTRODUODENAL DAMAGE: H.PYLORI, ACID AND BILE – ROOM Introduction: A proton pump inhibitor (PPI)-based triple regimen containing two
1.86_____________________ antibiotics (amoxicillin, APMC; and clarithromycin, CAM) was considered the
gold standard for the eradication of Helicobacter pylori for more than a decade.
OP043 PAN-EUROPEAN REGISTRY ON H. PYLORI MANAGEMENT However, low eradication rates have been reported worldwide because of
(HP-EUREG): INTERIM ANALYSIS OF THE RESCUE TREATMENT increased prevalence of clarithromycin-resistant H. pylori. Insufficient acid inhibi-
WITH BISMUTH, LEVOFLOXACIN AND AMOXICILLIN tion during treatment also causes eradication failure. This is because the antimi-
A.G. Mcnicholl1, F. Megraud2, B. Tepeš3, M. Venerito4, A. Gasbarrini5, D. crobial agents are unstable and degraded in the stomach.Esomeprazole (EPZ) is a
S. Bordin6, M. Castro7, J. Ortuño8, J. Molina Infante9, J. Barrio10, J. Delchier11, relatively new PPI available in Japan since September 2011. EPZ has an improved
M. G. Donday1, O.P. Nyssen12, C. O’Morain13, J. P. Gisbert14 pharmacokinetic profile as regards CYP2C19 genotype; therefore, it shows less
1
Digestive Services, Centro de Investigación Biome´dica en Red de Enfermedades individual variability. Vonoprazan (VPZ) is a potassium-competitive acid blocker
Hepáticas y Digestivas (CIBERehd), Madrid/Spain (P-CAB). P-CABs are a new class of gastric acid suppressants available since
2
Inserm U853, Hopital Pellegrin, Laboratoire de Bacteriologie, Bordeaux Cedex/ February 2015 in Japan. VPZ has a potent and long-lasting anti-secretory effect
France on Hþ,Kþ-ATPase due to its high accumulation in, and slow clearance from
3
Gastroenterology, Abakus Medico d.o.o., Rogaska Slatina/Slovenia gastric tissue. Therefore, VPZ is expected to have high eradication rates compared
4
Department Of Gastroenterology, Hepatology and Infectious Diseases, Otto-von- with conventional PPIs. The aim of this study was to compare H. pylori eradica-
Guericke University Magdeburg, Magdeburg/Germany tion rates with EPZ-based and VPZ-based triple therapies with CAM and AMPC.
5
Internal Medicine, Gastroenterology and Liver Diseases, Gemelli Hospital Dept. Aims & Methods: A total of 807 patients who had undergone upper gastrointest-
of Internal Medicine Dept. of Gastroenterology, Rome/Italy inal endoscopy and diagnosis with H. pylori infection from November 2013 to
6
Department Of Pancreatic, Biliary and Upper GI Diseases, Moscow Clinical March 2016 were enrolled. From December 2013 to September 2014, 431 patients
Scientific Center, Moscow/Russian Federation were treated with EPZ-based triple therapy, while 376 patients were treated with
7
Gastroenterology Unit, Hospital Nuestra Señora de Valme, Sevilla/Spain VPZ-based triple therapy from April 2015 to March 2016. At baseline, demo-
8
Hospital Universitario de La Fe, Valencia/Spain graphical and clinical characteristics including gender, age, body mass index
9
Dept. De Gastroenterologia, Hospital San Pedro de Alcantara, Caceres/Spain (BMI), smoking status, and consumption of alcohol were checked. The first-
10
Central Asturias University Hospital, Oviedo/Spain line eradication regimen was CAM 200 mg, AMPC 750 mg, and either EPZ 20
11
Hôpital H. Mondor Service de Gastroente´rologie, Cre´teil/France mg or VPZ 20 mg, each twice daily for 7 days. The second-line eradication
12
Digestive Services, Hospital Universitario de La Princesa, Madrid/Spain regimen was metronidazole 250 mg, AMPC 750 mg, and either EPZ 20 mg or
13
Faculty Of Health Sciences, Trinity College Dublin, Dublin/Ireland VPZ 20 mg, each twice daily for 7 days. The eradication of H. pylori infection
14
Digestive Services, Hospital Universitario de La Princesa, Instituto de was diagnosed using 13C-urea breath tests at 4–8 weeks after each of therapy.
Investigación Sanitaria Princesa (IP) and Centro, Madrid/Spain Results: The overall first-line eradication rate was 79.1% (341/431) for the EPZ
regimen and 84.6% (318/376) for the VPZ regimen based on Intension to treat
Contact E-mail Address: [email protected] (ITT) analysis. The eradication rate by Par protocol (PP) analysis for the EPZ
Introduction: H. pylori rescue therapy is still a major concern for clinicians treat- and VPZ regimens were 79.9% (341/427) and 85.3% (318/373) respectively.
ing this infection. Although several rescue treatments have been proposed and Significant differences were found both in ITT analysis (p ¼ 0.045) and in PP
tested, the selection of resilient strains or acquisition of resistance after failed analysis (p ¼ 0.046). The overall second-line eradication rate was 72.6% (45/62)
eradication hinders the success rate of most proposed regimens. Traditionally for the EPZ regimen and 85.3% (29/34) for the VPZ regimen based on ITT
rescue treatments in Europe have been divided in bismuth quadruple therapy or analysis. Using PP analysis, the eradication rate was 88.2% (45/51) for the
levofloxacin triple. Some authors have recently proposed a combination of both EPZ regimen and 87.9% (29/33) for the VPZ regimen. There were no statistically
strategies by adding bismuth to the traditional levofloxacin triple therapy. significant differences found between the eradication rates in both groups, from
Aims & Methods: To evaluate the use and outcomes of a quadruple therapy both the ITT and PP analyses.
containing a proton pump inhibitor, bismuth, levofloxacin and amoxicillin in Conclusion: In conclusion, VPZ has a rapid, sustained, and possibly more potent
the European Registry on H. pylori Management (Hp-EuReg). Methods: acid-inhibitory effect than EPZ, irrespective of CYP2C19 genotype. The rate of
Systematic prospective registry of the clinical practice of European gastroenter- H. pylori eradication obtained using the first-line VPZ regimen was significantly
ologists regarding H. pylori infection and treatment (31 countries and 280 higher than that for the first-line EPZ regimen. However, for the second-line
A20 United European Gastroenterology Journal 4(5S)
treatment, there were no significant differences between the eradication rates Aims & Methods: Using gastric tissue from humans, rats treated with proton
from EPZ and VPZ regimens. pump inhibitors and/or a cholecystokinin type B receptor (CCK-BR) antagonist,
Disclosure of Interest: All authors have declared no conflicts of interest. Hþ/Kþ-ATPase b-subunit knockout (H/K-b KO) mice and Mongolian gerbils
References infected with Helicobacter pylori and treated with a CCKBR antagonist, we
examined the expression pattern and gastrin-mediated regulation of CLU using
1. Chey WD, et al. American College of Gastroenterology guideline on the parallel reaction monitoring mass spectrometry, in situ hybridization and immu-
management of Helicobacter pylori infection. Am J Gastroenterol 2007; nohistochemistry. Human gastric cancer cell lines were used to study the gastrin-
102: 1808–1825. mediated regulation and biological function of secretory CLU in vitro.
2. Graham DY, et al. A report card to grade Helico- bacter pylori therapy. Results: CLU was highly expressed in neuroendocrine cells in normal oxyntic
Helicobacter 2007; 12: 275–278. mucosa of humans, rats and mice. In response to hypergastrinemia, expression of
3. Asaka M, et al. A multicenter, double-blind study on triple therapy with CLU was significantly increased and localization shifted from neuroendocrine
lansoprazole, amoxicillin and clarithromycin for eradication of Helicobacter cells to basal groups of proliferative cells in the mucous neck cell-chief cell lineage
pylori in Japanese peptic ulcer patients. Helicobacter 2001; 6: 254–61. in three different animal models. This shift was partly inhibited by antagonizing
4. Murakami K, et al. Eradication rates of clarithromycin-resistant the CCKBR in rats and Mongolian gerbils. The oxyntic mucosa of H/K-b KO
Helicobacter pylori using either rabeprazole or lansoprazole plus amoxicillin mice contained distinct areas with CLU-positive mucous cell hyperplasia, possi-
and clarithromycin. Aliment Pharmacol Ther 2002; 16: 1933–8. bly representing SPEM. In vitro, gastrin increased the secretion of CLU, and
5. Hunt RH, et al. pH and Hp–gastric acid secretion and Helicobacter pylori: both gastrin and secretory CLU promoted survival of gastric cells following
implications for ulcer healing and eradication of the organism. Am J starvation- and chemotherapy-induced stress.
Gastroenterol 1993; 88: 481–3. Conclusion: Our findings suggest that gastrin and CLU participate in premalig-
nant remodeling of the oxyntic mucosa by influencing the balance between sur-
vival and apoptosis in gastric epithelial cells.
Disclosure of Interest: All authors have declared no conflicts of interest.
OP045 STROMAL MYOFIBROBLASTS ORCHESTRATE GASTRIC
EPITHELIAL WNT-SIGNALING AND STEM CELL KINETICS IN
HEALTH AND DISAEASE
M. Sigal1, M. R. Amieva2, T. Meyer3 OP047 THE GREAT MAJORITY OF THE H. PYLORI INFECTED
1
Gastroenterology and Hepatology, Charite University Medicine Berlin, Berlin/ POPULATION HAS REDUCED INTRAGASTRIC ACIDITY WHICH
Germany IS MOST MARKED CLOSE TO THE GASTROESOPHAGEAL
2
Microbiology and Immunology, Stanford Universıty, Stanford/United States of JUNCTION.
America D. Mitchell1, M. Derakhshan1, A. Wirz2, C. Orange1, D. Hughes1,
3
Department Of Molecular Biology, Max Planck Institute for Infection Biology, S. Ballantyne2, J. Going1, K. Mccoll3
1
Berlin/Germany University of Glasgow, Glasgow/United Kingdom
2
NHS GGC, Glasgow/United Kingdom
Contact E-mail Address: [email protected] 3
BHF Glasgow Research Centre, University of Glasgow, Glasgow/United Kingdom
Introduction: The gastric epithelium is characterized by constant, rapid self-
renewal, which in the antrum is driven by long-lıved stem cells situated at the Contact E-mail Address: [email protected]
base of the glands. Infection with the gastric pathogen Helicobacter pylori is the Introduction: A negative association exists between H. pylori infection and both
main risk factor for gastric cancer and increases stem cell and the turnover gastroesophageal reflux disease1 and oesophageal adenocarcinoma2 and this may
kinetics of the glands. Wnt signaling is known to be crucial for stem cell home- be due to the infection reducing intragastric acidity. To exert such a protective
ostasis in several tissues and for long-term organoid culture of stomach epithe- effect the reduced acidity would need to be evident in the majority of H. pylori-
lium, but it is not clear how Wnt signaling is spatially organized in the stomach infected subjects. To investigate this we have examined the acid secretory capa-
in vivo and whether it modulates stem cell kinetics and glandular turnover. city of H. pylori-positive and negative volunteers in a Western population.
Aims & Methods: The aim of the present study was to characterize the cellular and Aims & Methods: We studied 31 H. pylori-positive and 28 H. pylori-negative volun-
molecular Wnt-network in the stomach and to explore its function in physiological teers, matched for age, gender and BMI. Jumbo biopsies were taken at eleven
epithelial turnover, as well as upon infection with H. pylori. Using in single molecule pre-determined locations from the gastroesophageal junction and stomach. High-
situ hybridization, different stem cell- and WNT-signaling reporter mice and the resolution pHmetry (12 sensors at 11 mm intervals) and manometry (36 sensors at
murine and as well as human 3D-organoid system we addressed these questions. 7.5 mm intervals) was performed for 20 minutes fasted and then for 90 minutes
Results: We found that Wnt-responsive cells are limited to the base of the antral following a standardised meal. The position of the squamocolumnar junction
glands where stem cells reside. However, in addition to previousy descibed Lgr5- (SCJ), marked with two endoscopically placed radio-opaque clips, was visualised
positive cells, we found another Wnt-dependent population of highly prolifera- radiologically relative to the probes. The biopsy specimens were scored quantitatively
tive Lgr5-negative stem cells in the gland base. We show that the positional for inflammation and stained with monoclonal antibody to Hþ/KþATPase and
identity of these Axin2-positive stem cells relies on R-spondin 3, which is pro- pepsinogen I for calculating parietal cell and chief cell densities respectively.
duced by stromal myofibroblasts. Wnt signaling stimulated by exogenous R- Results: The mean age of the H. pylori-positive group was 55 years (38y–78y)
spondin induces an expansion and increased proliferation of Axin2-positive compared to 56 years (24y–74y) for the H. pylori-negative group.
stem cells in the stomach antrum while the Lgr5-positive cells remain silenced. Under fasting conditions, the H. pylori-positive subjects had less intragastric
Infection of mice with H. pylori increases expression of R-spondin 3, which also acidity compared to the H. pylori-negatives at all sensors more than 1.1cm
induces the expansion of Axin2-positive cells and results in gland hyperplasia. By distal to the peak lower oesophageal sphincter (LOS) pressure (all p 5 0.01).
increasing gland turnover following infection, R-spondin counterbalances bac- Throughout the three 30-minute postprandial periods, intragastric acidity was
terial gland colonization through increased shedding of cell-attached bacteria. significantly less in H. pylori positives at the sensors 2.2, 3.3 and 4.4cm distal to
Conclusion: Thus, stromal R-spondin hierarchically organizes the stem cell com- the peak LOS pressure (all p 5 0.05), but there was no significant difference in
partment producing two Wnt–responsive populations that differ in position the sensors 5.5 and 6.6cm distal to peak LOS pressure (Table 1). The postpran-
within the gland, proliferation kinetics, and sensitivity to R-spondin. In addition dial acid pocket was thus attenuated in H. pylori positives compared to negatives.
to its role in physiological gland homeostasis R-spondin driven regeneration is The H. pylori positives had a significant reduction in density of both parietal and
increased by infection with H. pylori, limiting glandular colonization. This estab- chief cells compared to H. pylori negatives, and this was seen in 10 of the 11
lishes a new link between infection, stem cell signaling and epithelial homeostasis. gastric locations (p 5 0.01 for 9 locations). The degree of reduction was similar
Disclosure of Interest: All authors have declared no conflicts of interest. for the two cell types. The cardia mucosal length was longer in H. pylori positives
Reference (1.5 mm vs 0.7 mm; p ¼ 0.013).
17/31 (54.8%) of the H. pylori positives were also CagA seropositive and they
1. Sigal et al., Gastroenterology. 148. pp1392–1404. 2015. showed more a more marked reduction in intragastric acidity and increased
mucosal inflammation compared to the CagA negative subjects.

Table 1: Median pH (IQR) detected by sensors relative to the peak LOS pres-
OP046 THE ANTI-APOPTOTIC FACTOR CLUSTERIN IS INVOLVED IN
sure during the 30–60 minute postprandial period. NOTE: *p 5 0.05, **p 5 0.01
HYPERGASTRINEMIA-INDUCED REMODELING OF THE GASTRIC
OXYNTIC MUCOSA H. pylori negative H. pylori positive
P. Vange, T. Bruland, B. Doseth, M. M. Sousa, Ø. Sørdal, G. Qvigstad, Sensor location Median pH (IQR) Median pH (IQR)
R. Fossmark, H. L. Waldum, A. K. Sandvik, I. Bakke
Department Of Cancer Research and Molecular Medicine, Norwegian University 1.1cm proximal 7.06 (1.42) 7.00 (0.75)
of Science and Technology (NTNU), Trondheim/Norway Peak LOS pressure 6.76 (1.02) 6.88 (0.48)
Contact E-mail Address: [email protected] 1.1cm distal 5.25 (4.19) 6.40 (1.72)
Introduction: Gastrin is important for normal function and maturation of the 2.2cm distal 1.95 (1.00) 3.21 (4.46)**
gastric oxyntic mucosa. Hypergastrinemia is associated with several premalig- 3.3cm distal 1.59 (2.29) 2.07 (2.29)**
nant conditions in the stomach and might be involved in gastric carcinogenesis.
Previously, we have shown that gastrin regulates expression of the pro-survival 4.4cm distal 1.81 (2.09) 2.93 (3.25)*
factor clusterin (CLU). Expression of CLU is often dysregulated during tumor- 5.5 cm distal 2.13 (2.02) 3.48 (2.89)
igenesis and in the stomach, upregulation of CLU marks emergence of spasmo- 6.6cm distal 3.39 (2.19) 4.10 (2.23)
lytic polypeptide-expressing metaplasia (SPEM). Here, we study the expression
of CLU in gastric oxyntic mucosa of animal models with elevated levels of gastrin
and elucidate its role in gastric cells during prolonged stress.
United European Gastroenterology Journal 4(5S) A21
Conclusion: The majority of H. pylori-infected subjects have reduced intragastric non-erosive reflux disease. Afferent nerves can be found within the oesophageal
acidity compared to the uninfected population and this is most marked close to mucosa, and it is highly likely that these play a role in reflux perception.
the gastroesophageal junction. The density of parietal cells and chief cells is We have recently demonstrated that, in healthy volunteers, there is a differential
reduced in H. pylori infected subjects throughout the gastric mucosa. These location of afferent nerve fibres within the distal and proximal oesophageal
findings may explain the negative association between H. pylori infection and mucosa. In the proximal oesophagus these nerves lie superficially and close to
both gastroesophageal reflux disease and oesophageal adenocarcinoma. the lumen. In the distal oesophageal mucosa they lie much deeper and closer to
Disclosure of Interest: All authors have declared no conflicts of interest. the basal epithelium.
References Aims & Methods: We aimed to investigate the location of distal and proximal
oesophageal mucosal afferent nerves in well-phenotyped patients with non-ero-
1. Raghunath A, Hungin A, Wooff D and Childs S. Prevalence of Helicobacter sive reflux disease. We investigated mucosa from 10 patients with typical heart-
pylori in patients with gastro-oesophageal reflux disease: systematic review. burn symptoms, normal macroscopic oesophageal appearances, and all had
BMJ 2003; 326: 737–739. pathological oesophageal acid exposure on reflux testing (oesophageal pH expo-
2. Whiteman D, Parmar P, Fahey P, Moore S, Stark M, , et al, forthe sure 44.2%).
Australian Cancer Study. Association of Helicobacter pylori infection with In each patient, endoscopic mucosal biopsies were taken from 3 cm above the
reduced risk for esophageal cancer is independent of environmental and gastro-oesophageal junction (distal), and at 20 cm from the incisors (proximal).
genetic modifiers. Gastroenterology 2010; 139: 73–83. Biopsies were fixed in 4% paraformadehyde, cryoprotected, and 10 mm sections
were cut on a cryostat and prepared on slides. Slides were examined immunohis-
MONDAY, OCTOBER 17, 2016 10:30–12:00 tochemically for presence and location of calcitonin gene-related peptide
(CGRP)- and protein gene product (PGP) 9.5 - immunoreactive nerve fibres.
ABSTRACTS ON FIRE: GORD ON FIRE – HOTSPOT_____________________
Where fibres were identified their location in the mucosa was recorded in
OP048 ASSOCIATION BETWEEN LUMINAL BILE SALT CONTENT terms of cell layers from luminal surface.
AND DUODENAL MUCOSAL INTEGRITY IN HEALTHY Results: In the proximal oesophagus of patients with NERD, afferent nerves were
VOLUNTEERS found a mean of 7.7  1.3 cell layers from the surface. In the distal oesophagus
D. Beeckmans1, D. Riethorst2, R. L. Farré Marti1, P. Augustijns2, J. Tack1, nerves were found a mean of 8.9  2 cell layers from the surface.
H. Vanheel1 In contrast, in healthy volunteers proximal nerves were found 12.3  0.9 cell
1
Targid, KULeuven, Leuven/Belgium layers from the lumen in the proximal oesophagus, and 22.2  2.7 cell layers
2
Drug Delivery and Disposition, Department Of Pharmaceutical and from the lumen in the distal oesophagus. On ANOVA, the more superficial
Pharmacological Sciences, KULeuven, Leuven/Belgium location of distal oesophageal nerves in patients versus healthy controls was
statistically significant (p 5 0.001). There was a non-significant trend to more
Contact E-mail Address: [email protected] superficial proximal nerves in NERD patients versus healthy volunteers.
Introduction: Functional dyspepsia (FD) is a functional gastrointestinal disorder Conclusion: Distal oesophageal afferent mucosal nerves are significantly closer to
with a prevalence of up to 15–20% in the general population. Recently, impaired the lumen in patients with NERD versus healthy controls, and the usual differ-
duodenal mucosal integrity was reported as a potential pathophysiological ential location between proximal and distal fibre location is lost. This may be
mechanism in FD (Vanheel H, Gut 2014). However, the factors controlling duo- relevant for symptomatic acid perception in patients with reflux disease, and may
denal mucosal integrity remain unknown. In this pilot study, we evaluated be a target for topical treatment of these patients.
whether luminal bile salt content is associated with duodenal permeability in Disclosure of Interest: P. Woodland: Research grant from Reckitt Benckiser UK
healthy volunteers. D. Sifrim: Receives a research grant from Reckitt Benckiser
Aims & Methods: This study was carried out in 21 healthy volunteers (11 men, All other authors have declared no conflicts of interest.
25  6years). Duodenal biopsies were obtained by gastroduodenoscopy and used Reference
to measure the in vitro transepithelial resistance (TEER) using Ussing chambers.
Meantime, fluorescein isothiocyanate dextran (FITC-dx4, MW 4kDa) was 1. Woodland P et al. Distinct afferent innervation patterns within the human
applied to assess paracellular permeability. After the gastroduodenoscopy, an proximal and distal esophageal mucosa. Am J Physiol Gastrointest Liver
aspiration catheter was placed in the second part of the duodenum under fluoro- Physiol 2015.
scopic control. Duodenal fluid aspirates were collected at fixed time points
during 1 hour in fasted state and 1.5 hour after a liquid meal (Nutridrink,
200 ml). Concentration and composition of the bile salt pool (including glyco-
cholic acid, taurocholic acid, glycochenodeoxycholic acid, taurochenodeoxy- OP050 MUCOSAL INTEGRITY AND SENSITIVITY TO ACID OF THE
cholic acid, glycodeoxycholic acid, taurodeoxycholic acid, PROXIMAL ESOPHAGUS IN PATIENTS WITH
glycoursodeoxycholic acid and tauroursodeoxycholic acid) in these aspirates GASTROESOPHAGEAL REFLUX DISEASE
was evaluated. Correlation analysis was used to look for an association between F. B. Van, P.W. Hoeij1, M.A. Weijenborg2, R.M. Van Den Bergh Weerman3,
luminal bile salt content and duodenal mucosal integrity. J. Van Den Wijngaard4, A. Verheij5, A.J. Smout6, Bredenoord7
Results: Duodenal biopsies of healthy volunteers displayed a paracellular passage 1
Gastroenterology and Hepatology, Academic Medical Center, Amsterdam/
of 27.23  7.93 pmol and a TEER of 19.85  2.63 V.cm2. A negative correlation Netherlands
was found between the concentration of tauroursodeoxycholic acid and the duo- 2
Gastroenterology, Academic Medical Center, Amsterdam/Netherlands
denal TEER in fasted state as well as at the first bile salt peak after liquid meal 3
Pathology, Academic Medical Center, Amsterdam, Amsterdam/Netherlands
and in fed state (r ¼ 0.6268, p ¼ 0.0292; r ¼ 0.5154, p ¼ 0.0286; r ¼ 0.4957, 4
Tytgat Institute For Liver and Intestinal Research, Academic Medical Center,
p ¼ 0.0364 respectively). The concentration of glycodeoxycholic acid showed a Amsterdam/Netherlands
positive correlation with TEER in fed state (r ¼ 0.5747, p ¼ 0.0126). The total BA 5
Pathology, Academic Medical Center, Amsterdam/Netherlands
pool showed no correlation with paracellular permeability and TEER in healthy 6
Department Of Gastroenterology and Hepatology, Academic Medical Center,
volunteers. Amsterdam/Netherlands
Conclusion: These results imply that the composition of the duodenal bile salt 7
Dept. Of Gastroenterology, Academisch Med. Centrum Amsterdam, Amsterdam/
pool may contribute to variations in duodenal mucosal permeability in healthy Netherlands
volunteers. Whether the bile salt concentrations explored in the present study are
altered in patients with FD is addressed in ongoing studies. Contact E-mail Address: [email protected]
Disclosure of Interest: All authors have declared no conflicts of interest. Introduction: Reflux episodes that extend to the proximal esophagus are more
Reference likely to be perceived. Our hypothesis is that the enhanced sensitivity of the
proximal esophagus is related to more pronounced impairment of mucosal integ-
1. Hanne Vanheel, Maria Vicario, Tim Vanuytsel, Lukas Van Oudenhove, rity in this part of the esophagus.
Cristina Martinez, Åsa V Keita, Nicolas Pardon, Javier Santos, Johan D Aims & Methods: We aimed to assess acid sensitivity and mucosal integrity of the
Söderholm, Jan Tack, Ricard Farré. Impaired duodenal mucosal integrity proximal and distal esophageal segments separately in patients with gastroeso-
and low-grade inflammation in functional dyspepsia. Gut 2014; 63: 262–271. phageal reflux disease (GERD) and to investigate the relationship between these
parameters. We included patients with heartburn and evidence of GERD on
ambulatory pH-impedance measurement. After PPI washout, an esophageal
MONDAY, OCTOBER 17, 2016 10:30–12:00
hydrochloric acid perfusion test measuring segmental acid sensitivity proximally
ABSTRACTS ON FIRE: GORD ON FIRE – HOTSPOT_____________________ and distally in the esophagus (3 and 18 cm above the Z-line) and an upper
OP049 MUCOSAL AFFERENT NERVES ARE MORE SUPERFICIAL IN endoscopy with biopsies at both levels were performed. During endoscopy, elec-
THE DISTAL OESOPHAGUS OF PATIENTS WITH NERD trical tissue impedance spectroscopy was performed at the two levels and biopsies
COMPARED TO CONTROLS were taken from macroscopically unaffected mucosa. Biopsies were used to mea-
P. Woodland1, F. Grassi2, N. Koukias1, C. Lee1, R. Aktar1, M. Peiris1, sure dilation of intercellular spaces with transmission electron microscopy as a
A. Blackshaw1, D. Sifrim1 morphological measure of impaired integrity and to investigate transepithelial
1
Barts and the London School of Medicine and Dentistry, Queen Mary University electrical resistance and transepithelial fluorescein permeability in Ussing
of London, London/United Kingdom Chambers as a functional measure of mucosal integrity.
2
Università Vita-Salute San Raffaele, Milan/Italy Results: We included 12 GERD patients (mean age 48 years, range 28–65, M:F
4:8). Lag time to heartburn perception was shorter after proximal acid perfusion
Contact E-mail Address: [email protected] (mean (95% CI) 0.8 minutes (0.1–1.5)) than after distal acid perfusion (3.9 min-
Introduction: Patients with gastro-oesophageal reflux disease are more sensitive utes (2.4–5.4)); log rank p ¼ 0.02. In vivo extracellular tissue impedance was
to painful acid perception than healthy volunteers. This is true even when there is lower in the distal esophagus (median (95% CI) 4563
.m (3640–5429)) com-
no macroscopic mucosal inflammation. Impaired integrity of the oesophageal pared to the proximal esophagus (8170
.m (7353–10110)); p ¼ 0.02.
mucosa has been heavily implicated in this sensitivity, displaying the presence Transepithelial fluorescein permeability was higher in the distal than the prox-
of dilated intercellular spaces and an impaired barrier integrity in patients with imal segment (median 2051 nmolcm-2h-1 (IQR 1201–3708) and 368 nmolcm-2h-1
(IQR 0–1389); p ¼ 0.033). Intercellular space ratio and transepithelial electrical
A22 United European Gastroenterology Journal 4(5S)
resistance were not statistically significant between the proximal and distal OP052 INADEQUATE SYMPTOM CONTROL ON LONG-TERM PPI
esophagus. THERAPY IN GERD – FACT OR FICTION? (LOPA II STUDY)
Conclusion: The proximal segment of the esophagus in GERD patients off PPI is J. Labenz1, G. Labenz2, D. Stephan3, F. Willeke3
more rapidly sensitive to acid perfusion, while the distal esophagus shows a more 1
Abt. Für Innere Medizin, Diakonie Klinikum Abt. für Innere Medizin, Siegen/
pronounced impairment of mucosal integrity. These findings show that the Germany
enhanced sensitivity to acid in the proximal esophagus is not explained by 2
Praxis für Ernährungsmedizin und Prävention, Burbach/Germany
increased mucosal permeability. 3
St. Marienkrankenhaus Siegen, Siegen/Germany
Disclosure of Interest: A.J. Bredenoord: Received research funding from
Endostim, Medical Measurement Systems, Danone and Given and received Contact E-mail Address: [email protected]
speaker and/or consulting fees from MMS, Astellas, AstraZeneca and Almirall. Introduction: Randomized controlled trials report about 30% of GERD patients
All other authors have declared no conflicts of interest. complain of bothersome remaining symptoms (heartburn, regurgitation) despite
PPI. The LOPA (Lost Patients) I Study of 333 GERD patients seen in general
practice revealed 46% of patients experienced heartburn or regurgitation symp-
toms at least twice per week despite PPI. A total of 20% were dissatisfied with
OP051 LARYNGOPHARYNGEAL SYMPTOMS IN PRIMARY CARE: their treatment. Few patients had received specific GERD diagnostics or recom-
USEFULNESS OF SALIVARY PEPSIN MEASUREMENT IN mended other options (510%).
PREDICTING GERD Aims & Methods: The LOPA II study is a prospective, multicenter, observational
A. Bozzani1, R. De Bastiani2, M. Della Coletta3, E. Savarino4, I. Grattagliano5 study conducted in 7 general practice clinics. Patients with chronic GERD,
1
Primary Care, Carate Brianza/Italy taking PPI therapy for at least 1 year, and not satisfied with their treatment
2
Primary Care, Feltre/Italy were asked to complete a questionnaire. Patients were asked the duration of
3
Division Of Gastroenterology, Department Of Surgery, Oncology and their PPI therapy, satisfaction with their current condition, frequency of symp-
Gastroenterology, University of Padua, Padua/Italy toms in the last week, whether they had previously received diagnostic evaluation
4
Department Of Surgery, Oncology and Gastroenterology, University of Padua, or surgical consult related to GERD, whether they plan to consult a reflux
Padua/Italy specialist for further diagnostics, and reasons for dissatisfaction with their cur-
5
Primary Care, Monopoli/Italy rent medication treatment. ‘‘Lost Patients’’ were defined as those with a satisfac-
tion score of 1 or 2 on a 5-point Likert scale (1: very dissatisfied; 2: dissatisfied),
Contact E-mail Address: [email protected] GerdQ score at least 8, and have not previously received specialized GERD
Introduction: Incidence of chronic laryngeal symptoms in primary care is about diagnostics.
2%/year and, gastroesophageal reflux disease (GERD) is considered by far the Results: 200 consecutive patient responses were collected within one year.
main disorder associated to them, leading to a specific syndrome called Patients suffered from GERD an average of 9.7 years and prescribed PPI therapy
Laryngopharyngeal Reflux (LPR). Several studies demonstrated that pepsin for an average duration of 8.2 years. 74% were dissatisfied or very dissatisfied on
measurement in saliva can be adopted as surrogate marker of GERD in LPR their current PPI therapy (score of 1 or 2). 89% reported heartburn or regurgita-
patients. Recently, a low-cost, non-invasive salivary pepsin test (PeptestTM, RD tion at least 2 days in the prior week (57% 4–7 days). 53% reported using
Biomed Limited, UK) was found able to measure pepsin in the saliva/sputum additional medication other than their prescribed PPI at least 2 days per week
and to discriminate with good sensitivity and specificity between patients with (32% 4–7 days). In patients dissatisfied on PPI, most cited insufficient symptom
typical GERD (i.e. with heartburn and regurgitation), confirmed at impedance- control (91%) as a reason for dissatisfaction. In addition, 26% cited concern with
pH monitoring, from those without reflux disease (i.e. functional heartburn). long-term use of drugs and 23% the need for daily medication. 92% of patients
Thus, it has been hypothesized about the utility of using this novel device to had received an upper endoscopy, 8% had a prior pH-metry, 5% manometry,
diagnose LPR in primary care setting. and 7% received prior surgical consult for GERD. The rate of ‘‘Lost Patients’’ in
Aims & Methods: We aimed to investigate the usefulness of PeptestTM in pri- this study was 63%.
mary care patients presenting with chronic laryngeal symptoms suggestive of Conclusion: Chronic GERD patients who are dissatisfied with their PPI therapy
LPR. In a prospective multicenter, controlled, pilot study, consecutive patients are rarely offered specialized GERD diagnostic procedures or treatment alter-
presenting with chronic laryngeal symptoms were enrolled by primary care phy- natives. Half of the patients took medication in addition to PPI to control their
sicians. Uninvestigated individuals with no gastrointestinal symptoms or disease reflux. In addition to persistent symptoms, concerns of long-term PPI use and
(including GERD or dyspepsia) or history of surgery served as healthy controls burden of daily medication play a role in patient dissatisfaction with PPI therapy.
(HCs). All subjects completed the validated reflux symptom index (RSI) ques- Disclosure of Interest: All authors have declared no conflicts of interest.
tionnaire and in case of a score 413, a symptom-based diagnosis of LPR was
made. Also the gastrointestinal symptom scale (GIS) questionnaire was com-
pleted to investigate reflux symptoms and Quality of Life. All individuals were
asked to provide 2 samples of sputum collected one hour after lunch and dinner. OP053 EFFICACY OF ACOTIAMIDE IN PATIENTS WITH
A positive PeptestTM was considered in case of a concentration of pepsin higher GASTROESOPHAGEAL REFLUX DISEASE UNRESPONSIVE TO
than 25 mg/ mL. PROTON PUMP INHIBITOR THERAPY
Results: Between February and April 2014 and during August 2015, 86 patients H. Yamashita1, A. Kanamori2, A. Okada3
with LPR (37 Male/49 Female, age 54  14; RSI13, mean RSI 22  6, mean 1
Gastroenterology, Osakafu Saiseikai Nakatsu Hospital, Osaka/Japan
GSI 22  6.4) and 59 healthy controls (30M/29F, mean age 41  15; RSI55, 2
Gastrointestinal Medicine, Osakafu Saiseikai Nakatsu Hospital, Osaka/Japan
mean RSI 0.5  1, mean GSI 33  5.6) were tested. In total 256 samples were 3
Gastroenterology & Hepatology, Osakafu Saiseikai Nakatsu Hospital, Osaka/
examined, whereas 34 samples were discarded because of technical problems (i.e. Japan
unclear storage, poor/excessive quantity). At least one positive result was found
in 64/86 (74%) LPR patients and in 54/59 (92%) HCs (p 5 0.0095), whereas two Contact E-mail Address: [email protected]
positive results were observed in 34/70 (49%) LPR patients and 26/46 (57%) HCs Introduction: Acid suppression is the mainstay of gastroesophageal reflux disease
(p ¼ 0.4505). One (in case of a single test) or two negative tests were registered in (GERD) therapy, and proton pump inhibitors (PPIs) are the first choice of drug
22/86 (26%) LPR patients vs 4/59 (7%) of HCs (p 5 0.0039). PeptestTM had an treatment. Patients with GERD experience persistent heartburn or regurgitation
accuracy of 47% (IC95 39%–55%) a sensitivity of 74% (IC95 65%–84%), a up to 20–30% for PPI therapy. Reflux events are almost always accompanied by
specificity of 7% (IC95 0%–13%), a positive predictive value of 54% (IC95 transient lower oesophageal sphincter relaxations (TLESRs). Several studies
45%–63%) and a negative predictive value of 2% (IC95 0%–8%) in identifying showed that gastric dysmotility such as delayed gastric emptying or impaired
LPR as diagnosed by RSI. gastric accommodation increased TLESRs 1). Acotiamide is a new prokinetic
Conclusion: In this pilot study, PeptestTM was not able to discriminate among drug that improves gastric motility. We previously reported that acotiamide
primary care patients with LPR from those without and therefore cannot be significantly reduced TLESRs in healthy subjects 2). Our aim was to assess the
suggested as preliminary tool to select patients requiring pH monitoring. effect of acotiamide in patients with GERD, who are unresponsive to PPI
Further studies including investigated healthy controls are mandatory to eluci- therapy.
date the diagnostic utility of salivary pepsin measurement in primary care setting Aims & Methods: This study design was a randomized, placebo-controlled,
Disclosure of Interest: All authors have declared no conflicts of interest. double-blind, parallel-group study. Patients who had reflux symptoms despite
being on PPIs for at least 8 weeks were randomized to receive either acotiamide
(10 mg thrice daily) or a matching dose of placebo for 2 weeks. The medicine was
administered 30 min before every meal. In addition, patients continued their PPI
treatment regimen (maintaining the same dose and type during the study).
Symptoms were assessed at baseline and weeks 1 and 2 using questionnaires,
and graded as 1 (much improved) to 7 (severely worsened). Grade 1 or 2
(improved) was indicative of treatment efficacy. If possible, 24-h multichannel
intraluminal impedance-pH (24-h MII-pH) monitoring was performed at base-
line and week 2.
Results: In total, 22 patients were enrolled in this study. The acotiamide and
placebo groups consisted of 12 and 10 patients (6 and 7 women; mean age, 56
and 68 years, mean body mass index [BMI], 21 and 23, respectively). There were
no significant differences in patient characteristics between both groups. The
effective rate was 25 and 10% for acotiamide and the placebo after 2 weeks,
respectively, and no statistical significance was observed (p ¼ 0.368). Fifteen
patients consented to the 24-h MII-pH monitoring at baseline and after 2
weeks. The acotiamide group showed a significant decrease in the number of
total reflux events, acid and liquid reflux events (39.6 vs. 25.5, p ¼ 0.028; 14.7 vs.
5.4, p ¼ 0.034; and 17.6 vs. 8.3, p ¼ 0.009, respectively). The placebo group
United European Gastroenterology Journal 4(5S) A23
showed no significant change. In patients with a symptom index 4 50% or total OP055 EFFICACY AND SAFETY OF THE ENDOLUMINAL
reflux events 4 40, the effective rate was significantly different (p ¼ 0.038) at 60 MANAGEMENT OF REFRACTORY GASTROESOPHAGEAL
and 33% for the acotiamide and placebo groups, respectively. These results REFLUX WITH BAND LIGATION
suggest that acotiamide may be effective in patients with associated reflux events. W. M. Seleem, A. S. Hanafy
Conclusion: Acotiamide significantly reduced the reflux events and improved Internal Medicine, Zagazig University, Zagazig/Egypt
reflux symptoms in patients whose symptoms were associated with reflux
events. Co-administration of acotiamide and PPIs may be a new strategy for Contact E-mail Address: [email protected]
PPI-refractory GERD patients. Introduction: Gastroesophageal reflux disease is characterized by reflux of the
Disclosure of Interest: All authors have declared no conflicts of interest. gastric contents causing troublesome esophageal and extraesophageal symptoms
References that could affect adversely the quality of life. About 10–40% of patients with
GERD fail to show adequate symptomatic response to the standard dose of PPI.
1. Pauwels A, et al. The gastric accommodation response to meal intake deter- several mechanisms could explain refractory GERD as improper PPI dosing,
mines the occurrence of transient lower esophageal sphincter relaxations and patient non-compliance, esophageal hypersensitivity, residual acid reflux,alkaline
reflux events in patients with gastro-esophageal reflux disease. or bile reflux, nocturnal acid breakthrough. Alternative therapeutic options
Neurogastroenterol Motil 2014; 26: 581–8. included laparoscopic fundoplication, lower esophageal magnetic beads which
2. Yamashita H, et al. Novel prokinetic acotiamide reduces transient lower are expensive, and about 10% of patients experience persistanse of heart burn, or
esophageal sphincter relaxation in healthy subjects. Digestion 2015; 92: 90–8. develop dysphagia
Aims & Methods: We aimed to evaluate the safety and efficacy of endoluminal
rubber band ligation in the management of refractory GERD. 20 patients were
enrolled in the study after informed consent was taken. They were treated with
OP054 A RANDOMIZED CONTROLLED TRIAL TO ASSESS THE rubber band ligation and the cap used for ligation had a diameter of 11 mm and
CLINICAL EFFICACY OF ESOMEPRAZOLE VS. VONOPRAZAN loaded with 6 rings. The main outcome is reduction of reflux symptoms measured
FOR RESOLUTION OF GASTRO-ESOPHAGEAL REFLUX DISEASE by GERD health related quality of life Questionnaire. Patients were included if
SYMPTOMS IN NEWLY DIAGNOSED PATIENTS they were 18 years of age or older with typical symptoms of heartburn or regur-
S. Ishihara gitation refractory or less responsive to maximally optimized dose of PPI therapy
Internalmedicine, Ishihara Gastroenterology Clinic, Zentsuji/Japan (given twice, 30 min before food) and even after adding H2 receptor blocker
before bedtime and baclofen 10 mg twice daily to the unresponsive patients.
Contact E-mail Address: [email protected] Patients excluded if they had lower esophageal ulcers, pregnancy, red flag signs
Introduction: The potassium competitive acid blocker (P-CAB) Vonoprazan as loss of weight, fever, dysphagia, odynophagia, bleeding. Large hiatal hernia
(VPZ) has potent acid inhibitory efficacy. We assessed clinical efficacy for more than 2 cm, paraesopgageal hernia, active Helicobacter pylori infection,
Gastro-oesophageal reflux disease (GORD) symptom. eosinophilic esophagitis were also excluded. Band ligation was performed in
Aims & Methods: This study was a single-center, prospective, randomized con- the four quadrants 5 mm distal to the Z-line which is measured before and
trolled, open-label, parallel-group trial conducted to assess the clinical efficacy of after the sessions were completed.
Esomeprazole (EPZ) 20 mg once daily vs. VPZ 20 mg once daily for the resolu- Results: 13 males and 7 females were enrolled in the study. Their mean age
tion of GORD symptoms in newly diagnosed patients. 39.5  6.2 with a range (31–49 years). The pre-endoscopic intervention character-
Patients 20 years of age with upper gastrointestinal symptoms of at least mod- istics were mean hemoglobin 10.6  0.9 gm/dl, mean GERD related quality of life
erate severity (Global Overall Symptom score [GOS]  4 on a 7-point Likert questionnaire (GERD-QLQ) value was 35.4  6.9, depth of Z- line 34  1.1cm,
scale) were randomized to treatment with EPZ or VPZ. frequency of the sessions needed 1.6  0.6 times over 4 months. After 6 months of
The primary endpoint was the proportion of patients with sufficient relief of follow up, GERD-QLQ score had dramatically improved 15.4  4.6 (t ¼ 11.85,
upper gastrointestinal symptoms (GOS  2) after 4 weeks of treatment. p ¼ 0.000), depth of Z line became 35  0.9 cm (t ¼ 3.2, p ¼ 0.005), hemoglobin
Secondary endpoints were the proportion of patients with complete overall level showed non-significant increase (10.9  0.8 gm/dl, p ¼ 0.06). 5 patients
symptom relief (GOS ¼ 1), Frequency Scale for the Symptoms of experienced mild dysphagia (25%) improved after 6.5  2.2 days, 8 patients
Gastroesophageal Reflux Disease (FSSG) score, and tolerance for both treat- (40%) experienced transient epigastric pain which disappeared within 5.4  1.5
ment. All patients provided informed consent before enrolment in the trial. days. 13 patients stopped PPI use (65%), 6 patients were on demand therapy
Results: 88 patients were entered and randomly assigned to the EPZ group and (30%), and only one patient needed continuous low dose PPI which was signifi-
the VPZ group. cantly reduced when compared to pre-endoscopic PPI intake.
After 4 weeks, proportion of patients with sufficient relief was achieved by 88.6% Conclusion: Endoluminal band ligation is a safe, well tolerated and cost-effective
in the EPZ group, compared to 58.1% in the VPZ group (p 5 0.01). therapeutic option for refractory GERD.
The worsened provability in FSSG Functional Dyspepsia (FD) score were sig- Disclosure of Interest: All authors have declared no conflicts of interest.
nificantly lower in the EPZ group (6.8% / 4.5%) than in the VPZ group (27.9% / References
18.6%) after 2 weeks and 4 weeks treatment (p 5 0.05, p 5 0.01).
Both treatment were generally well tolerated, but a patient in the VPZ group 1. Inadomi JM, McIntyre L, Bernard L and Fendrick AM. Step-down from
withdrew because of the adverse events. multiple- to single-dose proton pump inhibitors (PPIs): a prospective study
Discussion: Despite VPZ has potent acid inhibitory efficacy, EPZ 20 mg once of patients with heartburn or acid regurgitation completely relieved with
daily provides significant clinical efficacy for the resolution of GORD symptoms PPIs. Am J Gastroenterol 2003; 98: 1940.
beyond that afforded by treatment with VPZ 20 mg once daily. In addition, the 2. Carlsson R, Dent J, Watts R, et al. Gastro-oesophageal reflux disease in
probability of worsen FD symptoms were significantly lower in the EPZ group primary care: an international study of different treatment strategies with
than the VPZ group. The result observed in this study was considered to be omeprazole. International GORD Study Group. Eur J Gastroenterol Hepatol
caused by the multifactorial pathophysiology of GERD. Various mechanisms 1998; 10: 119.
may contribute to dyspeptic symptoms, for example, finding that patients with 3. Crawley JA and Schmitt CM. How satisfied are chronic heartburn sufferers
gastric achlorhydria or hypergastrinemia showed impaired gastric motility may with their prescription medications? Results of the patient unmet needs
be supportive of this point (2). study. J Clin Outcomes Manag 2000; 7: 29.
These findings can suggest that increasing the degree of acid inhibition beyond 4. Dean BB, Gano Jr AD, Knight K, et al. Effectiveness of proton pump
that already achieved by EPZ 20 mg does not translate into increased clinical inhibitors in nonerosive reflux disease. Clin Gastroenterol Hepatol 2004; 2:
efficacy for the resolution of GORD symptoms in newly diagnosed patients. 656.
Conclusion: EPZ 20 mg once daily was more effective than VPZ 20 mg once daily 5. Fass R and Sampliner RE. Barrett’s oesophagus: optimal strategies for pre-
for the resolution of GORD symptoms in newly diagnosed patients. vention and treatment. Drugs 2003; 63: 555.
Disclosure of Interest: All authors have declared no conflicts of interest.
References
1. Sakurai Y, et al. Aliment Pharmacol Ther. 2015;42:719–30.
2. Tosetti C, et al. Dig Dis Sci. 2000;45:252–7.
A24 United European Gastroenterology Journal 4(5S)
OP056 ENDOSTIMÕ LES STIMULATION THERAPY IMPROVES GERD EST reported. Median GERD-HQRL score had improved from 12.5(8.3,20.5) to
IN PATIENTS WITH LAPAROSCOPIC SLEEVE GASTRECTOMY 6.0(3.0, 8.0). There was an improvement 4 50% in pH-exposure showing median
(LSG) esophageal ph at baseline of 25.75(10.2, 54.5) that improved to 9.1(8.4, 25.1). 4/5
Y. Borbély1, A. Nieponice2, L. Rodrı́guez3, H. Schulz4, C. Ortiz5, M. Talbot6, patients (80%) were either free of PPI or with a reduced those compared to pre-
D. Martin7, N. Bouvy8 op and all with good response, 2 of these patients were taking PPI due to chronic
1
Inselspital Bern, Bern/Switzerland immunosuppressant drugs for their lung transplant and not for reflux symptoms.
2
Fundación Favaloro, Buenos Aires/Argentina Interestingly, one of the lung transplanted patients improved his FEV1 from 49
3
CCO Obesidad Diabetes y RGE Dept. of Surgery, Santiago de Chile/Chile to 77 after the procedure while the second one remained stable at 47 under
4
Evangelisches Krankenhaus Castrop-Rauxel, Castrop-Rauxel/Germany chronic rejection.
5
Hospital El Tunal, Bogota/Colombia Conclusion: Our preliminary case-series represents the first report of successful
6
St. George Hospital, Sydney/Australia use of LES-EST in patients with GERD associated with severe esophageal dys-
7
Concord Hospital, Sydney/Australia motility or lung transplant. Our early results suggest that LES-EST maybe a safe
8
Clinical Research, Maastricht University Medical Center, Maastricht/ and effective treatment in these patients without the risk of new-onset dysphagia.
Netherlands A longer follow-up in a larger group of patients is required to fully establish the
role of LES-EST in this difficult group of patients.
Contact E-mail Address: [email protected] Disclosure of Interest: All authors have declared no conflicts of interest.
Introduction: LSG is the most commonly performed bariatric procedure in the
US /Canada and the Asia-Pacific region. However, LSG can result in new
GERD and may worsen preexisting GERD.i LSG patients with GERD not MONDAY, OCTOBER 17, 2016 14:00–15:30
well controlled with PPI do not have good treatment options except for more IMPROVING THE ADENOMA DETECTION RATE – ROOM E1_____________________
invasive, anatomy-altering gastric bypass surgery. LES electrical stimulation
therapy has shown to improve outcomes in GERD patients.ii-iii OP058 ENDOCUFF-ASSISTED COLONOSCOPY OUTPERFORMS
Aims & Methods: To evaluate the safety and efficacy of LES stimulation in LSG CONVENTIONAL COLONOSCOPY TO DETECT MISSED-
patients with GERD not controlled with maximum dose PPI therapy. Patients ADENOMAS: EUROPEAN MULTICENTER, RANDOMIZED, BACK-
with LSG-associated GERD with bothersome symptoms on maximum PPI dose TO-BACK STUDY
underwent LES stimulator implant procedure and were enrolled in an interna- K. Triantafyllou1, D. Polymeros2, P. Apostolopoulos3, C. Brandão4,
tional patient registry prospectively tracking outcomes in GERD patients treated P. Gkolfakis5, A. Repici6, I. S. Papanikolaou1, M. Dinis-Ribeiro7,
with LES electrical stimulation. Electrical stimulation was delivered at 5mA, G. Alexandrakis8, C. Hassan9
220uSec pulse in 12, 30 minute sessions daily. GERD outcomes pre and post- 1
2nd Dept Of Internal Medicine and Research Institute, Medical School, Athens
stimulation were evaluated. University 2nd Dept Internal Medicine and Research Institute, Athens/Greece
Results: 12 patients, 66% (8/12) women at 8 centers have been treated. Median 2
2nd Department Of Internal Medicine, Attikon University Hospital - Department
age was 46 (IQR ¼ 34–55) years. All (12/12) were on at least daily double-dose of Hepatogastroenterology, Athens/Greece
PPIs. At their last follow-up (median ¼ 12 months), 75% (6/8) were off-PPIs and 3
Gastroenterology, NIMTS General Hospital Dept. of Gastroenterology, Athens/
one each was using PPIs on 5 50% of days and standard dose once a day. The Greece
later was on daily PPI for GI prophylaxis for chronic steroid therapy for kidney 4
Gastroenterology Department, Oncology Portuguese Institute of Porto, Porto/
transplants and not GERD symptoms. Median esophageal pH at baseline was Portugal
16.4% (IQR 8.5–22.4), which improved to 1.3% (IQR 0.4–2.2) at last follow-up 5
Hepatogastroenterology Unit, Attikon University Hospital, Athens/Greece
at least 6 month post-implant (n ¼ 6; p ¼ 0.01). All patients improved esophageal 6
Dept. Of Gastroenterology, Ist. Clinico Humanitas Rozzano Dept. of
acid exposure, 83% (5/6) patients had normalized acid exposure and 1/6 patient Gastroenterology, Milano/Italy
had 440% improvement in distal esophageal acid exposure. Median GERD- 7
Dept. Of Gastroenterology, IPO Porto, Porto/Portugal
HRQL scores at baseline was 25 (IQR 18–31) which improved to 4 (IQR 3–10) at 8
Dept. Of Gastroenterology, NIMTS Hospital, Athens/Greece
last follow-up (n ¼ 6; p ¼ 0.015). No SAEs related to the device or procedure were 9
Gastroenterology, Nuovo Regina Margherita Hospital, Rome/Italy
reported. No dysphagia or other GI side effects were reported.
Conclusion: Preliminary results on patients with LSG and GERD with bother- Contact E-mail Address: [email protected]
some symptoms despite maximal medical therapy, treated with LES electrical Introduction: Endocuff (ARC Medical Design, Leeds, UK) is a device that
stimulation, revealed that LES stimulation is safe and results in a significant mounted on the tip of the scope promises inspection of greater surface of the
improvement in GERD symptoms and esophageal acid exposure. Most patients colonic mucosa as the endoscope is gradually withdrawn by pulling backwards,
were off their PPI therapy with remaining taking PPI at a reduced dose. Data flattening and stretching the colonic folds. We aimed to compare adenoma miss-
from a larger patient experience for this indication is being collected using the rates of Endocuff-assisted colonoscopy (EC) with that of the conventional one
international registry trial. (CC).
Disclosure of Interest: All authors have declared no conflicts of interest. Aims & Methods: Our study population underwent same-day, back-to-back, (EC
References as index procedure followed by CC or vice versa, randomly assigned 1:1) colo-
noscopies by six endoscopists with documented adenoma detection rates 435%,
1. JAMA Surgery 2014; 149: 328–34. in four tertiary endoscopy facilities. Missed-adenoma detection rate (overall and
2. Surg Endosc. 2013; 27(4):1083–1092. in the proximal colon) for the two procedures was the study’s primary end-point.
3. Aliment Pharmacol Ther. 2015; 42(5):614–25. Secondary endpoints included among others, measurement of missed-advanced
adenoma rate, modification of the surveillance schedule according to the second
exam, true negative index colonoscopies and early adverse events rate.
ClinicalTrials.gov Identifier: NCT02340065.
OP057 ELECTRICAL STIMULATION OF THE LES - AN EMERGING Results: We randomized 200 patients (aged 61  10 years; 86.4% CRC screening-
THERAPY FOR GERD PATIENTS WITH FAILED ESOPHAGEAL surveillance cases). There were 7 EC and 1 CC incomplete exams. Scope insertion
PERISTALSIS times were similar for EC and CC (5:44  3:13 min vs. 5:37  0.2:37 min, p ¼ 0.6);
M. Ramirez, C. Zubieta, F. Ciotola, C. Bilder, A. Ditaranto, A. Badaloni, however, there was a trend for longer EC withdrawal times (7:15  2:52 min vs.
A. Nieponice 6:50  1:52 min, p ¼ 0.06). Overall, we detected one cancer and 194 (EC ¼ 109;
Hospital Universitario, Fundacion Favaloro, Buenos Aires/Argentina CC ¼ 85) adenomas; 84 in the proximal colon. By per-lesion analysis (table), EC
showed significant lower overall and proximal colon adenoma miss-rates com-
Contact E-mail Address: [email protected] pared with CC (14.7 [8–21]% vs. 37.6 [27–48]%; p ¼ 0.0004 and 10.4 [1.8–19]%
Introduction: Antireflux surgery for GERD associated with failed peristalsis, vs. 39 [23–55]%; p ¼ 0.004, respectively). A similar superiority for EC was not
either primary or in patient with prior lung transplant can be a challenge. revealed regarding advanced adenomas either overall or in the proximal colon.
Traditional antireflux surgery i.e. fundoplication has high rates of dysphagia Index colonoscopy did not miss the cancer. By per-patient analysis, the second
and Roux-en-y reconstruction is very invasive. Partial fundoplication is tradi- exam indicated modification of the surveillance schedule, according to the ASGE
tionally employed but is not as effective in controlling reflux. Electrical stimula- guidelines, in 17 and 5 patients who underwent CC and EC index exams
tion of the LES (LES-EST) has emerged as a new alternative for the treatment of (OR ¼ 3.8 [95%CI: 1.4–10.9]; p ¼ 0.01), respectively; however no difference in
GERD. High-res manometry (HRM) studies reveal no negative effect on eso- the modification of the surveillance schedule was detected when European guide-
phageal peristalsis or LES relaxation, making it an attractive treatment option lines were taken into account. The CC index arm had significantly more false
for GERD patients with failed peristalsis. We report the outcome of LES-EST in negative (no adenoma) first examinations compared to EC (14 of 100 vs. 3 of 94;
this subgroup patients. p ¼ 0.01). There were no adverse events related to EC or CC.
Aims & Methods: Seven patients (6 men; mean age ¼ 58) diagnosed with severe Conclusion: In comparison with conventional colonoscopy, Endocuff-assisted
GERD and failed peristalsis (n ¼ 5), failed peristalsis and lung transplant (n ¼ 1) colonoscopy reduces adenoma miss-rate by more than three times, even when
or lung transplant (n ¼ 1) were found eligible for LES-EST and agreed to highly efficient endoscopists perform the procedures.
undergo the procedure. Esophageal body function was assessed with HRM Disclosure of Interest: All authors have declared no conflicts of interest.
and reflux was diagnosed with Multichannel Intraluminal Impedance-pH testing
(MII-pH). The LES Stimulation system (EndoStim, BV, The Hague, The
Netherlands) was implanted using standard technique (Surg Endosc.
2013;27:1083–92) and stimulation was delivered in 12, 30 minute sessions of
5mA, 215usec, at 20Hz. Postop follow-up endpoints included clinical symptoms,
MII-pH and PPI intake. Mean follow-up was 6 months (2–24).
Results: Surgical implant was completed successfully and electrical stimulation
was initiated in all cases. Short and mid-term data was available for 5 patients
while 2 patients were recently implanted and data will be included prior to the
meeting. At their last follow-up, there was no dysphagia associated with LES-
United European Gastroenterology Journal 4(5S) A25

Abstract No: OP058

Adenomas overall, N Proximal colon adenomas, N

Found at Missed and found Missed and OR Found Missed and

Index by EC found by CC (95%) at Index found by EC Missed and found by CC OR (95%)

CC Index 53 32 - 3.5 (1.8–7) 22 14 - 5.5 (1.7–17)

EC Index 93 - 16 43 - 5

Conclusion: The overall accuracy of ECV-CAD was comparable to that of

OP059 THE DIAGNOSTIC ABILITY OF A COMPUTER-AIDED experts and significantly better than that of novices. Thus, ECV-CAD could be
DIAGNOSIS SYSTEM FOR NARROW-BAND IMAGING a powerful decision-making tool for less experienced endoscopists.
ENDOCYTOSCOPY IS COMPARABLE TO THAT OF EXPERT Disclosure of Interest: All authors have declared no conflicts of interest.
ENDOSCOPISTS References
M. Misawa1, S. Kudo1, Y. Mori1, K. Takeda1, Y. Maeda1, S. Kataoka1,
1. Kudo SE, Misawa M, Wada Y, et al. Endocytoscopic microvasculature
H. Nakamura1, T. Kudo2, K. Wakamura2, T. Hayashi1, H. Miyachi1,
evaluation is a reliable new diagnostic method for colorectal lesions (with
A. Katagiri1, T. Baba1, F. Ishida1, H. Inoue3, M. Oda4, K. Mori5
1 video). Gastrointest Endosc 2015; 82: 912–23.
Digestive Disease Center, Showa University Northern Yokohama Hospital,
2. Misawa M, Kudo SE, Mori Y, et al. Characterization of colorectal lesions
Yokohama/Japan
2 using a computer-aided diagnostic system for narrow-band imaging endocy-
Digestive Disease Center, Showa University Northern Yokohama Hospital
toscopy. Gastroenterology 2016; in press.
Digestive Disease Center, Yokohama/Japan
3
Digestive Disease Center, Showa University Koto Toyosu Hospital, Tokyo/Japan
4
Graduate School Of Information Science, Nagoya University, Nagoya/Japan MONDAY, OCTOBER 17, 2016 14:00–15:30
5
Information and Communications, Nagoya University, Nagoya/Japan LONG-TERM MANAGEMENT OF IBD – ROOM G_____________________
Contact E-mail Address: [email protected] OP060 LYMPHOMA IN PATIENTS WITH INFLAMMATORY BOWEL
Introduction: Endocytoscopy (EC) can be used to evaluate not only cell nuclei but DISEASE: A FRENCH NATIONWIDE OBSERVATIONAL COHORT
also microvessels in vivo. We reported the efficacy of observing the endocyto- STUDY
scopic vascular (ECV) pattern by using EC with narrow-band imaging for diag- M. Lemaitre1, J. Kirchgesner2, A. Rudnichi1, F. Carrat2, A. Racine3, M. Zureik1,
nosing colorectal lesions (Kudo S, et al. GIE 2015.1). As the interpretation of the R. Dray-Spira1, F. Carbonnel3
ECV pattern is difficult for novice endoscopists and requires substantial training, 1
Department Of Epidemiology Of Health Products, French National Agency for
we have developed a tentative model of a computer-aided diagnosis (CAD) Medicines and Health Products Safety (ANSM), Saint-Denis/France
system for the ECV pattern (ECV-CAD) (Misawa M, et al. Gastroenterology, 2
Institut Pierre Louis D’Épide´miologie Et De Sante´ Publique (unite´ Mixte De
in press.2). However, in our previous study, we did not compare the performance Recherche En Sante´ 1136), INSERM, Paris/France
of ECV-CAD with that of human endoscopists. Therefore, it is uncertain 3
Gastroenterology Unit, CHU de Biceˆtre, APHP-Universite´ Paris Sud, Le Kremlin
whether ECV-CAD can achieve a diagnostic ability as high as that of expert Biceˆtre/France
endoscopists.
Aims & Methods: The aim of this study was to compare the diagnostic ability of Contact E-mail Address: [email protected]
ECV-CAD with that of human endoscopists in characterization of colorectal Introduction: Thiopurines are associated with an increased risk of lymphoma.
lesion. The algorithm of ECV-CAD is based on texture analysis, which can The risk of lymphoma associated with anti-TNFs is uncertain.
quantify the pattern of endoscopic images, and vessel features. ECV-CAD pro- Aims & Methods: The aim of this study was to assess the risk of lymphoma in
vides a 2-class diagnosis (neoplastic or non-neoplastic) including its probability patients with inflammatory bowel disease (IBD) treated with thiopurines, anti-
value. To validate the diagnostic ability of ECV-CAD, 173 randomly selected EC TNFs or the combination of both treatments (combotherapy). Every patient
images (non-neoplasm, 49; neoplasm, 124) that were not used for machine-learn- affiliated to the French national health insurance with a diagnosis of IBD,
ing processes were evaluated with ECV-CAD. To compare diagnostic ability based on listed long-term diseases and/or hospital discharge diagnosis, was
between ECV-CAD and manual endoscopy, we selected 4 expert endoscopists included from 1st July 2009 through 31st December 2013, and followed up
(with an experience of 4200 cases of EC) and 3 novices (with an experience of until December 31st, 2014. A propensity score was built, using a multinomial
520 cases of EC). The EC images used for the evaluation with ECV-CAD were logistic regression conditional of multiple covariates, to predict the probability to
randomly allocated to the assessors. The assessors recorded their diagnosis (non- receive thiopurines, anti-TNFs or combotherapy at baseline. Hazard ratios for
neoplasm or neoplasm) with its confidence level (high or low). For ECV-CAD, a lymphoma were estimated using Cox proportional hazards regression in which
probability of 490% was considered as a high-confidence computed diagnosis. each treatment was introduced as a time dependent covariate.
The sensitivity, specificity, accuracy, positive predictive value (PPV), and nega- Results: The cohort included 173 190 patients with IBD, followed for a median
tive predictive value (NPV) of distinguishing neoplasms from non-neoplasms, as time of 4.9 years, accounting for 522 487 persons-years (PY) unexposed to thio-
well as the ratio of high-confidence diagnosis were calculated. Furthermore, the purines or anti-TNFs, 111 113 PY exposed to thiopurines, 60 736 PY exposed to
diagnostic ability when the diagnosis was made in high confidence was also anti-TNFs and 11 514 PY exposed to combotherapy. Among them, 166, 56, 31
calculated. and 13 patients developed lymphoma, respectively. In multivariate analysis,
Results: The overall accuracy of ECV-CAD was 87.8%, whereas the accuracy for patients exposed to thiopurines or anti-TNFs monotherapy had an increased
high-confidence cases was 93.5%. These values were higher than those for trai- risk of lymphoma as compared to unexposed patients (Hazard ratio and 95%
nees (P ¼ 0.01, McNemar test) and comparable to those of experts (P ¼ 0.85, confidence interval (HR95%) 1.64 (1.08–2.26) and HR95%: 1.87 (1.15–3.03),
McNemar test). The high-confidence diagnosis ratio of ECV-CAD was 72.0% respectively). Patients exposed to combotherapy had a more than four-fold
(124 of 172). The NPV for neoplasms with a high confidence was 94.4%, 84.6%, increased risk of lymphoma as compared to unexposed patients (HR95%: 4.83
and 46.3% for ECV-CAD, experts, and novices, respectively. The details of the (2.51–9.16)).
diagnostic abilities are shown in the Table. Conclusion: The risk of lymphoma associated with combotherapy is more than
two-fold higher than that associated with thiopurines and anti-TNFs monother-
apy. This risk should be taken into consideration and weighed against potential
Table: Diagnostic Abilities
benefits of combotherapy.
Disclosure of Interest: F. Carbonnel: Franck Carbonnel had consulting fees from
ECV-CAD(%)Experts(%)Novices(%) Genentech, Otsuka, Vifor, and lecture fees from Hospira.
All other authors have declared no conflicts of interest.
Overall accuracy (total / high confidence)87.8 / 93.5 84.2 / 90.8 63.4 / 71.7
Sensitivity (total / high confidence) 94.3 / 99.0 85.6 / 92.9 61.5 / 71.2
Specificity (total / high confidence) 71.4 / 70.8 80.6 / 84.0 68.0 / 73.1
PPV (total / high confidence) 89.2 / 93.3 91.7 / 94.8 82.8 / 88.6
NPV (total / high confidence) 83.3/ 94.4 69.0 / 79.0 41.3 / 46.3
High confidence rate 72.0 70.9 39.7
A26 United European Gastroenterology Journal 4(5S)

Abstract No: OP060

Table: Hazard ratio for lymphoma in thiopurines, anti-TNFs monotherapy and combotherapy exposed patients compared to unexposed patients

Never exposed to
thiopurines Thiopurines
Treatment or anti-TNFs monotherapy Anti-TNFs monotherapy Combotherapy

Persons-years 522 487 PY 111 113 PY 60 736 PY 11 514 PY

Cases Cases Hazard Ratio (95% CI) Cases Hazard Ratio (95% CI) Cases Hazard Ratio (95% CI)
Crude Adjusted Crude Adjusted Crude Adjusted
Total 166 56 1.39 (1.02–1.90) 1.64 (1.08–2.26) 31 1.30 (0.88–1.93) 1.87 (1.15–3.03) 13 2.99 (1.69–5.29) 4.83 (2.51–9.16)
Non-Hodgkin lymphoma 150 45 1.19 (0.85–1.68) 1.56 (0.98–248) 25 1.10 (0.71–1.70) 1.94 (1.05–3.05) 9 2.19 (1.11–4.31) 4.09 (1.93–8.64)
Hodgkin lymphoma 16 11 3.32 (1.54–7.18) 2.41 (0.86–6.72) 6 3.31 (1.28–8.54) 2.52 (0.78–8.20) 4 11.50 (3.82–35.59) 9.09 (2.46–33.66)
Adjusted for age and propensity score

OP061 INCIDENT CANCER IN INFLAMMATORY BOWEL DISEASE: cancer overall (OR 1.95 [1.07–3.59] and 3.99 [1.55–11.14]); UC duration (OR 3.74
RISK FACTORS IN A LONG TERM MULTICENTER NESTED [1.37–13.17]) for CRC; pancolitis and left-sided vs distal UC (OR 2.11 [1.04–4.4]
CASE-CONTROL IG-IBD STUDY AT 4 YEARS and 2.47 [1.06–5.73]) and UC-related surgery (OR 3.07 [1.15–8.02] for extraco-
L. Biancone1, A. Armuzzi2, M.L. Scribano3, R. D’Inca4, F. Castiglione5, lonic cancers. The same risk factors (extensive UC, penetrating CD, IS and anti-
E. Angelucci1, M. Daperno6, C. Papi7, C. Petruzziello1, L. Spina8, L. Guidi9, TNF use) were at limit of the statistical significance for urinary tract and skin
A. Kohn10, F. Mocciaro11, P. Alvisi12, A. Ruffa1, W. Fries13, G. Riegler14, cancers.
E. Calabrese15, S. Renna16, R. Di Mitri11, F. Rogai17, G. Meucci18, Conclusion: In a long-term multicentre study, clinical characteristics of IBD (UC
S. Ardizzone19, M. Vecchi8, A. Rossi1, A. Orlando16, F. Pallone1 extent, penetrating CD, perianal CD). were risk factors for incident cancer. CRC
1
Systems Medicine, University "Tor Vergata", Rome, Rome/Italy was more frequent in UC and extracolonic cancers in CD.
2
Complesso Integrato Columbus, Internal Medicine and Gastroenterology - Disclosure of Interest: L. Biancone: The study was not sponsored by any phar-
Complesso Integrato Columbus Catholic University, Rome/Italy maceutical company. The author declares no conflicts of interest specifically
3
IBD Unit, A.O. San Camillo- Forlanini, Rome/Italy related to the study. LB: lecture fees from Zambon, MSD, Takeda, Abbvie,
4
Division of gastroenterology, Padova/Italy Wassermann, Sofar;
5
GI Unit, University "Federico II", Naples/Italy A. Armuzzi: The author declares no conflicts of interest specifically related to the
6
GI Unit, Ospedale Mauriziano, Turin/Italy study. Lecture fees from Abbvie, Astra Zeneca, Chiesi, Ferring, MSD, Otsuka,
7
GI Unit, AO S.Filippo Neri, Rome/Italy Takeda, Zambon, and served as consultant for Abbvie, Hospira, Lilly, MSD,
8
GI Unit, ‘S. Giuseppe’ University Hospital,Milan, Milan/Italy Sofar;
9
Internal Medicine and Gastroenterology, Complesso Integrato Columbus, M.L. Scribano: The study was not sponsored by any pharmaceutical company.
Complesso Integrato Columbus Catholic University,, Rome/Italy The author declares no conflicts of interest specifically related to the study.
10
IBD Unit, A.O. San Camillo- Forlanini, Rome, Rome/Italy Lecture fees from Zambon and for advisory boards for Biogen Idec, Takeda,
11
GI Unit, ARNAS Civico-DI Cristina Benfratelli,, Palermo/Italy Mundipharma;
12
GI Unit, Ospedale Maggiore, Bologna/Italy R. D’inca: No conflicts of interest specifically related to the study Conflicts of
13
GI Unit, University of Messina, Messina/Italy interest declared: consultant for Abbvie, MSD, Ca di Group, Hospira, lecture
14
GI Unit, SUN, Seconda Università, Napoli, Naples/Italy fees from Takeda, Zambon and Mundipharma;
15
Gastroenterology Unit, University of Rome Tor Vergata, Rome/Italy F. Castiglione: The study was not sponsored by any pharmaceutical company.
16
GI Unit, Ospedale Cervello, Palermo/Italy The author declares no conflicts of interest specifically related to the study.
17
GI Unit, AOU Careggi, Firenze, Florence/Italy Lecture fees from Takeda, Chiesi, MSD, Abbvie, Sofar;
18
GI Unit, Ospedale S. Giuseppe, Milan/Italy M. Daperno: No conflicts of interest specifically related to the study. Financial
19
GI Unit, Hospital " Fatebenefratelli ", Milan/Italy support for research not related to the present study from MSD, lecture fees from
Abbvie, MSD, Hospira, Mundipharma, Takeda, Sofar, Chiesi, Ferring;
Contact E-mail Address: [email protected] C. Papi: The study was not sponsored by any pharmaceutical company. The
Introduction: Risk factors for cancer in inflammatory bowel disease [IBD] are author declares no conflicts of interest specifically related to the study.
debated (1). In a prospective, multicentre, nested case-control study at 3 years Consultant for Takeda, Abbvie, MSD, Sofar, Chiesi;
(2012–2014), we reported IBD phenotype as a risk factor for cancer (2). The L. Guidi: No conflicts of interest related to the study. Lecture fees from Abbvie,
analysis included 44,619 IBD patients (21,953 Crohn’s disease (CD), 22,666 MSD, Takeda, Zambon, consultant for AbbVie, MSD Mundipharma, financial
ulcerative colitis (UC). Cancer occurred in 174 patients (99 CD [CD-K], 75 support for research not related to the study from AbbVie, MSD;
UC [UC-K]) (2). A larger study is required to identify risk factors for cancer, A. Kohn: Financial support for research not related to the study from Merck and
including cancer subtypes Abbvie;
Aims & Methods: In a prospective multicenter nested case-control-study, we W. Fries: The study was not sponsored. The author declares no conflicts of
aimed to assess, in a large IBD population followed up in the long term, risk interest specifically related to the study. Lecture fees from Abbvie, MSD,
factors for incident cases of cancer, including cancer subtypes. The role of clinical Hospira, Ferring;
characteristics of IBD vs immunomodulators (IMM) use as risk factors was also G. Riegler: The study was not sponsored by any pharmaceutical company. The
assessed. At this purpose, all IBD patients with incident cancer and their matched author declares no conflicts of interest specifically related to the study. Lecture
controls referring to the same 16 Units involved in the study at 3 years (Jan 2012- fees from Takeda, MSD;
Dec 2014) (2) were followed up for additional 15 months (Jan 2015-Mar. 2016: E. Calabrese: The study was not sponsored by any pharmaceutical company. The
follow up 44 years; 51 months). The study population also included all the author declares no conflicts of interest specifically related to the study. Lecture
additional IBD patients referring to the same Units, with incident cancer from fees from Abbvie, Takeda, MSD;
Jan. 2015 to Mar. 2016. Each IBD patient with cancer (IBD-K) was matched S. Ardizzone: The study was not sponsored by any pharmaceutical company. The
with 2 IBD patients without cancer (IBD-C) for: IBD type, gender, age. Risk author declares no conflicts of interest specifically related to the study. Lecture
factors considered: age (at last visit, at diagnosis of IBD, of cancer), IBD extent, fees from MSD, Abbvie.
CD phenotype [B1-B3], perianal CD, smoking, family history of IBD, IBD- M. Vecchi: No conflicts related to the study. Advisory Board from MSD,
related surgery, current/past use of thiopurines [IS], TNF antagonists (1), Hospira, Mundipaharma, Takeda, lecture fees: MSD, Abbvie, Hospira,
any IMM. Data were expressed as median (range),Wilcoxon, Chi-squared test,- Mundipharma, Chiesi, Zambon, financial support for research not related to
multivariate logistic regression analysis as appropriate. the study:MSD, Sofar, Giuliani;
Results: Incident cancer occurred in 208 IBD patients: 117 CD [CD-K], 91 UC A. Orlando: No conflicts of interest specifically related to the study. Lecture fees
[UC-K]. IBD-C included 416 patients: 234 CD [CD-C], 182 UC [UC-C]. IBD-K from: Abbvie, Chiesi, MSD, Otsuka, Takeda, Sofar, Zambon, Mundipharma
and IBD-C included 624 patients (351 CD [165 F;47%]; 273 UC [117F;43%]). and served as consultant for Abbvie, MSD, Sofar, Takeda.
Cases and controls did not differ in terms of age (CD-K vs CD-C:p ¼ 0.92; UC-K F. Pallone: The study was not sponsored by any pharmaceutical company. The
vs UC-C:p ¼ 0.32) and IBD duration (CD-K vs CD-C: p ¼ 0.63;UC-K vs UC-C: author declares no conflicts of interest specifically related to the study Lecture
p ¼ 0.53). In IBD, cancers (n ¼ 208) involved (n [%]): digestive system (76 fees from Zambon, Takeda.
[36.5%]: 53 [25.5%] colorectal cancer (CRC), 8 [10.5%] small bowel adenocarci- All other authors have declared no conflicts of interest.
noma, SBA), skin (28 [13.5%]), urinary tract (23 [11.1%]), breast (17 [8.1%]), References
lung 14 [6.7%], genital tract (11 [5.2%]), thyroid (8 [3.8%]), lymphoma (7
[3.4%]), others (24 [11.5%]). CRC (n ¼ 53) was more frequent in UC vs CD (n 1. N Engl J Med 2015; 373(2): 195.
[%]: 31/91 [34%] vs 22/117 [19%]; p ¼ 0.01), while extracolonic cancers (n ¼ 155) 2. J Crohns Colitis. 2016; pii: jjw048. [Epub ahead of print].
in CD vs UC (95/117 [81%] vs 60/91 [66%]; p ¼ 0.01). Lymphoma (n ¼ 7) and
SBA (n ¼ 8) occurred only in CD. In CD, risk factors included perianal disease
for CRC (3.61 [1.23–10.63]), penetrating (B3) vs non-penetrating non stricturing
CD (B1) for extracolonic cancers (OR 2.21 [1–4.99]). IS and anti-TNF use was
at limit of the statistical significance as risk factor for overall cancer in CD (OR
1.59 [0.96–2.66]). In UC, risk factors were: pancolitis and UC-related surgery for
United European Gastroenterology Journal 4(5S) A27
OP062 USE OF IMMUNOSUPRESSANTS AND BIOLOGICAL AGENTS OP063 RISK OF SERIOUS AND OPPORTUNISTIC INFECTIONS IN
IN IBD PATIENTS WITH PAST HISTORY OF CANCER PATIENTS WITH INFLAMMATORY BOWEL DISEASE: A
M. Mañosa Ciria1, A. Juan Juan1, J. Guardiola2, I. Alfaro Perez3, M. Minguez4, NATIONWIDE FRENCH COHORT STUDY
B. Velayos5, J.M. Benı́tez Cantero6, F. Mesonero7, M. Chaparro8, B. Sicı́lia J. Kirchgesner1, M. Lemaitre2, M. Zureik2, F. Carbonnel3, R. Dray-Spira2
Aladrén9, Y. Zabana10, A. Villoria11, R. Lorente Poyatos12, M.P. Martinez 1
Institut Pierre Louis D’Épide´miologie Et De Sante´ Publique (unite´ Mixte De
Montiel13, L. Bujanda Fernández De Piérola14, L. Márquez Mosquera15, Recherche En Sante´ 1136), INSERM, Paris/France
J. Barrio Andrés16, M. Piqueras Cano17, N. Jimenez18, C. Rodriguez Gutierrez19, 2
Department Of Epidemiology Of Health Products, French National Agency for
P. Nos Mateu20, M. Montoro21, M.C. Muñoz22, E. Rodriguez23, M. Martin- Medicines and Health Products Safety (ANSM), Saint-Denis/France
Arranz24, A. Rodriguez Perez25, M. Van Domselaar26, M. Rivero27, 3
Gastroenterology Unit, CHU de Biceˆtre, APHP-Universite´ Paris Sud, Le Kremlin
J.L. Cabriada28, M.T. Arroyo-Villarino29, P. Romero30, S. Garcia31, Biceˆtre/France
M. Charro32, J. P. Gisbert33, E. Domènech34
1
Gastroenterology, Hospital Universitari Germans Trias i Pujol, Badalona/Spain Contact E-mail Address: [email protected]
2
Gastroenterology, Hospital Universitario de Bellvitge, Barcelona/Spain Introduction: Serious and opportunistic infections are a major concern in patients
3
Gastroenterology, H Clinic, Barcelona/Spain with inflammatory bowel disease (IBD) treated with immunosuppressive agents
4
Gastroenterology Unit, Hospital Clı´nico Universitario de Valencia, Valencia/ and biologics.
Spain Aims & Methods: The aim of this study was to assess the risk of serious and
5
Hospital Clı´nico de Valladolid, Valladolid/Spain opportunistic infections associated with thiopurines monotherapy, anti-TNFs
6
Gastroenterology, University Hospital Reina Sofı´a, Córdoba/Spain monotherapy and the combination of both treatments (combotherapy). Every
7
Hospital Ramón y Cajal, Madrid/Spain patient affiliated to the French national health insurance with a diagnosis of IBD
8
Gastroenterology, Hospital Universitario de La Princesa, Madrid/Spain based on listed long-term diseases and/or hospital discharge diagnosis was
9
Hospital Universitario de Burgos, Burgos/Spain included from 2009 to 2013, and followed up until 31 December 2014. A pro-
10
Gastroenterology, Hospital Universitari Mutua Terrassa, Terrassa/Spain pensity score was built to predict the probability to receive a monotherapy with
11
Hospital de Sabadell, Institut Universitari Parc Taulı´, Sabadell/Spain thiopurines, anti-TNFs or combotherapy at baseline. Hazard ratios of infections
12
Hops.General Ciudad Real, Ciudad real/Spain were estimated based on Cox regression models, stratified on age at cohort entry
13
Hospital 12 de Octubre, Madrid/Spain (aged 18–64 years and  65 years) and with treatments considered as time-
14
Hospital de Donostia, san sebastian/Spain dependent variables. Serious and opportunistic infections were classified accord-
15
Gastroenterology, H Mar, Barcelona/Spain ing to infection sites and pathogens, respectively.
16
Rio Hortega University Hospital, Valladolid/Spain Results: 173 077 IBD patients were included and followed during 4.9 years in
17
Hospital Terrassa, Barcelona/Spain median, accounting for 512 805 persons-years (PY) unexposed to anti-TNFs or
18
H U G Elche, Eche/Spain thiopurines, 108 315 PY exposed to thiopurines monotherapy, 57 464 PY
19
CH Navarra, Navarra/Spain exposed to anti-TNFs monotherapy and 11 089 PY exposed to combotherapy.
20
Hospital La Fe, Valencia/Spain Among them, a total of 4926, 1144, 1096 and 252 serious infections and 245, 183,
21
H San Jorge, Huesca/Spain 120 and 47 opportunistic infections occurred, respectively. After adjustment
22
H Basurto, Basurto/Spain (based on propensity score, age, time-varying exposure to corticosteroids and
23
Hosp.de La Candelaria, Santa Cruz de Tenerife/Spain past history of serious infections), exposures to thiopurines monotherapy, anti-
24
Hospital Universitario La Paz, Madrid/Spain TNFs monotherapy and combotherapy were associated with an increased risk of
25
HU Salamanca, Salamanca/Spain serious and opportunistic infections, compared to unexposed patients.
26
Gastroenterology, Hospital de Torrejon, Madrid/Spain Combotherapy was associated with an increased risk of serious and opportunistic
27
Gastroenterology, Marque´s de Valdecilla Universitary Hospital, Santander/Spain infections compared to anti-TNFs exposure in patients aged 18–64 years (hazard
28
Hospital Galdakao, Galdakao/Spain ratio and confidence interval 95% (HR95%) 1.31 (1.14–1.51), HR95%: 2.12 (1.49–
29
Gastroenterologı´a, Hospital Clı´nico, Universidad de Zaragoza, IIS Aragón, 3.00), respectively), while exposure to anti-TNFs was associated with an
Zaragoza/Spain increased risk of serious infections compared to thiopurines in patients aged
30
Gastroenterology, H Santa Lucia, Cartagena/Spain 18–64 years and  65 years: HR95%: 1.82 (1.67–1.99) and HR95%: 1.83 (1.43–
31
Gastroenterology Unit, Hospital universitario Miguel Servet, Zaragoza/Spain 2.35), respectively. Exposure to thiopurines was associated with an increased risk
32
H Royo Villanova, Zaragoza/Spain of viral infections compared to anti-TNFs monotherapy in patients aged 18–64
33
Digestive Services, Hospital Universitario de La Princesa, Instituto de years (HR95%: 1.74 (1.20–2.52)). Similar results were observed in a sensitivity
Investigación Sanitaria Princesa (IP) and Centro, Madrid/Spain analysis conducted in incident patients.
34
Gastroenterology Unit, Hospital Germans Trias i pujol, Badalona, Barcelona/ Conclusion: Thiopurines, anti-TNFs monotherapy and combotherapy are all
Spain associated with an increased risk of serious infections in IBD patients compared
to unexposed patients. However, the risk of serious infections is higher with anti-
Contact E-mail Address: [email protected] TNFs than with thiopurines and the risk of serious and opportunistic infections
Introduction: Conventional immunosuppressants (thiopurines or methotrexate) is higher with combotherapy than with anti-TNFs. The risk of serious and
and anti-TNF agents (IMMs) can influence the immunologic control of cancer opportunistic infections should be taken into consideration and weighed against
and they might ease cancer spread and recurrence. Therefore, a past history of potential benefits of anti-TNFs.
cancer is a relative contraindication for their use in inflammatory bowel disease Disclosure of Interest: F. Carbonnel: Franck Carbonnel had consulting fees from
(IBD). Genentech, Otsuka, Vifor, and lecture fees from Hospira.
Aims & Methods: We aimed to describe the risk of incident cancers (recurrent or All other authors have declared no conflicts of interest.
new) in patients with IBD and a past history of malignancy treated with IMMs,
and to identify risk factors. IBD patients included in ENEIDA Project from
GETECCU with a past history of cancer were identified and compared between
those who were further treated with IMMs and those who never were treated OP064 THE COURSE OF HEALTH-RELATED QUALITY OF LIFE IN
with these drugs (controls). INFLAMMATORY BOWEL DISEASE FIVE, TEN AND 20 YEARS
Results: We identified 947 patients with previous cancer of whom 526 did not AFTER DIAGNOSIS - DATA FROM THE IBSEN STUDY
received IMMs before the diagnosis of cancer. Of these, 385 were controls and G. Huppertz-Hauss1, B. Moum2, T. Bernklev3
141 were subsequently treated with IMMs after a median of 60 (23–130) months 1
Dept. Of Gastroenterology, Telemark Hospital, Skien/Norway
from cancer diagnosis. After a median follow-up of 68 months (27–126), 52 2
Dept. Of Gastroenterology, Oslo University Hospital Ullevål, Oslo/Norway
patients(10%) developed incident cancers (50% recurrent and 50% new). The 3
Research and Development, Vestfold Hospital, Tønsberg/Norway
most frequent recurrent ones were breast (35%) and prostate (20%) cancers.
Incident cancers occurred similarly in patients further treated with IMMs and Contact E-mail Address: [email protected]
controls (9% vs. 12%p ¼ 0.33), as did regarding the type of the index cancer. Introduction: Previous population-based cross-sectional studies have shown that
However, cancer-related deaths were more frequent among controls (4% vs. health-related quality of life (HRQoL) in patients with the inflammatory bowel
0%;p ¼ 0.013). Cancer-free survival was 99%, 98% and 97% at 1, 2, and 5 diseases (IBD) ulcerative colitis (UC) and Crohn’s disease (CD) is reduced, espe-
years in patients further treated with IMMs and 97%, 96% and 92% at 1, 2 cially in association with disease activity. Data describing the course of HRQoL
and 5 years in controls, respectively (p ¼ 0.003). in IBD are scarce.
Conclusion: In this large, retrospective cohort, treatment with conventional immuno- Aims & Methods: The aim of the present study was to assess the course of
suppressants or anti-TNF agents in patients with IBD and a past history of cancer was HRQoL at three prescheduled time-points during 20 years of follow-up in an
not associated with an increased risk of new or recurrent cancers. inception cohort with IBD patients. IBD patients included in a population-based
Disclosure of Interest: All authors have declared no conflicts of interest. inception cohort from 1990–93 (Inflammatory Bowel Disease in South-East
Norway – IBSEN) were invited to follow-up visits five, ten and 20 years after
diagnosis. In addition to structured interviews and clinical examinations at inclu-
sion and follow-up visits, the Short Form 36 (SF-36) and the Norwegian version
of the Inflammatory Bowel Disease Questionnaire (N-IBDQ) were completed by
the patients at all follow-up visits. The mean N-IBDQ total scores and the mean
SF-36 dimensional scores were calculated. In this abstract, we present the total
N-IBDQ scores and the dimensional SF-36 scores for general health (GH), stra-
tified by diagnose and sex. Norman et al. (1) defined the difference between
HRQoL scores exceeding ½ standard deviation (SD) as clinically relevant.
Consequently, we defined patients with changes in scores less than 1/2 SD
during follow-up as to have stable HRQoL scores.
Results: Of the initially 756 included patients with confirmed IBD, 599 (79%)
were still alive after 20 years. HRQoL questionnaires were answered by 522, 327
A28 United European Gastroenterology Journal 4(5S)

Abstract No: OP063

Table: Hazard ratios for any serious or opportunistic infections according to medication exposure
Exposed to Exposed to Exposed to Exposed to Exposed to
thiopurines versus anti-TNFs monotherapy Combotherapy anti-TNFs monotherapy Combotherapy versus
unexposed to versus unexposed to versus unexposed to versus thiopurines exposed to anti-TNFs
thiopurines or anti-TNFs thiopurines or anti-TNFs thiopurines or anti-TNFs monotherapy monotherapy

Hazard Ratio (95% CI) Hazard Ratio (95% CI) Hazard Ratio (95% CI) Hazard Ratio (95% CI) Hazard Ratio (95% CI)

Crude Adjusted Crude Adjusted Crude Adjusted Crude Adjusted Crude Adjusted
Serious infections, all
18–64 years 1.29 (1.20–1.39) 1.27 (1.15–1.39) 2.40 (2.23–2.58) 2.31 (2.10–2.53) 3.02 (2.65–3.45) 3.03 (2.62–3.50) 1.86 (1.70–2.03) 1.82 (1.67–1.99) 1.26 (1.09–1.45) 1.31 (1.14–1.51)
 65 years 0.94 (0.81–1.10) 1.19 (0.97–1.47) 1.76 (1.43–2.16) 2.18 (1.73–2.76) 1.82 (1.03–3.22) 2.46 (1.37–4.39) 1.86 (1.45–2.38) 1.83 (1.43–2.35) 1.04 (0.57–1.89) 1.13 (0.62–2.05)
Serious infections,
excluding GI infections
18–64 years 1.31 (1.20–1.42) 1.31 (1.17–1.45) 2.60 (2.39–2.83) 2.54 (2.29–2.83) 3.21 (2.77–3.73) 3.29 (2.79–3.88) 1.99 (1.80–2.20) 1.95 (1.76–2.16) 1.24 (1.05–1.45) 1.29 (1.10–1.52)
65 years 0.89 (0.74–1.06) 1.09 (0.87–1.38) 1.86 (1.50–2.32) 2.28 (1.77–2.94) 1.84 (0.99–3.43) 2.45 (1.30–4.63) 2.10 (1.60–2.75) 2.09 (1.59–2.74) 0.99 (0.51–1.90) 1.07 (0.56–2.07)
Opportunistic infections, all
18–64 years 4.31 (3.48–5.36) 5.04 (3.88–6.55) 5.37 (4.20–6.87) 6.10 (4.56–8.16) 11.3 (8.13–15.8) 12.9 (8.95–18.6) 1.25 (0.98–1.59) 1.21 (0.95–1.54) 2.11 (1.49–2.98) 2.12 (1.49–3.00)
65 years 2.38 (1.41–3.99) 1.84 (0.87–3.91) 4.88 (2.55–9.31) 3.92 (1.75–8.78) 7.23 (1.77–29.5) 6.40 (1.45–28.2) 2.05 (0.97–4.36) 2.13 (1.00–4.54) 1.48 (0.33–6.70) 1.63 (0.36–7.38)
Opportunistic infections,
excluding
mycobacterial infections
18–64 years 5.30 (4.13–6.81) 6.07 (4.50–8.19) 5.31 (3.95–7.14) 5.91 (4.19–8.34) 10.4 (6.92–15.7) 11.6 (7.44–18.2) 1.00 (0.76–1.33) 0.97 (0.73–1.29) 1.96 (1.28–3.01) 1.97 (1.28–3.02)
 65 years 1.87 (1.00–3.47) 1.17 (0.46–2.97) 4.18 (1.98–8.84) 2.82 (1.07–7.44) 8.59 (2.10–35.1) 6.42 (1.37–30.0) 2.24 (0.91–5.50) 2.40 (0.97–5.91) 2.06 (0.44–9.71) 2.28 (0.48–10.8)

and 438 patients at the five, ten and 20 years follow up, respectively. Of these OP065 PROGNOSTIC FACTORS FOR LONG-TERM INFLIXIMAB
patients, 199 (139 UC, 60 CD) and 191 (133 UC, 58 CD) answered the N-IBDQ TREATMENT IN CROHN’S DISEASE PATIENTS: A 20-YEAR
and the SF-36 at every follow-up visit, respectively. We could not register clini- SINGLE CENTER EXPERIENCE
cally relevant changes between the mean N-IBDQ total scores and the mean GH T. Billiet1, I. Cleynen1, V. Ballet2, M. Ferrante2, G. Van Assche2, A. Gils3,
dimensional scores during the different follow-up visits (Table 1). Of 139 UC S. Vermeire2
patients and 60 CD patients, who answered the N-IBDQ at all follow-up visits, 1
KU Leuven TARGID, Leuven/Belgium
54 (38.9%) and 17 (28.3%) had stable scores. Of 133 UC patients and 58 CD 2
Department Of Gastroenterology and Hepatology, University Hospitals Leuven,
patients, who answered the SF-36 at all follow-up visits, 31 (23.3%) and 13 Leuven/Belgium
(22.4%) had stable scores. 3
Laboratory for Therapeutic and Diagnostic Antibodies, Department of
Pharmaceutical and Pharmacological Sciences, KU Leuven, Leuven/Belgium
Table 1: N-IBDQ total scores and General Health dimensional scores
Contact E-mail Address: [email protected]
UC UC CD CD
Introduction: The long-term efficacy of infliximab (IFX) in Crohn’s disease (CD)
Men Women Men Women patients is suboptimal and prognostic factors for real-life long-term efficacy are
Follow-up year 5 10 20 5 10 20 5 10 20 5 10 20 insufficiently studied.
Aims & Methods: The aim of this study was to identify patient- and disease-
All patients related factors influencing the real-life long-term response of infliximab in CD.
IBDQ N 180 108 140 168 113 154 88 61 72 86 45 72 All consecutive CD patients treated with IFX between December 1994 and
Mean scores 190 191 187 181 180 179 187 186 184 174 180 172 January 2016 at a tertiary centre, were retrospectively analysed. Only patients
SD 25 29 23 29 33 28 31 26 26 30 28 26 who responded to an induction dose (5 mg/ kg on week 0, 2 and 6), followed by
SF-36 N 178 104 142 165 110 153 86 61 73 86 45 69
scheduled IFX maintenance treatment were included. Exclusion criteria were:
prior infliximab use, ever episodic treatment, drug interval (414 weeks), CD-
GH Mean scores 68 68 70 64 62 65 66 63 69 57 60 58
related surgery during induction therapy and extra-intestinal manifestations as
SD 22 24 21 24 23 24 27 25 22 24 22 21
main indication. IFX failure was the primary endpoint, defined as stopping IFX
Patients participating due to one of the following reasons: 1) loss of response (LOR) despite treatment
in every follow-up
optimization, 2) presence of persistent antibodies towards infliximab (ATI), and
IBDQ N 62 77 39 21 3) the need for IBD related surgery. Since 2010–2011, IFX and ATI serum
Mean scores 191 195 191 182 183 181 182 188 181 175 178 180 concentrations at trough were measured in the majority of patients with an in-
SD 23 26 20 29 36 29 30 25 28 28 29 19 house-developed and clinically validated drug sensitive bridging enzyme-linked
SF-36 N 61 76 39 21 immunosorbent assay (ELISA). Therapeutic drug monitoring (TDM) was
GH Mean scores 72 73 72 65 64 64 64 69 66 58 62 64 defined as the use of serum IFX & ATI concentration measurements to guide
SD 20 21 21 25 22 24 29 23 22 20 23 16 treatment decisions and optimization. Patient- and disease-related factors were
used to identify independent predictors of IFX failure-free survival using Cox
proportional hazards model and Kaplan-Meier analysis. Internal validation of
N-IBDQ: Inflammatory Bowel Disease Questionnaire (Norwegian version). SF- the Cox regression analysis was performed with bootstrapping with 1000 replica-
36: Short Form 36. GH: General Health dimension. SD: standard deviation, N: tions. The c-statistic was used to assess the predictive accuracy of the regression
Number of participants model.
Results: A total of 261 CD patients were included in the final analysis. Median
time on IFX was 2.4 [IQR 1.4–4.7] years, and 65 (24.9%) patients experienced
IFX failure. Median age at start of IFX was 32.8 [22.6–44] years, after a median
Conclusion: Mean HRQoL scores in our IBD cohort did not vary during follow- disease duration of 3.4 [0.7–13.6] years. In total, 39 (14.9%) patients received
up visits five, ten and 20 years after diagnosis. However, only a minority of CD anti-TNF prior to IFX start (adalimumab or certolizumab pegol). TDM was
and UC patients had stable HRQoL scores during the 20 years of follow-up. used in 202 (77.4%) patients. Estimated 1, 5, and 10 year IFX failure-free survi-
Therefore, a more detailed reporting on changes in subgroups might help to val was 93.7% (95% CI 90.7–9i6.7), 65.9% (58.3–73.5) and 58.2% (45.6–70.9),
identify factors associated with an unstable course of HRQoL in IBD. respectively. When combining all available IFX measurements during the follow-
Disclosure of Interest: All authors have declared no conflicts of interest. up of the study, median IFX concentrations were lower in patients who experi-
Reference enced IFX failure (3.1 [0.3–7.5] mg/mL) compared to patients who did not fail
IFX (5.3 [3.1–8.4] mg/mL), p 5 0.0001). Multivariate Cox regression identified
1. Norman GR, Sloan JA and Wyrwich KW. Interpretation of changes in disease duration 5 1 year (hazard ratio (HR) 2.5 (95% CI 1.2–5.2), p ¼ 0.02),
health-related quality of life: the remarkable universality of half a standard isolated L1 disease location (HR 2.0 (1.1–3.5), p ¼ 0.02), prior anti-TNF use (HR
deviation. Medical Care 2003; 41: 582–592. 2.3 (1.1–4.8), p ¼ 0.03), hemoglobin 5 13.5 g/dL (HR 2.3 (1.2–4.4), p ¼ 0.02),
absence of TDM use (HR 8.0 (4.1–15.6), p ¼ 1x109), and first IFX dose opti-
mization within first year (HR 3.7 (2.1–6.6), p ¼ 5x106) as independent predic-
tors of IFX failure-free survival. All these factors remained significant after
internal validation with bootstrapping. This final model had a c-statistic of
0.80 which is considered as a well discriminating model. Stratifying patients
into risk groups resulted in estimated 3 year IFX failure-free survival rates of
95.3% (95% CI 94.2–96.4) for the low risk group (0 or 1 risk factor), 79.3%
(78.4–80.2) for the medium risk group (2–3 risk factors), and 26.3% (8.6–44.0)
for the high risk group ( 4 risk factors) (p ¼ 8x1013). IFX concentrations at
United European Gastroenterology Journal 4(5S) A29
week 14 were available in 199 (76.2%) patients, and in this subgroup of patients, OP067 CHANGES IN MUCOSAL-ASSOCIATED INTESTINAL
IFX concentration at week 14 was also a significant predictor of IFX failure-free MICROBIOTA AND FECAL BACTERIA IN INFLAMMATORY
survival (HR 0.87 (0.80–0.94), p ¼ 0.001). BOWEL DISEASE PATIENTS AND HEALTHY SUBJECTS: A PILOT
Conclusion: This study identified several predictors of clinically relevant IFX STUDY
failure in CD patients. Stratifying patients according to the amount of risk M. P.L. Guarino1, L. Putignani2, A. Altomare1, F. Del Chierico2, S. Cocca1,
factors can identify patients at high risk for IFX failure. Initiating IFX sooner S. Emerenziani1, B. Dalla Piccola2, M. Cicala1
rather than later and using TDM in this group to proactively strive for adequate 1
Gastroenterology Unit, Campus Bio Medico University, Rome/Italy
drug concentrations may ensure optimal disease outcome. 2
Parasitology and Metagenomics Unit, Bambino Gesù Children’s Hospital and
Disclosure of Interest: T. Billiet: Lecture Fee: Ferring Research Institute, Rome/Italy
M. Ferrante: - Research grant: Takeda - Speakers fee: Abbvie, Boehringer-
Ingelheim, Chiesi, Falk, Ferring, Janssen, Mitsubishi Tanabe, MSD, Takeda, Contact E-mail Address: [email protected]
Tillotts, Zeria - Consultancy: Abbvie, Boehringer-Ingelheim, Ferring, Janssen, Introduction: The existing literature on intestinal microbiota in inflammatory
MSD bowel diseases (IBD) reveals conflicting changes in microbiota composition in
G. Van Assche: - Financial support for research: Abbvie, MSD - Lecture fees: all patients, having most of studies been conducted only on fecal microbiota.
Abbvie, Ferring, MSD, Janssen, Takeda - Consultancy: Abbvie, MSD, Takeda Microbiota adhering to the gut mucosa might affect epithelial and mucosal
A. Gils: - Financial support for research: FWO grant G.0617.12, Pfizer IIR function to a greater degree than fecal bacteria.
grants - Speakers fee: MSD, Abbvie, Janssen Biologicals, Pfizer - Consultancy: Aims & Methods: The aim of the present study was to evaluate the mucosal and
UCB fecal microbiota composition in healthy controls (CTRLs) and IBD patients, in a
S. Vermeire: - Grant support: Abbvie, MSD, Takeda - Lectures: Abbie, MSD, case-control study exploited by 16S rRNA targeted metagenomics-based
Takeda, Ferring, Falk Pharma, Hospira, Tillotts - Consultancy: Abbvie, MSD, approach (phylotyping, PH). Fecal specimens were collected from 14 IBD
Takeda, Ferring, Genentech/Roche, Shire, Pfizer, Galapagos, Mundipharma, patients [10 Crohn’s disease (CD), 4 ulcerative colitis (UC)], and from 11 healthy
Hospira, Celgene, Second Genome, Janssen subjects, undergone colonoscopy for screening. Mucosal specimens were
All other authors have declared no conflicts of interest. obtained during colonoscopy from the terminal ileum, and descending colon.
PH was assessed by pyrosequencing as follows. All patients were in wash-out
from antibiotics, probiotics and corticosteroids. Genomic DNA was isolated
MONDAY, OCTOBER 17, 2016 14:00–15:30 from the entire set of samples. The V1-V3 region of 16S rRNA locus was ampli-
MICROBIOTA AND DIET: FROM BENCH TO BEDSIDE – ROOM K_____________________ fied on a 454-Junior Genome Sequencer. Reads were analyzed by Quantitative
Insights into Microbial Ecology (QIIME, v.1.8.0), grouped into operational
OP066 CYCLIC ENTERAL NUTRITION FOR THE MAINTENANCE OF taxonomic units (OTUs) at a sequence similarity level of 97% by PyNAST for
REMISSION IN PEDIATRIC CROHN’S DISEASE PATIENTS taxonomic assignment, and aligned by UCLUST for OTUs matching against
B. Pigneur1, S. Nóbrega2, F. Ruemmele3 Greengenes database (v. 13.8).
1
Pediatric Gastroenterology Unit, Necker Enfants Malades Hospital, PARIS/ Results: In adult IBD patients colonic biopsies showed a statistically significant
France increase of Proteobacteria and decrease of Firmicutes and Actinobacteria, com-
2
Hospital Dona Estefânia, Lisbon/Portugal pared to CTRLs. The microbiota analysis of stool samples from IBD patient
3
Paris-cite Hospital, Universite Sorbonne, Paris/France showed an increment of Proteobacteria and decrease of Bacteroidetes, although
the difference was not significant compared to CTRLs. Particularly, a predomi-
Contact E-mail Address: [email protected] nant presence of Enterobacteriaceae in IBD and a predominant presence of
Introduction: Enteral nutrition (EN) is a well-established treatment in pediatric Ruminococcaceae, Rikenellaceae and Prevotella in CTRLs were prevalent
Crohn’s disease (CD) for induction of remission as well as disease flares with (P 5 0.05). Stratifying patient findings, according to intestinal sampling site,
similar efficacy compared to steroid therapy and no side effects. Some reports the analysis revealed that only Ruminococcaceae resulted statistically increased
indicate a role for EN as maintenance therapy, but usually on top of other in the colon. Tacking in account only colon biopsy samples, a significant reduc-
treatment or after surgically induced remission. The aim of our study was to tion of Coprococcus, Faecalibacterium prausnitzii, Lachnospiraceae,
test feasibility and efficacy of cyclic EEN as sole maintenance therapy. Rikenellaceae, Roseburia, Ruminococcaceae was observed in patients and an
Aims & Methods: Nine patients with active luminal paediatric Crohn’s disease, increment of Enterobacteriaceae was observed in CTRLs. Finally, stratifying
L1 (n ¼ 2) or L3 (n ¼ 7), followed at Necker Hospital between 2012 and 2014 samples on the bases of disease activity a decrease of Ruminococcus,
were included in this prospective pilot study. After 8 weeks of exclusive enteral Peptostreptococcus and Paraprevotella and an increase in Enterococcus was asso-
nutrition with Modulen IBD, patients who came into complete CRP-negative ciated to active disease status (P 5 0.05).
remission were proposed to continue on cyclic EEN therapy as sole treatment in Conclusion: The present study shows that in the mucosal microbiota of IBD
an open manner. Cyclic EEN consists of a 6 weeks phase of normal feeding patients, irrespective of disease localization and activity, phylum Proteobacteria
followed by a 2 weeks phase of exclusive enteral nutrition, without any conco- was significantly more represented, while phylum Firmicutes and Actinobacteria
mitant CD-related medication. Patients were followed on a fixed scheme (3 were reduced. The profiles of fecal microbiota partially replicate those of the
months visits) with collection of anthropometric, clinical and biological data. mucosal microbiota being not statistically different from controls. It appears
Results: At inclusion, all patients were in deep remission (CRP-negative). At that microbiota adhering to the gut mucosa better discriminates patients from
month 6 and 12 follow-up visit, 8 of the 9 patients (89%) (wPCDAI 8.4  9.2) controls especially when considering family species. Our data suggest the high
and 5 of 6 patients (wPCDAI 5.7  3.2), respectively were in clinical remission. diagnostic potential of microbiota profiling with special reference to mucosal
Concomitant to the clinical response, biological scores markedly improved with biosystem
mean CRP 21.8  14.2 mg/L at M0, 9.8  11.7 mg/L at M6 (p 5 0.05) and Disclosure of Interest: All authors have declared no conflicts of interest.
5.4  2.7 at M12 (n ¼ 6) (p 5 0.05) and albumin normalization with 33.8  3.8
g/l at M0, 39.9  5.1 g/l at M6 (p 5 0.05) and 42.8  2.9 at M12 (n ¼ 6)
(p 5 0.05). 3 patients relapsed before M12. Patients presented catch up growth
with net improvement of their anthropometric measurements at M2 and stabili- OP068 BACTERIOPHAGE THERAPY: A NEW STRATEGY TO TARGET
zation thereafter (Table 1). ADHERENT-INVASIVE ESCHERICHIA COLI BACTERIA IN THE GI
TRACT OF CROHN’S DISEASE PATIENTS
M. Galtier1, L. De Sordi1, A. Sivignon2, A. De Vallée2, D. Maura1, C. Neut3,
O. Rahmouni4, K. Wannerberger5, P. Desreumaux6, N. Barnich2,
M0 (n ¼ 9) M2 (n ¼ 9) M6 (n ¼ 9) M12 (n ¼ 6) L. Debarbieux1
1
Dpt Of Microbiology, Institut Pasteur, Molecular Biology of the Gene in
Z score weight -0.96  1.13 -0.37  0.97 0.07  0.81 0.30  1.18 Extremophiles Unit, Paris/France
2
Universite´ d´Auvergne Inserm U 1071, Clermont-Ferrand/France
Z score height -0.18  0.84 -0.11  0.80 0.09  1.14 0.35  0.76 3
Universite´ Lille Nord De France, Division of Bacteriology, Lille/France
Z score BMI -1.37  1.07 -0.38  0.89 -0.82  1.15 -0.66  1.20 4
Univ. Lille, Inserm, LIRIC, UMR995, Lille/France
5
Ferring Pharmaceuticals, Saint-Prex/Switzerland
6
Univ Lille, Inserm, Chu Lille, LIRIC UMR995; Claude Huriez hospital, Lille/
France
Conclusion: This study demonstrates for the first time prolonged clinical, biolo-
gical remission and improved growth in pediatric CD patients treated only with Contact E-mail Address: [email protected]
cyclic enteral nutrition. Cyclic EN can be an efficacious non pharmacological Introduction: Adherent-invasive Escherichia coli (AIEC) are abnormally predo-
treatment of Crohn’s disease patients potentially acting ahead of the inflamma- minant on Crohn’s disease (CD) ileal mucosa. AIEC are pathobiont bacteria able
tory cascade in the intestinal mucosa. A sufficiently power randomized controlled to induce inflammatory responses that could initiate or perpetuate the chronic
trials is currently conducted by the GETAID pédiatrique to confirm these pilot gut inflammation. Antibacterial treatments, such as bacteriophages (viruses
data. infecting bacteria) represent a way to eliminate these bacteria from the GI
Disclosure of Interest: F. Ruemmele: Nestlé Nutrition Institute, Nestlé Health tract without disturbing the microbiota homeostasis. Here, we evaluated the
Science potential of bacteriophages to reduce AIEC colonization associated to intestinal
All other authors have declared no conflicts of interest. mucosa.
Aims & Methods: Three bacteriophages were selected to efficiently target AIEC
bacteria isolated from CD patient. Efficacy of this bacteriophage cocktail was
investigated using two in vivo experimental models: transgenic mice expressing
CEACAM6 colonized by AIEC strain LF82 and the DSS chemically-induced
colitis model infected with AIEC strain LF82.
Results: In LF82-colonized CEACAM6-expressing mice, 24h after the oral
administration of the selected cocktail of three bacteriophages, the fecal
A30 United European Gastroenterology Journal 4(5S)
concentration of LF82 bacteria has significantly dropped by two log in the OP070 CARD9 IMPACTS COLITIS BY ALTERING GUT MICROBIOTA
bacteriophage group and stays significantly lower than in control group four METABOLISM OF TRYPTOPHAN INTO ARYL HYDROCARBON
days post-treatment, without any additional bacteriophage administration RECEPTOR LIGANDS
demonstrating the benefit of self-amplification of bacteriophages over time. B. Lamas1, M. Lavie-Richard2, M. Michel2, V. Leducq1, C. Bridonneau2, G.
Furthermore, we found that administration of the cocktail during the first day Da Costa2, L. Beaugerie3, P. Langella2, H. Sokol1
reduces progressively over a period of five days the colonization level of LF82 1
Avenir Team Gut Microbiota, INSERM U1157/UMR CNRS 7203, UPMC,
bacteria through the entire gut. In addition, bacteriophage treatment reduced Paris/France
colitis symptoms in the DSS-induced model, with a reduction of LF82 bacteria 2
Micalis, UMR 1319, Jouy-en-Josas/France
levels in feces, compared to the control group. Then, we showed that bacterio- 3
Department Of Gastroenterology, APHP St Antoine, Paris/France
phages were driving a long-term digestive tract decolonization of AIEC LF82
bacteria which in turns reduces colitis symptoms. Contact E-mail Address: [email protected]
Conclusion: Bacteriophages targeting AIEC bacteria with high efficacy in murine Introduction: Inflammatory bowel diseases (IBD) develop as a result of a combi-
models suggest that such a treatment could reduce AIEC-associated symptoms in nation of genetic predisposition, dysbiosis of the gut microbiota, and environ-
CD patients, providing an incentive to initiate clinical studies. The use of bacter- mental influences. Caspase recruitment domain 9 (CARD9), one of the numerous
iophages provides therefore, a new ‘‘microbiota friendly’’ way to efficiently target IBD susceptibility genes, encodes an adaptor protein for innate immunity toward
gut pathogens. a wide range of microorganisms. Card9–/– mice are more susceptible to colitis as a
Disclosure of Interest: All authors have declared no conflicts of interest. result of impaired of the IL-22 pathway1. Our aim was to explore the role of the
gut microbiota in the susceptibility of Card9–/– mice to colitis.
Aims & Methods: Germ-free (GF) C57BL/6 wild-type (WT) mice were inoculated
by oral gavage with fresh stools from conventional WT (WT—4GF) or Card9–/–
OP069 CIPROFLOXACIN RESISTANCE IN INFLAMMATORY BOWEL (Card9–/–—4GF) mice. Colitis was induced by DSS. AHR activity in intestinal
DISEASE PATIENTS WITH ESBL-PRODUCING content was determined using a reporter cell line. Immune response was assessed
ENTEROBACTERIACEAE COLONIZATION at transcripts level, at the protein level and at the cellular level using flow cyto-
V. Skuja1, K. Pekarska2, Z. Straume3, E. Goida2, H. Dauvarte2, D. Rudzite4, metry. Patients with IBD were genotyped for the major IBD-associated SNPs
E. Lavrinovica4, L. Piekuse2, A. Derovs4, A. Lejnieks4, A. Krumina4 including CARD9. Statistical analysis was performed using parametric or non-
1
Internal Medicine Gastroenterology, Riga Stradins University, Riga/Latvia parametric tests as appropriate.
2
Riga Stradins University, Riga/Latvia Results: Bacterial and fungal gut microbiota of Card9–/– mice (assessed by 16s
3
University of Latvia, Riga/Latvia and ITS2 sequencing) were altered compared to WT mice. Card9–/–—4GF mice
4
Riga East Clinical University Hospital, Riga/Latvia were more susceptible to colitis than WT—4GF with impaired recovery.
Moreover, IL-22 defect was observed in Card9–/–—4GF mice at the gene expres-
Contact E-mail Address: [email protected] sion and protein levels in the colon and in MLNs. IL-22 production by T helper
Introduction: Ciprofloxacin is one of the most frequently used antibiotics in 22 cells, NKp46þ innate lymphoid cells, lymphoid tissue inducer cells, and
hospitalized inflammatory bowel disease (IBD) patients. In the last few years CD3–CD4–NKp46– cells was decreased in the colon of Card9–/–—4GF mice.
an emerging resistance to ciprofloxacin, ranging from 43% to 82%, has been AHR ligands are known to promote gut IL-22 production2. Indeed, the levels of
described in extended-spectrum beta-lactamase (ESBL)-producing bacteria colo- Indole-3-acetic acid (IAA), an AHR ligands, were decreased in stools of
nizing the gut [1; 2]. The objective of this study was to evaluate the gut coloniza- Card9–/–—4GF and Card9–/– mice. Moreover, feces from Card9–/– and
tion with ESBL-producing Enterobacteriaceae in IBD patients, resistance to Card9–/–—4GF mice were defective in their ability to activate AHR. In
ciprofloxacin and bacterial plasmid genes associated with that. Card9–/–—4GF mice, susceptibility of colitis, and IL-22 defect were rescued
Aims & Methods: Rectal swabs from all consecutive patients with confirmed after treatment with AHR agonist (6-formylindolo(3,2-b)carbazole), or inocula-
ulcerative colitis (UC) and Crohn’s disease (CD) hospitalized in Riga East tion with three Lactobacillus strains with strong AHR activity. These effects were
Clinical University Hospital 2012–2015 were collected, Enterobacteriaceae were abrogated in the presence of AHR antagonist (CH223191). Reduced production
cultured and analyzed for ESBL presence according to EUCAST guidelines, of AHR ligands was also observed in the microbiota from patients with IBD,
resistance to ciprofloxacin and bacterial plasmid genes CTX-M, TEM and particularly in those with CARD9 risk alleles.
SHV were detected. Conclusion: Card9 deletion has an effect on the gut microbiota in mice and its
Results: A total of 86 patients with confirmed IBD diagnosis were included in the transfer to WT GF recipient is sufficient to recapitulate the defective IL-22
study – 65 (75%) with UC, 21 (24%) with CD. We found that 7 (11%) of the UC activation and increased sensitivity to colitis observed in Card9–/– mice. These
patients and 2 (10%) of the CD patients were colonized with ESBL producing alterations were due to an impaired ability of the microbiota of Card9–/– mice to
Enterobacteriaceae. The isolated ESBL producing strains from UC patients catabolize tryptophan into AHR ligands. Our results are relevant to humans, as
included Escherichia coli (n ¼ 5), Klebsiella oxytoca (n ¼ 1) and Escherichia her- impaired microbial production of AHR ligands was observed in patients with
manii (n ¼ 1). The isolated ESBL-producing Enterobacteriaceae from CD IBD. Thus, defects in expression of factors involved in innate immunity, such as
patients included Escherichia coli (n ¼ 2). The isolated bacterial plasmid genes CARD9, can shape an altered microbiota, which can then modify the host
associated with ESBL-production in UC included CTX-M (n ¼ 7; 100%), immune response. Correcting impaired microbiota functions, such as ability to
TEM (n ¼ 2; 29%), SHV (n ¼ 1; 14%), in CD – TEM (n ¼ 2; 100%) and produce AhR ligands, is an attractive strategy in IBD.
CTX-M (n ¼ 1; 50%). In UC 4 (57%) of the isolated ESBL-producing Disclosure of Interest: All authors have declared no conflicts of interest.
Enterobacteriaceae were resistent to ciprofloxacin. In CD all of the ESBL- References
producing Enterobacteriaceae were sensitive to ciprofloxacin. In 1 case of
ESBL resistance CTX-M, TEM and SHV gene combination was observed, in 1. Sokol et al. Gastroenterology 2013.
1 case CTX-M and TEM gene combination was observed and in 2 cases only 2. Qiu et al. Immunity 2012.
CTX-M gene was present.
Conclusion: 1. High gut colonization rate (11%) with ESBL-producing bacteria in
UC patients, mostly E. coli, expressing CTX-M gene. 2. High resistance to cipro-
floxacin (57%) in UC patients. 3. CTX-M gene associated with resistance to OP071 FAECAL MICROBIOTA TRANSPLANTATION (FMT) IN
ciprofloxacin. ULCERATIVE COLITIS (UC) IS ASSOCIATED WITH SPECIFIC
Disclosure of Interest: All authors have declared no conflicts of interest. BACTERIAL CHANGES: STOOL AND COLONIC MUCOSA 16S
References MICROBIOTA ANALYSIS FROM THE RANDOMISED
CONTROLLED FOCUS STUDY
1. Lübbert, Christoph, et al. ‘‘Colonization with Extended-Spectrum Beta-
S. Paramsothy1, N. Kaakoush2, M.A. Kamm3, J. Faith4, J. Clemente4,
Lactamase-Producing and Carbapenemase-Producing Enterobacteriaceae
A. Walsh1, J. Van Den Bogaerde5, D. Samuel6, R. W. Leong6, S. Connor7,
inInternational Travelers Returning to Germany.’’. International Journal of
W. Ng7, R. Paramsothy7, E. Lin8, J. Colombel4, T.J. Borody8, H. Mitchell2
Medical Microbiology 2015; 305(1): 148–56 (Retrieved (http://linkinghub.el- 1
St Vincent’s Hospital, Sydney/Australia
sevier.com/retrieve/pii/S143842211400160X). 2
University of New South Wales, Sydney/Australia
2. Vervoort J., et al. ‘‘High Rates of Intestinal Colonisation with 3
St. Vincent’s Hospital, St Vincent’s Hospital and University of Melbourne,
Fluoroquinolone-Resistant ESBL-Harbouring Enterobacteriaceae in
Melbourne/Australia
Hospitalised Patients with Antibiotic-Associated Diarrhoea.’’. European 4
Icahn School of Medicine at Mount Sinai, New York/United States of America
Journal of Clinical Microbiology & Infectious Diseases: Official Publication 5
Nambour General Hospital, Nambour/Australia
of the European Society of Clinical Microbiology 2014; 33(12): 2215–21 6
Bankstown-Lidcombe Hospital, Sydney/Australia
(Retrieved April 23, 2016 (http://www.ncbi.nlm.nih.gov/pubmed/24993152). 7
Liverpool Hospital, Sydney/Australia
8
Centre for Digestive Diseases, Sydney/Australia
Contact E-mail Address: [email protected]
Introduction: In a randomised placebo-controlled trial, intensive FMT therapy
for active ulcerative colitis (UC) was significantly superior to placebo, producing
a clinical response in 450% and clinical remission with endoscopic remission or
response in 27% of patients (ECCO 2016 & DDW 2016)1. This part of the
FOCUS study aimed to characterise the microbial changes underlying FMT in
UC, and identify those predictive of, and associated with, response and lack of
response.
Aims & Methods: Active UC patients were randomised to intensive FMT or
placebo enemas 5 days/week for 8 weeks, with placebo-treated patients subse-
quently offered 8 weeks of open label FMT. Each FMT enema was derived from
3–7 unrelated donors. Faecal samples were collected from patients at week 0, 4
United European Gastroenterology Journal 4(5S) A31
and 8, open label mid and end of treatment (if applicable), and 8 weeks after MRI and portal hypertension using relaxin and relaxin magnetic nanoparticles
FMT; colonic biopsies were collected at week 0 and 8, and end of open label are currently ongoing.
treatment (if applicable). Faecal samples were also collected from individual Conclusion: This study presents a novel strategy to deliver RLN specifically to
donors and donor batches. DNA was extracted from faecal samples and 16S HSCs, key pathogenic cells involved in liver fibrogenesis, for the diagnosis and
ribosomal RNA gene sequencing performed using 2x300 bp Illumina Miseq treatment of liver fibrosis.
chemistry (F27 & 519R). Raw sequences were analysed using MOTHUR, and Disclosure of Interest: All authors have declared no conflicts of interest.
statistical tests performed on counts and relative abundances.
Results: Faecal and colonic samples were collected from 70 study patients. 14
donors contributed to 21 donor batches. 314 patient and 113 donor (individual þ
batch) faecal samples along with 160 patient colonic samples were analysed. OP073 A QUANTITATIVE IMAGING PLATFORM TO REAL-TIME
26976  540 clean sequences per faecal sample and 28093  881 per colonic MEASURE SPECIFIC ROS LEVELS IN LIVER DISEASES
biopsy were obtained with rarefaction curves suggesting sampling had reached
H. Wang1, X. Liang1, X. Liu1, R. Zhang2, M. Roberts1
saturation. In both faecal and colonic samples -diversity significantly increased 1
at all FMT treatment time points relative to baseline (p 5 0.005); this persisted 8 School Of Medicine, The University of Queensland, Brisbane/Australia
2
weeks after FMT in the faecal samples. On PCA, Cluster, and PERMANOVA Australian Institute For Bioengineering and Nanotechnology, The University of
analyses FMT significantly influenced patient microbial profiles, with the shift Queensland, Brisbane/Australia
towards healthy donor microbiota most notable at the genus and OTU levels. Contact E-mail Address: [email protected]
LEfSe analysis of both faecal and colonic samples showed a decrease in patient Introduction: Reactive oxygen species (ROS) are chemically reactive molecules
Bacteroides and an increase in donor Prevotella with FMT, independent of clin- containing oxygen, including hydrogen peroxide (H2O2), hypochlorous acid
ical outcome. A range of other microbial taxa were identified as transplanted or (HOCl), singlet oxygen (1O2), and superoxide (O2-). ROS have been reported
displaced with FMT across all taxanomic levels. Patients receiving FMT who to play an important role in the development of liver diseases.1 For example,
achieved remission had greater baseline faecal and colonic mucosal -diversity H2O2 can activate hepatic stellate cells in liver fibrogenesis. During hepatic
than those who did not achieve remission, and also had greater resultant diversity ischemia-reperfusion injury, HOCl is generated by neutrophils and diffuses
with and after FMT treatment. Specific taxa were consistently significantly asso- into hepatocytes, causing oxidant stress-mediated injury. O2- can react with
ciated with FMT remission across both faecal and colonic samples: taxa within nitric oxide to form peroxynitrite to modify the cell structure and function of
Barnesiella were associated with remission, while OTUs within Fusobacterium proteins in diseased liver. Various methods have been developed to monitor ROS
and Sutterella were associated with lack of remission. generation in the liver, but the presence of different cellular sources for ROS as
Conclusion: Baseline patient microbial diversity in UC appears to be predictive of well as the distinct chemical properties of specific ROS may lead to conflicting
therapeutic response to FMT. Intensive FMT is associated with increased micro- results.2 Most developed ROS-detection probes were difficult to be distinguished
bial diversity, with the greatest diversity noted in patients achieving remission. from endogenous fluorophores and only can be employed under one-photon
Increased diversity persists 8 weeks after cessation of therapy. Specific bacterial microscopy. Thus, an optimal strategy for precise real-time ROS detection is
taxa are transplanted or displaced by FMT, some of which are associated with highly required to rapidly and accurately reveal the cellular microenvironment
treatment outcome. A high level of concordance was observed between the faecal in liver diseases in clinic.
and colonic mucosal microbiota. These findings may be important in both under- Aims & Methods: Four different two-photon fluorescent probes were designed
standing the pathophysiology of the microbiota in UC and shaping future bac- and synthesized for selective detection of chemically reactive molecules of thiols
terial therapy. and ROS including glutathione (GSH), H2O2, HOCl, and O2-. Mouse models of
Disclosure of Interest: T.J. Borody: Thomas J. Borody has an interest in the hepatic steatosis, fibrosis and ischemia-reperfusion injury were developed to
Centre for Digestive Diseases, where faecal microbiota transplantation is a treat- mimic human liver diseases.3 After sacrificing the animals, unfixed live liver
ment option for patients and has filed patents in this field. tissues were collected and incubated with each probe at the final concentration
All other authors have declared no conflicts of interest. of 50 to 100 mmol for 10 min, and then imaged using multiphoton microscopy
Reference (JenLab GmbH, Jena, Germany).4
Results: Each probe exhibited a strong positive fluorescent response only in the
1. Paramsothy S, Kamm MA, Walsh A, et al. Multi-donor intense faecal micro-
presence of its specific chemically reactive molecule, whereas negligible fluores-
biota transplantation is an effective treatment for resistant ulcerative colitis:
cent signals were observed upon the additions of other reactive oxygen/nitrogen
a randomised placebo-controlled trial [abstract]. Journal of Crohn’s and
species and metal ions. There was a good linear relationship between the probe
Colitis 2016; 10(Suppl 1S14.
responsive fluorescent intensity and the concentration of specific ROS. In the
liver with ischemia-reperfusion injury, reduced autofluorescence was detected,
MONDAY, OCTOBER 17, 2016 14:00–15:30 indicating the hepatocyte necrosis. Remarkable enhancement of red fluorescence
FREE PAPER SESSION: THE FUTURE OF DIAGNOSTIC IN HBP AND UPPER GI – ROOM was observed in hepatocytes with decreased autofluorescence, indicating the
N1_____________________ reaction of with endogenous HOCl. The cellular concentration of GSH decreased
and H2O2 increased in the liver with fibrosis and steatosis compared to the
control. The concentration of each specific ROS was first calculated based on
OP072 RELAXIN-COATED IRON-OXIDE MAGNETIC the intensity of images at the cellular level.
NANOPARTICLES AS A NOVEL THERANOSTIC APPROACH FOR Conclusion: We developed a quantitative imaging platform to real-time measure
DIAGNOSIS AND TREATMENT OF LIVER FIBROSIS specific ROS changes in liver diseases at the cellular level. This technique can be
R. Bansal1, B. Nagórniewicz11, J. Prakash1, G. Storm2 used to investigate ROS-mediated liver injury and predict treatment response in
1
Mira Institute, University of Twente, Enschede/Netherlands human liver biopsy, and can be readily extended to examination of diseases and
2
Department Of Pharmaceutics, Utrecht University, Utrecht/Netherlands injury of other organs. We anticipate that in the near future this quantitative
imaging platform will be evaluated from bench to bedside, leading to real-time
Contact E-mail Address: [email protected] monitoring of cellular microenvironment in human diseases.
Introduction: Hepatic fibrosis is a growing health problem with no effective and
Disclosure of Interest: All authors have declared no conflicts of interest.
clinically approved therapy. Hepatic stellate cells (HSCs) are the key cells
involved in the pathogenesis of liver fibrosis. Upon activation, HSCs undergo
morphological and functional changes, and are transformed into contractile References
ECM-producing myofibroblasts leading to scar tissue formation. HSCs contrac-
tion contributes significantly to the portal hypertension thereby further impairing 1. Jaeschke H and Ramachandran A. Reactive oxygen species in the normal
the liver function. Relaxin (RLN) has been shown to inhibit HSC activation and and acutely injured liver. Journal of Hepatology 2011; 55(1): 227–8.
contraction thereby ameliorate liver fibrosis and portal hypertension. However, 2. Miller EW, Albers AE, Pralle A, Isacoff EY and Chang CJ. Boronate-based
RLN has very poor pharmacokinetics and administration of high or frequent fluorescent probes for imaging cellular hydrogen peroxide. Journal of the
doses can lead to detrimental side effects due to vasodilation. American Chemical Society 2005; 127(47): 16652–9.
Aims & Methods: In this study, we aimed to develop a nanoparticle-based deliv- 3. Wang H, Liang X, Mohammed YH, et al. Real-time histology in liver disease
ery system to improve pharmacokinetics and therapeutic efficacy of RLN for the using multiphoton microscopy with fluorescence lifetime imaging.
diagnosis and treatment of liver fibrosis. We conjugated human RLN-2 to Biomedical Optics Express 2015; 6(3): 780–92.
PEGylated magnetic nanoparticles (RLN-MNP) and characterized the size,
charge and stability. We examined RLN-MNP for RLN conjugation and
HSCs-specific binding/uptake. We analysed RLN receptor (RXFP1) expression
on activated HSCs and CCl4-induced liver fibrosis mouse model. Finally, we
assessed the effects of RLN-MNP on human HSCs and CCl4-induced advanced
8-weeks liver fibrosis mouse model.
Results: RLN-MNP was successfully synthesized and remained stable at 4 C.
RLN-MNP showed specific binding and uptake to TGFb-activated human
HSCs while MNP alone showed no binding/uptake. In vitro, RLN-MNP and
unconjugated RLN significantly inhibited TGFb-induced 3D-collagen gel con-
traction and HSCs migration. Significant up-regulation of RXFP1 in TGFb-
activated HSCs and CCl4-induced liver fibrosis mouse model was observed.
In vivo in established 8 weeks CCl4-induced liver fibrosis mouse model, both
RLN and RLN-MNP strongly attenuated fibrosis by inhibiting HSC activation,
ECM production and angiogenesis. Importantly, RLN-MNP, but not unconju-
gated RLN, increased Nitric oxide release by significant up-regulation of iNOS.
On the other hand, unconjugated RLN induced systemic side effects by inducing
systemic NO release (in serum) while RLN-MNP did not. In vivo studies for
A32 United European Gastroenterology Journal 4(5S)
4. Liang X, Grice JE, Zhu Y, et al. Intravital multiphoton imaging of the OP075 ESOPHAGEAL HIGH RESOLUTION MANOMETRY WITH A
selective uptake of water-dispersible quantum dots into sinusoidal liver SOLID TEST MEAL IMPROVES THE DETECTION OF
cells. Small 2015; 11(14): 1711–20. CLINICALLY RELEVANT ESOPHAGEAL DYSFUNCTION AND
SYMPTOM REPRODUCIBILITY: A VALIDATION STUDY IN A
MULTIRACIAL ASIAN COHORT
D. Ang1, M. Lee1, T. Tan1, M. Zhang1, M. Fox2
OP074 RANDOMIZED CONTROLLED TRIAL (RCT) OF DOPPLER 1
Gastroenterology, Changi General Hospital, Singapore/Singapore
ENDOSCOPIC PROBE (DEP) FOR BLOOD FLOW DETECTION IN 2
Department Of Gastroenterology, St. Claraspital, Basel/Switzerland
SEVERE NON-VARICEAL UGI HEMORRHAGE (NVUGIH)
D.M. Jensen1, T. O. Kovacs1, G. V. Ohning2, K. Ghassemi1, G. Machicado2, Contact E-mail Address: [email protected]
G. Dulai2, A. Sedarat1, R. Jutabha1, J. Gornbein3 Introduction: The Chicago Classification (CC) of esophageal motility disorders
1
Gastroenterology/medicine, UCLA, Los Angeles/United States of America/CA for high resolution manometry (HRM) is based on ten 5 mLs water swallows
2
Gastroenterology/medicine, Veterans Affairs Greater West Los Angeles, Los (WS). We have previously reported the use of a solid test meal (STM) in patients
Angeles/United States of America/CA undergoing HRM to improve diagnostic sensitivity(1). We further validate the
3
Biomathematics, UCLA David Geffen School of Medicine, Los Angeles/United use of a STM in a multiracial Asian cohort.
States of America/CA Aims & Methods: We aimed to determine if the use of a STM during routine
esophageal manometry improves diagnostic yield and symptom reproducibility.
Contact E-mail Address: [email protected] Methods: Prospective series of patients referred for esophageal HRM between
Introduction: For decades, stigmata of recent hemorrhage (SRH) in ulcers & November 2014-April 2016. All patients had undergone prior endoscopy with
NVUGIH have been used to guide endoscopic hemostasis. Arterial blood flow findings of normal or mild (LA grade A esophagitis). WS and STM studies were
underlying SRH is rarely monitored, yet determines rebleed risk after treatments. performed in the upright seated position. Diagnosis of major and minor esopha-
Aims & Methods: In a RCT, our primary aim was to compare 30-day rebleed geal motility disorders were based on CC version 3.0 for water swallows (2) and
rates of index lesions for patients treated with Standard vs. DEP guided endo- modified for solid swallows as appropriate (3). All medications known to inter-
scopic hemostasis. In a 2-center study, patients were resuscitated & consented. fere with GI motility were stopped for at least one week prior to the study.
They & managing medical-surgical teams were blinded to endoscopic treatments. Symptoms reported by the patients during HRM study were analyzed for any
Patients with severe inpatient or outpatient start of UGIH (clinical signs, hemo- corresponding manometric abnormalities. Symptom associated dysfunction
globin – Hgb - drop of 4 2 gms from baseline, & RBC transfusions) were (SAD) was defined as a symptom event reported during or up to 10 seconds
randomized at urgent endoscopy if they had benign appearing ulcers & some after concurrent esophageal dysmotility during STM.
SRH (active arterial bleed, non-bleeding visible vessel - NBVV, or adherent clot, Results: 119 (56 Male [47.1%]; mean age 50.9  16.2) consecutive patients (84
oozing without other SRH, or flat spot) or Dieulafoy’s lesions or Mallory Weiss Chinese: 17 Malay:9 Indian:9 others) underwent HRM with WS for evaluation of
tears- MWT (with active bleeding or NBVV). For Standard treatment, hemoclip- (i) dysphagia (n ¼ 56 [47.4%]), (ii) reflux symptoms (n ¼ 45 [38.1%]) and (iii)
ping &/or multipolar probe electrocoagulation (MPEC-large probe) with or atypical chest pain (n ¼ 17 [14.4%]). HRM with STM was performed in 114
without dilute epinephrine injection was used without DEP & visual end points (96%) patients. Compared to WS alone (n ¼ 2/119 [1.7%]), more patients were
were control of bleeding, flattening VVs, & a foot-print at the SRH. For the DEP diagnosed with esophago-gastric junction (EGJ) outflow obstruction during a
group, SRH & lesion base were interrogated for underlying blood flow at 5 4 STM (n ¼ 8/114 [7.0%]); p ¼ 0.05). (Table) Similarly, more patients were diag-
mm deep settings with an FDA approved control unit & disposable DEP probe nosed with esophageal spasm with a STM (n ¼ 5/114 [4.4%]) compared to WS (2/
(Vascular Technology, Nashua, NH). Then Standard RX was applied on & out 119 [1.7%], p ¼ 0.27) alone. Upper esophageal dysfunction (UES) was seen only
from the SRH, where the artery was traced. DEP was used to recheck & if during STM in 3/114 [2.6%] patients. Conversely, more patients were diagnosed
residual blood flow was detected, further hemostasis was performed until no with ineffective esophageal motility (IEM) during SWS (16/119 [13.4%]) com-
blood flow was detected. Standard group patients with flat spots were not treated pared to during STM (6/114 [5.3%], p ¼ 0.04) consistent with earlier reports of
endoscopically, but DEP patients were if they had blood flow detected. All improved peristaltic contractions in controls and patients with non-erosive reflux
patients with ulcers & Dieulafoy’s lesions received high dose PPI infusion X 72 disease (4) Symptom associated dysfunction during HRM occurred in signifi-
hours & then BID for 30 days. MWT patients were treated with anti-emetics & cantly more patients during the STM study (n ¼ 26/114 [22.8%] compared to
BID PPI. Rebleeding was determined by a 4 2 gm decrease of Hgb, with clinical SWS alone 1/119 [0.8%], p 5 0.0001). The study was well tolerated in all
signs of rebleeding, & repeat endoscopy with more hemostasis as needed. Patients patients.
were followed prospectively by research coordinators who recorded routine 30 Conclusion: The use of additional physiological stimuli during routine esophageal
day outcomes. HRM improves the detection of clinically relevant esophageal dysfunction,
Results: All blood flow detected by DEP was reproducible & arterial. For 148 including disorders of the upper esophageal sphincter (UES) and the eso-
patients randomized, see the Table for 30 day rebleed rates by SRH. There was a phago-gastric junction (EGJ). In addition, symptom associated dysfunction
significant difference in rebleed rates (15.2% higher) in Standard group vs. DEP occurred more frequently during the solid test meal. The improved diagnostic
group (p ¼ 0.02138) & surgery (4/76 vs. 0/72 – p ¼ 0.0484). 1 perforation occurred yield can guide effective treatment.
in the Standard group & none in the DEP group. Disclosure of Interest: All authors have declared no conflicts of interest.
References
Non-Variceal UGIB Doppler Probe RCT - Primary Outcome of 30 day Rebleeds 1. Fox et al., DDW 2014.
from the Same Lesion 2. Kahrilas P, Fox M, et al. NGM 2015.
3. Sweis R, Fox M, et al. NGM 2014.
Stigmata Standard DEP
4. Daum C, Fox M et al. NGM 2011.
Active Arterial bleed 5/10 (50.0%) 4/14 (28.6%)
NBVV 7/27 (25.9%) 4/26 (15.4%)
Adherent Clot 4/16 (25%) 0/13 (0%)
Flat Spots 3/16 (18.8%) 0/15 (0%)
Oozing bleeding 1/7 (14.3%) 0/4 (0%)
TOTALS 20/76 (26.3%) 8/72 (11.1%)*

*p ¼ 0.02138 by Fisher Exact test

Conclusion: In a RCT of patients with severe NVUGIH, use of Doppler probe as

a guide to endoscopic hemostasis significantly reduced 30 day rebleed & surgery
rates compared to Standard, visually guided hemostasis. We now recommend
DEP (along with SRH) as a new guide for risk stratification & definitive endo-
scopic hemostasis in patients with severe NVUGIH. RCT was supported by a
VA Clinical Merit Review Research Grant & in part by NIH-NIDDK AM 41301
CURE DDRC-Human Studies Core. Registered with ClinicalTrials.gov as
Project CLIN-013–07F.
Disclosure of Interest: All authors have declared no conflicts of interest.
United European Gastroenterology Journal 4(5S) A33

Abstract No: OP075

Summary of Manometry Findings with Single Water Swallows (SWS) and Solid Test Meal (STM)

Dysphagia Dysphagia Reflux Reflux Chest Pain

Diagnosis on High-Resolution Manometry (N ¼ 56) SWS (N ¼ 51) STM (N ¼ 46) SWS (N ¼ 46) STM (N ¼ 17) SWS Chest Pain (N ¼ 17) STM

Achalasia Types I/II/III 15 10

Esophago-gastric junction (EGJ) outflow obstruction 3 6 1 1
Spasm 1 2 1 2 1
Jackhammer 1 1 1 1 3 4
Aperistalsis 4 0 3 2
Ineffective esophageal motility 9 5 6 1 1
Upper esophageal dysfunction 1 2
Normal 23 26 35 37 13 11

OP076 THE NEW IMAGE ENHANCEMENT TECHNOLOGY USING OP077 EXOSOMES DERIVED FROM GASTRIC CANCER PATIENTS
LINKED COLOR IMAGING WITH ACETIC ACID INDIGOCARMINE AND CELLS COULD DELIVER MIR-21 TO ELICIT TUMOR
MIXTURE FOR DIAGNOSIS OF EARLY GASTRIC NEOPLASM PROGRESSION AND METASTASIS AND COULD BE USED AS A
Y. Kawahara1, H. Kanzaki2, H. Sakae2, K. Miura3, Y. Kono2, M. Iwamuro4, POTENTIAL DIAGNOSTIC BIOMARKER
S. Kawano5, H. Okada2 X. Zhou1, G. Zhang2
1 1
Department Of Endoscopy, Okayama University Hospital, Okayama/Japan Dept. Of Gastroenterology, Jiangsu Province Hospital, Nanjing/China
2 2
Department Of Gastroenterology and Hepatology, Okayama University, Department Of Gastroenterology, The First Affiliated Hospital of Nanjing
Okayama/Japan Medical University, Nanjing/China
3
Department Of Gastroenterology and Hepatolog, Okayama University, Okayama/
Japan Contact E-mail Address: [email protected]
4
Department Of Gastroenterology and Hepatolog, Okayama University, Okayama/ Introduction: Gastric cancer (GC) remains a global challenge due to high mor-
Japan bidity and mortality rates and poor response to chemotherapy treatment.
5
Department Of Gastroenterology and Hepatology, Okayama University, Increasing evidence suggests that exosomal microRNAs (miRNAs) possess
Okayama/Japan diverse cellular regulatory roles in cancer progression nowadays. The tumor
microenvironment is abundant with exosomes that are secreted by the cancer
Contact E-mail Address: [email protected] cells themselves. Exosomes are nanosized, organelle-like membranous structures
Introduction: A value of the combination of magnifying endoscopy of and image that are increasingly being recognized as major contributors in the progression of
enhancement endoscopy (IEE) technology (e.g. NBI, BLI) is reported in a diag- malignant neoplasms. For now, little is known about how cancer cell-derived
nosis for the early gastric neoplasm. This combination is effective, but it is exosomes and miRNAs in exosomes modulate the microenvironment to optimize
necessary to speculate in real histology from the pattern of a two-dimensional conditions for tumor progression and metastasis.
monotone. Therefore, this diagnostic method is still more difficult for general Aims & Methods: We aimed to investigate whether cancer cell-derived exosomal
endoscopists. Linked Color Imaging (LCI) was recently developed using a laser miRNA could modulate cancer progression and metastasis and can be used as a
endoscopic system (Fujifilm Co., Tokyo, Japan). LCI acquires images by simul- diagnostic marker. In this study, we used miRNA microarray technology to
taneously using narrow-band short wavelength light and white light in an appro- identify exosomal miRNAs that were differentially expressed in GC patients
priate balance. This combination of light provides more information about the and controls. We further examined the biological function of exosomal miR-21
vasculature and architecture on the mucosal surface than that obtained with on cell viability, apoptotic death and metastasis in human GC cells and explored
typical white-light imaging. When we use acetic acid indigocarmine mixture the possible downstream mechanism. We also included another 100 GC patients
(AIM) with LCI mode, we discovered that the magnifying images of early gastric and 100 controls to study whether exosomal miR-21 could be used as a potential
cancer are very clear, three-dimensional and near to real histology. So, we exam- biomarker.
ined the examined the utility of this method. Results: We found that exosomes derived from GC patients exhibited significant
Aims & Methods: This was a prospective observational study performed at a different miRNA expression patterns compared with those from controls. Of the
single tertiary referral center. The subjects are 72 lesions of 67 patients with 233 miRNAs that were differentially expressed, miR-21 stood out as one of the
gastric neoplasm. We are indicated of the endoscopic submucosal dissection most significantly upregulated miRNAs in cancer patients. miR-21 depletion in
(ESD), and were given pre-ESD endoscopy in our hospital from September GC cells led to decreased miR-21 levels in exosomes and significantly reduced cell
2014 to February 2016. Firstly we observed the lesions by magnifying endoscopy proliferation, migration, invasion and increased apoptosis, and the same phe-
with the BLI mode and diagnosed using VS classification system1). Secondly we nomenon was seen when transfect miR-21 inhibitor into the exosomes from GC
observed the lesions by magnifying endoscopy with LCIþAIM method and cells and co-culture the transfected exosomes with GC cells. Moreover, exosomal
diagnosed using VS classification system. Furthermore, we classified the visuali- miR-21 markedly enhanced snail and vimentin expression in GC cells, while
zation ability of the surface fine structure in Clear, Visible, and Invisible and significantly decreasing E-cadherin levels, suggesting that exosomal miRNA
evaluated it. Finally, we carried out ESD and compared the image with the might play a role in epithelial-to-mesenchymal transition (EMT) process.
histopathology. Finally, circulating exosomal miR-21 levels were closely associated with TNM
Results: By the pathology results, 60 lesions were gastric cancer and 12 lesions were stage, and lymph node metastasis in GC patients and could be used as a useful
gastric adenoma. The differentiation ability of a cancer and the non-cancer (ade- diagnostic biomarker with a sensitivity of 89.2% and specificity of 91.1%.
noma) did not have the significant difference between the BLI mode and the Conclusion: In conclusion, our findings suggest that GC cells could generate miR-
LCIþAIM methods. In the classification of visualization ability, 12 lesions were 21-rich exosomes that are delivered to surrounding normal cells to promote
Clear, 22 lesions were Visible, 38 lesions were Invisible by BLI mode. On the other prometastatic behaviors and prompt further investigation into the therapeutic
hand, 33 lesions were Clear, 34 lesions were Visible, 5 lesions were Invisible by value of exosome inhibition for cancer treatment and diagnostic marker for
LCIþAIM method. In the visualization ability of the surface fine structure, cancer diagnosis.
LCIþAIM method is significantly clearer than BLI mode (p 5 0.05). Disclosure of Interest: All authors have declared no conflicts of interest.
Conclusion: When we use AIM, indigocarmine accumulates in pit of the duct, and References
duct structures become clear by the acetic acid, By LCI mode, we can observe the
vascular pattern of the lesion clearly. So by the combination of AIM and LCI, we 1. Kalluri R. The biology and function of exosomes in cancer. J Clin Invest
can observe the lesion three-dimensionally. By this method, we can compare 2016Apr 1; 126(4): 1208–15.
histopathology with an endoscopic image intuitively, so we believe that a mag- 2. Halkein J, Tabruyn SP, Ricke-Hoch M, et al. MicroRNA-146a is a thera-
nifying endoscopy diagnosis of the gastric cancer is enabled even if we do not use peutic target andbiomarker for peripartum cardiomyopathy. J Clin Invest
various confusing classifications. 2013 May; 123(5): 2143–54.
Disclosure of Interest: All authors have declared no conflicts of interest. 3. Boelens MC, Wu TJ, Nabet BY, et al. Exosome transfer from stromal to
breast cancer cells regulates therapyresistance pathways. Cell 2014 Oct 23;
Reference
159(3): 499–513.
1. Yao K, Doyama H, Gotoda T, et al. Diagnostic performance and limitations
of magnifying narrow-band imaging in screening endoscopy of early gastric
cancer: a prospective multicenter feasibility study. Gastric Cancer 2014;
17(4): 669–79.
A34 United European Gastroenterology Journal 4(5S)
OP078 URINARY KALLIKREIN-10 PREDICTS INCURABILITY FOR country sample (27.9% IBS-C, 34.3% IBS-D, 33.3% IBS-M, 4.7% IBS-U) was
GASTRIC CANCER significantly different (p 5 0.0001) than with Rome III (16.6% IBS-C, 20.6%
T. Shimura1, M. Ebi2, T. Yamada3, T. Yamada4, T. Katano5, S. Nomura1, IBS-D, 60.1% IBS-M and 2.1% IBS-U).
Y. Mori1, H. Kataoka1, T. Joh1
1
Department Of Gastroenterology and Metabolism, Nagoya City University Table: Population Rome III and Rome IV IBS rates (%) by sex and age groups
Graduate School of Medical Sciences, Nagoya/Japan in the US, UK and Canada survey samples (without census weighting).
2
Aichi Medical University, Nagakute/Japan
3 ROME III IBS: Age 18–34 Age 35–49 Age 50–64 Age 65þ All age groups
Japanese Red Cross Nagoya Daini Hospital, Nagoya/Japan
4
Okazaki Public Health Center, Okazaki/Japan
5 US Females (n ¼ 962) 15.6 16.6 13.7 9.9 14.2
Nagoya City University Graduate School of Medical Sciences Gastroenterology
and Metabolism, Nagoya/Japan US Males (n ¼ 987) 7.2 9.3 8.4 5.6 7.6
UK Females (n ¼ 976) 14.2 15.4 15.1 8.9 13.9
Contact E-mail Address: [email protected]
UK Males (n ¼ 1018) 4.9 7.2 9.5 3.6 6.5
Introduction: Recent material and technical development enables us to get many
Canada Females (n ¼ 980) 14.6 16.8 15.4 12.9 15.1
therapeutic choices for gastric cancer (GC). Accurate diagnosis is thus needed to
choose an optimal treatment for GC, however, the current imaging diagnosis is Canada Males (n ¼ 1008) 6.3 10.3 8.2 5.9 7.6
not enough to identify incurable factors including peritoneal metastasis and local ROME IV IBS: Age 18–34 Age 35–49 Age 50–64 65þ All age groups
invasion. We have previously reported the usefulness of urinary biomarkers for US Females (n ¼ 962) 6.6 10.6 6.9 3.7 7.1
diagnosis of GC. With the goal of discovering non-invasive biomarkers for pro- US Males (n ¼ 987) 8.8 3.6 4.2 1.9 5.1
gression and incurability of GC, we conducted this study using urine samples UK Females (n ¼ 976) 6.7 10.2 8.6 3.2 7.5
from GC patients and healthy control. UK Males (n ¼ 1018) 1.8 5.1 5.5 1.6 3.6
Aims & Methods: Urine samples from 189 patients composed of 111 patients with
Canada Females (n ¼ 980) 7.1 9.8 8.1 5.3 7.8
GC and 78 healthy controls were analyzed in this study. According to tumor
Canada Males (n ¼ 1008) 2.5 5.4 5.0 2.1 3.7
stage and operability, GC cohort was analyzed.
Results: We conducted a protease protein array analysis to identify potential
candidate biomarkers, and three proteins were found to be elevated in the
urine of advanced GC patients compared to early GC patients. Among them,
urinary kallikrein-10 (KLK10) and proteinase 3 were positively associated with
tumor stage progression. Moreover, urinary level of KLK10 (uKLK10) was Conclusion: These first-ever national population prevalence estimates for Rome
significantly elevated in the urine of inoperable GC patients compared to oper- IV IBS show that IBS prevalence and demographic distribution is equivalent in
able GC patients (uKLK10: median, 33.5 ng/ml vs. 10.8 ng/ml; P ¼ 0.006), and the US, UK and Canada, and confirm that the disorder is female-predominant
disease-free survival (DFS) was significantly lower in GC patients with high and less common in older individuals. IBS prevalence is significantly lower when
uKLK10 compared to low uKLK10 (HR: 2.53 (95%CI, 1.23–5.21), P ¼ 0.007). Rome IV criteria are used than with Rome III, and the new criteria also change
Urinary KLK10 distinguished operability of GC with an area under the curve IBS subtype distribution, markedly reducing the IBS-M proportion. [Support:
(AUC) of 0.710 and the combination of uKLK10 with tumor size showed an The Rome Foundation]
AUC of 0.835. Immunohistochemical analyses also demonstrated a positive cor- Disclosure of Interest: O.S.S. Palsson: Salary support from research grants from
relation between tumor stage and KLK10 expression in GC tissues. In addition, Salix, Takeda, and Ironwood, and honoraria for participation in educational
GC patients with high expression of pathological KLK10 (pKLK10) significantly programs by these companies. Research support from the Rome Foundation.
showed a shorter DFS than those with low pKLK10 M. van Tilburg: Research grant from Takeda Pharmaceuticals. Research support
Conclusion: uKLK10 is a promising non-invasive biomarker for incurable GC. from the Rome Foundation.
Disclosure of Interest: All authors have declared no conflicts of interest. M. Simrén: Research grants from Danone and Ferring. Consultant/Advisory
Board member for AstraZeneca, Danone, Nestlé, Chr Hansen, Almirall,
Allergan, Albireo, Glycom, Shire. Speaker for Tillotts, Takeda, Shire, Almirall.
MONDAY, OCTOBER 17, 2016 14:00–15:30 Rome Foundation board member.
FROM SYMPTOMS TO DIAGNOSIS IN IBS – ROOM N2_____________________ A.D. Sperber: Consultant, Takeda-Israel. Rome Foundation Board Member.
W.E. Whitehead: Research grants from Takeda Pharmaceuticals. Educational
OP079 POPULATION PREVALENCE OF ROME III AND ROME IV grants from Takeda and Ferring. Consultant/Advisory Board member for
IRRITABLE BOWEL SYNDROME (IBS) IN THE UNITED STATES Ono, Ferring, and Biomerica USA. Rome Foundation board member.
(US), CANADA AND THE UNITED KINGDOM (UK)
O.S. S. Palsson1, M. Van Tilburg2, M. Simrén3, A. D. Sperber4, W.
E. Whitehead5
1
Dept. Of Medicine, University of North Carolina, Chapel Hill, NC/United States OP080 FUNCTIONAL HEARTBURN OVERLAPS WITH IRRITABLE
of America BOWEL SYNDROME MORE OFTEN THAN GERD -
2
Dept. Of Medicine, University of North Carolina, Chapel Hill/United States of DEVELOPMENT OF A PREDICTIVE MODEL FOR CLINICAL
America/NC PRACTICE
3
Dept Of Internal Medicine, Sahlgrenska University Hospital, Gothenburg/Sweden S. Tolone1, N. De Bortoli2, L. Frazzoni3, E. Savarino4, M. Frazzoni5,
4
Ben-Gurion Univ. of the Negev, Tel Aviv/Israel I. Martinucci6, E. Marabotto7, M. Furnari8, G. Bodini9, L. Fuccio10,
5
Dept. Of Medicine, University of North Carolina at Chapel Hill, Chapel Hill, NC/ V. Savarino11, S. Marchi2
1
United States of America Surgery, Second University of Naples, Naples/Italy
2
Dept. Of Gastroenterology, University of Pisa, Pisa/Italy
Contact E-mail Address: [email protected] 3
Gastroenterology Unit, Department Of Medical and Surgical Sciences, University
Introduction: The new Rome IV criteria make several adjustments in diagnostic of Bologna, Bologna/Italy
requirements for IBS compared to Rome III. It is unknown how this will affect 4
Department Of Surgery, Oncology and Gastroenterology, University of Padua,
the prevalence and demographic distribution of IBS Padua/Italy
Aims & Methods: We used data from a large internet survey of the general 5
Digestive Pathophysiology Unit, Baggiovara Hospital, Modena/Italy
population in 3 countries to measure and compare Rome IV vs. Rome III IBS 6
Gastroenterology Unit, University of Pisa, Pisa/Italy
rates and the demographics of the disorder. A community sample of 6,300 indi- 7
Division Of Gastroenterology, Department Of Internal Medicine, University of
viduals age 18 and older in the US, UK and Canada (2,100 in each country) Genoa, Genoa/Italy
completed the secure online survey. Quota-based sampling was used to ensure 8
Di.m.i., Gastroenterology Unit, DiMI, Gastroenterology Unit, University of
equal proportion of sex (50%/50%) and age groups (40% aged 18–39, 40% aged Genoa., Genoa/Italy
40–64, 20% aged 65þ) across countries, and to control education distributions 9
Department Of Internal Medicine, IRCCS San Martino DIMI, Genova/Italy
(30% maximum with college degree or equivalent). The survey included the 10
Deprtment Of Medical and Surgical Sciences, S.Orsola-Malpighi University
Rome IV Diagnostic Questionnaire for Adults, Rome III diagnostic modules Hospital, Bologna/Italy
for IBS, and demographic questions. Latest national census figures were used 11
Dept Internal Medecine, Universita di Genova, Genova/Italy
to calculate correction weights for age (in 5-year bins) and gender proportions
and obtain census-adjusted IBS prevalence estimates for each country. Contact E-mail Address: [email protected]
Results: Of the 6,300 survey completers, 5,931 were retained for analysis (49.2% Introduction: Gastroesophageal reflux disease (GERD) and irritable bowel syn-
female; mean age ¼ 47.4, range 18–92; 1,949 US, 1,994 UK, 1,988 Canada) after drome (IBS) are gastrointestinal (GI) disorders affecting a large part of the
369 inconsistent responders were eliminated. Due to the quota-based sampling, general population, with relevant impact on quality of life and health care
sex or age group proportions did not differ between countries. Rome IV vs. costs. To date, population- and clinical-based studies have reported a certain
Rome III IBS prevalence rates (census-corrected estimates in parentheses) were degree of overlap between GERD and IBS, which cannot be explained solely
6.1% (6.1%) vs. 10.8% (11.1%) in the US, 5.7 (5.8%) vs. 11.3% (11.7%) in by chance. By means of multichannel intraluminal impedance and pH (MII-pH)
Canada, and 5.5% (5.5%) vs. 10.1% (10.6%) in the UK. There were no IBS monitoring, patients with proton pump inhibitor (PPI)-refractory heartburn can
prevalence differences between countries, but Rome IV IBS prevalence was sig- be distinguished into PPI-refractory GERD and functional heartburn (FH), the
nificantly lower than Rome III IBS in all countries (p 5 0.0001 for all compar- latter to be considered a functional GI disorder separate from GERD. Symptoms
isons). Women were more likely (p 5 0.0001) to have IBS than men by both of IBS have not yet been assessed in patients with reflux symptoms as distin-
Rome IV (7.1% vs. 4.1%; OR 1.87) and Rome III (14.4 vs. 7.2; OR 2.17) criteria guished into GERD and FH. Recently, it has been reported that patients with
in the combined 3-country sample, and people age 65þ were significantly less GERD as well as patients with IBS have increased levels of anxiety, in turn
likely (p 5 0.0001) than younger respondents to have IBS according to either associated with increased perception of symptoms and reduced quality of life.
criteria. Similar age group and gender difference patterns were seen in the 3 Again, the prevalence of anxiety in patients with reflux symptoms as clearly
countries (Table). The Rome IV IBS subtype distribution for the combined 3- distinguished into GERD and FH has not yet been assessed.
United European Gastroenterology Journal 4(5S) A35
Aims & Methods: Our aim was to assess the prevalence of IBS as well as anxiety Table 1: Probabilities for IBS-related symptoms to persist or subside over a five-
and depression in patients with typical reflux symptoms subdivided into GERD year period.
and FH by means of upper GI endoscopy and MII-pH monitoring. We also
aimed to assess the prevalence of various clinical and endoscopic characteristics Symptom persists Symptom subsides
in GERD and FH patients in order to develop a predictive model for distinguish-
ing FH from GERD in patients presenting with typical reflux symptoms, poten- Probability 95% CI Probability 95% CI
tially useful in clinical practice. Patients underwent a structured interview based Depression 22% 18–26% 23% 16–28%
on questionnaires for GERD (GERDQ), IBS (RIIIAQ), anxiety and depression
Sense of coherence 21% 18–24% 17% 13–22%
(HADS). Upper GI endoscopy and 24h MII-pH off-therapy monitoring were
performed in all cases. In patients with IBS, fecal calprotectin was measured and Coping resources 19% 18–21% 20% 17–23%
colonoscopy was scheduled for values 4100 mg/kg to exclude organic disease. GI-specific anxiety 16% 14–18% 27% 23–31%
Multivariate logistic regression analysis was performed to identify independent Quality of life 16% 14–18% 27% 23–31%
risk factors for FH. A predictive model for FH diagnosis based on clinical and
Anxiety 12% 10–14% 44% 40–50%
endoscopic findings was developed by applying the purposeful selection of cov-
ariates. The coefficients estimated in the multivariate logistic regression analysis GI symptom severity 8% 7–9% 47% 41–50%
were used to predict FH diagnosis. The performance of the predictive model was
then assessed by examining measures of discrimination and calibration.
Discrimination was considered as the ability of the predictive model to differ-
entiate between patients with FH diagnosis and patients with GERD diagnosis
and was quantified by calculating the area under the ROC curve (AUC). A Conclusion: For the first time, we show that IBS-related symptoms develop dif-
calculator to help clinicians in automatically computing the predicted probability ferentially over time. GI symptoms had a high likelihood of subsiding over time,
of FH versus GERD in patients presenting with heartburn was built. in contrast to depression, sense of coherence, and coping resources. We suggest
Results: Of the 701 consecutive heartburn patients who entered the study, 458 more attention needs to be paid to the management of depression, and to provid-
(65%) had GERD whereas 243 (35%) had FH. IBS was found in 143/458 (31%) ing tools for better coping resources in IBS patients.
GERD but in 187/243 (77%) FH patients (P 5 0.001). At multivariate analysis Disclosure of Interest: J. Tack: Scientific advice to, or speaker bureau for: Abbott,
IBS, anxiety, and smoking resulted independent risk factors for FH whereas AlfaWasserman, Almirall, AstraZeneca, Danone, Janssen, Menarini, Novartis,
hiatal hernia resulted protective. We developed a predictive model based on Nycomed, Ocera, Ono pharma, Shire, SK Life Sciences, Theravance, Tranzyme,
clinical and endoscopic characteristics (IBS. Smoking, Anxiety, Age  45, Xenoport, and Zeria Pharmaceuticals.
Hiatal hernia, i.e. ISAAH). The area under ROC curve in an external validation H. Törnblom: Consultant/Advisory Board member for Almirall, Danone and
cohort of 51 patients was 0.920. Considering the previously established cut-off, Shire.
sensitivity and specificity of the predictive model in diagnosing FH against M. Simrén: Unrestricted research grants from Danone, and Ferring
GERD were 84.3% and 78.9%, respectively. A calculator to help clinicians in Pharmaceuticals; Consultant/ Advisory Board member for AstraZeneca,
automatically computing the predicted probability of FH versus GERD in Danone, Nestlé, Chr Hansen, Almirall, Allergan, Albireo, Glycom and Shire;
patients presenting with heartburn was built (URL: http://app.calculoid.com/#/ Speaker for Tillotts, Takeda, Shire and Almirall.
calculator/7012). All other authors have declared no conflicts of interest.
Conclusion: IBS overlaps more frequently with FH than with GERD, suggesting
common pathways and treatment. The score derived from ISAAH predictive
model allows a high level of suspicion for FH and can be useful in clinical
practice. OP082 SYMPTOMS COMPATIBLE WITH FUNCTIONAL BOWEL
Disclosure of Interest: All authors have declared no conflicts of interest. DISORDERS IN PATIENTS WITH ULCERATIVE COLITIS IN DEEP
REMISSION
M. Simrén1, B. Jonefjäll1, O. Palsson2, W. E. Whitehead3, H. Törnblom1,
L. Öhman4, H. Strid1
OP081 IRRITABLE BOWEL SYNDROME: WHICH SYMPTOMS ARE 1
Dept Of Internal Medicine, Sahlgrenska University Hospital, Gothenburg/Sweden
PERSISTENT AND WHICH ARE NOT? 2
UNC Center For Functional GI and Motility Disorders, University of North
E. Clevers1, J. Tack1, H. Törnblom2, M. Simrén2, L. Van Oudenhove1 Carolina at Chapel Hill, Chapel Hill/United States of America/NC
1 3
Targid, KU Leuven, Leuven/Belgium Center For Functional GI and Motility Disorders, University of North Carolina,
2
Internal Medicine & Clinical Nutrition, University of Gothenburg, Göteborg/ Chapel Hill/United States of America/NC
4
Sweden Sahlgrenska Academy, University of Gothenburg Sahlgrenska Academy Dept. of
Microbiology and Immunoly, Gothenburg/Sweden
Contact E-mail Address: [email protected]
Introduction: Irritable bowel syndrome (IBS) is characterised by many comorbid Contact E-mail Address: [email protected]
symptoms as well as core symptoms, all of which are relevant for the clinical Introduction: Several studies have reported high prevalence of symptoms compa-
management of this group of patients. However, the evolution of these symptoms tible with irritable bowel syndrome (IBS) in patients with ulcerative colitis (UC)
over time is poorly understood. in remission. However, previous studies have not excluded mild inflammatory
Aims & Methods: The aim of this study was to determine the probability of IBS- changes as a cause of these symptoms, and nothing is known about the preva-
related symptoms to persist or subside over time. The study consisted of three lence of symptoms compatible with other functional bowel disorders (FBD) than
parts. First, we addressed the question which factors can determine the prob- IBS in this group of patients and the burden of these symptoms.
ability of a symptom to persist or subside over time. A simulation showed there Aims & Methods: In a cross-sectional study, patients with UC (n ¼ 291) were
were five: length of follow-up period, autocorrelation, the interaction between the divided into active disease or deep remission (a total Mayo score 2, physiciańs
autocorrelation and symptom severity, the cut-off for symptom severity, and global assessment ¼ 0, rectal bleeding ¼ 0 and an endoscopic subscore ¼ 0, with
skewness. Second, we used the five factors in a Monte Carlo simulation, gener- no relapse during the 3-month period prior to visit). The patients completed the
ating a reference-table of probabilities for symptoms to persist or subside. Third, Rome III FBD module to define presence of symptoms compatible with FBD,
our theoretical reference-table was matched with real data from a cohort of 276 and questionnaires to measure psychological distress (Hospital Anxiety and
IBS patients (70% female; age range 19 to 76 years, median age 39 years). These Depression Scale; HADS), stress (Perceived stress scale; PSS), GI symptom sever-
subjects were thoroughly characterised at baseline, and completed questionnaires ity (GI Symptom Rating Scale; GSRS), somatic symptoms (Patient Health
annually over a five-year period, covering the following IBS-related symptoms / Questionnaire-15; PHQ-15), disease-specific quality of life (Inflammatory
aspects: gastrointestinal (GI) symptom severity (GSRS), GI-specific anxiety Bowel Disease Questionnaire; IBDQ), and general fatigue (Multidimensional
(VSI), quality of life (IBS-QOL), coping resources (CRI), sense of coherence Fatigue Inventory; MFI).
(KASAM), and anxiety/depression (HADS). The cohort was used to retrieve Results: Active UC was present in 159 patients (55%). The 132 patients (45%) in
the five factor properties mentioned above (e.g. autocorrelations). deep remission were assessed by the Rome III diagnostic criteria and 37% ful-
Results: A summary of the main results is shown in table 1. In IBS patients, filled criteria for a FBD: 18% IBS (11% IBS-M, 4% IBS-C, 3% IBS-D), 12%
depression was the most persistent symptom over time, i.e. a 22% chance for functional bloating, 4% functional diarrhea, and 3% functional constipation.
depression to persist, versus 23% to subside over a five-year period. Poor coping Additionally, among the UC patients in deep remission who did not meet diag-
resources and sense of coherence yielded similar percentages. Values were differ- nostic criteria for FBD, a substantial proportion reported some subthreshold
ent for anxiety (12% to persist and 44% to subside) and GI symptom severity (8 symptoms compatible with a functional bowel disorder, and only 18% of patients
and 47%), with no major differences between the different GI symptoms (i.e. with UC in deep remission reported no symptoms compatible with FBD (5one
diarrhoea, constipation, abdominal pain, satiety, indigestion, and reflux). For day/month). Compared with UC patients in deep remission with symptoms meet-
IBS-QOL, there were differences between the domains: sexual relations (20% ing diagnostic criteria for other FBDs (functional bloating, functional diarrhea,
chance to persist, 18% chance to subside) and sleep (20 and 25%), in contrast functional constipation), or who did not meet diagnostic criteria for a FBD,
to the domains mental health (7 and 56%), physical functioning (5 and 64%), patients who fulfilled diagnostic criteria for IBS reported more severe psycholo-
and emotional (5 and 57%). The QOL domains physical role, social role, and gical distress (p 5 0.0001), somatic symptoms (p 5 0.0001), and general fatigue
food were intermediate. (p ¼ 0.004), as well as reduced quality of life (p 5 0.0001), and they tended to
have higher levels of perceived stress (p ¼ 0.06). None of these factors differed
between patients who met diagnostic criteria for a FBD other than IBS and
patients who did not meet diagnostic criteria for FBD. Age, disease duration,
fecal calprotectin levels or high-sensitive CRP did not differ between the groups.
Overall GI symptom severity (GSRS total score) was highest in patients with
symptoms compatible with IBS (p 5 0.0001 vs no FBD and other FBD groups)
and intermediate in patients who fulfilled one of the other FBDs (p 5 0.05 vs no
FBD group).
A36 United European Gastroenterology Journal 4(5S)
Conclusion: Symptoms compatible with functional bowel disorders in general, OP084 HEALTHCARE RESOURCE UTILISATION AMONG PATIENTS
and not only IBS, are common in patients with UC in deep remission. WITH IRRITABLE BOWEL SYNDROME WITH DIARRHOEA IN
However, the overall disease burden seems to be greater in patients with symp- THE EU5
toms compatible with IBS than with the other FBDs. These observations are of C. Tucker1, J. L. Abel2, R. T. Carson2, N. M. Flores3, R. Liebert3
great importance when managing patients with IBD to avoid escalating anti- 1
Health Economics & Outcomes Research, Allergan plc, Buckinghamshire/United
inflammatory treatment, and instead focus on other treatment options to help Kingdom
these patients to manage their symptoms. 2
Allergan plc, Jersey City/United States of America/NJ
Disclosure of Interest: M. Simrén: Unrestricted research grants from Danone, and 3
Kantar Health, New York/United States of America/NY
Ferring Pharmaceuticals; Consultant/ Advisory Board member for AstraZeneca,
Danone, Nestlé, Chr Hansen, Almirall, Allergan, Albireo, Glycom and Shire; Contact E-mail Address: [email protected]
Speaker for Tillotts, Takeda, Shire and Almirall. Introduction: Irritable bowel syndrome (IBS) affects an estimated 10–15% of
B. Jonefjäll: Speaker for Abbvie, MSD and MEDA. adults, with the diarrhoea subtype (IBS-D) estimated to account for 30–40%
O. Palsson: Salary support from research grants from Salix Pharmaceuticals, of cases. IBS is a chronic, unpredictable disorder associated with increased
Takeda Pharmaceuticals and Ironwood pharmaceuticals, as well as honoraria healthcare-seeking behaviour and significant resource utilisation and costs.
for participation in educational programs supported by these companies. However, information on the economic burden of IBS-D in Europe is limited.
W.E. Whitehead: Unrestricted research grants from Takeda Pharmaceuticals; Aims & Methods: The objective of this study was to assess healthcare resource
Unrestricted educational grants from Takeda and Ferring Pharmaceuticals; utilisation associated with IBS-D among a sample of adults in the EU5 (Spain,
Consultant/ Advisory Board member for Ono and Ferring Pharmaceuticals France, Italy, Germany, United Kingdom). Respondents were identified from
and from Biomerica USA. the 2013 National Health and Wellness Survey, a self-administered, internet-
H. Törnblom: Consultant/Advisory Board member for Almirall, Danone and based survey. Diagnosed IBS-D patients were defined as those respondents
Shire. who reported a physician diagnosis of IBS-D; undiagnosed IBS-D patients
L. Öhman: Unrestricted research grant from AstraZeneca; Consultant/ Advisory included respondents who reported experiencing IBS-D symptoms but did not
Board member for Genetic Analysis; Speaker for Takeda and Abbvie. self-report a physician diagnosis. Controls included all respondents without IBS
H. Strid: Consultant/Advisory Board member for Takeda, Abbvie, Ferring (diagnosed or undiagnosed) or inflammatory bowel disease. IBS-D severity was
Pharmaceuticals, Tillotts, and MSD; Speaker for Takeda, Abbvie, Ferring evaluated based on a single item assessing disease severity (mild, moderate, or
Pharmaceuticals, Tilotts, MSD and Shire. severe). Healthcare resource utilisation was evaluated based on the number of
patient-reported healthcare provider visits (any healthcare provider, gastroenter-
ologist, or general practitioner [GP]), emergency room (ER) visits, and hospita-
lisations in the past 6 months. Descriptive statistics were conducted to examine
OP083 ENHANCED DIAGNOSTIC PERFORMANCE OF SYMPTOM- sample characteristics. Bivariate analyses were used to compare resource use by
BASED CRITERIA FOR IRRITABLE BOWEL SYNDROME BY IBS-D severity. To further assess the burden of IBS-D specifically, multivariable
HISTORY AND DIAGNOSTIC EVALUATION generalised linear models compared resource use across groups, controlling for
R. Sood1, M. Camilleri2, D. J. Gracie1, M. J. Gold3, N. To1, G. R. Law4, demographic and health characteristics, including age, gender, and
A.C. Ford1 comorbidities.
1
Leeds Gastroenterology Institute, Leeds Teaching Hospitals NHS trust, Leeds/ Results: A total of 58,161 respondents were included (859 diagnosed IBS-D; 370
United Kingdom undiagnosed IBS-D; 56,932 controls). Overall, the mean age was 47 years, and
2
Clinical Enteric Neuroscience Translational and Epidemiological Research 52.6% of respondents were female. Unadjusted analyses revealed that patients
(C.E.N.T.E.R.), Mayo Clinic, Rochester/United States of America (diagnosed and undiagnosed) with moderate (n ¼ 499) or severe (n ¼ 110) IBS-D
3
School Of Medicine, University of Leeds, Leeds/United Kingdom had significantly greater healthcare resource utilisation compared with patients
4
Division Of Epidemiology & Biostatistics, Leeds Institute Of Cardiovascular and with mild IBS-D (n ¼ 620), including more visits to any provider (8.65 and 10.10
Metabolic Medicine, University of Leeds, Leeds/United Kingdom vs. 6.22; both p 5 0.05), a gastroenterologist (0.22 and 0.35 vs. 0.08; both
p 5 0.05), the ER (0.37 and 0.46 vs. 0.19; both p 5 0.05), and a greater
Contact E-mail Address: [email protected] number of hospitalisations (0.21 and 0.36 vs. 0.11; both p 5 0.05). After control-
Introduction: Symptom-based criteria to diagnose irritable bowel syndrome (IBS) ling for demographic and health characteristics, diagnosed IBS-D patients had a
positively perform only modestly. Our aim was to assess whether including other significantly greater mean number of visits to any provider, a gastroenterologist,
items from the clinical history and diagnostic workup improves their a GP, and the ER, compared with both controls and undiagnosed IBS-D patients
performance. (Table).
Aims & Methods: We collected complete symptom, colonoscopy, and histology Conclusion: IBS-D patients utilised significantly greater outpatient healthcare
data from 318 consecutive, unselected adult patients with lower gastrointestinal resources compared with controls, with diagnosed patients using more resources
(GI) symptoms in secondary care. The reference standard used to define presence than those who are undiagnosed. In addition, patients with moderate or severe
of true IBS was patient-reported lower abdominal pain or discomfort associated IBS-D have the greatest healthcare resource utilisation. The substantial burden
with a change in bowel habit, in the absence of organic GI disease. Sensitivity, imposed by IBS-D patients on healthcare systems highlights the need for treat-
specificity, and positive and negative likelihood ratios (LRs), with 95% confi- ments to more effectively treat and manage IBS-D symptoms.
dence intervals, were calculated for Rome III criteria, as well as for modifica- Disclosure of Interest: C. Tucker: Catherine Tucker is an employee of Allergan
tions, incorporating nocturnal symptoms, results of simple blood tests plc.
(haemoglobin (Hb) and C-reactive protein (CRP)), measures of somatisation, J.L. Abel: Jessica L. Abel is an employee of Allergan plc and owns stock/stock
and/or affect (hospital anxiety or depression scale (HADS) score). options in Allergan plc.
Results: Sensitivity and specificity of Rome III criteria for identifying IBS was R.T. Carson: Robyn T. Carson is an employee of Allergan plc and owns stock/
69.6%, and 82.0% respectively, with positive and negative LRs of 3.87 and 0.37. stock options in Allergan plc.
Clinically useful enhancements in positive LRs when combining Rome III criteria N.M. Flores: Natalia M. Flores is an employee of Kantar Health, which was
with items from the clinical history, and blood tests, are shown in the table. contracted by Allergan plc for work relating to this study.
Conclusion: Incorporating nocturnal symptoms, somatisation, and affect from R. Liebert: Ryan Liebert is an employee of Kantar Health, which was contracted
the clinical history, and haemoglobin and CRP measurements, enhances perfor- by Allergan plc for work relating to this study.
mance of symptom-based criteria for IBS. Our findings suggest a different
approach to the development of future diagnostic criteria should be used.
Disclosure of Interest: All authors have declared no conflicts of interest.

Abstract No: OP083

Sensitivity (95% CI) Specificity (95% CI) Positive LR (95% CI) Negative LR (95% CI)
Rome III Criteria and normal Hb and CRP 49.0% (34.8%–63.4%) 89.2% (83.2%–93.6%) 4.53 (2.67–7.64) 0.57 (0.42–0.73)

Rome III criteria and HADS score 8 47.2% (35.3%–59.4%) 89.1% (84.2%–92.9%) 4.33 (2.76–6.76) 0.59 (0.46–0.72)
Rome III criteria and high somatisation 37.9% (26.2%–50.7%) 94.8% (90.6%–97.5%) 7.27 (3.74–14.2) 0.66 (0.53–0.77)
Rome III criteria, normal Hb and CRP, and HADS score 8 34.0% (20.9%–49.3%) 93.2% (87.9%–96.7%) 5.04 (2.48–10.2) 0.71 (0.55–0.84)
Rome III criteria, normal Hb and CRP, and high somatisation 24.4% (12.4%–40.3%) 96.8% (92.0%–99.1%) 7.56 (2.63–21.7) 0.78 (0.63–0.90)
Rome III criteria, no nocturnal passage of stool, and HADS score 8 22.2% (13.3% –33.6%) 95.4% (91.7%–97.8%) 4.84 (2.33–10.0) 0.82 (0.70–0.91)
Rome III criteria, no nocturnal passage of stool, and high somatisation 18.2% (9.8%–29.6%) 99.0% (96.3%–99.9%) 17.3 (4.45–67.6) 0.83 (0.72–0.90)
United European Gastroenterology Journal 4(5S) A37

Abstract No: OP084

Table

Adjusted mean, Diagnosed IBS-D Undiagnosed Controls p-value: Diagnosed p-value: Diagnosed p-value:
number in past 6 months (SE) (n ¼ 859) IBS-D (n ¼ 370) (n ¼ 56,932) vs. controls vs. undiagnosed Undiagnosed vs. controls

Any provider visits 7.23 (0.31) 5.17 (0.35) 4.14 (0.02) 50.001 50.001 0.001
Gastroenterologist visits 0.19 (0.02) 0.01 (0.01) 0.03 (0) 50.001 50.001 0.146
General practitioner visits 2.69 (0.12) 2.06 (0.15) 1.70 (0.01) 50.001 0.001 0.007
Emergency room visits 0.27 (0.04) 0.12 (0.03) 0.17 (0) 0.002 0.012 0.264
Hospitalisations 0.14 (0.03) 0.08 (0.03) 0.11 (0) 0.099 0.148 0.430

morphology, pre-resection biopsies). The two main endpoints were curative

MONDAY, OCTOBER 17, 2016 14:00–15:30 resection and post-procedural bleeding. We defined curative resection as a resec-
WHAT IS NEW IN GASTRIC ENDOSCOPIC SUBMUCOSAL DISSECTION (ESD) – ROOM tion meeting the standard or expanded criteria of the Japanese Gastric Cancer
L7_____________________ Treatment guidelines. For the analysis and model construction, morphology was
recoded into polypoid (0-Is, 0-Isp, 0-Ip), depressed (0-IIaþc, 0-IIcþa, 0-IIc and
OP085 LONG-TERM OUTCOMES OF ENDOSCOPIC SUBMUCOSAL 0-III) and non-polypoid non-depressed (0-IIa, 0-IIb, 0-IIaþb). Univariate ana-
DISSECTION (ESD) AND GASTRECTOMY BASED ON lysis was conducted with chi-squared test to identify associations between pre-
INDICATIONS FOR ESD treatment factors and the two endpoints, for a significance level of 5%. Logistic
W. Choi1, J. Park1, J.A. Lee1, Y.R. Sim1, T. Kim1, M.K. Joo1, B.J. Lee1, regression and Bayesian networks were then built for each outcome. Stratified
H.J. Chun2, S.W. Lee3, Y. Bak1 10-fold cross-validation was performed to assess the predictive accuracy and
1
Korea University College of Medicine Guro Hospital, Seoul/Korea, Republic of discriminative power (ROC curves) of the models. Clinical decision support
2
Korea University College of Medicine Anam Hospital, Seoul/Korea, Republic of was then enabled by the definition of risk matrices, direct use of Bayesian infer-
3
Korea University College of Medicine Ansan Hospital, Seoul/Korea, Republic of ence software and through the use of an online platform.
Results: In our sample, 85% were curative resections and PPB occurred in 8%. In
Contact E-mail Address: [email protected] the univariate analysis, age 463 (p ¼ 0.039), male sex (p ¼ 0.027), ASA status
Introduction: Endoscopic submucosal dissection (ESD) has been established as a (p ¼ 0.008), carcinoma histology (p 5 0.001), polypoid or depressed morphology
standard treatment modality of early gastric cancer (EGC), however, long term (p ¼ 0.015) and lesion size greater than 20 mm (p ¼ 0.006) were associated with
outcomes between ESD and gastrectomy were rarely reported, especially in terms non-curative resection, while age 470 (p ¼ 0.041), ASA status (p ¼ 0.017), antith-
of ESD criteria. rombotic medication (p 5 0.001) and lesion size greater than 420 mm
Aims & Methods: This study aimed to compare long term outcomes between ESD (p ¼ 0.026) were associated with PPB. Logistic regression and Bayesian models
and gastrectomy, and according to the histopathologic ESD criteria; absolute presented AUCs above 80% (in-sample) and 75% (cross-validation) on both
criteria (AC), expanded criteria (EC) and beyond expanded criteria (BEC). outcomes. Lesions with cancer at biopsies, 420 mm, proximal and polypoid
Between 2006 and 2012, 925 EGC patients were enrolled; ESD was performed are more prone to non-curative resection (table 1). Risk matrices for PPB were
in 468 patients, and gastrectomy in 457 patients. also defined yielding a posteriori probabilities of PPB 55% in lesions 520 mm
Results: Recurrence rate was 1.9% in ESD patients, 0.7% in gastrectomy patients in the absence of antithrombotic medications while the risk of PPB increased in
(p ¼ 0.08); 1.0%, 3.1% and 1.4% in AC, EC and BEC groups in ESD patients, greater lesions and in the presence of antithrombotic medications. The Bayesian
(p ¼ 0.062) and 2.0% and 1.4% in the ACþEC and BEC groups in ESD patients network can be interactively used in clinical practice to estimate individual prob-
(p ¼ 0.069), which were not significantly different between criteria groups. In ability of outcomes after ESD. Table 1 - Risk (a posteriori probabilities) matrix
concrete, recurrence rate was 1.1% and 0% in AC group of ESD and gastrect- for curative resection based on morphology, localization, size and pre-resection
omy patients, respectively, 3.1% and 1.9% in EC group, and 1.4% and 0% in histology, using a Bayesian model (cross-validation AUC ¼ 78%,
BEC group. 394 of 468 (84.2%) ESD patients were within criteria. (ACþEC 95%CI ¼ [75%,81%]).
group), and 273 of 457 (59.7%) gastrectomy patients were out of ESD criteria
(BEC group).
Conclusion: The recurrence rate was neither significantly different between ESD
and gastrectomy patients, nor was significantly different between three criteria
Size Size Size Size Size Size
groups among total patients. Thus, ESD with EC or even BEC might be an 520 mm 520 mm 520 mm 20 mm 20 mm 20 mm
alternative option in EGC patients who refuse gastrectomy or with high opera-
tion risk. Morphology Local LGD HGD IMC LGD HGD IMC
Disclosure of Interest: All authors have declared no conflicts of interest. Polypoid Middle 85 74 42 66 49 20
(0-Is, 0-Ip, 0-Isp)
Upper 91 83 56 77 62 30
Lower 93 86 61 81 67 35
OP086 PREDICTING CLINICAL OUTCOMES OF GASTRIC
Depressed Middle 93 87 64 83 70 38
ENDOSCOPIC SUBMUCOSAL DISSECTION USING A BAYESIAN
(0-IIc, 0-IIaþc, 0-IIcþa, III)
APPROACH
Upper 96 92 75 89 80 51
D. Libânio1, M. Dinis-Ribeiro1, P. Pimentel-Nunes1, C. C. Dias2, P. Lower 97 94 79 91 83 57
P. Rodrigues3
1 Non-polypoid, non-depressed Middle 97 94 79 91 83 57
Gastroenterology Department, Portuguese Oncology Institute of Porto, Porto/ (0-IIa, 0-IIaþb, 0-IIb)
Portugal
2 Upper 98 96 87 95 90 69
Health Information and Decision Sciences Department, Faculty Of Medicine Of
Lower 98 97 89 96 91 74
Porto and Cintesis- Center For Health Tecnology and Services Research, Porto,
Portugal, Centro Hospitalar São João, Porto/Portugal
3
Cintesis - Health Information and Decision Sciences Department, Faculty of LGD - Low-grade dysplasia; HGD - High-grade dysplasia; IMC - intramucosal
Medicine of Porto, Porto/Portugal carcinoma

Contact E-mail Address: [email protected]

Introduction: In patients with gastric superficial neoplasms, the probabilities of Conclusion: The derived models presented good discriminative power in the pre-
success and of adverse events influence the decision process regarding treatment diction of outcomes. Bayesian models and risk matrices can be used to predict
allocation. These probabilities may be predicted using a priori patients’ and individualized probabilities, which can improve the information transmitted to
lesions’ factors. However, the knowledge of risk factors alone is not readily patient regarding a posteriori probabilities and can aid in the decision process
and completely usable by patients and clinicians in the decision process since it regarding allocation for endoscopic or surgical treatment. Additionally, a poster-
is difficult to predict the addictive effect of risk factors in the outcome, in a given iori probabilities of adverse events can guide management after gastric ESD,
patient. Bayesian networks are increasingly used for clinical decision support namely regarding the timing of discharge from hospital.
since Bayesian statistical methods allow taking into account prior knowledge Disclosure of Interest: All authors have declared no conflicts of interest.
when analyzing data and can aid in capturing and reasoning with uncertainty Reference
in medicine[1].
Aims & Methods: The aim of this study was to develop a Bayesian model and a 1. Lucas PJ, van der Gaag LC and Abu-Hanna A. Bayesian networks in bio-
computerized tool that can be used in clinical practice to predict outcomes after medicine and health-care. Artificial Intelligence in Medicine 2004; 30: 201–14.
ESD and aid in the decision-making process. Methods: Data from 245 ESDs
performed in our institution was collected, including pre-resection patient factors
(age, sex, ASA, antithrombotics) and lesion factors (size, localization,
A38 United European Gastroenterology Journal 4(5S)
OP087 LONG-TERM OUTCOMES OF GASTRIC ENDOSCOPIC the current curative criteria for ESD and additionally underwent radical surgery.
SUBMUCOSAL DISSECTION: FOCUS ON METACHRONOUS AND The exclusion criteria were patients merely positive for horizontal margin and
NON-CURATIVE RESECTION MANAGEMENT those with a follow-up period of 53 years. The overall survival (OS) and disease-
D. Libânio1, P. Pimentel-Nunes1, L. Afonso2, R. Henrique2, M. Dinis-Ribeiro1 specific survival (DSS) were calculated according to the Kaplan-Meier method
1
Gastroenterology Department, Portuguese Oncology Institute of Porto, Porto/ and analyzed by the log-rank test. In addition, the risk factors for recurrence
Portugal were calculated using Cox proportional hazards model. The estimated factors
2
Pathology Department, Portuguese Oncology Institute of Porto, Porto/Portugal were location (lower third or the other), tumor size (430 or 30 mm), tumor
depth (submucosal invasion 500 mm (SM2) or shallower than SM2), histo-
Contact E-mail Address: [email protected] pathological type (undifferentiated or differentiated), lymphatic invasion, vascu-
Introduction: Endoscopic submucosal dissection (ESD) is an effective treatment lar invasion, ulceration (scar), positive vertical margin and lymph node
for gastric superficial neoplasms, being curative in 80–85%. Identification of risk metastasis (LNM). In this study, recurrence was defined as the metastatic one.
factors for a non-curative resection is of paramount importance to improve Results: A total of 1,064 patients were analyzed with a median follow-up period
patient selection. Furthermore, it is important to evaluate the management of 67 months. LNM was found in 89 patients (8.4%) and 14 patients (1.3%)
after an unsuccessful treatment in order to assess the clinical outcomes of each developed recurrence. All recurrent sites at the time of initial diagnosis were
option (careful surveillance or surgical treatment). Moreover, patients with an distant lymph node or other organs, no regional lymph node. Multivariate ana-
early neoplastic lesion are at risk of developing metachronous lesions and endo- lysis showed that the independent risk factors for recurrence were LNM (hazard
scopic surveillance will still be needed after endoscopic resection. The identifica- ratio [95% confidence interval] ¼ 28.2 [7.12–112], p 5 0.001) and vascular inva-
tion of risk factors for metachronous development is also important to adequate sion (4.37 [1.25–15.3], p ¼ 0.021). The 3-year and 5-year OSs were 96.8% and
surveillance. 92.6%, respectively, and the 3-year and 5-year DSSs were 99.4% and 98.8%,
Aims & Methods: The aims of this study were to identify risk factors for non- respectively.
curative resection and metachronous development and to evaluate management Conclusion: This multicenter study with the largest cohort revealed that addi-
and outcomes after non-curative resection. Methods: Single centre assessment of tional radical surgery for patients who do not meet the current curative criteria
a cohort of consecutive patients submitted to gastric ESD, with a minimum for ESD of EGC has a low recurrence rate and excellent prognosis. Submucosal
follow-up of 18 months. The Japanese Gastric Cancer Treatment Guidelines operation during ESD for EGC does not make risk of LNM and prognosis
criteria were used in clinical practice; resections were also classified according worse.
with the recently published European Society of Gastrointestinal Endoscopy Disclosure of Interest: All authors have declared no conflicts of interest.
guidelines. Univariate analysis (independent samples t-test, Mann-Whitney U
test or chi-square test as appropriate) and multivariate logistic regression were
performed to identify risk factors. Odds ratio (OR) were computed along with
95% confidence intervals (CI). Survival was analyzed with Kaplan-Meyer curves OP089 ENDOSCOPIC FULL-THICKNESS RESECTION WITH DEFECT
and log-rank test. Significance level was defined as p 5 0.05. CLOSURE IN THE STOMACH BY USING A NOVEL GRASP-AND-
Results: ESD was performed in 194 lesions (164 patients) between 2005–2014. LOOP (GAL) CLOSURE METHOD (WITH VIDEOS)
The median follow-up time was 40 months. En-bloc and complete resection rates J. Hu, P. Zhou, M. Xu, Q. Li, T. Chen
were 95.3% and 93.8%, respectively. Overall adverse events occurred in 13%. Endoscopy Center and Endoscopy Research Institute, Endoscopy Center and
Male sex, tumor size 20 mm, longer procedural time and more advanced histol- Endoscopy Research Institute, Zhongshan Hospital, Fudan University, Shanghai/
ogy in pre-resection biopsies were associated with non-curative resection China
(p 5 0.05) but only intramucosal carcinoma on pre-resection biopsies was iden-
tified as a significant risk factor on multivariate analysis (adjusted OR 3.04, 95% Contact E-mail Address: [email protected]
CI 1.02–9.06). Histological upgrade (from low-grade dysplasia to high-grade Introduction: Endoscopic full-thickness resection (EFTR) is a minimally invasive
dysplasia or from high-grade dysplasia to carcinoma) occurred in 49.5% of the method for en bloc resection of GI lesions originating from the muscularis pro-
cases. Metachronous lesions occurred in 18.4% and the incidence rate was 4.7 pria layer. Successful closure of the wall defect is a critical step.
lesions/100 person-years. The median time for metachronous detection was 24 Aims & Methods: The aim of this study was to evaluate the feasibility and efficacy
months (interquartile range 9–50.25 months). Older age at diagnosis was identi- of a novel and simplified endoscopic Grasp-and-Loop (GAL) closure method
fied as the only predictor of metachronous development in logistic regression using an endoloop assistant with a grasping forceps for defect closure. From
(OR10 years 1.68, 95% CI 1.03–2.74). Overall survival was 94.5% and 89.5% at January 2015 to March 2016, 13 patients with SMTs originating from the mus-
1 and 3 years, respectively; disease-specific survival was 99.4%, with only one cularis propria layer who underwent EFTR were enrolled in this study. After
patient dying of gastric cancer. Survival was significantly higher in patients with successful tumor resection, an endoloop was anchored onto the circumferential
curative resections (log-rank 4.538, p ¼ 0.033). In the non-curative resection margin of the gastric defect with a grasping forceps assistant and tightened gently
group, patients submitted to surgery were significantly younger (mean age (with videos). Patient characteristics, tumor size, en bloc resection, and post-
66.7  9.4 versus 73.6  7.5 in the follow-up group, p ¼ 0.037) and were less fre- operative complications were evaluated.
quently classified as ASA III/IV (23.1% versus 31.3%, p ¼ 0.62). However, sur- Results: Of the 13 lesions in the stomach, 2 were located in the greater curvature
vival was not significantly different in the two groups (log-rank 0.009, p ¼ 0.929). of mid-upper body, 11 were located in the fundus. The endoscopic GAL closure
In gastrectomy specimens, there was no residual neoplasia in 75%. Comparing method was successfully performed after EFTR in all 13 patients without laparo-
survival according to ESGE criteria, survival in patients with high-risk resection scopic assistance. The mean procedure time was 43.5 min (range 20–80 min),
was significantly worse than in patients with low-risk resection (log rank 7.539, while the GAL closure procedure took a mean of 9.4 min (range 3–18 min). The
p ¼ 0.006), while no significant differences were found in the survival of patients mean resected lesion size was 1.5 cm (range 0.5–3.5 cm). Pathological diagnosis
with low and local-risk resection (log rank 0.133, p ¼ 0.715). of these lesions were 11 gastrointestinal stromal tumors (GISTs) and 2 leiomyo-
Conclusion: The identified risk factors for non-curative resection help to improve mas. No major adverse events occurred during or after the procedure. All
patient selection for endoscopic resection and also patient information regarding patients were discharged after a mean time of 2.4 days (range 1–4 days). No
probability of success. Metachronous incidence is significant, being older patients residual lesion or tumor recurrence was found during the follow-up period
at increased risk for its development. In the non-curative resection group, survi- (median, 5 months; range, 1–15 months).
val did not differ between patients allocated to surveillance and those submitted Conclusion: The endoscopic Grasp-and-Loop closure method is feasible, effective
to gastrectomy. An individualized decision is adequate after a non-curative resec- and safe for closing the gastric defect after EFTR in patients.
tion and surveillance seems to be an adequate option in selected cases. Disclosure of Interest: All authors have declared no conflicts of interest.
Disclosure of Interest: All authors have declared no conflicts of interest.
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Oudenhove, J. Tack
Targid, KU Leuven, Leuven/Belgium

OP090 A CLINICAL STUDY OF ENDOSCOPIC FULL-THICKNESS Contact E-mail Address: [email protected]

RESECTION BY SEROSA SEALING METHOD FOR SUBMUCOSAL Introduction: Activation of gastrointestinal (GI) sweet taste receptors by caloric
INVASIVE GASTRIC CANCER WITHOUT SENTINEL NODE sweeteners such as glucose or fructose induces the secretion of GI peptides to
METASTASIS regulate food intake. The effect of non-caloric sweeteners on GI peptide secretion
and satiation is controversial. We have recently shown that motilin-induced
H. Kitakata1, T. Itoh1, S. Kinami2, S. Azukisawa1, R. Kobayashi1, K. Hamada1, gastric phase III contractions of the migrating motor complex (MMC) signal
K. Kawaura1, T. Kosaka2 hunger feelings. The mechanism underlying interruption of the MMC by specific
1
Gastoenterological Endoscopy, Kanazawa Medical University, Ishikawa/Japan sweet tastants has not yet been studied. It is conceivable that this requires sweet
2
Surgical Oncology, Kanazawa Medical University, Ishikawa/Japan taste receptor activation and accompanying changes in the release of GI peptides.
Aims & Methods: The aim was to determine the effect of caloric and non-caloric
Contact E-mail Address: [email protected] sweeteners on GI motility and GI peptide secretion as well as on hunger feelings
Introduction: Endoscopic full-thickness resection (EFTR) and laparoscopic and in healthy volunteers. The study was a randomized, double-blind, cross-over
endoscopic cooperative surgery (LECS) are useful procedures to avoid excessive trial. 12 healthy volunteers were included. Participants underwent gastroduode-
resection of the gastric wall and postoperative complications, such as stenosis or nal manometry recording for the occurrence of one phase III contraction fol-
deformity, because the location of tumor can be confirmed endoscopically to lowed by the intragastric administration of 250 mL tap water (control), or
determine an appropriate resection line. However, these methods have some equisweet caloric (50g glucose, 25g fructose) and non-caloric sweeteners
disadvantages, such as loss of endoscopic view caused by collapse of the stomach (220 mg acesulfame-K (ace-K)) dissolved in 250 mL tap water. Measurement
and peritoneal infection or tumor dissemination by outflow of gastric juice. Thus, was continued until at least one subsequent phase III occurred. Recording of
we developed new technique of EFTR, we called sealed EFTR, for sealing the antroduodenal pressures was performed using a ManoscanÕ high resolution
serosa of stomach with silicon sheet to prevent collapse of the stomach and manometry catheter. Blood samples were collected for determination of plasma
outflow of gastric juice. glucose and motilin concentrations. Visual analogue scales were used to rate
Aims & Methods: We introduce our sealed EFTR technique and describe a hunger and satiety feelings. Data were analyzed using mixed model analysis.
clinical study of EFTR in patients with submucosal invasive gastric cancer Post-hoc analyses were corrected using Bonferroni.
who were diagnosed as negative for lymph node metastasis by laparoscopic Results: Antral motility was significantly reduced in response to the caloric sweet-
sentinel lymph node biopsy. Patients: Between December 2012 and April 2016, eners (glucose: p ¼ 0.004 and fructose: p ¼ 0.010, respectively); antral motility
9 patients with clinical T1 gastric cancer, who were outside of indication of ESD, after ace-K administration did not differ significantly from placebo. Glucose
were enrolled in this study. Before surgery, written informed consent was induced a significant reduction in antral motility compared to ace-K
obtained from each patient. All procedures were conducted in accordance with (p ¼ 0.010). In contrast, duodenal motility was significantly reduced by both
the ethical standards of the institution’s Committee on Human Experimentation. the caloric as well as non-caloric sweeteners compared to placebo (glucose:
Laparoscopic sentinel node biopsy. On the day before surgery, indocyanine green p ¼ 0.043, fructose: p ¼ 0.006 and ace-K: p ¼ 0.032, respectively). The change
solution (5mg/ml) is injected at a volume of 0.2 ml into each of 4 points in the over time of plasma glucose concentrations was significantly increased after
submucosal layer around the lesion. Using an infrared fluorescence laparoscope, glucose and fructose compared to placebo administration (p ¼ 0.026 and
sentinel nodes emitting fluorescence are identified. The lymphatic basins contain- p ¼ 0.002, respectively); ace-K had no effect on plasma glucose concentrations.
ing the bright nodes are dissected laparoscopically and subjected to rapid intrao- The change over time of plasma motilin concentrations was significantly
perative pathological examination. When the sentinel lymph nodes are negative decreased after fructose (p ¼ 0.001) administration; ace-K administration
for malignancy, EFTR is performed. On the other hand, when they are positive induced no difference compared to placebo. Plasma motilin levels were signifi-
for tumor cells, standard gastrectomy with D2 lymphadenectomy is performed. cantly decreased after the caloric sweeteners compared to the non-caloric sweet-
Sealed EFTR At first, circumferential mucosal incision is performed in the same ener ace-K (glucose: p ¼ 0.005 and fructose: p ¼ 0.008, respectively). The time
manner as ESD. Continuously, silicon sheet and polyglycolic acid (PGA) sheet course of satiation scores differed significantly between glucose and ace-K
are put on the serosa of the lesion and pasted with fibrinogen, thrombin solution. (p ¼ 0.041) with a slower decrease in satiation scores after glucose compared to
Then, full-thickness incision is performed by Hook knife and/or IT knife. The ace-K administration.
tumor, silicon sheet and PGA sheet are removed through oral cavity. Finally, the Conclusion: Caloric and non-caloric sweeteners have dissociable effects on antral
defect of gastric wall is closed laparoscopically using hand-sewn sutures. but not duodenal motility; the reduction in antral motility after glucose and
Results: Seven patients (78%) were negative for sentinel node metastasis, and fructose administration parallels changes in motilin secretion. These findings
were performed EFTR. Four patients who were enrolled after 2014 were per- provide an important contribution to the current discussion about possible phy-
formed EFTR using serosa sealing method (sealed EFTR). In sealed EFTR, it siological effects of non-caloric sweeteners on appetite metabolism.
was possible to incise all-layer of the stomach with keeping good endoscopic view Disclosure of Interest: All authors have declared no conflicts of interest.
without collapse of the stomach by covering the serosa using silicon sheet and
PGA sheet. Postoperative diet intake was almost the same as before surgery. All
patients were preserved QOL without postoperative complications such as small
stomach syndrome or early satiety. During follow-up of 1 to 4 years, all patients OP092 XYLITOL AND ERYTHRITOL INDUCE SATIATION PEPTIDE
except one, who died of other cancer, are alive without recurrence or metastasis. RELEASE AND RETARDATION IN GASTRIC EMPTYING IN
Conclusion: Serosa sealing method (Sealed EFTR) was considered to be useful HEALTHY HUMANS
technique as one of the minimally invasive surgeries for lymph node negative A.C. Meyer-Gerspach1, R. Peterli2, A. Doody3, J.F. Rehfeld4, J. Drewe1,
gastric cancer, because it was possible to incise all-layer of the stomach while C. Beglinger1, B. Wölnerhanssen1
1
confirming the incision line from the inside of the stomach without exposure the Inst. Für Biomedizin, University Hospital Basel, Basel/Switzerland
2
tumor to the abdominal cavity. Department Of Surgery, St. Claraspital Basel, Basel/Switzerland
3
Disclosure of Interest: All authors have declared no conflicts of interest. Diabetes Complications Research Centre, Conway Institute University College
Dublin, Dublin/Ireland
4
Department Of Clinical Biochemistry, Rigshospitalet, University of Copenhagen,
Reference Copenhagen/Denmark
1. T. Itoh, H. Kitakata, S. Kinami, et al: New treatment strategy for submu- Contact E-mail Address: [email protected]
cosa-infiltrating gastric cancer without sentinel node metastasis: a pilot study Introduction: With the increasing prevalence of obesity and its possible associa-
of laparoscopy-assisted endoscopic full-thickness resection in an in vivo por- tion with increasing sucrose consumption, non-nutritive sweeteners are gaining
cine model. Endoscopic Forum for digestive disease 31. 1. pp.17–26; 2015. popularity. Artificial sweeteners might have adverse effects and alternative solu-
tions are sought. Polyols such as xylitol and erythritol have been known for a
long time and their beneficial effects on caries prevention and potential health
benefits in diabetic patients have been demonstrated in several studies. Incretins
such as glucagon-like peptide-1 (GLP-1) and gastrointestinal peptides such as
cholecystokinin (CCK) are released from the gut in response to food intake,
promote satiation, reduce gastric emptying (GE) and modulate glucose home-
ostasis. While glucose ingestion stimulates sweet taste receptors in the gut, and
leads to incretin and gastrointestinal peptide release, the effect of xylitol and
erythritol has not been studied.
Aims & Methods: The aim was to study gastrointestinal peptide and incretin
release as well as effects on gastric emptying in response to xylitol and erythritol
intake. The study was conducted as a randomized, double-blind, parallel-group
trial. A total of 10 healthy lean and 10 non-diabetic obese (BMI 4 30) partici-
pants were included. Subjects received intragastric equisweet loads of 50 g xylitol
or 75 g erythritol dissolved in 300 mL tap water; 75 g glucose solution and 300
A40 United European Gastroenterology Journal 4(5S)
mL tap water were control treatments. Solutions were enriched with 13C-sodium OP094 INFLAMMATORY AND ANTIOXIDANT RESPONSE
acetate (for determination of gastric emptying). We measured plasma GLP-1 and FOLLOWING STANDARD MEAL CONSUMPTION IN PATIENTS
CCK, as well as plasma insulin and glucose levels. GE was measured by a 13C- WITH FUNCTIONAL DYSPEPSIA AND HEALTHY VOLUNTEERS
sodium acetate breath test. M. Di Stefano1, B. Valvo1, M. Bergonzi1, I. Benedetti1, M. De Amici2, C. Torre2,
Results: i) xylitol and erythritol lead to a marked increase in CCK (p 5 0.001, G. Testa2, E. Pagani1, G. Marseglia2, G.R. Corazza1
respectively) and GLP-1 (p ¼ 0.001 and p 5 0.001, respectively); ii) plasma insu- 1
1st Department Of Internal Medicine, IRCCS S. Matteo Hospital Foundation,
lin and glucose are not (erythritol) or minimally (xylitol) affected; iii) xylitol and University of Pavia, Pavia/Italy
erythritol induce a significant retardation in gastric emptying rates (p 5 0.001, 2
Pediatrics, IRCCS S. Matteo Hospital Foundation, University of Pavia, Pavia/
respectively). Italy
Conclusion: There is emerging evidence to indicate a beneficial role for dietary
polyols: erythritol and xylitol are low in calories, have no or only a small effect on Contact E-mail Address: [email protected]
plasma glucose and insulin release, yet stimulate gastrointestinal satiation pep- Introduction: The Rome III criteria recognize two distinct subgroups of func-
tides. A potential therapeutic application requires further studies. tional dyspepsia (FD): the postprandial distress syndrome (PDS) and the epigas-
Disclosure of Interest: All authors have declared no conflicts of interest. tric pain syndrome (EPS). The underlying pathophysiological mechanisms of
these syndromes are partially known. Recently, the worsening of hypersensitivity
in the postprandial period was shown in PDS (1–2) and an impairment of gastric
compliance was detected in EPD (2). Moreover, in FD patients an altered per-
OP093 INFLUENCE OF LIRAGLUTIDE, A GLUCAGON-LIKE PEPTIDE- meability of intestinal mucosa, an altered expression of cell adhesion proteins and
1 ANALOG, ON HUNGER AND SATIETY, INTERDIGESTIVE the presence of mucosal infiltration of mast cells and eosinophils were shown (1),
MOTILITY, GASTRIC ACCOMMODATION AND GASTRIC suggesting a role for inflammation and permeability alterations in the pathogen-
EMPTYING IN HEALTHY VOLUNTEERS esis of this condition.
A. Rotondo, C. Morlion, A.C. Meyer-Gerspach, A. Luypaerts, E. Deloose, Aims & Methods: Our aim was the evaluation of postprandial modification of
K. Verbeke, J. Tack both inflammatory and antioxidant markers in a group of PDS patients in com-
Targid, Katholieke Universiteit Leuven, Leuven/Belgium parison with healthy volunteers (HV). 14 consecutive, non-smoking patients (9
females, mean age 42.8  11.2 yrs) affected by FD, subtype PDS, according to
Contact E-mail Address: [email protected] Rome III criteria and a group of 13 HV comparable for age and gender were
Introduction: Liraglutide (LG) was recently approved for the treatment of obe- enrolled. Chronic inflammatory and autoimmune diseases were excluded. Serum
sity. However, the mechanism by which it induces weight loss is incompletely levels of inflammatory cytokines (IL-1, IL-6 and TNF), insulin, glucose, uric
understood and involvement of altered gastrointestinal motility has been impli- acid (UA) and lipopolysaccharide (LPS) were evaluated at fast and every 30
cated. Recent studies have implicated gastric phase III of the interdigestive minutes after the ingestion of a standard meal (proteins 15.7%, lipids 28.3%,
migrating motor complex (MMC), gastric accommodation (GA) and gastric carbohydrates 56%) for a 4-hour period. The presence and severity of symptoms
emptying (GE) in the control of hunger and food intake. (abdominal pain, abdominal distension, bloating, flatulence, nausea, vomiting,
Aims & Methods: The aim of this study was to investigate the effect of LG on belching, heartburn, regurgitation, diarrhea, headache) were evaluated while
MMC, GA, GE and hunger or satiation in healthy volunteers (HVs). The study fasting and in the postprandial period by VAL.
was an open-label, crossover trial conducted in 10 lean HVs. Liraglutide Results: Mean fasting values of TNF, IL-1 and insulin were significantly higher
(VictozaÕ, Novo Nordisk, Belgium, 0.6 mg) was administered subcutaneously in PDS patients (1.62  1.21, 0.37  0.24, 15.4  10.24, respectively) in compar-
14 hours before the start of the study protocol. No administration was done in ison with HV (0.26  0.15, 0.13  0.11 and 7.45  6.08, respectively; p 5 0.05 for
the placebo arm. The study consisted of protocol 1 (MMC) and protocol 2 (GA/ all). Similarly, postprandial values of TNF, IL-1 and insulin were significantly
GE); in both protocols a high-resolution manometry probe was advanced via the higher in PDS (2.65  1.76, 0.64  0.59, 30.39  12.60, respectively) than in HV
nose to the duodenum. Protocol 1: Gastroduodenal motility was registered for (0.23  0.17, 0.19  0.11, 21.04  7.02 respectively) (p 5 0.05 for all). In FD but
the duration of 1 MMC cycle. Antral and duodenal motility index (MI) were not in HV, mean postprandial levels of TNF were significantly higher than
calculated as (number of contractions*average amplitude contractions*average fasting values (p 5 0.05). As far as the antioxidant system is concerned, mean
duration contractions)/5 min. Average MI was calculated by averaging 6 conse- postprandial values of UA were significantly higher in PDS (52.94  19.16) than
cutive antral or duodenal channels. Occurrence of antral or duodenal phase III in HV (34.46  5.61) (p 5 0.05). Serum levels of LPS and IL-6 did not show
contractions was evaluated. Protocol 2: After a stabilization period, HVs ingested significant differences between PDS and HV. As expected, only in PDS and
a liquid test meal (200 ml, 300 kcal; 89% carbohydrate, 11% protein) labeled not in HV was there a significant increase of postprandial symptoms. Finally,
with 100 mg 13C-sodium octanoate. GA was measured as the intragastric pres- the severity of symptoms was significantly correlated with the postprandial serum
sure (IGP) drop in the first 30 min after the drink and was calculated as the levels of both inflammatory and antioxidant markers.
average pressure over 5 channels in the fundus compared to baseline 5 minutes Conclusion: Our results show that in PDS the ingestion of a standard meal
before the drink. GE rates were determined from breath test samples collected induces an inflammatory response and a secondary activation of the endogenous
before the meal and at 15-min intervals for 4 hours. Occurrence of antral or antioxidant system, strictly correlated with symptom occurrence. Further studies
duodenal phases III within the 4 hours was evaluated. In both protocols feelings are needed to confirm the pathogenetic role of postprandial inflammatory
of hunger, satiation and epigastric symptoms were measured using 100 mm visual response in a condition characterized by low-grade inflammatory alterations.
analogue scales (VAS). All data are expressed as mean  SEM. Outcomes were Disclosure of Interest: All authors have declared no conflicts of interest.
analyzed using mix-model analysis (MI, IGP, symptoms), paired t-test (half GE References
time (t1/2) or chi square test (phase III occurrence and origin). p 5 0.05 was
considered significant 1. Farrè, Gastroenterology 2013.
Results: LG was well tolerated by all HVs[AR1]. Protocol 1: LG significantly 2. Di Stefano AJG 2014.
reduced the number of phase III contractions with a gastric origin from 65%
(placebo) to 5% (LG) (p ¼ 0.0001). The antral MI of both first and second phase
III contractions was significantly lower after LG (p ¼ 0.01 and 0.002 respec-
tively). Similarly, the duodenal MI was also lower after LG for both phases III OP095 A DOUBLE-BLIND, PLACEBO-CONTROLLED, CROSS-OVER
(p ¼ 0.007 and 0.005 respectively). Protocol 2: LG administration did not affect STUDY USING BACLOFEN IN THE TREATMENT OF
the IGP drop but it significantly delayed the GEt1/2 (p ¼ 0.005) (Table). In the RUMINATION SYNDROME
control condition all volunteers had a phase III within 4 hours after the meal. A. Pauwels1, C. Broers1, B. Van Houtte1, N. Rommel2, T. Vanuytsel1, J. Tack1
After LG this number decreased to 70 [AR2]% (ns). LG administration comple- 1
Clinical and Experimental Medicine, Translational Research Center For
tely switched the origin of phase III contractions with a gastric origin from 90% Gastrointestinal Disorders (targid), KU Leuven, Leuven/Belgium
(control) to 0% (LG) (p ¼ 0.0004). Antral and duodenal motility were signifi- 2
Experimentel Oto-rhino-laryngology, KU Leuven, Leuven/Belgium
cantly lower in the LG arm compared to control (p ¼ 0.002 and p ¼ 0.05, respec-
tively). Hunger or satiation ratings [JT3] were not affected by LG treatment in Contact E-mail Address: [email protected]
both protocols. Introduction: Rumination syndrome and supra-gastric belching are two condi-
tions with limited treatment options. Baclofen, a -aminobutyric acid agonist,
increases lower oesophageal sphincter (LOS) pressure. We previously demon-
strated, in an open-label study, that baclofen reduces pressure flow events in
patients with clinically suspected rumination and/or supra-gastric belching.
Parameter placebo LG p value Aims & Methods: To study the effect of baclofen in a placebo-controlled, double-
blind, cross-over study in patients with clinically suspected rumination and/or
Average IGP drop 30 min 7.7  1 6.6  0.6 0.6 supra-gastric belching. Consecutive patients with clinically suspected rumination
from the drink (mmHg) and/or supra-gastric belching were randomized in a double-blind fashion to
GE t1/2 (min) 69.6  5.1 119.4  18.4 0.005 receive baclofen (10 mg, 3 t.i.d) or placebo for 2 weeks with cross-over to the
alternative intervention after 1 week wash-out. At the end of each treatment
period, patients underwent a solid state high resolution impedance manometry
Conclusion: Acutely administered LG decreases both antral and duodenal moti- (HRiM) measurement. After positioning of the probe, 10 wet swallows were
lity during the interdigestive state and delays gastric emptying after a standard performed to assess oesophageal function. After 30 min recording, patients
liquid meal. However, at this dose it does not seem to influence gastric accom- received a 1000 kcal solid meal and recordings continued for 1 hour. Patients
modation or hunger and satiation feelings. filled out daily diaries, questionnaires at the end of each treatment period (i.e.
Disclosure of Interest: All authors have declared no conflicts of interest. overall treatment evaluation (OTE) on -3 to þ3 scale) and registered symptoms
during the HRiM using an event marker. The number of symptoms registered
and number and type of flow events during the HRiM were compared between
placebo and baclofen.
United European Gastroenterology Journal 4(5S) A41
Results: We enrolled 20 patients (mean age 42y (range 18–61), 13f). Lower oeso- MONDAY, OCTOBER 17, 2016 14:00–15:30
phageal sphincter (LOS) pressure was significantly higher in the baclofen treat- BASIC MECHANISMS IN PANCREATIC CANCER – ROOM 1.86_____________________
ment arm compared to the placebo arm (17.81.4 vs. 12.8  1.4 mmHg,
p ¼ 0.001). The number of transient LOS relaxations was lower (6  1 vs. 8  2, OP097 BCL-3 ACTS AS A PROTO-ONCOGENE IN PANCREATIC
p ¼ 0.05) and the integrated relaxation pressure was higher (11.8  1.0 vs. CANCER IN HUMANS AND MICE
8.1  1.2 mm Hg, p ¼ 0.003) after baclofen compared to placebo. The number J. Ai, S. M. Wörmann, K. N. Diakopoulos, D. Ruess, M. Lesina, H. Algül
of reflux events did not differ between both arms (4  1 vs. 3  1, NS). The Ii. Medizinische Klinik, Klinikum rechts der Isar, München/Germany
number of rumination episodes was significantly lower in the baclofen treatment
arm (15  3 vs. 9  2, p ¼ 0.018), but the number of supra-gastric belching epi- Contact E-mail Address: [email protected]
sodes was similar in both treatment groups (43  18 vs. 65  32, NS). In the Introduction: Despite numerous efforts to develop novel therapies, pancreatic
placebo arm 60% of rumination episodes were classified as primary rumination, ductal adenocarcinoma (PDAC) has remained one of the most devastating and
20% as secondary rumination and 20% as supra-gastric belch associated rumi- lethal malignancies worldwide. B-cell chronic lymphatic leukemia protein 3 (Bcl-
nation. In the baclofen arm, distribution was similar, with 66% being primary 3) is an atypical member of the ankyrin repeat-containing IB family of NF-B
rumination, 11% secondary rumination and 22% supra-gastric belch associated inhibitors that was first identified as a candidate proto-oncogene in chronic
rumination. There was no difference in straining episodes between placebo and lymphocytic leukemia. Accumulating evidence reveals that elevated Bcl-3 expres-
baclofen arm, but the percentage of straining episodes associated with rumina- sion results in increased cell proliferation, cell survival and malignant potential.
tion was significantly lower in the baclofen arm (14.64  3.84 vs. 31.29  5.96, However, the functional role of Bcl-3 in pancreatic cancer has not been eluci-
p ¼ 0.0005). The number of postprandial regurgitation symptoms marked by the dated so far. In this study, we aim to identify whether Bcl-3 impacts pancreatic
patients tended to be lower in the baclofen treatment arm (p ¼ 0.09). OTE was cancer development and progression in humans and mice.
superior after baclofen compared to placebo (1 (0–2) vs. 0 (1–0), p ¼ 0.04). Aims & Methods: PDAC tissues and cell lines obtained from humans and a
Conclusion: This study confirms that baclofen is an effective treatment option for KrasG12D mouse model (KC) of pancreatic cancer were investigated for Bcl-3
patients with rumination syndrome, probably through its effect on LOS pressure. expression. The overall survival of human PDACs expressing high and low levels
Disclosure of Interest: All authors have declared no conflicts of interest. of Bcl-3 was compared. Further, Bcl-3 was deleted in a KrasG12D mouse model
(KCB) and tumor incidence, metastases as well as proliferation, and apoptosis in
tumor tissues and primary tumor cells of KC and KCB mice were investigated.
Pancreatic Intraepithelial Neoplasia (PanIN) in KC and KCB mice at 13 and 24
OP096 GASTRIC ELECTRICAL STIMULATION (GES) FOR weeks was analyzed.
REFRACTORY VOMITING: RESULTS OF A PROSPECTIVE Results: We show that Bcl-3 is highly expressed in human PDACs and in a KC
MULTICENTER DOUBLE-BLINDED RANDOMIZED CONTROLLED mouse model of pancreatic cancer, correlating with prognosis and overall survi-
CROSS-OVER TRIAL val. Bcl-3 promotes cell growth and cell survival in vivo and in vitro. Further,
P. Ducrotté1, B. Coffin2, N. Mathieu3, S. Fontaine4, S. Bruley Des Varannes5, Bcl-3 leads to acceleration in PanIN progression, tumor development and metas-
F. Zerbib6, B. Caiazzo7, J. C. Grimaud8, F. Mion9, S. Hadjadj10, L. Vuitton11, tases in a KC mouse model of pancreatic cancer.
A. Ropert12, P. Pouderoux13, M. Dapoigny14, J. Sabate15, B. Bonaz16, Conclusion: In summary, our data provide the first insights into the function of
G. Gourcerol17, B. Guerci18 Bcl-3 in pancreatic cancer, and indicate that Bcl-3 has an important pro-tumori-
1
Rouen University Hospital, UMR 1073, Rouen/France genic role in pancreatic cancer development and progression.
2
Hopital Louis Mourier Dept. de Gastroente´rologie, Colombes Cedex/France Disclosure of Interest: All authors have declared no conflicts of interest.
3
Gastroenterology, Grenoble university hospital, Grenoble/France
4
Diabetology Unit, Toulouse University Hospital, Toulouse/France
5
Gastroenterology Department, Nantes university Hospital, Nantes/France
6
He´pato-gastroente´rologie, Hôpital Saint Andre´ - CHU de Bordeaux, Bordeaux/ OP098 INTEGRIN ALPHA5 AS A NOVEL PROGNOSTIC AND
France THERAPEUTIC TARGET IN PANCREATIC TUMOR STROMA
7
Surgery, Lille University Hospital, Lille/France P. Kuninty1, S. W.l. De Geus2, R. Bansal3, P. J.k. Kuppen4, A. Vahrmeijer5,
8
Gastroenterology, Hopital Nord, Marseille/France A. Ostman6, C. F. Sier5, J. Prakash6
9 1
Digestive Physiology, Hospices Civils de Lyon, Lyon/France University of Twente, Enschede/Netherlands
10 2
Diabetology Unit, Poitiers University Hospital, Poitiers/France Leiden University Medical Centre, Enschede/Netherlands
11 3
Franche-comte´, CHRU Jean Minjoz, Besancon/France Mira Institute, University of Twente, Enschede/Netherlands
12 4
Gastroenterology Department, Rennes University Hospital, Rennes/France Leiden University Medical Centre, Leiden/Netherlands
13 5
Caremeau Gastroente´rologie, Nimes/France Surgery, Leiden University Medical Centre, Leiden/Netherlands
14 6
Dept. De Me´decine Digestive, CH Estaing Me´decine Digestive, Clermont Oncology-pathology, Karolinska Institutet, Stockholm/Sweden
Ferrand Cedex /France
15
Dept. De Gastroenterologie, Hopital Louis Mourier, Colombes/France Contact E-mail Address: [email protected]
16
Gastroenterologie, Chu Nord He´pato-Gastroente´rologie, Grenoble Cedex /France Introduction: Pancreatic cancer is the deadliest tumor type with less than 5%
17
Dept. of Digestive Physiology, CHU Rouen Hopital C. Nicolle Dept. de survival rate, characterized by the presence of abundant stroma. Pancreatic stel-
Physiologie Digestive, Rouen Cedex/France late cells (PSCs) are the main precursor of myofibroblasts (cancer-associated
18
Diabetology Unit, nancy university hospital, nancy/France fibroblasts; CAFs) in tumor stroma and therefore become key target in pancrea-
tic tumor stroma (1). CAFs secrete growth factors, exosomes and extracellular
Contact E-mail Address: [email protected] matrix (ECM) and thereby aggravate tumor growth and metastasis (2). This is of
Introduction: Open trials have suggested that GES could be effective for the relief paramount importance to find out new targets in stromal myofibroblasts which
of refractory vomiting, associated or not with delayed gastric emptying (GE). could be used for developing novel prognostic, diagnostic and therapeutic
But, short randomized trials carried out in gastroparetic patients led to negative strategies.
results. Our aim was to perform a large multicenter randomized double-blind Aims & Methods: In this study, we investigated integrin 5 (ITGA5), a receptor
controlled trial in patients with refractory vomiting associated or not with gas- for the ECM protein fibronectin, for its prognostic and therapeutic significance
troparesis, to confirm or not the efficacy of GES. in pancreatic tumor stroma. The ITGA5 expression was investigated using
Aims & Methods: Any patient, aged 18 to 70, with chronic (412 months) refrac- immunohistochemical staining on tissue microarray consist of 137 patient sam-
tory vomiting, either idiopathic or associated with a type 1 or 2 diabetes mellitus ples of pancreatic tumors. In vivo, Panc-1 and PSCs were co-injected subcuta-
or possurgical, was eligible. After a screening period of 4 months to assess symp- neously into the flank of SCID mice and investigated the expression of ITGA5
toms prospectively, patients were implanted with an ENTERRA (R) device with versus Panc-1 tumor alone. To elucidate the role of ITGA5, we knocked down
2 electrodes sewn in the antrum. During the first month post surgery, the device the expression of ITGA5 in PSCs using shRNA-ITGA5. We investigated the
was not activated. Then each subject was randomized in a masked fashion to one phenotypic changes in ITGA5-KD PSCs after TGFb activation, using immunos-
of 2 treatment arms: 4 months ‘‘ON’’ then 4 months ‘‘OFF’’ or 4 months ‘‘OFF’’ tainings, quantitative PCR and RT2 profiler human fibrosis array. We also
then 4 months ‘‘OFF’’. During the cross-over phase, both patients and physicians examined the paracrine effect of TGF-b activated ITGA5-KD PSCs on the pro-
were blinded to the stimulation status. When the device was ‘‘ON’’, stimulation liferation of pancreatic tumor cells (Panc-1).
parameters were 14 Hz, 5mA, pulses of 330 msec. Two follow-up visits were Results: In human patient tumor samples, a total of 85% and 66% of patients
scheduled at 5 and 9 months after implantation. The primary end-points were were positive for stromal -SMA and ITGA5, respectively and well co-localized,
the vomiting score ranging from 0 (daily vomiting) to 4 (no vomiting) and the shown with double immunostaining. The ITGA5 expression was positively cor-
QoL assessed by the GIQLI score. related with -SMA in 72% patients. Overall, clinical data analysis reveals that
Results: In 19 centers, 172 patients (women:66%), 45þ/12 years old, with the overexpression of ITGA5 (log-rank p ¼ 0.022) and -SMA (log-rank
symptoms lasting from 5.1þ/5.9 years, associated with gastroparesis in 133, p ¼ 0.006) are linked to significant decreased overall survival. In vivo, in mice
were implanted. Among the 172 patients, 149 patients were evaluated at 9 co-injected with Panc-1 and PSCs showed a significant increase of tumor growth
months. Vomiting score was significantly better during the ‘‘ON’’ than during and a higher ITGA5 expression compared to Panc-1 tumors. Next, we studied
the ‘‘OFF’’ period (median score: 2 vs 1, p 5 0.001), without any carry-over the effect of ITGA5 knockdown in PSCs on their phenotypic characteristics.
effect. The greater symptomatic benefit during the ‘‘ON’’ period was observed Knockdown (60%) of ITGA5 led to a dramatic reduction of several ECM mole-
both in diabetic and non diabetic patients and was more important in case of cules and integrin receptors, shown with RT2 human profiler array. ITGA5-KD
gastroparesis (p 5 0.009) than when GE was normal (p:0.05). GE was not sig- PSCs had morphological changes, as they became flattened and lost FAK, Rac,
nificantly faster during the ‘‘ON’’ period. The greater symptomatic effect with an Cdc4 signaling, indicating the loss of lamelopodia and filopodia formation.
effective GES, was not associated with a better QoL. Furthermore, functional assays showed that ITGA5-KD PSCs had a substantial
Conclusion: An effective GES reduced significantly the frequency of refractory decrease in cell adhesion, migration (wound healing assay), proliferation and 3D
vomiting both in diabetic and non diabetic patients. spheroid formation compared to control shRNA-PSCs. Also, knockdown of
Disclosure of Interest: All authors have declared no conflicts of interest. ITGA5 abolished the tumor cell proliferation induced by TGF-b activated
PSCs. These data indicated that ITGA5 induces differentiation and phenotypic
behavior of PSCs as well as PSC-induced paracrine effects on tumor cells.
A42 United European Gastroenterology Journal 4(5S)
Conclusion: In conclusion, the present study reveals ITGA5 as a novel prognostic identified 187 miRNAs that were decreased by 5 0.87 fold in Panc-1 cells treated
and therapeutic target in pancreatic tumor stroma. These data make a strong with TGF-b compared to control. Of these, miR-622 was predicted to target
base to utilize this target for developing novel diagnostic and therapeutic state- HULC by miRanda. miR-622 expression was reduced by TGF-b by 0.5 to 0.9-
gies against pancreatic tumor. fold in a panel of pancreatic cancer cells. Overexpression of miR-622 using
Disclosure of Interest: All authors have declared no conflicts of interest. miRNA mimic significantly decreased expression of HULC, increased expression
References of E-cadherin and decreased expression of Snail, N-cadherin and Vimentin
(p 5 0.05). In addition, miR-622 overexpression significantly reduced cell inva-
1. Kuninty PR, Bojmar L, Tjomsland V, Larsson M, Storm G, Ostman A, sion and migration.
Sandström P, and Prakash J. MicroRNA-199a and -214 as potential ther- Conclusion: These findings provide mechanistic insights into EMT in pancreatic
apeutic targets in pancreatic stellate cells in pancreatic tumor. Oncotarget cancer by (a) identifying HULC as a highly induced lncRNA by TGF-b, (b)
2016, Feb 24. doi: 10.18632/oncotarget.7651.. demonstrating that HULC promotes EMT, (c) identifying that miR-622, as a
2. Prakash J. Cancer-associated fibroblasts: Perspectives in cancer therapy. down regulated miRNA by TGF-b, can target HULC, and (d) showing a func-
Trends in Cancer 2016 (in press). tional role for miR-622 in EMT via targeting HULC. These observations impli-
cate miR-622 would suppress invasion and metastasis by inhibiting EMT
signaling through targeting HULC and suggest potential strategies to inhibit
invasion and metastasis in human pancreatic cancer.
OP099 MICRORNA-622 INHIBITS EPITHELIAL-MESENCHYMAL Disclosure of Interest: All authors have declared no conflicts of interest.
TRANSITION BY TARGETING LONG NON-CODING RNA HULC IN
HUMAN PANCREATIC CANCER
K. Takahashi, Y. Ota, Y. Suzuki, H. Iwamoto, K. Yamakita, Y. Kitano,
Y. Makino OP100 ESSENTIAL ROLE OF THE NON-RECEPTOR TYROSINE-
Division Of Metabolism and Biosystemic Science, Department Of Internal PHOSPHATASE PTPN11/SHP-2 IN ORGAN DEVELOPMENT AND
Medicine, Asahikawa Medical University, Asahikawa/Japan HOMEOSTASIS OF THE MURINE EXOCRINE PANCREAS
D. Ruess, H. Algül
Contact E-mail Address: [email protected] Ii. Med. Klinik, TU Munich, Klinikum rechts der Isar, Munich/Germany
Introduction: Transforming growth factor (TGF)-b-induced epithelial-mesenchy-
mal transition (EMT) is a trigger of invasion and metastasis in pancreatic cancer. Contact E-mail Address: [email protected]
Although long non-coding RNAs (lncRNAs), which are defined as non-coding Introduction: The Src-homology-2 (SH2) domain containing protein tyrosine
RNAs (ncRNAs) more than 200 nucleotides in length, have been implicated in phosphatase SHP-2 is expressed ubiquitously and is involved in an array of
disease pathogenesis, their contributions to pancreatic cancer are not well under- intracellular signal transduction processes (Ras-Raf-MAPK, JAK-STAT,
stood. Recently, the inter-relationship between two classes of ncRNA, Pi3K-Akt-mTOR, NFB,...). Thus, for instance, SHP-2 plays a role in cellular
microRNAs (miRNAs) and lncRNAs, has been reported to contribute to the responses to growth factors (PDGF, EGF, FGF, IGF-1,...), cytokines (IL6, IL3,
epigenetic regulation of gene expression in several cancers. IL5, GM-CSF,...) and extracellular matrix (via integrins, focal adhesion com-
Aims & Methods: Our aims were to investigate the involvement and functional plex). Via these pathways SHP2 mediates transcriptional regulation of mitogenic
roles of TGF-b induced lncRNA during EMT and reveal contributions of the activation, cell proliferation, survival, differentiation, migration and metabolism.
inter-relationship between the TGF-b induced lncRNA and miRNA to the reg- The role of SHP-2 in organ development and homeostasis of the pancreas has so
ulatory mechanisms of EMT in human pancreatic cancer. We used human pan- far not been explored.
creatic cancer (Panc-1, BxPC-3, MiaPaCa-2, QGP-1 and KP-3) and non- Aims & Methods: Mouse models with pancreas specific deletion of SHP-2 (Ptf1a-
malignant pancreatic ductal epithelial (hTERT-HPNE) cells. Expression profil- Creex1/Ptpn11fl/fl) with or without mutated Kras (LSL-KrasG12D) and/or lineage
ing of 90 lncRNAs and 2565 miRNAs were performed using qPCR and miRNA tracing allele (ACTB-TdTomato;-EGFP) were used for analysis.
microarray. miRNA targets were predicted by miRanda. Cells were treated with Results: Early embryologic Deletion of SHP-2 in the pancreas via Ptf1a-Cre
10 ng/ml of TGF-b for 72 hours to induce EMT. siRNA or miRNA mimic were preserves organ architecture and endocrine function. However, adequate expan-
used to modulate RNA expression. Cell viability was assessed by MTS assay and sion of the exocrine compartment in the growing pancreas is impaired. In adult
trypan blue. Cell invasion and migration were examined by transwell and wound mice, organ weight is reduced by about 50%, compared to unrecombined litter-
healing assay. Expression of RNA was assessed by qPCR and of protein by mate-controls. In the organ growth phase, (centro-)acinar cells display enhanced
Western blot. cell death (necrosis and apoptosis) which is accompanied by markedly reduced
Results: LncRNA expression profiling identified 22 lncRNAs that were induced proliferation. In aged SHP-2
panc mice acinar lobuli are consecutively replaced
by TGF-b in Panc-1 cells by 41.4-fold. Of these, HULC was amongst the top by adipocytes. Lineage-tracing experiments provide insight into the origin of this
most significantly up-regulated. HULC expression was induced by TGF-b by 1.5 cell population (invasion vs. transdifferentiation) and will be presented.
to 2.7-fold in a panel of pancreatic cancer cells and up-regulated by 2.4 to 8.9- Interestingly, introduction of mutated Kras (LSL-KrasG12D) into the model
fold in pancreatic cancer cells compared to hTERT-HPNE cells. In Panc-1 cells, fully compensates for the deletion of SHP-2. Finally, in the pancreas, we not
knockdown of HULC by siRNA significantly increased expression of E-cadherin only observe an essential role of SHP2 in adequate activation of the RTK-Ras-
and decreased expression of N-cadherin, Snail and Vimentin (p 5 0.05). Raf-MEK-ERK-signaling axis but also in positive regulation of RTK-expression
Moreover, siRNA to HULC decreased cell viability, invasion and migration. levels.
Furthermore, to identify miRNAs that can target HULC and suppress EMT, Conclusion: The central role of the non-receptor tyrosine phosphatase SHP-2 in
miRNA microarray and bioinformatics analysis were performed. Microarray organ development and homeostasis of the murine pancreas is linked to the
RTK-Ras-Raf-MEK-ERK-signaling axis. SHP-2 is essential for adequate trans-
mission of growth factor signals and thereby influences proliferation and survival
of the acinar cell.
Disclosure of Interest: All authors have declared no conflicts of interest.
United European Gastroenterology Journal 4(5S) A43
Aims & Methods: Here we describe several applicable tools, using live cell and
OP101 RELA CONTROLS KRAS-DRIVEN PANCREATIC time-lapse microscopy, co-cultures of tumour cells or ex vivo PDAC xenograft
CARCINOGENESIS BY MEDIATING ONCOGENE-INDUCED tissues with freshly isolated dorsal root ganglia (DRG), primary DRG neurons
SENESCENCE VIA THE CXCL1/KC/CXCR2 AXIS and F11 hybridoma neurons to investigate the reciprocal interaction at the
D. Kabacaoglu1, S. M. Wörmann1, J. Morton2, K. N. Diakopoulos1, tumour cell-nerve interface.
H. Einwächter1, M. Heikenwälder3, H. Algül1, M. Lesina1 Results: To study the invasion of tumour cells along neurites we have combined
1
Ii. Medizinische Klinik, Klinikum rechts der Isar der TU München, München/ 3D co-culture assays of dorsal root ganglia (DRG) and tumour cells with time-
Germany lapse microscopy and specifically track the unidirectional movement of indivi-
2
Beatson Institute for Cancer Research, Glasgow/United Kingdom dual tumour cells along neurites extending from DRGs. Quantification of the
3
Chronic Inflammation and Cancer, German Cancer Research Center, Heidelberg/ dynamic process revealed that neuronal scaffolds provide the infrastructure for
Germany an accelerated and consistent migration of tumour cells towards the DRG as the
source of chemotactic gradients. In another approach, using explanted PDAC
Contact E-mail Address: [email protected] xenograft tissues instead of tumour cell colonies, it occurred that neurite out-
Introduction: The IKK/NF-B pathway has been shown to be a crucial mediator growth from DRGs is skewed towards the tumour tissue. Thus, neurites facing
of tumour growth and progression, exhibiting both tumour-promoting and the tumour were more elongated than neurites at the opposite site of the DRG,
tumour-suppressive properties. How IKK/NF-B possesses these opposite activ- suggesting that tumour gradients stimulate and/or attract neurite outgrowth and
ities during tumor development remains elusive. elongation. In support of a tumour-derived chemotactic effect, supernatants
Aims & Methods: In this study, we aimed to elucidate mechanisms by which from different tumour cell lines displayed varying neurotrophic effects on the
IKK/NF-B mediates its tumorigenic functions in pancreatic carcinogenesis. outgrowth of freshly isolated primary neurons in transwell assays. In order to
To determine the role of RelA/p65, the functional subunit, which is responsible gain a more dynamic representation on how neurites explore a chemoattractant
for the transcriptional activity of NF-B, we used a mouse model of pancreatic gradient, F11 hybridoma neurons were co-cultured with PDAC cell lines in
ductal adenocarcinoma (PDAC). We generated compound mutants KrasG12D separate patches divided by a 500 mm gap. These assays use time-lapse imaging
mice with specific deletion of the p65 gene in the pancreas. Pancreata were and endpoint analysis in order to track the locomotion of individual neurite
investigated histologically and biochemically. extensions, monitor their outgrowth from neurons and elongation towards the
Results: Our data clearly demonstrate a dual role of NF-B/RelA activation in tumour cell front, and allow to quantitate length, velocity, forward migration
pancreatic carcinogenesis. In early stages of tumorigenesis, the tumor-suppressive index, and directness of each protruding trajectory in response to different
function of NF-B is beneficial because it controls oncogene-induced senescence PDAC cell lines. Moreover, the extent of growth cone formation and collapse
(OIS) by regulating the CXCL1/KC-CXCR2 axis. However, as soon as OIS is can be scored by determining dynamic changes in circumferential size and area of
bypassed during late stages of tumorigenesis, NF-B supports tumor progression growth cones.
by enhancing proliferation of the transformed pancreatic cancer cells. Conclusion: These in vitro and ex vivo models emulate several important aspects
Conclusion: Examining these context-dependent activities of RelA will be impor- of nerve-tumour interactions and allow pharmacological or gain and loss-of-
tant for effective clinical use of NF-kB inhibitors. Furthermore, these findings function manipulations. In addition, semi- to fully-automated quantification
underscore that caution should be exercised, when exploring the use of pharma- for high-throughput screening may offer investigators reliable tools to test
ceuticals targeting the CXCR2 receptor as a therapeutic option for the treatment their candidate target genes or drugs.
of various solid tumors. Disclosure of Interest: All authors have declared no conflicts of interest.
Disclosure of Interest: All authors have declared no conflicts of interest.
References MONDAY, OCTOBER 17, 2016 15:45–17:15
1. Ling J, Kang Y, Zhao R, Xia Q, Lee DF, Chang Z, Li J, Peng B, Fleming JB, FUTURE DRUGS IN IBD – ROOM C_____________________
Wang H, et al. KrasG12D-induced IKK2/beta/NF-kappaB activation by IL-
1alpha and p62 feedforward loops is required for development of pancreatic OP103 SELECTIVE IL-23 INHIBITION BY RISANKIZUMAB
ductal adenocarcinoma. Cancer Cell 2012; 21(1): 105–20. MODULATES THE MOLECULAR PROFILE IN THE COLON OF
2. Maier HJ, Wagner M, Schips TG, Salem HH, Baumann B and Wirth T. ACTIVE CROHN’S DISEASE PATIENTS
Requirement of NEMO/IKKgamma for effective expansion of KRAS-
S. Visvanathan1, P. Baum2, R. Vinisko1, R. Schmid2, W. Boecher3, S. Padula3,
induced precancerous lesions in the pancreas. Oncogene 2013; 32(21): 2690–5.
A. Salas4, J. S. Fine1, J. Panés4
3. Maniati E, Bossard M, Cook N, Candido JB, Emami-Shahri N, Nedospasov 1
N/a, Boehringer Ingelheim Pharmaceuticals Inc., Ridgefield/United States of
SA, Balkwill FR, Tuveson DA and Hagemann T. Crosstalk between the
America
canonical NF-kappaB and Notch signaling pathways inhibits Ppargamma 2
Boehringer Ingelheim Pharma GmbH & Co. KG, Biberach/Germany
expression and promotes pancreatic cancer progression in mice. The Journal 3
Boehringer Ingelheim Pharma GmbH & Co. KG, Ingelheim/Germany
of Clinical Investigation 2011; 121(12): 4685–99. 4
Hospital Clinic Barcelona, IDIBAPS, CIBERehd, Barcelona/Spain
4. Maeda S, Kamata H, Luo JL, Leffert H and Karin M. IKKbeta couples
hepatocyte death to cytokine-driven compensatory proliferation that pro- Contact E-mail Address: [email protected]
motes chemical hepatocarcinogenesis. Cell 2005; 121(7): 977–90. Introduction: IL-23 contributes to the activation, maintenance and proliferation
5. Luedde T, Beraza N, Kotsikoris V, van Loo G, Nenci A, De Vos R, of Th17 cells, and the IL-23 pathway has been implicated in the pathogenesis of
Roskams T, Trautwein C and Pasparakis M. Deletion of NEMO/ Crohn’s disease (CD). Risankizumab is a humanized IgG1 monoclonal antibody
IKKgamma in liver parenchymal cells causes steatohepatitis and hepatocel- that binds the p19 subunit of IL-23 and inhibits binding of IL-23 to its receptor.
lular carcinoma. Cancer Cell 2007; 11(2): 119–32. In a Phase II trial (NCT02031276), risankizumab was more effective than pla-
6. Chien Y, Scuoppo C, Wang X, Fang X, Balgley B, Bolden JE, Premsrirut P, cebo for inducing clinical and endoscopic remission in patients with active CD
Luo W, Chicas A, Lee CS, et al. Control of the senescence-associated secre- through 12 weeks.
tory phenotype by NF-{kappa}B promotes senescence and enhances chemo- Aims & Methods: We investigated the underlying mechanism of risankizumab in
sensitivity. Genes Dev 2011; 25(20): 2125–36. this Phase II trial by characterising the molecular profile in the colon and/or
7. Morton JP, Timpson P, Karim SA, Ridgway RA, Athineos D, Doyle B, ileum tissue in a subset of patients with CD, who received either 200 mg (n ¼ 26),
Jamieson NB, Oien KA, Lowy AM, Brunton VG, et al. Mutant p53 drives 600 mg (n ¼ 27) risankizumab or placebo (n ¼ 26). From each patient, 6–9 biopsy
metastasis and overcomes growth arrest/senescence in pancreatic cancer. samples were obtained from inflamed lesions in the colon or ileum at baseline and
Proc Natl Acad Sci U S A 2010; 107(1): 246–51. at 12 weeks post-treatment. Biopsy samples from ileum and from colon were
separately analysed by transcriptome-wide RNA-Seq profiling. Univariate asso-
ciations were assessed using linear regression. Effect size, p-values and FDR were
calculated for significant genes. CDEIS response (450% reduction from base-
OP102 MODELLING TUMOR CELL NERVE INTERACTIONS IN line) and CDEIS remission (4; for patients with isolated ileitis of 2) were
PANCREATIC CANCER evaluated at Week 12 by an independent blinded reviewer.
A. Göhrig1, K. M. Detjen2, A. Behm1, A. Dumoulin3, H. Schmidt3, F. Results: Risankizumab treatment significantly decreased the expression of 1146
G. Rathjen3, M. Welzel1, B. Wiedenmann2, C. Fischer1 genes from baseline to Week 12 in the colon tissue of CD patients vs placebo
1
, Experimental and Clinical Research Center, a joint cooperation between the (p 5 0.05). Of note, risankizumab treatment was associated with a significant
Charite´ Medical Faculty and the Max-Delbrück Center for Molecular Medicine, reduction in the expression of genes associated with the IL-23 pathway (IL-
Berlin, Germany, Berlin/Germany 23A, IL-26, IL-21R, IL-17A, STAT3), innate immunity (IL6, IL7, IL7R, IL8,
2
Medizinische Klinik Mit Schwerpunkt Hepatologie Und Gastroenterologie, ICAM1, IL1, IL11, IL13RA2, IL15RA, IL18R1, TNF), tissue turnover (S-
Campus Virchow-klinikum, Charite´-Universitätsmedizin Berlin, Germany, Berlin/ 100A8, A9, A12, MMP1, MMP3, MMP9, MMP12, ADAM8, ADAM12,
Germany ADAM33) and solute carrier family (SLC11A1, SLC1A3, SLC2A3, SLC2A6,
3
Max-Delbrück Center for Molecular Medicine, Berlin, Germany, Berlin/Germany SLC6A14, SLC7A11, SLC7A5). These overall changes in gene expression in the
risankizumab-treated cohort reflected the molecular changes observed in patients
Contact E-mail Address: [email protected] achieving CDEIS response and remission at Week 12. A comparison of gene
Introduction: Neural invasion (NI) has emerged as a key pathologic feature of expression changes in the colon significantly modulated by risankizumab at
pancreatic ductal adenocarcinoma (PDAC) and represents a distinct route of Week 12 vs anti-TNF treatment at Week 14 in a published patient cohort high-
tumour cell spread independent from lymphatic and haematogenous tumour lighted larger decreases in suppression of pathways associated with epithelial
cell dissemination. NI is associated with an unfavourable course of the disease biology (cell–cell adhesion, morphogenesis, intracellular signal transduction,
and also constitutes a major cause of neuropathic pain, thus limiting the quality second messenger signalling) following risankizumab treatment. In contrast, no
of life. NI is considered as a mutual interaction between tumour cells and nerves significant changes were observed in the molecular profile in the ileum from
and involves both, the unidirectional tracking and invasion of tumour cells along patients treated with risankizumab vs placebo from baseline to Week 12.
neural routes but also implicates tumour mediated changes in neural plasticity Conclusion: The superior efficacy observed with risankizumab in active CD
resulting in nerve hypertrophy and increased nerve density in PDAC. patients at Week 12 was associated with significant molecular changes in the
A44 United European Gastroenterology Journal 4(5S)
colon of CDEIS responding patients. The molecular profile appears to be differ- was observed in the primary randomized maintenance population, but small
entiated from anti-TNF treatment. sample sizes (UST n ¼ 46; PBO n ¼ 24) precluded definitive conclusions. In the
Disclosure of Interest: S. Visvanathan: Sudha Visvanathan: Employee of larger post-hoc pooled maintenance population (Table 1b), consistent trends in
Boehringer Ingelheim. support of UST maintenance, especially UST 90 mg q8w, were observed across
P. Baum: Patrick Baum: Employee of Boehringer Ingelheim. endoscopic endpoints at Wk44.
R. Vinisko: Richard Vinisko: Employee of Boehringer Ingelheim. Conclusion: The endoscopy substudy primary endpoint was met; a single IV dose
R. Schmid: Ramona Schmid: Employee of Boehringer Ingelheim. of UST induced significantly greater reduction in endoscopic disease activity vs
W. Boecher: Wulf Boecher: Employee of Boehringer Ingelheim. PBO, despite a relatively early evaluation at Wk8. Results in the small primary
S. Padula: Steven Padula: Employee of Boehringer Ingelheim. randomized maintenance population were supported by the larger post-hoc
A. Salas: Azucena Salas: Grants from Boehringer Ingelheim. pooled maintenance population; greater proportions of subjects receiving UST
J.S. Fine: Jay S. Fine: Employee of Boehringer Ingelheim. maintenance, especially UST 90 mg q8w, achieved maintenance endoscopic end-
J. Panés: Julián Panés: Personal fees from Boehringer Ingelheim, during the points vs PBO. Together, these data support the efficacy of UST in inducing &
conduct of the study; personal fees from Abbvie, Galapagos, Genentech maintaining endoscopic healing of the mucosa in CD.
Roche, Pfizer, Takeda, TiGenix and Topivert, outside the submitted work. Disclosure of Interest: P. Rutgeerts: Investigator for Janssen Research and
Development, LLC
C. Gasink: Employee of Janssen Research and Development, LLC
D. Chan: Employee of Janssen Research and Development, LLC
OP104 EFFICACY OF USTEKINUMAB FOR INDUCTION AND Y. Lang: Employee of Janssen Research and Development, LLC
MAINTENANCE OF ENDOSCOPIC HEALING IN PATIENTS WITH P. Pollack: Employee of Janssen Research and Development, LLC
CROHN’S DISEASE S. Hanauer: Investigator for Janssen Research and Development, LLC
P. Rutgeerts1, C. Gasink2, D. Chan2, Y. Lang2, P. Pollack3, S. Hanauer4, D. Wolf: Investigator for Janssen Research and Development, LLC
D. Wolf5, D. Jacobstein3, J. Johanns2, P. Szapary2, B.G. Feagan6, W. Sandborn7 D. Jacobstein: Employee of Janssen Research and Development, LLC
1
University of Leuven, Leuven/Belgium J. Johanns: Employee of Janssen Research and Development, LLC
2
Janssen Research and Development, LLC, Spring House/United States of P. Szapary: Employee of Janssen Research and Development, LLC
America/PA B.G. Feagan: Investigator for Janssen Research and Development, LLC
3
Janssen Research and Development, LLC, Spring House/United States of W. Sandborn: Investigator for Janssen Research and Development, LLC
America
4
Feinberg School of Medicine, Chicago/United States of America
5
Atlanta Gastroenterology Associates, Atlanta/United States of America
6
Robarts Clinical Trials Inc., Robarts Res Inst, U of Western Ont, London, ON/ OP105 FILGOTINIB, A SELECTIVE JAK1 INHIBITOR, INDUCES
Canada CLINICAL REMISSION IN PATIENTS WITH MODERATE-TO-
7
UCSD, La Jolla/United States of America SEVERE CROHN’S DISEASE: FINAL ANALYSIS OF THE PHASE 2
FITZROY STUDY
Contact E-mail Address: [email protected] S. Vermeire1, S. Schreiber2, R. Petryka3, T. Kuehbacher4, X. Hebuterne5,
Introduction: Ustekinumab (UST) has been shown to induce & maintain clinical X. Roblin6, M. Klopocka7, A. Goldis8, M. Wisniewska Jarosinska9,
response & remission in 2 induction (UNITI-1&2) & 1 maintenance (IM-UNITI) A. Baranovsky10, R. Sike11, K. Stoyanova12, C. Tasset13, A. Van Der Aa13,
trials in moderate-severe Crohn’s disease (CD). A substudy evaluated the efficacy P. Harrison13
of UST in the induction & maintenance of endoscopic healing. 1
Department Of Gastroenterology, University Hospitals Leuven, Leuven/Belgium
Aims & Methods: Patients in the substudy had up to 3 colonoscopy evaluations 2
UKSH, Universität Kiel UKSH Medizinische Abt. I, Kiel/Germany
(i.e. at UNITI-1 or 2 baseline [BL] and Wk8, and IM-UNITI Wk44) in 5 ileo- 3
Gastroenterol., NZOZ Vivamed, Warszawa, Poland, Warsaw/Poland
colonic segments (i.e. ileum, right colon, transverse colon, left colon, rectum) 4
Dept Of Gastroenterology, Asklepios Wet Hospital Clinic of Internal Medicine,
within the 52-Wk study period. A single central reader blindly scored all video Hamburg/Germany
endoscopies for ulcerations and simplified endoscopic activity score for CD 5
Hepatogastroenterology and Clinical Nutrition, Hospital Arche 2, Nice/France
(SES-CD). At induction Wk0, patients received a single IV dose (UST 130 mg, 6
Gastroenterology Dept, North Hospital, Saint Priez en Jarez/France
UST 6 mg/ kg, or PBO). At maintenance Wk0 (i.e. induction Wk8), UST induc- 7
Jan Biziel University Hospital #2, Bydgoszcz/Poland
tion responders [Primary randomized maintenance population] were re-rando- 8
Dept. Of Gastroenterology, Dr Goldis Center, Timisoara/Romania
mized to subcutaneous (SC) PBO, UST 90 mg every 12 wks (q12w), or UST 9
Santa Llc, Santa Familia Research, Prevention and Treatment Centre, Lodz/
90 mg every 8 wks (q8w). For the 3 non-randomized maintenance groups: Poland
(1)UST induction non-responders received SC UST 90 mg, then continued SC 10
City Clinical Hospital, St Petersburg/Russian Federation
UST 90 mg q8w if CDAI decreased 100 after 8wks; (2)PBO induction nonre- 11
St. Margit Hospital, Budapest/Hungary
sponders received UST IV 130 mg, then continued SC UST 90 mg q12w if CDAI 12
PSI CRO, Sofia/Bulgaria
decreased 100 after 8wks; and (3)PBO induction responders received PBO 13
Galapagos, Mechelen/Belgium
throughout. Patients with SES-CD 3 (i.e. ulceration in any segment) at induc-
tion BL were eligible for analysis. The primary endpoint was change in SES-CD Contact E-mail Address: [email protected]
from BL at induction Wk8 in the integrated UST group (data across induction Introduction: Filgotinib is an oral, selective Janus kinase 1 (JAK1) inhibitor,
studies & dose groups) vs PBO. Efficacy at IM-UNITI Wk44 was evaluated in which has demonstrated high efficacy in patients with rheumatoid arthritis.
the primary randomized maintenance population and the post-hoc pooled main- This 20-week Phase 2 study was designed to evaluate the efficacy and safety of
tenance population (i.e. randomized & nonrandomized IM-UNITI populations filgotinib in patients with active Crohn’s disease (CD).
combined). Additional induction & maintenance endpoints included clinically Aims & Methods: 174 patients with moderate-to-severe CD (CDAI: 220 to 450,
meaningful endoscopic improvement, endoscopic response, endoscopic remission endoscopic evidence of active disease) were randomized 3:1 to receive 200 mg
& mucosal healing; in both combined and individual treatment groups. filgotinib (FIL) or placebo (PBO) QD for 10 weeks. Based on Week 10 clinical
Results: The substudy primary endpoint was met, as UST induced significantly response, patients continued to receive filgotinib (200 mg or 100 mg QD) or
greater reduction in SES-CD from BL at Wk8 vs PBO. Results were similar by placebo for an additional 10 weeks. Patients who demonstrated clinical response
induction study & UST dose. Other induction endoscopic endpoints also con- (CDAI-100) underwent corticosteroid tapering after Week 10. Anti-TNF-naı̈ve
sistently favored UST vs PBO (Table 1a). At IM-UNITI Wk44, trends for as well as anti-TNF non-responders were included. Immunosuppressants were to
greater efficacy with UST vs. PBO maintenance, especially UST 90 mg q8w, be discontinued prior to treatment initiation. Final data for the primary endpoint
of clinical remission (CDAI 5 150) at Week 10 are presented.
Results: Baseline characteristics were comparable in both groups, including mean
Table 1a: Induction Week 8 (UNITI-1&2) disease duration (8.3 y), mean CDAI score (293), mean CRP (15.6 mg/L, 41% 4
10 mg/ L), oral corticosteroids (51%, mean daily dose 21.6 mg/day). Primary
PBO (N ¼ 97) UST (N ¼ 155) endpoint of the study was met: Filgotinib induced clinical remission in 47% of
x
the patients, compared to 23% in placebo recipients (p ¼ 0.0077), and led to
SES-CD Change from BL, mean (SD) 0.7 (4.97) 2.8 (8.10)*
improvement in PRO2 score, and quality of life (IBDQ changes from baseline)
Clinically meaningful endoscopic improvement1 29.9% 47.7%* compared to placebo (table 1). Numerically more patients on filgotinib normal-
Endoscopic Response2 13.4% 20.6% ized CRP (FIL:27%, PBO:14%) and showed an improvement of at least 50% in
Endoscopic Remission3 4.1% 7.7% SES-CD endoscopy score (FIL:25%, PBO:13.6%), Histopathology overall total
Mucosal Healing4 4.1% 9.0% score was decreased more significantly in the filgotinib group compared to pla-
(Table 1b) Maintenance Week 44 (IM-MUNITI) cebo (p 5 0.05).
PBO 90 mg q12w 90 mg q8w
(N ¼ 51) (N ¼ 47) (N ¼ 74) Table 1: Key efficacy parameters
SES-CD Change from BL, mean (SD) 2.0 (5.35) 1.5 (4.22) 3.8 (6.02)
Placebo filgotinib
Clinically meaningful endoscopic improvement1 27.5% 29.8% 48.6%* Variable/unit/population n ¼ 44 n ¼ 128 p-value
Endoscopic Response2 4.2% 5.9% 24.1%*
Endoscopic Remission3 9.8% 12.8% 20.3% Clinical remission 23 47 0.0077
Mucosal Healing4 9.8% 12.8% 21.6% (CDAI 5 150), %, ITT-NRI
PRO2, mean change from 15.6 21.9 0.0321
*P 50.05 xPrimary endpoint 1SES-CD reduction 3 from induction BL 2SES- baseline, ITT-LOCF
CD reduction 50% from induction BL 3SES-CD total score 2 4Complete 17.6 33.8 0.0045
absence of ulcers (continued)
United European Gastroenterology Journal 4(5S) A45
Table 1 Continued 8 included Inflammatory Bowel Disease Questionnaire (IBDQ) remission (total
score 170) and IBDQ response (16-point increase from baseline). For binary
Placebo filgotinib endpoints, the comparison of tofacitinib 10 mg BID vs PBO was assessed using
Variable/unit/population n ¼ 44 n ¼ 128 p-value the Cochran-Mantel-Haenszel (CMH) chi-square test stratified by study, prior
TNFi treatment, corticosteroid use at baseline and geographic region. Within
Total IBDQ score, mean change each subgroup, the CMH chi-square test stratified by study was used.
from baseline, ITT-LOCF Results: At Wk 8, significantly more pts achieved remission, mucosal healing and
SES-CD improvement by at 13.6 25 NS clinical response with tofacitinib 10 mg BID vs PBO (all p 5 0.0001, Table). The
least 50%, %, ITT-LOCF difference generally remained significant regardless of prior TNFi exposure, prior
overall total histopathology –0.6 –3.5 0.0359 TNFi failure, reason for TNFi failure (primary or secondary) or disease severity
score, mean change from (based on baseline Mayo score 9 or 59; Table). For all three endpoints, greater
baseline, ITT-LOCF effects were observed when comparing secondary vs primary TNFi failure sub-
populations and baseline Mayo score 59 vs baseline Mayo score 9. IBDQ
CDAI: Crohn’s Disease Activity Index; ITT: Intent-to-treat; NRI: Non-respon- remission and response were significantly greater with tofacitinib 10 mg BID
der imputation; LOCF: Last observation carried forward; PRO2: Patient vs PBO at Wk 8 regardless of prior TNFi exposure/prior TNFi failure.
Reported Outcome ¼ 7x (mean daily number of liquid or very soft stools) þ Conclusion: Tofacitinib demonstrated efficacy vs PBO, regardless of prior TNFi
7x (mean daily abdominal pain score); IBDQ: Inflammatory Bowel Disease therapy in pts with moderately to severely active UC. PRO results were similar in
Questionnaire; SES-CD: Simple Endoscopic Score for Crohn’s Disease; pts with/without prior TNFi exposure or failure.
Histopathology score ¼ Adaptation from histopathology score D’haens
Overall, filgotinib was safe and well tolerated. Similar incidences in early dis- Table: Summary of efficacy endpoints in OCTAVE Induction 1 and OCTAVE
continuations, SAEs and AEs including infections were observed, with the major- Induction 2 at Wk 8
ity of the SAEs related to worsening of CD. An increase in mean haemoglobin
concentration was observed, without difference between filgotinib and placebo. Tofacitinib
No clinically significant changes from baseline in mean neutrophil counts or liver Placebo Difference
function tests were observed. Filgotinib showed a favourable lipid profile with an 10 mg BID N ¼ 905 N ¼ 234 (95% CI)
increase in HDL and no change in LDL, resulting in an improved atherogenic
index. Remission, n (%)i 159 (17.6) 14 (6.0) 11.6 (7.7, 15.5)***
Prior TNFi exposurea 60 (12.3) 1 (0.8) 11.5 (8.2, 14.8)***
No prior TNFi exposureb 99 (23.7) 13 (12.5) 11.2 (3.7, 18.8)*
Conclusion: Inhibition of JAK1 with filgotinib induces clinical remission, sup-
ported by CRP, endoscopy and histopathology results, and improves quality of Prior TNFi failurec 53 (11.4) 1 (0.8) 10.6 (7.3, 13.9)**
life in patients with moderate to severe CD. The efficacy and safety data of No prior TNFi failured 106 (24.1) 13 (11.8) 12.3 (5.0, 19.5)*
filgotinib suggest a favourable risk/benefit profile, showing its potential as an Prior TNFi failure (primary 19 (7.5) 1 (1.4) 6.2 (2.0, 10.3)*
oral treatment with a novel mechanism of action for the treatment of CD. non-responder)e
Disclosure of Interest: S. Vermeire: Grant support: Abbvie, MSD, Takeda Prior TNFi failure (secondary 31 (16.6) 0 (0.0) 16.6 (11.2, 21.9)*
Lectures: Abbvie, MSD, Takeda, Ferring, Falk Pharma, Hospira, Tillotts non-responder)f
Consultancy: Abbvie, MSD, Takeda, Ferring, Genentech/Roche, Shire, Pfizer,
Galapagos, Mundipharma, Hospira, Celgene, Second Genome, J&J Baseline Mayo score 59g 91 (28.3) 6 (7.3) 21.0 (13.5, 28.5)***
S. Schreiber: Paid consultancies to AbbVie, Galapagos, Pfizer, Takeda Baseline Mayo score 9h 68 (11.7) 8 (5.3) 6.4 (2.0, 10.8)*
T. Kuehbacher: Advising and /or speaking fees for Abbvie Takeda MSD Shire Mucosal healing, n (%)i 271 (29.9) 32 (13.7) 16.3 (11.0, 21.6)***
Falk Prior TNFi exposurea 112 (23.0) 8 (6.2) 16.8 (11.2, 22.4)***
X. Hebuterne: Educational activities: ARARD, Abbvie, Ferring, MSD, Nutricia
Educational activities and consultancy: Takeda Member of board: Janssen, No prior TNFi exposureb 159 (38.1) 24 (23.1) 15.1 (5.7, 24.4)*
Fresenius-Kabi Prior TNFi failurec 103 (22.2) 8 (6.5) 15.7 (10.0, 21.4)***
X. Roblin: MSD, Abbvie, Takeda, Hospira, Janssen, Theradiag No prior TNFi failured 168 (38.2) 24 (21.8) 16.4 (7.4, 25.3)*
M. Klopocka: Payment for lectures/ Royalty- Abbvie, Alvogen, Takeda, Polish Prior TNFi failure (primary 38 (15.0) 5 (6.8) 8.3 (1.0, 15.5)NS
Foundation for Gastroenterology Travel/accommodations/ meeting expenses non-responder)e
Ferring, Alvogen, Abbvie, Polish Foundation for Gastroenterology
K. Stoyanova: employee of PSI Pharma Support Ltd Prior TNFi failure (secondary 57 (30.5) 2 (4.7) 25.8 (16.7, 34.9)**
C. Tasset: employee of Galapagos NV non-responder)f
A. Van der Aa: employee of Galapagos NV Baseline Mayo score 59g 145 (45.2) 17 (20.7) 24.4 (14.1, 34.8)***
P. Harrison: employee of Galapagos NV Baseline Mayo score 9h 126 (21.6) 15 (9.9) 11.7 (5.9, 17.5)*
All other authors have declared no conflicts of interest. Clinical response, n (%)i 521 (57.6) 72 (30.8) 26.8 (20.1, 33.5)***
Prior TNFi exposurea 254 (52.0) 29 (22.3) 29.7 (21.3, 38.2)***
No prior TNFi exposureb 267 (64.0) 43 (41.3) 22.7 (12.2, 33.2)***
OP106 TOFACITINIB HAS INDUCTION EFFICACY IN MODERATELY Prior TNFi failurec 237 (51.0) 29 (23.4) 27.6 (18.9, 36.3)***
TO SEVERELY ACTIVE ULCERATIVE COLITIS, REGARDLESS OF No prior TNFi failured 284 (64.5) 43 (39.1) 25.5 (15.3, 35.6)***
PRIOR TNF INHIBITOR THERAPY
Prior TNFi failure (primary 116 (45.8) 19 (25.7) 20.2 (8.5, 31.9)*
G. R. D’Haens1, B. E. Sands2, W.J. Sandborn3, T. Hibi4, C. Su5, non-responder)e
W. Niezychowski5, S. Ghosh6, H. Zhang5, D. Yu5, D. Woodworth5, P. Healey7,
Prior TNFi failure (secondary 102 (54.5) 9 (20.9) 33.6 (19.5, 47.7)**
A. Marren5, J. Panés8
1 non-responder)f
Dept Of Gastroenterology, Academic Medical Centre, Amsterdam/Netherlands
2
Janowitz Division Of Gastroenterology, Icahn School of Medicine at Mount Sinai, Baseline Mayo score 59g 205 (63.9) 30 (36.6) 27.3 (15.6, 39.0)***
New York/United States of America/NY Baseline Mayo score 9h 316 (54.3) 42 (27.8) 26.5 (18.3, 34.7)***
3
Division Of Gastroenterology, University of California, San Diego/United States
of America/CA
4
Kitasato Institute Hospital, Kitasato University, Tokyo/Japan Full analysis set, non-responder imputation NSNot significant; *p 5 0.05;
**
5
Pfizer Inc, Collegeville/United States of America/PA p 5 0.001; ***p 5 0.0001 vs placebo 95% confidence interval was based on
6
University of Calgary, Calgary/Canada/AB normal approximation for the difference in binomial proportions aN ¼ 488 for
7
Pfizer Inc, Groton/United States of America/CT tofacitinib 10 mg BID and N ¼ 130 for placebo; bN ¼ 417 for tofacitinib 10 mg
8
Hospital Clı´nic Barcelona, IDIBAPS, CIBERehd, Barcelona/Spain BID and N ¼ 104 for placebo;cN ¼ 465 for tofacitinib 10 mg BID and N ¼ 124
for placebo; dN ¼ 440 for tofacitinib 10 mg BID and N ¼ 110 for placebo;
e
Contact E-mail Address: [email protected] N ¼ 253 for tofacitinib 10 mg BID and N ¼ 74 for placebo; fN ¼ 187 for tofaci-
Introduction: Tofacitinib is an oral, small molecule JAK inhibitor that is being tinib 10 mg BID and N ¼ 43 for placebo; gN ¼ 321 for tofacitinib 10 mg BID and
investigated for ulcerative colitis (UC). Two Phase 3 randomised placebo (PBO)- N ¼ 82 for placebo; hN ¼ 582 for tofacitinib 10 mg BID and N ¼ 151 for placebo;
i
controlled studies (OCTAVE Induction 1, NCT01465763; OCTAVE Induction statistical significance based on the Cochran-Mantel-Haenszel chi-squared test
2, NCT01458951) demonstrated efficacy of tofacitinib 10 mg twice daily (BID) vs stratified by study, prior treatment with tumour necrosis factor inhibitors, corti-
PBO as induction therapy for patients (pts) with moderate to severe UC.1 costeroid use at baseline and geographic region BID, twice daily; CI, confidence
Aims & Methods: We investigated the effect of prior tumour necrosis factor interval; TNFi, tumour necrosis factor inhibitor; Wk, week
inhibitor (TNFi) therapies or disease activity (baseline Mayo score) on clinical Disclosure of Interest: G.R. D’Haens: Study-related disclosures: Dr D’Haens
efficacy endpoints and patient-reported outcomes (PROs) in pooled data from received speaker fee from and is an advisor for Pfizer Inc
OCTAVE Induction 1 and 2. Adults with moderately to severely active UC B.E. Sands: Grant(G), Personal Fee(P), NonFinancial:Pfizer G, P:Amgen,
(baseline Mayo score 6, rectal bleeding subscore 1 and endoscopic subscore MedImmune, Celgene, Millennium, Prometheus, AbbVie, Takeda, Janssen,
2) and prior failure/intolerance to 1 of corticosteroids, thiopurines or TNFi BMS P:BI, Salix, Luitpold, Shire, Lilly, TiGenix, Immune, Arena, Akros,
were randomised (4:1) to receive tofacitinib 10 mg or PBO BID for up to 9 weeks Forward, Theravance, Receptos, Vedanta, Synergy, Topivert
(wks). Efficacy endpoints at Wk 8 included: remission (primary endpoint; Mayo W.J. Sandborn: Study-related disclosures: Dr Sandborn received grant support,
score 2, no subscore 41 and rectal bleeding subscore of 0), mucosal healing at personal fees and non-financial support from Pfizer during the conduct of the
Wk 8 (Mayo endoscopic subscore 1), clinical response (decrease from baseline study; grant support from Pfizer
Mayo score of 3 points and 30%, plus decrease in rectal bleeding subscore 1 T. Hibi: Grants, personal fees: Mitsubishi Tanabe Pharma, Ajinomoto Phama,
or absolute subscore 1). All endoscopic scores were read centrally. PROs at Wk JIMRO, Zeria Pharma Grants: Abbvie Personal fees: Eizai, Takeda Pharma
A46 United European Gastroenterology Journal 4(5S)
C. Su: Employee and shareholder: Pfizer Inc OP108 SAFETY AND EFFICACY OF LONG-TERM TREATMENT WITH
W. Niezychowski: Employee and shareholder: Pfizer Inc OZANIMOD, AND ORAL S1P RECEPTOR MODULATOR, IN
S. Ghosh: Consultant: Abbott, Pfizer Inc, Merck, Shire, Centocor, BMS MODERATE TO SEVERE ULCERATIVE COLITIS: TOUCHSTONE
Research grants: Merck, Abbott Lectures: Abbott, Merck, Shire, Millenium, EXTENSION
Centocor and Ferring Development of educational presentation: Abbott. W.J. Sandborn1, B.G. Feagan2, G. R.a.m. D’Haens3, S. Hanauer4, D. Wolf5,
H. Zhang: Employee and shareholder: Pfizer Inc S. Vermeire6, S. Ghosh7, A. Olson8, H. Smith8, M. Cravets8, P. A. Frohna8,
D. Yu: Employee and shareholder: Pfizer Inc R. Aranda8
D. Woodworth: Employee and shareholder: Pfizer Inc 1
University of California, San Diego/United States of America
P. Healey: Employee and shareholder: Pfizer Inc 2
Robarts Clinical Trials Inc., Robarts Research Institute, University of Western
A. Marren: Employee and shareholder: Pfizer Inc Ontario, London, ON/Canada
J. Panés: Consultant: Pfizer Inc 3
Academic Medical Center, Amsterdam/Netherlands
4
Reference Feinberg School of Medicine, Chicago/United States of America
5
Atlanta Gastroenterology Associates, Atlanta/United States of America
1. Sandborn WJ et al. J Crohns Colitis 2016;10 (S1):S15, Abstract OP19. 6
Dept. Of Gastroenterology, University Hospital Leuven, Leuven/Belgium
7
Division of Gastroenterology, Department of Medicine, University of Calgary,
Calgary/Canada
8
Celgene, Summit/United States of America
OP107 CLINICAL DISEASE ACTIVITY INFLUENCES THE
THERAPEUTIC EFFICACY OF THE TOLL LIKE RECEPTOR-9 Contact E-mail Address: [email protected]
AGONIST COBITOLIMOD IN PATIENTS WITH MODERATE TO Introduction: Ozanimod (RPC1063) is an oral, selective sphingosine 1-phosphate
SEVERE ACTIVE ULCERATIVE COLITIS (S1P) 1 and 5 receptor modulator in clinical development for the treatment of
R. Atreya1, L. Peyrin-Biroulet2, W. Reinisch3, F. Scaldaferri4, C. Admyre5, Inflammatory Bowel Disease (ulcerative colitis [UC] and Crohn’s disease) and
T. Knittel5, J. Kowalski5, M.F. Neurath6, C.J. Hawkey7 relapsing multiple sclerosis. The objective of the open-label extension (OLE) of
1
Medical Department 1, University Erlangen-Nuremberg, Erlangen/Germany the TOUCHSTONE trial is to evaluate the long-term efficacy and safety of daily
2
Department Of Gastroenterology, Nancy University Hospital, Vandoeuvre les 1 mg ozanimod in patients with moderate to severe UC who had initially parti-
Nancy/France cipated in the TOUCHSTONE trial.
3
Dep. of Internal Medicine Iv, Division Of Gastroenterology and Hepatology, Aims & Methods: A total of 197 patients were randomized (1:1:1) and treated
Medizin. Universität Wien Abt. für Innere Medizin III, Wien/Austria with daily ozanimod at 0.5 mg, 1 mg (n ¼ 67), or placebo in the TOUCHSTONE
4
Internal Medicine, Gastroenterology Division, Ibd Unit, Catholic University of trial. Of the initial 197 patients randomized 170 (86%) entered the OLE and
Rome Dept. of Internal Medicine Dept. of Gastroenterology, Roma/Italy received daily 1 mg ozanimod with 109 (64%) remaining in the OLE as of the
5
Index Pharmaceuticals, Stockholm/Sweden data cut-off (March 2016). At the data cut-off, all remaining patients had
6
Department Of Medicine 1, University of Erlangen-Nuremberg, Erlangen/ received treatment in the OLE for  1 year.
Germany Results: At entry into the OLE, the partial Mayo Score (pMS) for patients on
7
Queen’s Medical Centre, University of Nottingham Nottingham Digest. Disease placebo, ozanimod 0.5 mg, and 1.0 mg was 4.6, 4.5, and 3.3 respectively. At the
Centre Queen’s Medical Centre, Nottingham/United Kingdom time of the data-cut in the OLE, the pMS had improved in all groups (1.7, 1.7,
and 1.9) at Week 44. The greatest improvement was reported in patients who
Contact E-mail Address: [email protected] received placebo or ozanimod 0.5 mg in the TOUCHSTONE trial with a change
Introduction: In the COLLECT study the Toll like receptor (TLR-) 9 agonist in pMS at Week 44 of –2.6, –2.7 and –1.3 in the placebo, 0.5 mg and 1 mg groups.
cobitolimod (formerly known as DIMS0150, KappaproctÕ) was evaluated for its Improvement occurred rapidly, in the first 4 to 8 weeks of the OLE. The greatest
therapeutic efficacy in ulcerative colitis (UC) patients refractory to conventional improvement was reported for patients who received placebo or ozanimod 0.5
therapy. mg in the TOUCHSTONE trial with a change in pMS at Week 4 of –1.8, –1.5
Aims & Methods: In this post hoc analysis the therapeutic effects were analysed and –0.8 and a change in pMS at Week 8 of –2.4, –1.9 and –1.1 in the placebo, 0.5
with respect to disease activity of the patients at baseline. Cobitolimod was mg and 1 mg groups. At the Week 44 visit in the OLE, 119/131 (90.9%) had little
studied in a randomized, double blind, placebo-controlled, multicentre, pan- or no active disease based on the physician global assessment (PGA 0 or 1), 129/
European trial named COLLECT in 131 patients with moderate to severe 131 (98.4%) had little or no blood in their stools (rectal bleeding subscore [RBS]
active ulcerative colitis. Patients were on mandatory steroid therapy and could 0 or 1), 111/131 (84.7%) had no blood in the stools (RBS 0), and 105/131 (80.2%)
be taking sulphasalazine, aminosalicylates, or thiopurines at stable doses. had little or no increase in their number of stools (Stool Frequency subscore of 0
Patients were randomly assigned to receive two single doses of cobitolimod (30 or 1). The most common adverse events (AEs) (42.0%) during OLE were UC
mg) or placebo (in a 2:1 ratio) topically through the endoscope to the inflamed flare, anemia, upper respiratory tract infection, nasal pharyngitis, back pain,
mucosa at baseline (week 0) and after 4 weeks (week 4). For this post-hoc arthralgia, headache, alanine aminotransferase (ALT) or aspartate aminotrans-
analysis efficacy was studied using the secondary endpoint symptomatic remis- ferase (AST) elevation. The only serious AEs in 2 patients were anemia, and
sion (SR) (absence of blood in stool and mean weekly stools 5 35) at week 4, 8 ulcerative colitis flare. ALT and AST 4 3x upper limit of normal occurred in 4
and 12. As endoscopic examination was performed at week 4 and 12 sympto- (2.4%) of the 170 patients in the OLE. All elevations were asymptomatic,
matic remission in combination with mucosal healing (MH) defined as endo- 55xULN, transient, and resolving while receiving continued treatment.
scopic Mayo score of  1 were assessed at week 4 and 12. Disease activity was Conclusion: Long-term treatment with ozanimod continues to be safe and well
measured using the CAI score, which ranges from 0–23. In the FAS (full analysis tolerated with good compliance and evidence of durable efficacy.
set) population 28% of the patients had moderate disease (CAI ¼ 9), 46% had Disclosure of Interest: W.J. Sandborn: William J. Sandborn receives financial
moderate to severe disease setting (CAI ¼ 10–11), while 26% had severe disease support for research and consultancy fees from Celgene, Inc.
(CAI  12) at baseline. B.G. Feagan: Brian G. Feagan receives consulting fees from Celgene, Inc.
Results: In the moderate UC patient population (CAI ¼ 9) symptomatic remis- G.R.A.M. D’Haens: Geert D’Haens receives consulting fees from Celgene, Inc.
sion was achieved in 50/64/59% of the cobitolimod vs. 15/23/23% of placebo- S. Hanauer: Stephen Hanauer receives consulting fees from Celgene, Inc.
treated patients at week 4/8/12, respectively. In the moderate to severe UC D. Wolf: Douglas Wolf receives financial support for research and consulting
patient population (CAI ¼ 10–11) symptomatic remission was evident in 32/40/ fees from Celgene, Inc.
46% of the cobitolimod vs. 15/35/40% in placebo-treated patients at week 4/8/ S. Vermeire: Severine Vermeire receives consulting fees from Celgene, Inc.
12, respectively. In the severe UC patient population (CAI ¼ 12 and more) 14/31/ S. Ghosh: Subrata Ghosh receives consulting fees from Celgene, Inc.
22% of the cobitolimod vs. 10/20/30% of the placebo-treated patients showed A. Olson: Allan Olson is an employee of Celgene, Inc.
symptomatic remission at week 4/8/12. With respect to the endpoint sympto- H. Smith: Heather Smith is an employee of Celgene, Inc.
matic remission plus mucosal healing the patients with moderate disease M. Cravets: Matt Cravets is an employee of Celgene, Inc.
showed remission rates of 32/40% for cobitolimod vs. 8/8% for placebo-treated P.A. Frohna: Paul A. Frohna is an employee of Celgene, Inc.
patients at week 4/12, respectively. In patients with moderate to severe disease R. Aranda: Richard Aranda is an employee of Celgene, Inc.
rates for SR plus MH were 22/35% in the cobitolimod vs. 0/35% in placebo-
treated patients at week 4/12, respectively. In patients with severe disease these
rates were 9/18% in the cobitolimod vs. 0/20% in placebo-treated patients for MONDAY, OCTOBER 17, 2016 15:45–17:15
week 4/12, respectively. NON-BLEEDING EMERGENCIES OF THE OESOPHAGUS – ROOM
Conclusion: The results of the COLLECT study demonstrate that the TLR-9 E1_____________________
agonist cobitolimod is able to induce clinical remission in UC patients both
with moderate and severe disease activity. The concept of TLR-9 activation OP109 SELF ASSEMBLING PEPTIDE MATRIX FOR THE PREVENTION
represents a promising and well-tolerated novel therapeutic option for ulcerative OF ESOPHAGEAL STRICTURE AFTER ENDOSCOPIC RESECTION:
colitis patients with active disease and warrants further trials. A RANDOMIZED CONTROLLED TRIAL IN A PORCINE MODEL
Disclosure of Interest: R. Atreya: Consultancy for Index Pharmaceuticals M. Barret1, B. Bordaçahar1, F. Beuvon2, B. Terris2, M. Camus1, R. Coriat1,
L. Peyrin-Biroulet: Consultancy for Index Pharmaceuticals S. Chaussade1, F. Batteux3, F. Prat1
W. Reinisch: Consultancy for Index Pharmaceuticals 1
Gastroenterology, Cochin Hospital, Assistance Publique- Hôpitaux de Paris,
F. Scaldaferri: Consultancy for Index Pharmaceuticals Paris/France
C. Admyre: Employment at and stock options of Index Pharmaceuticals 2
Pathology, Cochin Hospital, Assistance Publique- Hôpitaux de Paris, Paris/
T. Knittel: Consultancy for and share holding of Index Pharmaceuticals France
J. Kowalski: Consultancy for and share holding of Index Pharmaceuticals 3
Immunology, Cochin Hospital, Assistance Publique- Hôpitaux de Paris, Paris/
M.F. Neurath: Consultancy for Index Pharmaceuticals France
C.J. Hawkey: Consultancy for Index Pharmaceuticals
Contact E-mail Address: [email protected]
Introduction: Esophageal stricture formation after extensive endoscopic resection
remains a major limitation of endoscopic therapy for early esophageal neoplasia.
United European Gastroenterology Journal 4(5S) A47
We assessed a recently developed self-assembling peptide matrix as a wound 2. Isomoto H, Yamaguchi N, Nakayama T, Hayashi T, Nishiyama H, Ohnita
dressing after endoscopic resection for the prevention of esophageal stricture. K, et al. Management of esophageal stricture after complete circular endo-
Aims & Methods: Ten pigs were randomly assigned to the self-assembling peptide scopic submucosal dissection for superficial esophageal squamous cell carci-
RADA-16 (4 [Arg-Ala-Asp-Ala]) or the control group after undergoing a 5 cm noma. BMC Gastroenterology 2011; 11: 46.
long circumferential endoscopic submucosal dissection of the lower esophagus. 3. Yamaguchi N, Isomoto H, Nakayama T, Hayashi T, Nishiyama H, Ohnita
Esophageal diameter on endoscopy and esophagogram, weight variation, and K, et al. Usefulness of oral prednisolone in the treatment of esophageal
histological measurements of fibrosis, granulation tissue, and neoepithelium stricture after endoscopic submucosal dissection for superficial esophageal
were assessed in each animal. squamous cell carcinoma. Gastrointestinal Endoscopy 2011; 73: 1115–21.
Results: The rate of esophageal stricture at day 14 was 40% in the group treated 4. Hanaoka N, Ishihara R, Takeuchi Y, Uedo N, Higashino K, Ohta T, et al.
with self-assembling peptide vs. 100% in the control group (p ¼ 0.04). Median Intralesional steroid injection to prevent stricture after endoscopic submu-
(IQR) esophageal diameter at day 14 was 8 mm (2.5–9) in the self-assembling cosal dissection for esophageal cancer: a controlled prospective study.
peptide group vs. 4 mm (3–4) in the control group (p ¼ 0.13). The median (IQR) Endoscopy 2012; 44: 1007–11.
stricture indexes on esophagograms at day 14 were 0.32 (0.14–0.48) and 0.26 5. Sato H, Inoue H, Kobayashi Y, Maselli R, Santi EG, Hayee B, et al. Control
(0.14–0.33) in treated and control groups, respectively (p ¼ 0.42). Median of severe strictures after circumferential endoscopic submucosal dissection
(IQR) weight variation during the study was þ0.2 (7.4; þ1.8) and 3.8 for esophageal carcinoma: oral steroid therapy with balloon dilation or bal-
(5.4; þ0.6) in the treated and control groups, respectively (p ¼ 0.9). No differ- loon dilation alone. Gastrointestinal Endoscopy 2013; 78: 250–7.
ences were observed between the groups in terms of histological outcomes. All 6. Nonaka K, Miyazawa M, Ban S, Aikawa M, Akimoto N, Koyama I, et al.
animals eventually developed esophageal strictures at day 28. Different healing process of esophageal large mucosal defects by endoscopic
Conclusion: The application of a self assembling peptide matrix on esophageal mucosal dissection between with and without steroid injection in an animal
wounds after circumferential endoscopic submucosal dissection is safe and fea- model. BMC Gastroenterology 2013; 13: 72.
sible, and prevents early esophageal stricture occurence in our model. 7. Zuercher BF, George M, Escher A, Piotet E, Ikonomidis C, Andrejevic SB,
Disclosure of Interest: All authors have declared no conflicts of interest. et al. Stricture prevention after extended circumferential endoscopic mucosal
resection by injecting autologous keratinocytes in the sheep esophagus.
Surgical Endoscopy 2013; 27: 1022–8.

OP110 INTRALESIONAL STEROID INJECTION COMBINED WITH

ORAL STEROID ADMINISTRATION TO PREVENT ESOPHAGEAL MONDAY, OCTOBER 17, 2016 15:45–17:15
STRICTURE AFTER ENDOSCOPIC SUBMUCOSAL DISSECTION OF HOT TOPICS IN ERCP – ROOM K_____________________
LESION NO LESS THAN A HALF OF CIRCUMFERENCE
M. Xu, Y. Chu, C. Zhang OP111 CLINICAL UTILITY OF SINGLE OPERATOR
Endoscopy Center and Endoscopy Research Institute, Zhongshan Hospital of CHOLANGIOSCOPY USING SPYGLASSTM DS COMPARED WITH
TM
Fudan University, Shanghai/China SPYGLASS LEGACY – RESULTS FROM A LARGE MULTI-
NATIONAL REGISTRY
Contact E-mail Address: [email protected] J.H. Moon1, M. K. Ramchandani2, A. Maydeo3, T. Itoi4, R. Rerknimitr5,
Introduction: Endoscopic submucosal dissection (ESD) is becoming an important D. Seo6, J. Y. w. Lau7, M.K. Goenka8, A. Aljebreen9, S. Niaz10, J. Lee11,
and main therapy for early esophagus carcinoma or precancerous lesion. T. Ang12, N. Q. Nguyen13, J. Reichenberger14, R. Sud15, R. Kochhar16,
However, stricture ofter occurs when the mucosal defects created by ESD are B. Devereaux17, I. Yasuda18, A. J. Kaffes19, M. Kitano20
larger than a half of circumference. It’s an urgent task to find out a safe and 1
Soon Chun Hyang University Bucheon Hospital, Bucheon/Korea, Republic of
effecient method to prevent stenosis. 2
Asian Institute of Gastroenterology, Hyderabad/India
Aims & Methods: To investigate the safety and efficiency of local steroid injection 3
Baldota Institute of Digestive Science Global Hospital, Mumbai/India
combined with oral steroid administration in preventing esophageal stricture 4
Tokyo Medical University, Tokyo/Japan
after ESD of esophagus carcinoma or precancerous lesion which are no less 5
King Chulalongkorn Memorial Hospital, Bangkok/Thailand
than a half of circumference. A single-center randomized controlled trial was 6
Gastroenterology, Asan Medical Center, Seoul/Korea, Republic of
designed to examine the effects and safety of intralesional steroid injection com- 7
Prince of Wales Hospital, Shatin/Hong Kong Prc
bined with oral steroid administration in preventing stricture after esophageal 8
Apollo Gleneagles Hospital, Kolkata/India
ESD. 43 patients with mucosal defects no less than a half of circumference 9
King Khalid University Hospital, Riyadh/Saudi Arabia
following esophageal ESD were randomized to receive intralesional triamcino- 10
Civil Hospital Karachi, Karachi/Pakistan
lone injection immediately after ESD and oral prednisone administration for 11
Samsung Medical Center, Seoul*/Korea, Republic of
consecutive 12 weeks, which starting at a dose of 30 mg daily, tapered gradually 12
Changi General Hospital, Singapore/Singapore
at a speed of 5 mg in every two weeks (n ¼ 20, treatment group) or to be treated 13
Royal Adelaide Hospital, Adelaide/Australia/SA
conventionally (n ¼ 23, control group). The primary endpoint was the frequency 14
Netcare Unitas Hospital, Centurion/South Africa
of stricture. Secondary endpoints were the number of balloon dilatation, rate of 15
Medanta, the Mediciti, Gurgaon/India
other complications and hospital stays. 16
Postgraduate Institute of Medical Education & Research, Chandigarh/India
Results: The frequency of stricture (20% vs. 69.6%) and the number of balloon 17
Royal Brisbane and Women’s Hospital, Brisbane/Australia/QLD
dilatation (mean 0.5 vs. 1.3) were less in treatment group, and the former one had 18
Teikyo University Mizonokuchi Hospital, Kawasaki/Japan
a significant difference. The hospital stays and rate of complications were similar 19
Royal Prince Alfred Hospital, Sydney/Australia/NSW
between two groups. One patient suffered perforation of stomach in the treat- 20
Kinki University School of Medicine, Osaka/Japan
ment group, which was not a direct result of steroid injection or ESD.
Contact E-mail Address: [email protected]
Frequency of stricture formation, number of endoscopic balloon dilations Introduction: Addition of single operator cholangioscopy (SOC) to endoscopic
(EBDs) performed, hospital stays after ESD and other complications in two retrograde cholangiography (ERC) may improve diagnostic accuracy and
groups. increase therapeutic efficiency in bile duct diseases. Indications for SOC, proce-
dural success and impact on subject management are investigated in a multi-
Treatment Control national prospective registry.
group group Aims & Methods: SOC registry using the SpyGlassTM Legacy (Spy Legacy) or
(n ¼ 20) (n ¼ 23) p-value new SpyGlass DSTM (Spy DS) system and SpyBiteTM biopsy forceps (Boston
Scientific Corp, Marlboro, MA, USA) at 20 centers in 10 countries. The registry
Frequency of stricture, n (%) 5(20) 16(69.6) 0.004* was not designed as a comparative study. Procedural success defined as: Group
Number of EBDs, n mean  SD 0.5  1.1 (0–3) 1.3  2.0 (0–8) 0.241 A: Indeterminate strictures/filling defects: ability to visualize lesions, provide
(range) visual impression of malignancy, and, when applicable, obtain biopsies adequate
Perforation by procedure, n per 1/30 (3.7) 0/53(0) 0.361 for histology. Group B: Biliary stones: ability to achieve stone clearance in one or
session (%) more SOC procedures. Group C: Other indications: ability to establish diagnosis
and/or complete therapy as intended.
Bleeding by procedure, n per 0/30(0) 1/53(1.9) 1.0 Results: Total of 504 patients (pts) have completed primary endpoint informa-
session (%) tion, 207 (41%) pts using Spy DS. Average age 61 years, 54% male. Indications
Hospital stays after ESD, days 4.1  4.4 (1–22) 3.3  2.0 (1–8) 0.469 for SOC were Group A in 278 (55%) pts, Group B in 190 (38%) pts and Group C
mean  SD (range) in 62 (12%) pts, principally including pre-operative assessment of tumor margins
(20), confirmation of stone clearance (15), selective guidewire placement (8),
*Significant difference extraction of migrated stent (5) assessment of cause of occluded self-expanding
metal stent (3), unexplained hemobilia (3), dilated left hepatic duct (2), and
Conclusion: Intralesional steroid injection combined with oral steroid adminis- presence of residual IPNB after photodynamic therapy (1). Investigators rated
tration appears to be safe and effective in preventing esophageal stricture follow- image quality as ‘‘Excellent or Good’’ in 98% Spy DS cases and 78% of Spy
ing ESD of lesions no less than a half of circumference. Legacy cases (P 5 0.0001). Procedural success was reached in 504 (84%) proce-
Disclosure of Interest: All authors have declared no conflicts of interest. dures overall, namely in 279 (85%) procedures in Group A, 190 (82%) in Group
B, and 56 (89%) in Group C. Thirteen (7%) pts in Group B required 2 or more
SOC procedures to reach stone clearance. Failures were inability to provide
References
impression of malignancy (31 Group A), intraductal biopsies not yielding deter-
1. Ono S, Fujishiro M, Niimi K, Goto O, Kodashima S, Yamamichi N, et al. minate histopathology (8 Group A), inability to reach stone clearance (33 Group
Predictors of postoperative stricture after esophageal endoscopic submucosal B), inability to assess ductal tumor (3 Group C) and failed guidewire placement
dissection for superficial squamous cell neoplasms. Endoscopy 2009; 41: (3 Group C). Overall procedural success trended to be higher in Spy DS than in
661–5. Spy Legacy group namely 86% (178/207) versus 82% (244/297) (p ¼ 0.262). SOC
A48 United European Gastroenterology Journal 4(5S)
altered diagnosis/therapy and/or influenced management in 417 (85%) pts. OP114 RECTAL INDOMETHACIN MAY NOT DECREASE THE
Malignant visual impression as a predictor for malignant pathology of SpyBite INCIDENCE OF POST-ERCP PANCREATITIS IN CONSECUTIVE
biopsies is better for Spy DS than Spy Legacy (p ¼ 0.014). Adverse events in 7 PATIENTS: A META-ANALYSIS OF RANDOMIZED AND
(1%) pts: 2 mild pancreatitis, 2 mild and 1 moderate cholangitis, 1 moderate CONTROLLED TRIALS
bleeding and 1 micro perforation. Y. Feng1, U. Navaneethan2, S. Varadarajulu3, R. Hawes2, M. Hasan2, A. Yang1
Conclusion: SOC, especially using Spy DS, has high procedural success and 1
Gastroenterology, Peking Union Medical College Hospital, Beijing/China
provides important impact on diagnosis, therapy and/or management in a wide 2
Center For Interventional Endoscopy, Florida Hospital, Orlando/United States of
range of indications, with excellent safety profile. America/FL
Disclosure of Interest: All authors have declared no conflicts of interest. 3
Center For Interventional Endoscopy, Florida Hospital Orlando, Orlando/United
States of America/FL
Contact E-mail Address: [email protected]
OP113 PROPOSAL OF A MACROSCOPIC CLASSIFICATION FOR Introduction: Data on the efficacy of prophylactic rectal indomethacin to prevent
TISSULAR LESIONS OF THE BILE DUCT DETECTED DURING post-ERCP pancreatitis in consecutive patients is inconsistent. We therefore con-
PER ORAL CHOLANGIOSCOPY (POCS) ducted a meta-analysis of high-quality randomized clinical trials specifically
C. Robles-Medranda1, M. Soria2, M. Valero1, M. Puga1, H. Alvarado1, studying rectal indomethacin in prevention of post-ERCP pancreatitis in conse-
J. Ospina1, H. Pitanga Lukashok1 cutive patients.
1
Endoscopy, Instituto Ecuatoriano de Enfermedades Digestivas-IECED-University Aims & Methods: Relevant studies for the meta-analysis were identified through
Hospital Omni, Guayaquil/Ecuador search of MEDLINE, EMBASE and Cochrane Central Register of Controlled
2
Endoscopy, Instituto Ecuatoriano de Enfermedades Digestivas - IECED, Trials databases. Randomized controlled clinical trials employing rectal indo-
Guayaquil/Ecuador methacin for the prevention of post-ERCP pancreatitis were included. The pri-
mary outcome was the overall rates of post-ERCP pancreatitis.
Contact E-mail Address: [email protected] Results: A total of 2473 patients from 6 studies were included. The incidence of
Introduction: The macroscopic aspects to determine malignancy of the bile duct post-ERCP pancreatitis across all 2473 patients was 7% (95% CI, 6%–9%). We
during per oral cholangioscopy (POCS) are: presence of irregular surface with found that there was no significant difference in overall rates of post-ERCP
bleeding and drooling or tortuous vessels. For benign lesions the typical aspects pancreatitis in consecutive patients between rectal indomethacin and placebo
are lesions with smooth surface ‘‘without vessels or mass’’. However, many mis- (OR, 0.67; 95% CI, 0.46–1.00, p ¼ 0.050). There was also no difference in rates
diagnosis are made due to a lack of correlation between the macroscopic aspects of moderate to severe (OR, 0.66; 95% CI, 0.28–1.56, p ¼ 0.345) or mild (OR,
and histology. Moreover, masses are many times benign, and reported data 0.71; 95% CI, 0.45–1.10, p ¼ 0.127) post-ERCP pancreatitis between indometha-
shows 78% of sensitivity for visual impression diagnosing malignancy. cin and placebo.
Aims & Methods: Propose a macroscopic classification of bile duct tissular lesions Conclusion: In a contemporary meta-analysis of available randomized controlled
for differentiation between benign and malignant lesions. trials of consecutive patients undergoing ERCP, rectal indomethacin did not
A retrospective study from Sept-2013 to Sept-2015 was made at our institution in show significant prevention effect of post-ERCP pancreatitis.
patients evaluated by POCS (using SpyGlassÕ legacy and DS). Inclusion criteria: Disclosure of Interest: U. Navaneethan: Udayakumar Navaneethan is a consul-
tissular lesions detected by POCS. Exclusion criteria: absence of histology con- tant for AbbVie, Janssen and Takeda.
firmation (either biopsy or surgical resection for malignancy) and/or absence of S. Varadarajulu: Shyam Varadarajulu is a consultant for Boston Scientific and
POCS at 6 months follow-up (for benign lesions). To determine the macroscopic Olympus.
classification all patients’ records were evaluated. 315 images were analyzed and R. Hawes: Robert Hawes is a consultant for Olympus and Boston Scientific.
classified as benign or malignant by an expert with more than 140 POCS cases, All other authors have declared no conflicts of interest.
and compared to histology. Based on the morphological and vascular pattern the References
lesions were classified as follows:
Benign lesions: Type 1 ‘‘Villous pattern’’ (micronodular or villous pattern with- 1. Sotoudehmanesh R, Khatibian M, Kolahdoozan S, et al. Indomethacin may
out vascularity), Type 2 ‘‘Polypoid pattern’’ (adenoma or granuloma pattern reduce the incidence and severity of acute pancreatitis after ERCP. Am J
without vascularity) and Type 3 ‘‘Inflammatory pattern’’ (regular or irregular Gastroenterol 2007; 102(5): 978–983.
fibrous and congestive pattern with regular vascularity). Malignant lesions: Type 2. Elmunzer BJ, Scheiman JM, Lehman GA, et al. A randomized trial of rectal
1 ‘‘Flat pattern’’ (flat and smooth or irregular surface with irregular or spider indomethacin to prevent post-ERCP pancreatitis. N Engl J Med 2012;
vascularity); Type 2 ‘‘Polypoid’’ (polypoid or mass with fibrosis and irregular or 366(15): 1414–1422.
spider vascularity), Type 3 ‘‘ulcerated" (irregular pattern ulcerated and infiltra- 3. Dumonceau JM, Andriulli A, Elmunzer BJ, et al. Prophylaxis of post-ERCP
tive with or without fibrosis with irregular or spider vascularity) and type 4 pancreatitis: European Society of Gastrointestinal Endoscopy (ESGE)
‘‘honey-comb pattern’’ (fibrous honey-comb pattern with or without irregular Guideline - updated June 2014. Endoscopy 2014; 46(9): 799–815.
or spider vascularity). Inter-observer and intra-observer agreement was calcu- 4. Levenick JM, Gordon SR, Fadden LL, et al. Rectal Indomethacin Does Not
lated using 40 random images of lesions for 1 expert and 2 non-expert in Prevent Post-ERCP Pancreatitis in Consecutive Patients. Gastroenterology
POCS. Finally a prospective, non randomized, double blind evaluation of diag- 2016; 150(4): 911–917.
nostic accuracy, sensitivity, specificity, PPV, NPV using the new classification 5. Yaghoobi M, Rolland S, Waschke KA, et al. Meta-analysis: rectal indo-
was performed for consecutive tissular lesions detected from Oct-2015 to April- methacin for the prevention of post-ERCP pancreatitis. Aliment Pharmacol
2016 correlated with histology. Ther 2013; 38(9): 995–1001.
Results: 130 patients were studied, (retrospective: 87 / prospective: 43); 30 female, 6. Ahmad D, Lopez KT, Esmadi MA, et al. The effect of indomethacin in the
mean age 61 (50–74). Absence of statistical difference in genre (p value ¼ 0.606) prevention of post-endoscopic retrograde cholangiopancreatography pan-
or age (p ¼ 0.107) between groups. For retrospective evaluation 46/87 patients creatitis: a meta-analysis. Pancreas 2014; 43(3): 338–342.
were evaluated, 21 female, mean age 61 (52–73). 18/46 cases were malignant and 7. Montaño Loza A, Garcı́a Correa J, González Ojeda A, et al. Prevention of
28/46 benign. The overall interobserver agreement was substantial when lesions hyperamilasemia and pancreatitis after endoscopic retrograde cholangiopan-
were classified as benign or malignant (K ¼ 0.75 – CI 0.46–0.89) and when lesions creatography with rectal administration of indomethacin. Rev Gastroenterol
were classified by sub-types (K ¼ 0.71 – CI 0.39–0.88).The intraobserver agree- Mex 2006; 71(3): 262–268.
ment was almost perfect when lesions were classified as benign and malignant 8. Döbrönte Z, Toldy E, Márk L, et al. Effects of rectal indomethacin in the
(K ¼ 0.88 – CI 0.66–1.0) and when lesions were classified by sub-types (K ¼ 0.90 prevention of post-ERCP acute pancreatitis. Orv Hetil 2012; 153(25):
– CI 0.71–1.0). For the prospective evaluation 23/43 patients were evaluated, 9 990–996.
female, mean age 61 (48–72) years old. 13/23 cases were malignant and 10/23 9. Döbrönte Z, Szepes Z, Izbéki F, et al. Is rectal indomethacin effective in
benign. The accuracy was 86.9%, sensitivity 100%, specificity 70%, PPV 81.3%, preventing of post-endoscopic retrograde cholangiopancreatography pan-
NPV 100%. creatitis?. World J Gastroenterol 2014; 20(29): 10151–10157.
Conclusion: The proposed macroscopic classification could help physicians to 10. PataiÁ, Solymosi N and Patai ÁV. Effect of rectal indomethacin for pre-
distinguish benign from malignant lesions with a good inter and intra-observer venting post-ERCP pancreatitis depends on difficulties of cannulation:
concordance. results from a randomized study with sequential biliary intubation. J Clin
Disclosure of Interest: All authors have declared no conflicts of interest. Gastroenterol 2015; 49(5): 429–437.
11. Elmunzer BJ, Waljee AK, Elta GH, et al. A meta-analysis of rectal NSAIDs
Reference
in the prevention of post-ERCP pancreatitis. Gut 2008; 57(9): 1262–1267.
1. Chen YK, Parsi MA, Binmoeller K, et al. Single operator cholangioscopy in 12. Zheng MH, Xia HH and Chen YP. Rectal administration of NSAIDs in the
patients requiring evaluation of bile duct disease or therapy for biliary prevention of post-ERCP pancreatitis: a complementary meta-analysis. Gut
stones. Gastrointest Endosc 2011; 74: 805–14. 2008; 57(11): 1632–1633.
13. Shi N, Deng L, Altaf K, et al. Rectal indomethacin for the prevention of
post-ERCP pancreatitis: A meta-analysis of randomized controlled trials.
Turk J Gastroenterol 2015; 26(3): 236–240.
United European Gastroenterology Journal 4(5S) A49

Table (OP114)

Characteristics of Included Trials

Montano Loza, 2007 Sotoudehmanesh, 2007 Dobronte, 2012 Dobronte, 2014 Patai, 2015 Levenick, 2016

Methodology
Intervention 100 mg PR before 100 mg PR before ERCP 100 mg PR before 100 mg PR before 100 mg PR before 100 mg PR during
ERCP ERCP ERCP ERCP ERCP
Location Mexico-multicenter Iran-single center Hungary-single center Hungary-multicenter Hungary-single center US-single center
Definition of post- Clinical, amylase Clinical, amylase Pain, amylase, pro- Clinical, amylase, pro- Pain, amylase, pro- Pain, amylase, pro-
ERCP pancreatitis longed admission longed admission longed admission longed admission
Pancreatic stent used? Yes (10 cases in indo- No N/A No No Yes (36 cases in indo-
methacin group; 9 methacin group; 35
cases in placebo cases in placebo
group) group)
Randomization
Total randomized 150 490 228 686 539 449
Total analysed 150 442 228 665 539 449
Indomethacin 75 221 130 347 270 223
Placebo 75 221 98 318 269 226
Baseline demographics
Mean age (y)
Indomethacin 55 58 66 66 66 65
Placebo 51 58 67 68 65 64
% Female
Indomethacin 65 56 63 62 67 53
Placebo 68 53 70 67 67 52
Procedure
demographics
% Difficult cannulation
Indomethacin N/A N/A N/A 18 29 21
Placebo N/A N/A N/A 16 30 19
% Pancreatic duct
injection
Indomethacin 7 20 63 71 23 22
Placebo 8 19 68 68 30 22

OP115 PREVENTION OF POST-SPHINCTEROTOMY BLEEDING BY Conclusion: The use of high-dose PPI did not appear to significantly reduce the
PROTON PUMP INHIBITOR: A PROSPECTIVE RANDOMIZED risk of both immediate and delayed bleeding in patients undergoing EST.
TRIAL Disclosure of Interest: All authors have declared no conflicts of interest.
W.K. Leung, D. Y. But, S.Y. Wong, K. Liu, I. Hung
Department Of Medicine, University of Hong Kong, Hong Kong/Hong Kong Prc
Contact E-mail Address: [email protected] OP116 IMPACT OF INTENSIVE HYDRATION ON THE INCIDENCE OF
Introduction: Bleeding after endoscopic sphincterotomy (EST) is one of the most POST-ERCP PANCREATITIS: DOUBLE-BLINDED RANDOMIZED
frequent complications of therapeutic ERCP. Although the use of proton pump CONTROLLED TRIAL
inhibitor (PPI) has been shown to reduce the risk of rebleeding in patients with P. Boal Carvalho1, F. Dias De Castro1, M. Barbosa1, J. Magalhães1, B. Rosa1,
peptic ulcer bleeding after endoscopic hemostasis, the role of acid suppression in J. Cotter2
preventing EST bleeding has not been evaluated. We hypothesized that preemp- 1
Gastroenterology Department, Hospital Senhora da Oliveira, Guimaraes/Portugal
tive high dose PPI could reduce the risk of post-EST bleeding. 2
Life and Health Sciences Research Institute, University of Minho, Braga/Portugal
Aims & Methods: The aim of this study was to study the role of high-dose PPI in
patients undergoing EST. It was a prospective randomized open-label study Contact E-mail Address: [email protected]
performed in the endoscopy centre of a university teaching hospital. Introduction: Pancreatitis is the most frequent complication following endoscopic
Consecutive patients who were scheduled to have ERCP and EST were enrolled. retrograde cholangiopancreatography (ERCP), with an estimated incidence of
We excluded patients who had previous EST, prior gastric surgery, or were 1.6% to 15.7%, depending on patient and procedure-related factors. Intensive
taking PPIs. Antiplatelet therapies were continued as usual. Anti-coagulants hydration with lactated Ringer’s solution has been shown in small studies to
(warfarin or heparin) were stopped with coagulopathy corrected prior to reduce post-ERCP pancreatitis (PEP) incidence and severity.
ERCP. Eligible patients were randomized to receive either PPI or standard Aims & Methods: We aimed to assess whether intensive hydration impacts on the
care (SC). PPI group would receive esomeprazole given intravenously at 80 mg incidence and severity of PEP. We performed a prospective, double-blinded
every 12h for Day 1, starting 4 hours prior to ERCP, and followed by oral randomized controlled trial, including consecutive patients submitted to ERCP
esomeprazole 40 mg bid from Day 2 to 10. Standard care arm would receive in our institution. Patients with previous sphincterotomy, chronic pancreatitis,
usual care without any acid suppressive therapy. Endoscopists were unaware heart failure (NYHA 3), chronic kidney disease (stage3) and shock were
of the treatment allocation of the patients. Primary outcome was the proportion excluded. Patients were randomized (1:1) to either intensive hydration with lac-
of patients with immediate or delayed post-EST bleeding. Immediate bleeding tated Ringer’s solution (3 mL/kg/h during the procedure, 20 mL/ kg bolus after
was defined as bleeding that occurred during the procedure and required endo- the procedure, and 3 mL/kg/h for 8 hours after the procedure), or standard
scopic hemostasis. Delayed bleeding was defined as bleeding after the completion hydration (1.5 mL/kg/h of lactated Ringer’s solution during and for 8 hours
of ERCP which manifested as overt GIB with melena or hematemesis. All after the procedure). A blood panel including serum levels of amylase and
patients were followed up for 30 days. Secondary outcomes included drop in lipase was obtained at 4 and 24 hours after ERCP. Primary outcome was the
hemoglobin 42 g without overt bleeding, transfusion requirement and all- incidence of PEP (defined as epigastric pain plus either amylase or lipase levels
cause mortality at 30 days. Analysis was based on modified intention-to-treat, 43 times the upper limit of normal at 24h). Secondary outcomes were severity of
which included only randomized patients who had undergone EST. PEP, incidence of volume overload, patient and procedure-related factors asso-
Results: 196 patients were enrolled and 71 patients did not have EST. The ana- ciated with PEP, and the predictive values of serum amylase/lipase at 4 hours
lysis included 125 patients who had undergone EST with 60 in the PPI group and after ERCP for PEP development.
65 in SC group. The mean age was 70.9 (SD ¼ 14.8) years with 62 (49%) men. Results: Included were 75 patients, 38 in the intensive hydration arm, and 37 in
The baseline characteristics of the two groups including indications for ERCP, the standard hydration arm. Both groups were homogeneous for patient and
use of anti-platelet agents or anti-coagulants, and comorbidity were comparable. procedure-related factors. PEP incidence was 9.3% (n ¼ 7), and was lower in
Immediate bleeding was noted in 9 (15%) patients in the PPI group and 4 (6.2%) the intensive hydration arm (5.3% versus 13.5%, p ¼ 0.204). Additionally, both
in the SC groups (P ¼ 0.14). Overt delayed ES bleeding was respectively seen in 2 PEP in the intensive hydration arm were mild, while out of the 5 PEP in the
(3.3%) and 5 (7.7%) patients in PPI and SC arms (P ¼ 0.44). There was also no normal hydration arm, two patients presented with moderate and severe PEP,
significant difference in the proportions of patients with hemoglobin drop of 42 respectively. Contrast injection of the Wirsung was significantly associated with
g without overt bleeding (Day 10: 13.3% in PPI group and 9.2% in SC group; PEP (28.6% versus 7.1%, p ¼ 0.016), while no other patient or procedure-related
P ¼ 0.57). Other outcomes including hospital stay (13.1 vs 11.8 days; P ¼ 0.69), factors associated with PEP incidence. Finally, both amylase levels 52 times and
transfusion requirement (5% vs 7.7%; P ¼ 0.72) and 30-day mortality (3.3% vs lipase levels 5 3 times the upper limit of normal at 4 hours demonstrated a
1.5%; P ¼ 0.61) were also comparable between the PPI and SC groups.
A50 United European Gastroenterology Journal 4(5S)
negative predictive value of 100% for the development of PEP. No complication developed a transdiagnostic model of CBT which is applied via distance mode,
was observed as a consequence of intensive hydration. primarily via internet but also by telephone.
Conclusion: In our series, the incidence of PEP was 9.3%, and a non-significant Aims & Methods: This study sought to pilot a new form of iCBT designed for
risk reduction trend was observed in patients undergoing intensive hydration, chronic health conditions, including functional gastrointestinal disorders, with
with no severe pancreatitis being observed in this group. Wirsung contrast injec- respect to: 1. Reduction in abdominal symptom burden, anxiety and depression
tion significantly increased the risk of PEP. Lower serum amylase and lipase 2. Identify changes in psychological factors that correlate with improvements in
levels at 4 hours after ERCP were excellent predictors for absence of PEP at abdominal symptom burden. These aims were addressed using a single arm
24 hours, displaying a negative predictive value of 100%. design with measurements of psychological factors and symptoms pre, mid and
Disclosure of Interest: All authors have declared no conflicts of interest. post-therapy. n ¼ 27 individuals from across Australia were recruited at the
eCentreClinic at Macquarie University (Australia) which specialises in online
psychological threapies. Abdominal symptoms were assessed using the
MONDAY, OCTOBER 17, 2016 15:45–17:15 Gastrointestinal Symptom Rating Scale (GSRS) while anxiety was measured
UPPER GI NERVE-GUT INTERACTIONS – ROOM N2_____________________ via the GAD-7 and depression via the PHQ-9. Aim 1 was addressed via
change from pre- to post-treatment in scores while aim 2 was addressed by
OP117 INTRAGASTRIC BITTER TASTANT ALTERS BRAIN ACTIVITY correlating change in GSRS scores with change in anxiety, depression and pain
IN HOMEOSTATIC AND HEDONIC REGIONS AND DECREASES catastrophising scores.
OCTANOYLATED GHRELIN LEVELS AND HEDONIC FOOD Results: Of 27 patients who commenced therapy 22 completed the entire course
INTAKE and provided post-therapy measures. There was no difference in baseline scores
J. Iven, J. Biesiekierski, D. Zhao, I. Depoortere, L. Van Oudenhove, J. Tack for any measure between completers and non-completers. Scores for both
Targid, University of Leuven, Leuven/Belgium abdominal symptom and psychological traits were substantially and statistically
significantly improved at the end of therapy (Table 1).
Contact E-mail Address: [email protected]
Introduction: Intragastric administration of bitter tastants decreases hunger rat- Table 1: Baseline and change in scores for abdominal symptoms and psycho-
ings in the fasted state. Activation of bitter taste receptors can alter ghrelin levels, logical factors
a gut hormone which increases hunger in between meals and becomes active after
octanoylation. This indicates a potential role for bitter agonists in the regulation Score Baseline Change Cohen’s d
of appetite and food intake, putatively via interference with gut-brain signals to
regions involved in homeostatic (brainstem, hypothalamus) and hedonic (meso- GSRS 44.2 (11.0) 7.6 (10.5) 0.72
limbic reward system) control of feeding. Anxiety 10.0 (5.2) 5.1 (4.4) 1.16
Aims & Methods: The aim of this project was to study the effect of intragastric Depression 9.7 (4.8) 4.1 (5.3) 0.78
administration of the bitter tastant Quinine Hydrochloride (QHCl) on brain
activity in homeostatic and hedonic regions and on circulating ghrelin plasma Catastrophising 19.8 (11.3) 11.5 (11.9) 0.97
levels. Furthermore, to test the hypothesis of lower hunger and prospective food
consumption ratings, and lower hedonic food intake after QHCl administration
compared to placebo. Fifteen healthy women were studied after an overnight At end of therapy 77% of patients had reduced GSRS scores and 95% reported
fast. Brain activity before and up to 50 minutes after infusion of QHCl (10 mmol/ the program was worth the effort expended. The percentage change in GSRS
kg) or distilled water (placebo) was recorded using functional magnetic reso- score was positively correlated with percentage change in pain catastrophising
nance imaging (MRI). Hunger and prospective food consumption scores were ( ¼ 0.53, p ¼ 0.01) and depression ( ¼ 0.53, p ¼ 0.01) and to a lesser extent with
assessed every 10 min using Visual Analogue Scales. Blood samples were taken at change in anxiety ( ¼ 0.36, p ¼ 0.1).
the same time points. Hedonic food intake was measured immediately after Conclusion: Based on this pilot trial, a transdiagnostic iCBT program developed
scanning using an ad libitum chocolate milkshake drink test. MRI preprocessing specifically for functional gastrointestinal disorders shows considerable promise
and analysis was conducted using SPM12. Brain responses over time to QHCl with improvements in both gastrointestinal symptoms as well as psychological
versus placebo infusion were compared in a priori defined regions of interest functioning. The correlation between change in both mood scores and catastro-
(ROI) at both voxel- and cluster-level threshold of pFWEcorrected 5 0.05. The phizing with change in abdominal symptoms opens avenues for further under-
infusion-by-time interaction effect was tested on hunger and prospective food standing of the mechanisms by which iCBT improves the gastrointestinal
consumption scores with mixed models. Hedonic food intake was compared sufferings of these patients. The low cost of iCBT compared with conventional
between infusions using a one-tailed paired T-test. Blood plasma was analysed face-to-face therapy is attractive given challenges to public health budgets and its
for circulating ghrelin levels using radioimmunoassays. modality makes therapy accessible to potential patients who are not able to travel
Results: Compared to placebo, intragastric QHCl infusion significantly increased to a psychologist. Further, the transdiagnostic model on which this particular
neural activity in 5 different clusters within the ROIs, with local maxima in the iCBT treatment is based is readily adaptable to other functional somatic syn-
putamen, insula, caudate, amygdala, anterior cingulate cortex, medial prefrontal dromes so offers hope to a wide range of disorders.
cortex, medial orbitofrontal cortex and hippocampus. A decrease of neural activ- Disclosure of Interest: All authors have declared no conflicts of interest.
ity was observed in the brainstem. Significantly lower prospective food consump- References
tion scores were observed after QHCl administration compared to placebo
(p ¼ 0.02), but no significant differences were observed for hunger scores. 1. Drossman DA. Psychosom Med. 1998;60(3):258–67.
Milkshake intake was significantly lower after QHCl administration, compared 2. Talley NJ, Kellow JE, Boyce P, Tennant C, Huskic S, Jones M. Digestive
to placebo (p ¼ 0.04; Cohen’s d ¼ 0.50). A significant decrease of octanoylated diseases and sciences. 2008;53(1):108–15.
ghrelin plasma levels was observed post-infusion after bitter administration com- 3. Ford AC, Quigley EMM, Lacy BE, Lembo AJ, Saito YA, Schiller LR, et al.
pared to placebo (p ¼ 0.05). The Am J Gastro. 2014;109(9):1350–65.
Conclusion: Intragastric administration of the bitter tastant QHCl significantly 4. Andersson G, & Titov N. (2014). World Psychiatry 13: 4–11.
altered activity in homeostatic and hedonic brain regions. Prospective food con- 5. Ljótsson B, Andersson G, Andersson E, Hedman E, Lindfors P,
sumption ratings, circulating octanoylated ghrelin levels and hedonic food intake Andréewitch S, et al. BMC Gastroenterology. 2011;11:110.
were decreased after QHCl. These observations indicate a potential role for bitter
agonists in the treatment of obesity.
Disclosure of Interest: All authors have declared no conflicts of interest.
OP119 DYSBIOSIS INDUCES GUT INFLAMMATION AND
DEPRESSIVE-LIKE BEHAVIOR ASSOCIATED WITH BRAIN
BIOCHEMICAL AND FUNCTIONAL ALTERATIONS WHICH ARE
OP118 TRANSDIAGNOSTIC COGNITIVE BEHAVIOUR THERAPY RESTORED BY PROBIOTIC TREATMENT
SHOW PROMISE FOR BOTH MOOD AND GASTROINTESTINAL F. Turco1, F. Guida2, I. Palumbo1, M. Iannotta2, A. Furiano2, L. Luongo2,
SYMPTOMS IN PATIENTS WITH FUNCTIONAL R. Cuomo1, S. Maione2, V. De Novellis2
GASTROINTESTINAL DISORDERS 1
Clinical Medicin and Surgery, Federico II University of Naples, Naples/Italy
M.P. Jones1, B. Dear1, N. Titov1, V. J. Fogliati1, N.J. Talley2 2
Department Of Experimental Medicine, Section Of Pharmacology L. Donatelli,
1
Psychology, Macquarie University, North Ryde/Australia/NSW Second University of Naples, Naples/Italy
2
University of Newcastle Faculty of Health PVC Office, Callaghan/Australia
Contact E-mail Address: [email protected]
Contact E-mail Address: [email protected] Introduction: The gut-brain axis has been indicated as major substrate of patho-
Introduction: Irritable Bowel Syndrome (IBS) is a heterogenous disorder charac- physiological mechanisms in psychiatric comorbidities associated with chronic
teristised by recurrent abdominal pain combined with alteration in bowel habit. inflammatory bowel disorders. In particular, intestinal microbiota alterations
It is associated with reduced quality-of-life and significant economic cost to may play a role in communication between these two systems1. However, such
society. IBS sufferers also have elevated scores for anxiety and depression communication is not fully understood and probably involves multiple
which have been speculated to be part of the disease etiology [1]. Indirect evi- mechanisms.
dence for the role of mood in IBS prevalence comes from studies showing that a Aims & Methods: In the present study we examined the presence of gut inflam-
proportion of patients show improvement in abdominal symptoms with antide- mation, the behavior, as well as, the brain biochemical and functional alterations
pressants [2] but also in response to psychological therapies including cognitive in an antibiotic-induced dysbiosis animal model. Young male mice received a
behaviour therapy (CBT) [3]. Newer forms of CBT including internet-delivered mixture of nonabsorbable antimicrobials (ampicilline, streptomicin and clynda-
CBT (iCBT) have shown similar effect sizes to conventional CBT in patients with micin), which has been associated to the microflora composition alteration2, for 2
mood disorder [4]. iCBT provides access to therapy for patients who are geogra- weeks. Afterwards, animals were treated with probiotic (Lactobacillus Casei DG,
phically or culturally isolated from qualified psychologists and has been shown to 109 cells) or vehicle up to 7 days. Whereupon, various behavioral testing were
be cost-effective [5]. The eCentreClinic at Macquarie University (Australia) has performed. After sacrifice, mice intestine was cut in segments (duodenum, jeju-
num, ileum and colon) and expression of pro-inflammatory markers (IL-1b,
United European Gastroenterology Journal 4(5S) A51
TNF and iNOS) was evaluated by Western Blot analysis. Extracellular record- OP121 OXIDATIVE STRESS ACTIVATES NLRP3 INFLAMMASOME
ing from CA3 region of dorsal hippocampus was performed. Astrocytes and AND IMPAIRS GASTRIC ANTRUM SMOOTH MUSCLE ACTIVITY
microglial cells markers (GFAP and Iba-1, respectively) expression was evaluated IN OBESE PATIENTS
by immunohistochemistry. A. Scirocco1, L. Pallotta2, M. Carabotti3, G. Silecchia4, A. Ignazzi1, G. Tellan5,
Results: Biochemical evaluations indicated that dysbiosis induced an overall gut F. Abbatini4, M.A. Maselli1, M. Rengo6, A. Cicenia2, E.S. Corazziari2, C. Severi2
inflammatory condition (significant increase in IL-1b, TNF and iNOS expres- 1
Experimental Pharmacology Laboratory, Scientific Institute of Gastroenterology
sion), associated with a depressive-like behavior and a reduced social interaction. ‘‘S. de Bellis’’, Castellana Grotte/Italy
Altered behavior was accompanied by significant changes CA3 pyramidal neu- 2
Dep. of Internal Medicine and Medical Specialties, University Sapienza, Rome/
rons firing activity. Moreover, the number of GFAP and Iba-1 positive cells was Italy
significantly increased by dysbiosis. Very intriguingly, probiotic treatment sig- 3
Department Of Internal Medicine and Medical Specialties, University Sapienza
nificantly decreased IL-1b, TNF and iNOS expression, normalized mice beha- Rome, Rome/Italy
vior, restored the spontaneous ongoing activity of CA3 pyramidal neurons and 4
Dep. of Medical-Surgical Sciences and Biotechnology, University Sapienza,
reduced the GFAP and Iba-1 positive cells number. Rome/Italy
Conclusion: We found that, in mice, dysbiosis induced gut inflammation and 5
Dep. of General Surgery Francesco Durante, University Sapienza, Rome/Italy
sickness behaviours associated with biochemical and electrophysiological altera- 6
Dept. Of Radiological Sciences, Sapienza University of Rome, Rome/Italy
tions in hippocampus. Probiotic treatment counteracted the gut inflammation
and restored the behavioural phenotype as well as the biochemical and functional Contact E-mail Address: [email protected]
changes occurring in the brain of dysbiotic mice. These data suggest that intest- Introduction: Obesity is associated to oxidative stress and chronic inflammation.
inal dysbiosis, via the gut-brain axis, might contribute to the psychiatric co- Oxidative stress activates NLRP3 inFammasome with recruitment of ASC and
morbidity in patients with bowel disorders associated with an altered microflora pro caspase-1, leading to caspase-1 (CASP) activation and subsequent interleu-
and that probiotic treatment may improve this condition. kin-1b (IL-1b) secretion. Motor disorders of the gastric antrum are observed in
Disclosure of Interest: All authors have declared no conflicts of interest. obese patients (OB) with in vitro impairment of VIP-induced relaxation both of
References smooth muscle cells (SMC) and strips
Aims & Methods: Our aim was to evaluate in vivo obese antral smooth muscle
1. Collins SM, Kassam Z and Bercik P. The adoptive transfer of behavioral impairment and to study in vitro the roles for oxidative stress and inflammation
phenotype via the intestinal microbiota: experimental evidence and clinical on SMC motor alterations. Antral scans were obtained by Magnetic Resonance
implications. Curr Opin Microbiol 2013 Jun; 16(3): 240–5. Imaging (MRI) before and after a liquid meal in OB and normal weight (NW)
2. Lamousé-Smith ES, Tzeng A and Starnbach MN. The intestinal flora is patients. SMC were isolated from human gastric antrum from 19 OB
required to support antibody responses to systemic immunization in infant (40.95BMI552.0 kg/m2) submitted to sleeve gastrectomy and 9 NW patients
and germ free mice. PLoS One 2011; 6(11): e27662. submitted to gastrectomy for gastric cancer (19.05BMI525.0 kg/m2).
Antioxidant capacity was evaluated by ELISA; qPCR analysis was performed
for mRNA for NLRP3, ASC, CASP, IL-1b, TNF and COX-2 and the data
were normalized to b-actin mRNA levels. The effect of NADPH inhibitor
OP120 QUORUM SENSING MOLECULES OF GUT MICROBIOTA Apocynin (APO:1mg/ml) in reverting OB SMC alterations was tested both on
AFFECT INTESTINAL TASTE RECEPTORS AND ANOREXIGENIC mRNA expression and on VIP (1mM) induced antral relaxation. Data are
PEPTIDES TO CONTROL SATIETY IN THE HOST expressed as mean  SE, p 5 0.05 considered significant.
P. Brun1, A. Pellizzaro1, M. Fassan2, A. Porzionato1, C. Mucignat-Caretta1, Results: In respect to NW, RMI scans showed a reduced antral motility, both
I. Castagliuolo1 during fasting and post-prandial periods, in OB consisting in a significant reduc-
1
Dep Of Molecular Medicine, University of Padova, Padova/Italy tion of the width of antral contraction waves and magnitude of antral diameters
2
Dep Of Medicine, University of Padova, Padova/Italy variations. OB SMC presented a statistically significant decrease in antioxidant
capacity (%59.02  0.13) associated to a stronger increase of mRNA encoding
Contact E-mail Address: [email protected] for the inflammatory proteins TNF (%46.60  0.80), COX 2 (%348.18  0.63)
Introduction: Accumulating evidence suggests that the gut microbiota controls and NLRP3 inFammasome-related molecules. Pretreatment of OB gastric SMC
host satiety and hungry (1). Even if quantitative modifications of the gut micro- with APO restored by 84.71  0.2 antioxidant capacity and completely inhibited
biota have been described in obesity, bacterial derived soluble factors are likely the expressions in OB NLRP3 (26.25  0.35), ASC (34.52  2.18), CASP-1
involved in host dietary habits. (31.80  1.50) and IL-1b transcripts (3.58  0.86), all undetermined after APO
Aims & Methods: In this study we investigated the role of quorum sensing mole- treatment. Associated to inhibition of the inflammasome components expression,
cules (the autoinducers, AI) used for communication within gut microbial com- APO completely restored VIP-induced relaxations in obese SMC (OB:
munities (2), in modifying food intake in the host. Adults CD1 male mice were %79.60  11.84 vs NW: %79.96  5.78).
fed a high-fat diet (HFD, 35% energy by fat) or a normal diet (4% energy by fat) Conclusion: Our study indicates a role for ROS in activation of NLRP3 inflam-
and then daily rectally dosed with vehicle or 30 ng/g body weight of purified AI masome in obese gastric smooth muscle leading to a significant dysmotility that
namely N-(3-oxododecanoyl)-L-homoserine lactone (AHL-12) or 2-Heptyl-3- could be restored by the use of antioxidants
hydroxy-4(1H)-quinolone (PQS). Two weeks later we determined: a) gut micro- Disclosure of Interest: All authors have declared no conflicts of interest.
biota composition by quantitative PCR (qPCR) on fecal DNA; b) enteroendo-
crine cells (EECs) density in colonic mucosa by immunohistochemistry (IHC) for
synaptophysin; c) mRNA levels specific for taste receptors and for anorectic or
orexigenic peptides by qRT-PCR on colon and hypothalamus; d) food intake, OP122 ACOTIAMIDE-SENSITIVE IMPAIRED RECEPTIVE
body weight gain, oral glucose tolerance test. RELAXATION OF LOWER ESOPHAGEAL SPHINCTER IN
Results: In HFD-fed mice rectally administration of AHL-12 or PQS restored the PATIENTS WITH ESOPHAGOGASTRIC JUNCTION OUTFLOW
gut microbiota composition and normalized EECs density in colonic mucosa, OBSTRUCTION
altered by fat diet. AI administration increased the mRNA levels of Tas2r5, K. Muta1, E. Ihara1, B. Xiaopeng1, O. Tsuchida2, T. Toshiaki Ochiai2, T. Iwasa1,
Tas2r38 and Tas2r105 whereas did not affect Tas2r131 and Tas1r3 allelic var- A. Aso1, K. Nakamura1
iants of bitter taste receptors. Moreover, AHL-12 and PQS significantly 1
Department Of Medicine and Bioregulatory Science, Graduate School Of Medical
increased mRNA levels of anorectic peptides namely Cholecystokinin, Leptin Sciences, Kyushu University, Fukuoka city/Japan
and Neurotensin in the gut and Brain-Derived Neurotrophic Factor in the 2
Fukuoka Prefecture Saiseikai General Hospital, Fukuoka/Japan
hypothalamus. Intraperitoneal administration of AHL-12 or PQS had no effects,
supporting an intestinal direct action. Accordingly, the rectal but not the perito- Contact E-mail Address: [email protected]
neal administration of PQS and to a lesser extent AHL-12 significantly reduced Introduction: The pathogenesis and treatment of esophagogastric junction out-
food intake, decreased fat-diet induced body weight gain and improved oral flow obstruction (EGJOO) are not fully understood. The lower esophageal
glucose tolerance test. sphincter (LES) reportedly exhibits accommodation responses, and LES pressure
Conclusion: We speculate that gut microbial AI mediate satiety through activa- is suppressed by swallowing and pharyngeal water stimulation (PWS) (Mittal,
tion of taste receptors expressed by EECs and the release of gut peptides involved RK et. al. Gastroenterology. 1996;111:378–384); PWS-induced LES relaxation
in food intake. appears to be analogous to gastric receptive relaxation. We have previously
Disclosure of Interest: All authors have declared no conflicts of interest. reported that acotiamide was effective for patients with EGJOO.
References Aims & Methods: This study aimed to evaluate the physiologic characteristics of
acotiamide-sensitive LES relaxation in patients with EGJOO. High-resolution
1. Breton J, et al. Cell Metabolism 2016; 23:1–11. manometry was performed according to a standard protocol with the participant
2. Thompson JA, et al. Cell Reports 2015;10:1861–1871. in the supine position, while swallowing ten 5-mL liquid boluses. 13 patients with
EGJOO (mean age 65.5  standard deviation 4.1 years, eight of whom were
women) and 19 participants with normal esophageal pressures (mean age
50.0  3.0 years, 11 of whom were women) were enrolled. Basal LES pressure
(BLESP) and the integrated relaxation pressure (IRP) were measured. The extent
of PWS-induced LES relaxation (mmHg) was calculated as the difference
between BLESP and the mean LES pressure in the 5-s period before PWS.
Results: There was no difference in BLESP between normal subjects (34.6  2.1
mmHg) and patients with EGJOO (32.7  1.8 mmHg), but IRP was significantly
higher in patients with EGJOO (20.3  1.4 mmHg) than normal subjects
(10.8  0.6 mmHg). In normal subjects, LES pressure immediately declined
from 34.6  2.1 mmHg to 25.6  1.4 mmHg when the fluid bolus stimulated
the mouth and pharynx on the first swallow. Mean PWS-induced LES relaxation
was 9.0  1.7 mmHg in normal subjects, but was absent in patients with EGJOO.
A52 United European Gastroenterology Journal 4(5S)
The mean LES pressure induced by PWS was 33.0  1.6 mmHg, and did not for these large SMTs in esophagus and esophagogastric junction (EGJ). We
differ significantly from the BLESP 32.7  1.8 mmHg). Acotiamide was adminis- described a new technique, submucosal tunneling endoscopic resection (STER),
tered to address severe symptoms in six out of 13 patients with EGJOO. for the resection of upper gastrointestinal SMTs. Recently, reports about STER
Acotiamide normalized impaired receptive LES relaxation and substantially are increasing. However, it is unclear whether STER is feasible for large SMTs.
improved symptoms. Moreover, studies about comparasion of STER and surgery for upper gastro-
Conclusion: Normal subjects have receptive LES relaxation, but this is impaired intestinal SMTs are still little known.
in EGJOO. Acotiamide normalizes IRP in EGJOO, mainly by restoring LES Aims & Methods: The aim of this study is to compare the clinical outcomes of
receptive relaxation. STER and thoracoscopic surgery for large symptomatic SMTs in esophagus and
Disclosure of Interest: All authors have declared no conflicts of interest. esophagogastric junction, as well as to analyze the clinicopathological factors
Reference that effect the feasiblilty of STER. Patients with large SMTs originating from
the MP layer in esophagus and EGJ were enrolled in this retrospective study
1. Mittal, RK et. al. Gastroenterology. 1996;111:378–384. between May 2011 and December 2013. The clinicopathological data of a total of
145 patients were collected and analyzed.
MONDAY, OCTOBER 17, 2016 15:45–17:15 Results: Among the 145 patients, 39 patients (26.9%) complained specific symp-
toms, while 106 patients (73.1%) had non-specific complaints. In the STER
ENDOSCOPIC MANAGEMENT OF UPPER GASTROINTESTINAL CANCER – ROOM group, the mean tumor long and transverse diameters were 5.8 cm and 2.2 cm.
L7_____________________ Meanwhile, in the TS group, the mean tumor long and transverse diameters were
6.5 cm and 3.1 cm, respectively. Among all SMTs, 64 had regular shapes (44.1%)
OP123 EFFICACY AND SAFETY OF ESD FOR SUPERFICIAL CANCER and 81 had irregular shapes (55.9%). All of the tumors were located in esophagus
OF THE CERVICAL ESOPHAGUS (84, 57.9%), and EGJ (61, 42.1%). There was no significant difference between
T. Iizuka1, D. Kikuchi1, S. Hoteya2, M. Kaise3 the two groups in age, gender, symptom, tumor size, tumor location, tumor
1
Dept. Of Gastroenterology, Toranomon Hospital, Tokyo/Japan shape, and tumor histopathology. No recurrence was found in both groups
2
Dept. Of Gastroenterology, Toranomon Hospital Dept. of Gastroenterology, during the follow up period. In this study, en bloc resection was achieved in
Tokyo/Japan 84.1% of the cases in the STER group and 85.7% of the cases in the TS
3
Toranomon Hospital, Tokyo/Japan group, and there was no significance (p ¼ 0.794). In addition, the incidence of
complications in this study was 8.5% in STER group and 4.8% in TS group.
Contact E-mail Address: [email protected] There was no significant difference in complications rates of the 2 groups.
Introduction: It is a difficult to observe a lesion in the cervical esophagus because However, the procedure time and the hospital stay in the STER group were
of the difficulty in spreading the lumen. It is a challenge not only to find eso- significantly shorter than those of the TS group. Based on statistical analysis,
phageal cancers at an early stage, but also to successfully treat them by ESD tumors with long diameter larger than 7.0 cm, transverse diameter lager than 3.5
compared with lesions located at the thoracic esophagus. cm and irregular shape were 3 significant risk factors for STER-related piecemeal
Aims & Methods: The aim of this study was to clarify the safety and efficacy of resection, while tumor with transverse diameter lager than 3.5 cm was the risk
ESD for superficial cancer located at the cervical esophagus. Patients who met factor for STER-related complications.
the following criteria (case group) were enrolled in this retrospective study: 1) Conclusion: STER is feasible and safe for large symptomatic SMTs in esophagus
ESD was performed from January 2006 to December 2015; 2) the lesion was and EGJ. It is associated with a shorter procedure time and hospital stay com-
located at the cervical esophagus; and 3) squamous cell carcinoma (SCC) was pared with TS. Besides long diameter and irregular shape, transverse diameter of
proven histologically. Forty-five patients met those criteria. As a control group, SMTs is the critical factor for en bloc resection. STER for tumors with large
379 patients with 405 lesions of SCC which were located at the middle thoracic transverse diameter and irregular shape is feasible, but associated with a rela-
esophagus were enrolled. The lesions with entire circumferential mucosal defect, tively high risk of difficulty in retrieval of tumors.
recurrent lesions after radiotherapy, and the lesions located near the scar were Disclosure of Interest: All authors have declared no conflicts of interest.
excluded in both groups. We evaluated adverse events including stricture and
pneumonia, procedure time, en bloc resection rate, and frequency of local
recurrence.
Results: In the case group, the average age was 67.3 years old, and the male-to- OP125 CHARACTERISTICS OF METACHRONOUS GASTRIC
female ratio was 38:7. The average maximum size of lesions was 20.7 mm, and NEOPLASMS OCCURRING AFTER ENDOSCOPIC SUBMUCOSAL
the histological depth of invasion was EP/LPM, MM, and SM2 in 39, 5, and 1 DISSECTION FOR GASTRIC ADENOMAS AND CANCERS
cases, respectively. The en bloc resection rate and R0 resection rate was 100% S. Kondo1, T. Fujita1, Y. Tsuzuki1, Y. Sobajima1, H. Goto2, M. Sakakibara1
and 91.1%, respectively, and the mean procedure time was 57 min. ESD was 1
Gastroenterology, Aichi Cancer Center Aichi Hospital, Okazaki/Japan
performed under general anesthesia in 32 patients (71.1%). Damage of the 2
Gastroenterology, Nagoya University Graduate School of Medicine, Nagoya/
muscle layer during treatment was observed in 5 patients, for which clipping Japan
was performed in 2 patients. Esophageal stricture was observed in 9 patients
(41%), for which local injection of steroid was administered in 6 patients. No Contact E-mail Address: [email protected]
post-ESD bleeding was observed. Although perforation was identified in one Introduction: With the progress of endoscopic diagnosis and treatment, endo-
patient, he recovered with conservative treatment. Chemoradiotherapy as addi- scopic treatment has come to be used for gastric adenomas and early gastric
tional treatments were conducted in 1patient. No local recurrence was observed cancers (EGCs). Endoscopic submucosal dissection (ESD) has become accepted
during an average duration of follow-up of 34.1 months. In the control group, as a minimally invasive treatment for superficial gastric neoplasms. However, the
the average age was 67.3 years old, and the male-to-female ratio was 334:45. The development of metachronous gastric neoplasms has been occasionally detected
average maximum size of lesions was 24.2 mm, and the histological depth of during follow-up after ESD. The clinicopathologic characteristics of these lesions
invasion was EP/LPM, MM/SM1, and SM2 in 306, 67, and 32 cases, respec- occurring after ESD were investigated.
tively. The en bloc resection rate and R0 resection rate was 100% and 96%, Aims & Methods: From August 2006 to December 2015, stomach ESD was
respectively, and the mean procedure time was 54 min. ESD was performed performed for 375 patients with 426 lesions of gastric adenoma and differen-
under general anesthesia in 45 patients (11.1%). Damage of the muscle layer tiated-type EGC at Aichi Cancer Center Aichi Hospital. Periodic upper gastro-
during treatment was observed in 91 patients (22.5%), for which clipping was intestinal endoscopy, blood tests, and chest and abdominal computed
performed in 38 patients. Esophageal stricture was observed in 14 patients (6.6%) tomography were performed every 6 to 12 months after treatment. During the
of 213 patients with more than half of mucosal defect, for which local injection of follow-up period, 31 metachronous lesions (27 patients) were discovered at endo-
steroid or PGA sheet were administered in 38 patients. No post-ESD bleeding scopy more than 1 year after initial ESD. The characteristics of these lesions were
was observed. Although perforation was identified in three patients, they recov- examined retrospectively.
ered with conservative treatment.Surgery or chemoradiotherapy as additional Results: The median age at initial ESD was 72 (range, 56–82) years. The male to
treatments were conducted in 19 or 49 patients respectively. Local recurrence female ratio was 23:4. On endoscopy, all patients were found to have atrophic
was observed in one patient during an average duration of follow-up of 41.8 gastritis of the open-type according to the Kimura-Takemoto classification.
months. Helicobacter pylori testing was positive in 18 patients (66.7%), negative in 8
Conclusion: Safe ESD for superficial esophageal cancer in the cervical esophagus patients (29.6%), and unknown in 1 patient (3.7%). Of these 18 H. pylori-positive
could be achieved under an appropriate management and successful local control patients, 17 underwent H. pylori eradication therapy after initial ESD, and it was
was also confirmed. The stricture after ESD in the cervical esophagus developed successful in 16(94.1%). The median duration from initial ESD to the detection
significantly higher than those in the middle esophagus. of a metachronous lesion was 25.9 (range, 12.4–83.8) months. The locations of
Disclosure of Interest: All authors have declared no conflicts of interest. the lesions were classified as follows: upper third (U), middle third (M), and
lower third (L). Of 29 primary lesions (27 patients), 1 lesion (3.4%) was U, 11
lesions (37.9%) were M, and 17 lesions (58.6%) were L. The gross type was 0-I in
one lesion (3.4%), 0-IIa in 15 lesions (51.7%), 0-IIc in 12 lesions (41.4%), and 0-
OP124 SUBMUCOSAL TUNNELING ENDOSCOPIC RESECTION VS. IIaþIIc in one lesion (3.4%). The median tumor size was 10 (range, 2–50) mm.
THORACOSCOPIC SURGERY FOR LARGE SYMPTOMATIC En bloc resection was performed for 28 lesions (96.6%). Aspiration pneumonia
SUBMUCOSAL TUMORS IN THE ESOPHAGUS AND occurred in one patient after ESD, but the patient was successfully treated by
ESOPHAGOGASTRIC JUNCTION intravenous antibiotics. There were no treatment-related deaths. On pathological
T. Chen, M. Xu examination, 21 were tubular adenocarcinoma, and 8 were tubular adenoma.
Endoscopy Center and Endoscopy Research Institute, Zhongshan Hospital of Histologically, curative resection was obtained in 27 lesions (93.1%). In contrast,
Fudan University, Shanghai/China the location of 31 metachronous lesions was U in 9 lesions (29%), M in 8 lesions
(25.8%), and L in 14 lesions (45.2%). The gross type was 0-IIa in 16 lesions
Contact E-mail Address: [email protected] (51.6%), 0-IIb in 1 lesion (3.2%), 0-IIc in 13 lesions (41.9%), and 0-IIaþIIb in 1
Introduction: Small gastrointestinal submucosal tumors (SMTs) are asympto- lesion (3.2%). The median tumor size was 9 (range, 1.5–38) mm. En bloc resec-
matic and undetectable, while patients with larger tumors have symptoms, and tion was performed for 28 lesions (90.3%). Aspiration pneumonia occurred in
require intervention. Previously, thoracoscopic surgery (TS) is the gold standard one patient after ESD, but the patient was successfully treated by intravenous
United European Gastroenterology Journal 4(5S) A53
antibiotics. There were no treatment-related deaths. On pathological examina- this procedure is known to have several disadvantages such as greater technical
tion, 20 were tubular adenocarcinoma, and 11 were tubular adenoma. difficulty, longer procedure time and increased risk of related complications.
Histologically, curative resection was obtained in 26 of the 31 lesions (83.9%). Aims & Methods: The aim of this study is to find the best method for treating
There were no differences in gross type (elevated type/flat and depressed type), early gastrointestinal neoplasia. Fifty-one patients (mean patient age 71, range
tumor size, or histology between primary and metachronous lesions. However, 32–92 years, male: female ratio 25/26) including 19 involved adenoma with low-
location (U/M/L) was significantly different (P ¼ 0.029). Furthermore, there were grade dysplasia, 21 intraepithelial cancers with high-grade dysplasia, 3 minute
significant differences in U/M (P ¼ 0.016) and U/L (P ¼ 0.014). Therefore, there submucosal cancers, 6 submucosal deep cancers and 2 carcinoid tumors sub-
was a slightly higher frequency of metachronous lesions in the U area. mitted to ESD, were compared to 98 patients (mean patient age 62.7, range
Conclusion: Metachronous lesions tended to develop in the U area. These results 20–88 years, male: female ratio 52/46) who underwent EMR (20 involved ade-
suggest that it is necessary to carefully observe the U area by surveillance endo- noma with low grade dysplasia, 42 intraepithelial cancers with high-grade dys-
scopy after ESD for gastric neoplasms. plasia, 24 minute submucosal cancers, 3 submucosal deep cancers, 4 carcinoid
Disclosure of Interest: All authors have declared no conflicts of interest. tumors, 3 granular cell tumors and 2 Brunner’s adenoma). In ESD group, the
mean operation time was 1.6 hrs and the mean size of resected specimen was 25.5
mm (range 10–80 mm); in EMR group, the mean operation time was 0.5 hrs and
the mean size of resected specimen was 26.2 mm (range 10–100 mm). En-bloc
OP126 A SIMPLE SCORING SYSTEM TO STRATIFY CURABILITY resection rate, curative resection rate, piecemeal resection, recurrence rate, post-
AFTER ENDOSCOPIC SUBMUCOSAL DISSECTION FOR EARLY operative bleeding and perforation rate were compared with the use of the chi-
GASTRIC CANCER WHICH HAS PATHOLOGICAL FACTORS square test.
HIGHLY RELATED WITH LYMPH NODE METASTASIS: Results: En-bloc resection rate (ESD: 82.4%, 42/51 vs EMR: 51%, 50/98;
DEVELOPMENT AND VALIDATION OF ‘‘ECURA SYSTEM’’ p 5 0.01) and curative resection rate (ESD: 88.2%, 45/51 vs EMR: 72.9%, 71/
W. Hatta, T. Gotoda, T. Oyama, N. Kawata, A. Takahashi, Y. Yoshifuku, 98; p 5 0.05) were significantly higher in ESD group in comparison with EMR
S. Hoteya, M. Nakagawa, M. Hirano, M. Esaki, M. Matsuda, K. Ohnita, group. Piecemeal resection was significantly lower in ESD (17.7%, 9/51) when
K. Yamanouchi, M. Yoshida, O. Dohi, J. Takada, K. Tanaka, S. Yamada, compared to EMR group (49.9%, 48/98) (p 5 0.01). In the EMR group, 6
T. Tsuji, H. Ito, Y. Hayashi, N. Nakaya, T. Nakamura, T. Shimosegawa patients developed local recurrences (6.1%): five were successfully treated by
The EAST study group, Tokyo/Japan additional EMR and one by surgical resection; in contrast, there was no recur-
rence in the ESD group (p ¼ NS). The post-operative bleeding rate was 3.92% (2/
Contact E-mail Address: [email protected] 51) in ESD and 3.1% (3/98) in EMR group (p ¼ NS). Perforation rate for ESD
Introduction: According to the European and Japanese guidelines for endoscopic was 3.9% (2/51) when compared to conventional EMR (2%, 2/98) (p ¼ NS).
submucosal dissection (ESD) of early gastric cancer (EGC), radical surgery is Conclusion: In the present study, we evaluated the efficacy of 2 endoscopic resec-
recommended for patients after ESD that does not meet the curative criteria tion methods from the perspectives of the en-bloc and curative resection rates.
because of the potential risk of lymph node metastasis (LNM). However, as Based on these aspects, an ESD was found to be the best method for early
LNM occurs in only 5–10% of patients who undergo radical surgery, this recom- gastrointestinal cancers; EMR would be a good alternative to an ESD, especially
mendation for all such patients may be overestimated. in poor-risk patients or when performed by less experienced endoscopists.
Aims & Methods: This multicenter study aimed to establish a scoring system Disclosure of Interest: All authors have declared no conflicts of interest.
(eCura system) for deciding the potential risk of LNM after ESD with patholo-
gical factors related with LNM. Of the 15,785 consecutive patients who under-
went ESD for EGC from January 2000 to August 2011, we retrospectively Reference
reviewed 2,006 patients who did not meet the curative criteria for ESD of 1. Ishihara R, Iishi H, Uedo N, et al. Comparison of EMR and endoscopic
EGC. This study consisted of two stages. First, the risk-scoring system for submucosal dissection for en-bloc resection of early esophageal cancers in
LNM was developed using multivariate logistic regression analysis in 1,101
Japan. Gastrointest Endosc 2008; 68: 1066–72.
patients who underwent radical surgery after having failed to meet the curative
criteria. The estimated factors were tumor size (430 mm), tumor depth (sub-
mucosal invasion 500 mm: SM2), histopathological type (undifferentiated-type),
lymphatic invasion, venous invasion, ulceration (scar), and positive vertical
margin (VM). We assigned weighted points proportional to b regression coeffi- OP128 LONG-TERM OUTCOME OF THE INCIDENCE RATE OF
cient values for the factors determined in the multivariate analysis. Second, for METACHRONOUS GASTRIC CANCERS AFTER HELICOBACTER
validating the risk-scoring system, the validity by survival analysis was evaluated PYLORI ERADICATION – A FOLLOW-UP AND ANALYSES OF
in 905 patients without additional treatment. JAPAN GAST STUDY GROUP ENROLLED PATIENTS
Results: In the development stage, based on accordant regression coefficients, five K. Fukase
risk factors for LNM were weighted with point values: 3 points for lymphatic Gastroenterology, Yamagata Prefectural Central Hospital, Yamagata/Japan
invasion and 1 point each for tumor size 430 mm, positive VM, venous invasion,
and SM2. Then, the patients were categorized into three LNM risk groups: low Contact E-mail Address: [email protected]
(0–1 point: 2.5% risk), intermediate (2–4 points: 6.7%), and high (5–7 points: Introduction: The author and Japan Gast Study Group (JGSG) reported that the
22.7%). The C statistic (95% confidence interval (CI)) of the system for LNM eradication of Helicobacter pylori reduced the incidence of metachronous gastric
was 0.74 (0.62–0.87) and the bootstrapping analysis showed similar results (95% cancers (GC) after endoscopic mucosal resection significantly in the Lancet
CI, 0.62–0.86). In the validation stage, cancer-specific survival differed signifi- 20081).
cantly among these groups (99.6%, 95.5%, and 90.1%, respectively, at 5 years; Aims & Methods: We analyse long-term outcomes of the incidence rate of meta-
p 5 0.001). Cox proportional hazards regression analysis showed that the high- chronous GC for JGSG enrolled patients at Yamagata Prefectural Central
risk [hazard ratio (95% CI) ¼ 15.5 (4.03–59.4), p 5 0.001] and intermediate-risk Hospital. Out of 89 enrolled patients, 6 patients died by other diseases and 43
[6.63 (1.75–25.1), p ¼ 0.005] groups had significantly higher cancer-specific mor- patients were introduced to other clinics and hospitals, therefore 40 patients (the
tality compared with the low-risk group. Moreover, the C statistic of the system eradication group 21, the non-eradication group 19) were followed-up at
for cancer-specific mortality was 0.78. Yamagata Prefectural Central Hospital. After this Lancet study, non-eradication
Conclusion: This scoring system predicted cancer-specific survival, which may be patients were recommended to receive an eradication therapy. Patients have been
helpful to value the risk of LNM in patients after ESD that does not meet the followed-up once a year endoscopically. Among 40 patients the longest follow-up
curative criteria. case is in 15th observation year. A long-term incidence rate of metachronous GC
Disclosure of Interest: All authors have declared no conflicts of interest. was analysed and compared between the two groups.
Results: Out of the eradication group, 1 metachronous GC was detected (9 years
7 months after the enrollment). Out of the non-eradication group, 4 metachro-
nous GC were detected (5 years 3 months, 6 years 7 months, 10 years 2 months,
OP127 COMPARISON OF EMR AND ENDOSCOPIC SUBMUCOSAL 13 years 10 months after the enrollment). When these 4 lesions were detected, 3
DISSECTION FOR RESECTION OF EARLY STAGE cases were not yet eradicated and 1 case was eradicated unsuccessfully. The
GASTROINTESTINAL CANCER incidence rate of metachronous GC of the eradication group was 4.8% but
that of the non-eradication group was 21.1%.
P. Gambitta1, F. Iannuzzi2, A. Ballerini2, E. Bareggi2, S. Pallotta2, P. Fontana2, Conclusion: The incidence rate of metachronous GC of the non-eradication
M. Vertemati3 group was about four times higher than that of the eradication group even in
1
Digestive Endoscopy, ASST Fatebenefratelli-Sacco, Milano/Italy 15th observation year. All 4 cases of metachronous GC of the non-eradication
2
Digestive Endoscopy, ASST Fatebenefratelli-Sacco, milano/Italy group were persistent infected cases. The earlier eradication of Helicobacter
3
Scienze Biomediche E Cliniche, ‘‘L. Sacco’’ Universita’ Studi Milano, milano/Italy pylori is recommended.
Contact E-mail Address: [email protected] Disclosure of Interest: All authors have declared no conflicts of interest.
Introduction: Endoscopic mucosal resection (EMR) and endoscopic submucosal
dissection (ESD) are now being increasingly used for the treatment of gastro-
intestinal neoplasia. However, their efficacies (en-bloc and curative resection) Reference
have not been compared. EMR is associated with local recurrences, especially 1. Fukase K, et al. Effect of eradication of Helicobacter pylori on incidence of
when lesions larger than 20 mm are resected in a piecemeal manner (1). In metachronous gastric carcinoma after endoscopic resection of early gastric
piecemeal-resected specimens, histologic assessment becomes difficult, because cancer: an open-label, randomised controlled trial. Lancet 2008; 372: 392–97.
of the effects of burning on the lesion. ESD permits a larger resection of the
tissue over the muscularis propria, including large lesions and positive non-lifting
sign lesions, with its major advantage being the ability to achieve a higher en-bloc
resection rate due to submucosal dissection with a direct view. This results in
enhanced curability and more accurate histopathological assessment. However,
A54 United European Gastroenterology Journal 4(5S)

Table (OP130)

Risk factors for enterococcal cholangitis

Enterococcus spp. Non-enrerococcus
isolation spp. isolation Univariate analysis Mutivariate analysis
Adjusted odds ratio
(N ¼ 109) (N ¼ 82) Odds ratio (95% CI) P value (95% CI) P value

Age(years) 76.4(42–97) 71.4(34–97)

age=75 65(60%) 35(43%) 1.984(1.109–3.548) 0.028 1.637(0.844–3.191) 0.144
Male gender 72(66%) 55(67%) 0.955(0.520–1.754) 1
Onset after 48 h admission 21(19%) 19(23%) 0.791(0.393–1.593) 0.591
Biliary tract malignancies 54(50%) 38(46%) 1.137(0.640–2.018) 0.77
Diabetes mellitus 22(20%) 19(23%) 0.838(0.419–1.679) 0.722
Prior cholecystitis 12(11%) 4(4.9%) 2.412(0.749–7.774) 0.187
CBD stone 48(44%) 38(46%) 0.911(0.512–1.620) 0.77
Gallstone or biliary sludge 63(58%) 52(63%) 0.790(0.439–1.423) 0.458
Prior PTCD 12(11%) 9(11%) 1.003(0.401–2.508) 1
Prior EST 51(47%) 11(13%) 5.676(2.713–11.87) 50.0001 4.480(1.907–11.26) 0.0005
Presence of device in biliary tract 45(41%) 15(18%) 3.141(1.595–6.183) 0.0009 1.442(0.600–3.419) 0.408
Biliary tract reconstruction 14(13%) 2(2.4%) 5.895(1.301–26.71) 0.015 8.945(2.247–60.12) 0.001
Prior cholecystectomy 24(22%) 10(12&) 2.033(0.912–4.532) 0.088
Stay in ICU in present admission 53(49%) 35(43%) 1.244(0.698–2.218) 0.467
Stay in ICU in past admission 44(40%) 17(21%) 2.588(1.342–4.992) 0.005 1.731(0.826–3.675) 0.146
Any antibiotic treatment within previous 14 days 25(23%) 11(13%) 1.921(0.884–4.175) 0.134
Cephalosporins 17(16%) 10(12%) 1.330(0.574–3.081) 0.537
Penicillins 9(8.1%) 1(1.2%) 7.29(0.905–58.74) 0.045 3.157(0.461–64.83) 0.269

OP130 A STUDY TO INVESTIGATE RISK FACTOR FOR

MONDAY, OCTOBER 17, 2016 15:45–17:15 ENTEROCOCCUS SPECIES ISOLATION FROM BILE AND /OR
HEPATIC CYSTS AND HEPATO-BILIARY TRACT DISORDERS – ROOM BLOOD CULTURE OBTAINED FROM PATIENTS WITH
L8_____________________ CHOLANGITIS
Y. Karasawa, N. Toda, K. Kurokawa, J. Arai, C. Shibata, K. Hunato,
OP129 THE EFFECT OF PASIREOTIDE IN CYST REDUCTION OF S. Kurosaki, S. Kawamura, S. Maeshima, M. Kondo, K. Kojima, T. Oki,
ASPIRATION SCLEROTHERAPY IN PATIENTS WITH LARGE M. Seki, K. Tagawa
SYMPTOMATIC HEPATIC CYSTS, A RANDOMIZED CONTROLLED Gastroenterology, Mitsui Memorial Hospital, Tokyo/Japan
TRIAL
T.F.m. Wijnands1, T.J.G. Gevers1, M. A. Lantinga1, L. J. Schultze Kool2, Contact E-mail Address: [email protected]
J.P.h. Drenth1 Introduction: Knowledge of pathogenic spectrum for cholangitis is important for
1
Gastroenterology and Hepatology, Radboud university medical center, Nijmegen, adequate empiric therapy. Enterococcus species, which come well equipped with a
Nijmegen/Netherlands variety of intrinsic antibiotic resistances, are sometimes isolated. However, little
2
Radiology, Radboud University Medical Center, Nijmegen, Nijmegen/Netherlands is known of risk factors for this organism’s isolation in patients with cholangitis.
We conducted a study to investigate them on the basis of single-center experience
Contact E-mail Address: [email protected] in Japan.
Introduction: Aspiration sclerotherapy is a therapeutical option for large sympto- Aims & Methods: Consecutive 191 hospitalized patients with cholangitis with
matic hepatic cysts. However, inadequate cyst reduction is frequently reported. positive bile and /or blood culture between January 2009 and October 2015
Somatostatin analogues are able to curtail cyst volume. We hypothesized that were enrolled. Diagnosis of cholangitis was based on clinical symptoms, blood
combining the long-acting somatostatin analogue pasireotide (SOM230) with chemistry and radiological imaging. Potential risk factors for Enterococcus spe-
aspiration sclerotherapy would enhance hepatic cyst reduction. cies isolation such as patient attributes (Age, sex, underlying conditions, and past
Aims & Methods: Our aim was to test whether pasireotide could improve the history) were retrospectively investigated. Univariate and multivariate analyses
efficacy of aspiration sclerotherapy of large symptomatic hepatic cysts. We con- to identify risk factors were performed using a proportional hazards model.
ducted a single-center, randomized (1:1 ratio), double-blind, placebo-controlled Results: 127 patients were men (67%). The average age was 74.2(34–97) years.
trial in patients with a large (4 5 cm) symptomatic hepatic cyst. All patients Enterococcus species were isolated in 128 episodes from bile and /or blood cul-
underwent aspiration sclerotherapy. In addition, we randomized patients ture. Age over 75 years old(Odds Ratio [OR]¼1.984; 95% Confidence Interval
between two arms: (1) pasireotide 60 mg long-acting release (LAR) injection or [CI] 1.109–3.548; P ¼ 0.028), prior endoscopic sphinterotomy(OR ¼ 5.676; CI
(2) placebo (saline) injection. Injections were administrated two weeks prior and 2.713–11.87; P50.0001), presence of device in biliary tract(OR ¼ 3.141; CI
two weeks after aspiration sclerotherapy. Primary endpoint was proportional 1.595–6.183; P ¼ 0.0009), biliary reconstruction(OR ¼ 5.895; CI 1.301–26.71;
cyst diameter reduction after six weeks, as measured by ultrasonography. P ¼ 0.015), stayed in Intensive Care Unit in past admission(OR ¼ 2.588; CI
Secondary outcomes included long-term diameter reduction at 26 weeks, symp- 1.342–4.992; P ¼ 0.005), administration of penicillins(OR ¼ 7.29; CI 0.905–
tomatic change at 26 weeks, and safety during the study. Symptomatic change 58.74; P ¼ 0.045) were identified as risk factors for Enterococcus species isolation
was evaluated using the polycystic liver disease-questionnaire (PLD-Q) that by the univariate analysis. Multivariate analysis revealed that prior endoscopic
assesses frequency and severity of 14 disease-specific symptoms leading to a sphinterotomy (OR ¼ 4.480; 95%CI 1.907–11.26; P ¼ 0.0005) and biliary
total PLD-Q sum score. reconstruction(OR ¼ 8.945; CI 2.247–60.12; P ¼ 0.001) were independent signifi-
Results: Thirty-four patients (32 females (94%); mean age 53.6  7.8 years) were cant risk factors.
randomized between pasireotide (n ¼ 17) and placebo (n ¼ 17). Pasireotide did Conclusion: We found prior endoscopic sphinterotomy and biliary reconstruction
not improve efficacy of aspiration sclerotherapy at six weeks compared to con- were independent risk factors for Enterococcus species isolation in cholangitis.
trols (23.6% [IQR 9.6–31.8%] versus 21.8% [IQR 9.6–31.8%], respectively; We should consider empirial therapy with anti-enterococcal antibiotics when
p ¼ 0.96). Long-term cyst diameter reduction was similar in both groups managing patients with these attributes.
(49.1% [IQR 27.0–73.6%] and 45.5% [IQR 29.2–59.6%]; p ¼ 0.90). Mean Disclosure of Interest: All authors have declared no conflicts of interest.
PLD-Q scores improved significantly in both groups (p 5 0.01) indicating symp-
tomatic relief, but there were no differences between groups (p ¼ 0.92). Transient
hyperglycaemia was seen in all patients allocated to pasireotide.
Conclusion: Aspiration sclerotherapy is a highly effective treatment option of OP131 MENOPAUSAL HORMONE THERAPY AND RISK OF BILIARY
large symptomatic hepatic cysts, spiking with pasireotide does not further TRACT CANCER
improve efficacy. C. Kilander1, J. Lagergren2, O. Sadr-Azodi3, N. Brusselaers1
Disclosure of Interest: J.P.H. Drenth: Novartis provided the study drug and 1
Dept Of Molecular Medicine and Surgery, Karolinska Institutet, Stockholm/
partially funded this investigator-initiated study. Novartis did not have any influ- Sweden
ence on the execution of the trail or the preparation of the manuscript. 2
Division Of Cancer Studies, Kings’ College London, London/United Kingdom
All other authors have declared no conflicts of interest. 3
Institute Of Environmental Medicine, Unit Of Epidemiology, Karolinska Institutet
UGIR, MMK, Stockholm/Sweden
Contact E-mail Address: [email protected]
Introduction: The risk of developing biliary tract cancer, including cancers of the
gallbladder and the extra-hepatic bile ducts, may be influenced by estrogen
United European Gastroenterology Journal 4(5S) A55
exposure.1 Exogenous estrogens are used extensively to alleviate symptoms of valuable to preoperative diagnosis of ECC. MUC3A is expected to become one
menopause, but the effect on biliary tract cancer risk is not known.2 of diagnosis and detection indicator of ECC.
Aims & Methods: This was a population-based cohort study conducted in Sweden Disclosure of Interest: All authors have declared no conflicts of interest.
between July 2005 and December 2011 aiming to investigate the risk of biliary
tract cancer after menopausal hormonal therapy (MHT). The National
Prescribed Drug Register was used to identify MHT exposed women during
the study period. For each exposed woman, three unexposed women were ran- OP133 KINETICS OF PULMONARY ANGIOGENESIS IN MOUSE
domly selected from the same study base. Unexposed individuals were exactly COMMON BILE DUCT LIGATION-INDUCED LIVER FIBROSIS
matched for history of delivery, thrombotic events and hysterectomy, creating 8 S. Raevens1, L. Devisscher1, A. Paridaens1, S. Lefere1, C. Casteleyn1,
strata. Furthermore, additional matching (nearest neighbor) was performed for K.R. Bracke2, T. Maes3, X. Verhelst1, H. Van Vlierberghe1, C. Van Steenkiste1,
age, smoking status, alcohol use, obesity and diabetes within each stratum. A. Geerts1, I. Colle1
Record linkage to the Swedish Patient Register allowed collection of potential 1
Dpt Of Gastroenterology-hepatology, Ghent University, Ghent/Belgium
confounding factors and status of the matching variables. The cohort was fol- 2
Repiratory Medicine, Ghent University Hospital, Ghent/Belgium
lowed-up for biliary tract cancer and death by linkage to The Swedish Cancer 3
Respiratory Medicine, Ghent University Hospital, Ghent/Belgium
Register and the Cause of Death Register. Logistic regression models were esti-
mated to calculate odds ratios and matching 95% confidence intervals for the Contact E-mail Address: [email protected]
association between MHT exposure and biliary tract cancer. All analyses were Introduction: Hepatopulmonary syndrome (HPS) is a severe pulmonary compli-
stratified according to MHT regimen (estrogen or estrogen/progestogen combi- cation of liver disease for which no medical treatment is available. In rats,
nations). All matching variables were included in the logistic models. common bile duct ligation (CBDL) has been documented as a model for
Additionally, the risk of developing symptomatic gallstone disease was evaluated human HPS, which is characterized by pathological pulmonary angiogenesis.
using a similar logistic regression model. Studies in genetically modified mice could offer opportunities for further
Results: The final cohort included 290,186 MHT exposed, and 870,165 unex- research, however, in this species the development of pulmonary angiogenesis
posed, women. The resulting total cohort consisted of more than 1.1 million in biliary cirrhosis has not been outlined yet.
women and follow-up was performed over 7 years. The odds of gallbladder Aims & Methods: We aimed to elucidate the temporal changes in proangiogenic
cancer was decreased in MHT-exposed women (OR 0.6, 95% CI 0.4–0.8), signature of hepatic and pulmonary vasculature after CBDL in mice and in
whereas no clear association between MHT-exposure and cancers of the extra- addition identify potential proangiogenic factors contributing to the pathogenesis
hepatic bile ducts was seen (OR 0.8, 95% CI 0.6–1.2). There were no clear of HPS. Male Swiss mice underwent CBDL or sham surgery and were sacrificed
differences when the analyses were stratified for estrogen or estrogen/progester- at a weekly basis for 6 consecutive weeks. Pulmonary inflammation was studied
one-combinations. Adjusting for clinically manifest gallstone disease attenuated by cytology on broncho-alveolar lavage fluid, myeloperoxidase assay and lumi-
the odds of gallbladder cancer in MHT-exposed women (OR 0.8, 95% CI 0.6– nex bead based assay on lung tissue. Liver and lungs were collected for protein
1.2). Additionally, MHT exposure significantly increased the risk of gallstone analysis and histology to assess liver fibrosis and hepatic and pulmonary angio-
disease (OR 7.0, 95% CI 6.6 – 7.3). genesis. Scanning electron microscopy was performed on vascular corrosion casts
Conclusion: In conclusion, this large cohort study did not support a clear asso- to visualize pulmonary vasculature during cirrhosis ex vivo.
ciation between MHT and BTC. Furthermore, the reduced risk of GBC after Results: CBDL progressively induced liver fibrosis from week 1 (F0–1) to week 6
MHT exposure is likely to be explained by increased risk of symptomatic gall- (F4). This was accompanied by a gradual increase in hepatic immunopositivity
stone disease resulting in cholecystectomy. Thus, this study supports the role of for Endoglin and von Willebrand Factor, two markers of endothelial cell activa-
gallstones as an intermediate step in the development of GBC. tion (P 5 0.0001). Hepatic levels of vascular endothelial growth factor (VEGF),
Disclosure of Interest: All authors have declared no conflicts of interest. VEGF receptor 1 and 2 were significantly increased at week 6, whereas placental
References growth factor (PlGF), which is exclusively involved in pathological angiogenesis,
was already upregulated at week 2 (P 5 0.0001). In the pulmonary compartment,
1. Moerman CJ, Berns MP, Bueno de Mesquita HB and Runia S. Reproductive CBDL resulted in neutrophil infiltration and increased pro-inflammatory med-
history and cancer of the biliary tract in women. Int J Can 1994; 57(2): iators from week 2 to 6 (all P 5 0.001). Pulmonary immunoreactivity for
146–53. Endoglin and von Willebrand Factor progressively increased from week 4 to 6,
2. Maclennan AH, Broadbent JL, Lester S, Moore V. Oral oestrogen and while PlGF was already increased from week 2 onwards (all P 5 0.0001).
combined oestrogen/progestogen therapy versus placebo for hot flushes. Scanning electron microscopy revealed regions of abnormal vascular architec-
The Cochrane database of systematic reviews. 2004(4):CD002978. ture, mainly located at the pleural side, decreased intercapillary distance
(P 5 0.001) and increased capillary density (P 5 0.05) in lungs of cirrhotic mice.
Conclusion: CBDL in mice is associated with pathological pulmonary angiogen-
esis and may represent a model for human HPS. In addition, we point to PlGF as
OP132 MUCIN3A, A PROMISING TUMOR MARKER FOR DIAGNOSIS an early indicator of pathological hepatic and pulmonary angiogenesis.
OF EXTRAHEPATIC CHOLANGIOCARCINOMA Disclosure of Interest: S. Raevens: Sarah Raevens is sponsored by the Research
J. Yang, X. Zhang, H. Jin, H. Shen Foundation Flanders (FWO14/ASP/200)
Gastroenterology, Hangzhou First People’s Hospital, Hangzhou/China S. Lefere: Sander Lefere is sponsored by the Research Foundation Flanders
(FWO15/ASP/146)
Contact E-mail Address: [email protected] X. Verhelst: Xavier Verhelst is sponsored by the Research Foundation Flanders
Introduction: The prognosis of extrahepatic cholangiocarcinoma (ECC) was poor (1700214N).
for the difficulty of early diagnosis due to their anatomical location and insidious H. Van Vlierberghe: Hans Van Vlierberghe is senior clinical investigator of the
onset, and little effective tumor markers. Our previous study showed Mucin3A Research Foundation Flanders.
(MUC3A) was the main differential protein in bile with proteomics technology All other authors have declared no conflicts of interest.
using isobaric tags for relative and absolute quantitation (iTRAQ) in 20 patients
with ECC and 20 patients with sphincter of oddi dysfunction (SOD).
Aims & Methods: Aim: To validate the histologic expression of MUC3A in ECC
and explore diagnosis value of serum MUC3A as the potential tumor marker for OP134 EPIDEMIOLOGY OF GALLBLADDER POLYPS ON
diagnosis of ECC. Methods: (1) The expression of MUC3A was detected in 15 HISTOLOGICAL ASSESSMENT AFTER CHOLECYSTECTOMY
specimens of ECC and 20 normal bile duct tissues specimens by immunohisto- S. Z. Wennmacker1, A. H. Van Dijk2, J. Raessens1, P. R. De Reuver3,
chemistry method. The relationship between MUC3A and the clinicopathologic J.P.h. Drenth4, C. J.h.m. Van Laarhoven1, I. D. Nagtegaal5
features of ECC were investigated. (2) Serum MUC3A were detected in 16 pre- 1
Surgery, Radboudumc, Nijmegen/Netherlands
operative patients with ECC and 15 preoperative patients with SOD, Serum 2
Academical Medical Center, Amsterdam/Netherlands
MUC3A in 16 patients with ECC were compared preoperative with postopera- 3
Radboudumc, Nijmegen/Netherlands
tive one month. (3) The clinical diagnosis application of serum MUC3A was 4
Gastroenterology and Hepatology, Radboudumc, Nijmegen/Netherlands
compared with CEA, CA19–9 in 20 patients with ECC and 20 patients with 5
Pathology, Radboudumc, Nijmegen/Netherlands
SOD.
Results: (1) The positive cells rates of MUC3A in ECC specimens were significant Contact E-mail Address: [email protected]
higher than in normal bile duct tissues specimens (83.3% vs. 35.0%, P 5 0.01). Introduction: Gallbladder polyps can be divided in neoplastic polyps (adenoma,
The expression of MUC3A was significant correlated with metastasis of lymph dysplastic polyp, and carcinoma) and nonneoplastic polyps (eg. cholesterol
node, infiltration and UICC stage of carcinoma, differentiation grade of carci- polyp, inflammatory polyp or adenomyoma).1 Cholecystectomy is only indicated
noma (P 5 0.05). (2) The preoperative serum values of MUC3A in patients with for neoplastic polyps, as they are (pre)malignant.2 Annually, over 23,000 chole-
ECC were significant higher than patients with SOD (57.8  19.6 vs. cystectomies are performed in the Netherlands.3 However, there is scarce pathol-
25.1  9.2ng/ml, P 5 0.01). Compared with the preoperative results, postopera- ogy data on the prevalence of gallbladder polyps and attribution of neoplastic
tive one month serum MUC3A in patients with ECC were significant decreased and nonneoplastic polyps.
(26.8  4.6 vs. 57.8  19.6ng/ml, P 5 0.01). ROC curve analysis showed serum Aims & Methods: We aimed to assess nationwide pathology data on gallbladder
MUC3A could distinguish ECC with SOD while 40.7 ng/ml as the cut-off value polyps over a 10-year period. Methods: The PALGA database, the Dutch
(AUC ¼ 0.907, 84.6% sensitivity, 90% specificity). (3) The serum MUC3A has Pathology Registry,4 was used to identify all histopathologically proven gallblad-
much higher sensitivity (84.6%, 38.5%, 76.9%), specificity (90%, 95%, 85%), der polyps over the period 2003–2013. The search was restricted to histological
diagnostic accuracies (86.6%, 63%, 80.4%) and less false positive rates (10%, samples of patients  18 years of age. Biopsies, and cholecystectomies performed
5%, 15%) than serum CA19–9, CEA in diagnosing ECC. as part of primary non-gallbladder surgery (e.g. whipple or hepatectomy), were
Conclusion: MUC3A is high expression in tumor tissue of ECC, and related to excluded. All excerpts concerning primary gallbladder surgery containing a polyp
the differentiation grade and stage of tumor. The MUC3A in peripheral blood is or (focal) wall thickening 4 5 mm were included. These excerpts were rated as
neoplastic (adenoma, dysplasia, carcinoma or other malignancies) or nonneo-
plastic (all other types of polyp). If both neoplastic and nonneoplastic lesions
were present, the excerpt was classified as neoplastic. Prevalence of gallbladder
A56 United European Gastroenterology Journal 4(5S)
polyps and the attribution of neoplastic polyps and nonneoplastic polyps was OP136 HEPATITIS B VIRUS GENOTYPE, ZINC RIBBON DOMAIN-
calculated. To determine prevalence of gallbladder polyps, we obtained the total CONTAINING 1 ANTISENSE RNA 1 POLYMORPHISMS AND
number of cholecystectomies between 2003–2013 from PALGA. THEIR INTERACTIONS IN HEPATOCELLULAR CARCINOMA: A
Results: In total 220,612 cholecystectomies were performed over the period 2003– MULTI-CENTER CASE-CONTROL STUDY
2013. The PALGA search identified 4532 excerpts, representing 4349 patients. A Z. Liu, L. Liu, Z. Fan
total of 337 patients were excluded due to primary non-gallbladder surgery, Digestive Endoscopy Center, the First Affiliated Hospital of Nanjing Medical
leaving 4012 unique cholecystectomies. In 2083 cholecystectomies (0.9%), a poly- University, Nanjing/China
poid leasion was present. Which results in a calculated prevalence of polyps in
944/100,000 patients who undergone cholecystectomy. Of the polyps, 1172 Contact E-mail Address: [email protected]
(56.3%) were neoplastic; 278 (13.3%) adenomas (incl. cystadenoma), 190 Introduction: Zinc ribbon domain-containing 1 antisense RNA 1 (ZNRD1-AS1)
(9.1%) dysplastic polyps, 647 (31.1%) adenocarcinomas, and 57 (2.7%) other genetic polymorphisms have been associated with hepatocellular carcinoma
malignancies. Nine hundred and ten (43.7%) polyp were nonneoplastic; 375 (HCC) development. We aimed to determine impacts of ZNRD1-AS1 poly-
(18%) cholesterol polyps, 334 (16%) adenomyoma’s, 70 (3.7%) hyperplastic morphisms and their interactions with HBV genotypes on the risk of HCC.
polyps, 54 (2.6%) mucosal polyps, 42 (2.0%) inflammatory polyps, 18 (0.9%) Aims & Methods: We conducted a large multi-center case-control study with a
papiloma’s and 17 (0.8%) other types of polyps. total of 1,507 HBV-related HCC cases and 1,560 HBV persistent carriers. Three
Conclusion: Approximately one percent of gallbladders contain a polyp on his- single nucleotide polymorphisms (SNPs) in ZNRD1-AS1 (rs3757328, rs6940552
topathological assessment after cholecystectomy. Fifty-six percent of the polyps and rs9261204) were genotyped using TaqMan allelic discrimination assay, and
after cholecystectomy are neoplastic. HBV genotypes were identified by multiplex PCR.
Disclosure of Interest: All authors have declared no conflicts of interest. Results: We found consistently significant associations between ZNRD1-AS1
References rs6940552/rs9261204 and increasing risks of HCC (dominant genetic model:
adjusted OR ¼ 1.16, 95% CI ¼ 1.03–1.32 for rs6940552; adjusted OR ¼ 1.20,
1. Christensen AH and Ishak KG. Benign tumors and pseudotumors of the 95% CI ¼ 1.06–1.35 for rs9261204), and a borderline significant association of
gallbladder. Report of 180 cases. Arch Pathol 1970; 90(5): 423–32. rs3757328 with HCC risk. Besides, a dose-dependent manner was observed
2. Kozuka S, et al. Relation of adenoma to carcinoma in the gallbladder. between the increasing number of variant alleles of the three SNPs and the
Cancer 1982; 50(10): 2226–34. risk for HCC (P for trend 50.001). Moreover, a strong combined effect of
3. NVvH. Evidence-based guideline. Diagnosis and treatment of gallstones. three SNPs was observed among the subjects infected with non-B groups
Dutch Society for Surgery, 2016. (adjusted OR ¼ 1.26, 95% CI ¼ 1.05–1.50) on HCC risk, compared with those
4. Casparie M, et al. Pathology databanking and biobanking in The in HBV B-related genotype groups (adjusted OR ¼ 0.89, 95% CI ¼ 0.69–1.15)
Netherlands, a central role for PALGA, the nationwide histopathology (P¼ 0.029 for heterogeneity test). We also detected a significant multiplicative
and cytopathology data network and archive. Cell Oncol 2007; 29(1): 19–24. interaction between the variant alleles and HBV genotype on HCC susceptibility
(P ¼ 0.030).
Conclusion: ZNRD1-AS1 SNPs (rs3757328, rs6940552 and rs9261204) and their
MONDAY, OCTOBER 17, 2016 15:45–17:15
interaction with HBV genotypes may serve as susceptibility biomarkers for risk
MECHANISMS OF LIVER CANCER AND PORTAL HYPERTENSION – ROOM of HBV-related HCC.
1.86_____________________ Disclosure of Interest: All authors have declared no conflicts of interest.

OP135 CHANGES IN CIRCULATING MICRORNA AFTER TREATMENT:

MICRORNA SIGNATURES TO PREDICT THERAPY RESPONSE
AND DISEASE FREE SURVIVAL IN HEPATOCELLULAR OP137 HMGB1-DEPENDENT AUTOPHAGY: A NEW PATHWAY TO
CARCINOMA MAINTAIN REGULATORY T CELL FUNCTION IN PATIENTS
D. Pascut1, H. Krmac2, R. Patti1, D. Licastro3, S. Dal Monego3, N. Mezzina1, WITH CHRONIC HEPATITIS B
C. Abazia4, F. Masutti4, L. S. Crocè4, R. Calligaris2, C. Tiribelli1 J. Li1, W. Jiang2
1 1
Italian Liver Foundation, Trieste/Italy Gastroenterology, Tongji Hospital of Tongji University, Shanghai/China
2 2
International School for Advanced Studies (SISSA), Trieste/Italy Gastroenterology, Zhongshan Hospital of Fudan University, Shanghai/China
3
CBM S.c.r.l., Trieste/Italy
4
Teaching Hospital Cattinara, Trieste/Italy Contact E-mail Address: [email protected]
Introduction: Recent studies suggest autophagy is highly active in regulatory T
Contact E-mail Address: [email protected] (Treg) cells. High-mobility group box-1 protein (HMGB1), enriched in the
Introduction: Hepatocellular carcinoma (HCC) is the second leading cause of microenvironment of damaged and injured livers, is critical for T cell autophagy.
cancer-related death worldwide. Although treatment options have improved in Aims & Methods: This study is designed to determine whether and how HMGB1-
the past 30 years, prognosis remains unfavorable in many patients. The lack of dependent autophagy maintains the immunesuppressive features of Treg cells
effective models for outcome prediction prevents the opportunity for individua- during chronic hepatitis B virus (HBV) infection. Blood samples from patients
lized treatment protocols. The potential role of microRNAs (miRNA) as prog- with chronic hepatitis B (CHB, n ¼ 36), at immune-tolerant stages (IT, n ¼ 25)
nostic biomarker has witnessed an increasing interest, owing to the non-invasive and healthy controls (n ¼ 50) were collected. By flow cytometry,
nature of miRNA-based screening assays. While many studies have suggested CD4þCD25þCD127- (Treg) cells were purified from peripheral blood mononuc-
several miRNAs as biomarker candidates, dynamic variations over extended time lear cells (PBMCs) for further analysis. Serum samples were prepared to deter-
period have not been assessed until now. mine HMGB1 levels. The autophagy in Treg cells were in vitro determined with
Aims & Methods: To identify potential circulating miRNA signatures for the Lysotracker Green probes in the presence or absence of HMGB1, rapamycin and
prediction oftherapy response and patient follow-up. Methods: 15 consecutive 3-methyladenine. HMGB1-dependent autophagy pathway and its effects on Treg
patients with early/intermediated stage HCC were enrolled and treated according functions were determined by both western blot and quantitive real-time PCR.
to the ESSL/AASLD practice guidelines. Patients were staged (CT scan and/or The microtubule-associated protein 1 light chain 3 (LC3)-GFP mice were injected
MRI) at time 0 (T0, before treatment), 1 month (T1) and 6 months (T6) from with AAV-1.3HBV to further determine HMGB1-dependent autophagy in Treg
therapy. Pax-gene Blood RNA tubes and Vacuette tubes where used to collect cells in the microenvironment of livers during chronic HBV infection.
total blood and serum at T0,T1,T6. Small RNAs were isolated and hybridized on Results: Treg cells from patients in IT group had significantly up-regulated base-
Affymetrix GeneChip miRNA arrays 3.0. qRT-PCR was used for miRNA vali- line autophagy levels compared to both CHB and HC groups, reflected by
dation in an independent cohort of 15 matched patients. The Kaplan-Meier increased intracellular mass of lysosomes. The mean fluorescence intensity
model was used to estimate disease-free survival (DFS). (MFI) of lysosomes in Treg cells significantly and positively correlated with
Results: 80 single miRNA profiles have been analyzed using a microarray serum HMGB1 levels. In vitro, HMGB1 mainly acted through the receptor for
approach. We analyzed 1733 miRNas over the 6 months period. The analysis advanced glycation end-products (RAGEs) of Treg cells to up-regulate the
yielded different profile in serum and blood identifying the two biofluids as two autophagy levels, with significantly decreased phosphorylation of mTOR and
distinctive sources of miRNA carrying the same message. Only a small portion of increased Beclin-1/Vps34 proteins. Besides, HMGB1-RAGEs induced autophagy
the circulating mirnome remained significant in all time points indicating a was indispensible to maintain Foxp3, CTLA-4, IL-10 and TGF-beita mRNA
dynamic variation in the miRNA expression. Blood mir-3179, 373, 4773 signifi- levels of Treg cells. In HBV-infected mouse models, the intra-hepatic HMGB1,
cantly increased from T0 to T6 while mir-2277–5p, 106b, 202 decrease. In serum, RAGEs and LC3 expressions were significantly increased. Moreover, down-regu-
mir-4649–3p, 3148, 371 increase while mir-103b decrease. The hierarchical clus- lated p-mTOR and up-regulated Beclin-1/Vps34 proteins were detected in the
tering of the most 150 variable miRNAs on log scale clearly differentiated T0 intra-hepatic Treg cells.
profiles from T1 and T6 both in blood and serum. Interestingly at T1 two main Conclusion: HMGB1-dependent autophagy is a new mechanism to maintain the
clusters distinguished patient with a complete response from whose having only a immunosuppressive features of Treg cells during chronic HBV infection.
partial response to therapy. Further validation of miR-106b showed a correlation Disclosure of Interest: All authors have declared no conflicts of interest.
between mir-106b levels and treatment response (P 5 0.001), and the longer DFS
(P 5 0.0038). MiRNA-106b was also significantly correlated with the with BCLC
staging A1 and A2 (P 5 0.001).
Conclusion: This study underlines the importance of the different information
provided by miRNA profiles during the follow-up of a single patient. Circulating
mir-106b detection offers a promising non-invasive analysis tool to identifyg
patients with the longest disease-free survival in response to anticancer therapies.
Disclosure of Interest: All authors have declared no conflicts of interest.
United European Gastroenterology Journal 4(5S) A57
OP138 RIOCIGUAT, A STIMULATOR OF THE GUANYLYL CYCLASE, clarify the mechanisms responsible for liver atrophy, pathological analysis
REDUCES LIVER FIBROSIS AND PORTAL PRESSURE IN should be carried out within this time period. However, to the best of our knowl-
CIRRHOTIC RATS edge, these time-course studies have not yet been carried out4–5.
P. Schwabl1, K. Brusilovskaya1, F. Riedl1, D. Bauer1, B. Strobel1, P. Supper1, Aims & Methods: We attempted to investigate the mechanism of liver atrophy by
N. Rohr-Udilova1, H. Hayden1, B. Podesser2, T. Reiberger1, M. Trauner1, portal vein obstruction and clarify the role of autophagy and apoptosis. As pig
M. Peck-Radosavljevic1 lobule structures were well-defined as compared with human specimen, we per-
1
Div. Of Gastroenterology and Hepatology; Department Of Internal Medicine Iii, formed percutaneous transhepatic portal embolization (PTPE) in 5 pigs. And
Medical University of Vienna, Vienna/Austria then sacrificed them at day 0, week 2, 4 or 6 (d0, w2, w4 and w6, respectively).
2
Department Of Biomedical Research, Medical University of Vienna, Vienna/ In specimens of embolized lobe (E) and non-embolized lobe (control, Cont), we
Austria measured the distance between portal vein and central vein (PV-CV), area and
hepatocyte number per lobule and apoptotic activity. Immunohistochemical
Contact E-mail Address: [email protected] reactivates of microtubule-associated protein-light chain 3 beta (LC3) as autop-
Introduction: Intrahepatic nitric oxide (NO) signaling including activation of its hagy and glutamine synthetase (GS) and cytochrome 2E1 (CYP2E1) as zonation
receptor guanylyl cyclase (GC) is impaired in cirrhosis. The GC stimulator rio- were evaluated.
ciguat (RIO) is approved for treatment of pulmonary hypertension. Results: PV-CV and lobule area showed no significant difference between E and
Experimental studies suggest antifibrotic effects of RIO. We investigated the Cont at d0, but were lower in E than in Cont at w2, w4 or w6 (P  0.001).
effects of RIO in cirrhotic rats with portal hypertension (PHT). Hepatocyte number was not significantly reduced in E at d0 and w2 but was
Aims & Methods: Two early and advanced cirrhotic rat models were used to reduced at w4 and w6 (P  0.01). Apoptotic activity was higher in E than in Cont
assess changes in hemodynamics and fibrosis after RIO treatment. Cirrhosis at d0 and w4. LC3 staining peaked in E at w2, with no significant difference
was induced by i.p. carbontetrachloride (‘‘early’’: 1 mL/ kg - ‘‘advanced’’: between E and Cont at w4 and w6. GS and CYP2E1 areas in E at w2, w4 and w6
2 mL/ kg 50%CCl4, 8 weeks) or by bile duct ligation (BDL, ‘‘early’’: 3 weeks - were narrower than those in Cont.
or ‘‘advanced’’: 5 weeks) in 100 male Sprague Dawley rats. Controls received Conclusion: Our morphological study focused on changes in the lobules over
olive-oil (OO) or underwent sham operation (SO), respectively. RIO (1 mg/ kg/d) time, and we observed two distinct phases of liver atrophy following portal
or vehicle was gavaged from weeks 5–8 in CCl4/OO and from weeks 2–3 [or 4–5] blood flow disruption. The first (the autophagic phase) was characterized by
in BDL/SO animals. Systemic hemodynamics, portal pressure (PP), superior lobular shrinkage without hepatocytes loss and high LC3 expression, and
mesenteric blood flow (SMABF) and porto-systemic shunting (PSS) were mea- lasted for the first two weeks following PTPE. The second phase, termed the
sured. Hepatic fibrosis was quantified by hydroxyproline content (HP) and apoptotic phase, was characterized by reduced hepatocyte number without
chrome aniline blue (CAB) staining. Expression of TNF, endothelial nitric reduced lobular size but with reduced LC3 expression and increased TUNEL
oxide synthase (eNOS) and inducible NOS (iNOS) were quantified in liver staining, and lasted 2–4 weeks.
tissue by western blotting. Disclosure of Interest: All authors have declared no conflicts of interest.
Results: BDL and CCl4 rats presented with cirrhosis, elevated PP, SMABF and References
PSS, which was more pronounced in the advanced setting. In early BDL cirrho-
sis, preventive RIO treatment (W2–3) reduced PP (13.2  2.5 vs. 10.1  2.4 1. Pfeifer U. Cellular autophagy and cell atrophy in the rat liver during long-
mmHg; p ¼ 0.048), HP content (286  147 vs. 144  74 mg/g; p ¼ 0.039) and term starvation. A quantitative morphological study with regard to diurnal
CAB area (24.7  4.6 vs. 13.3  2.1%; p 5 0.001) without affecting systemic variations. Virchows Arch B Cell Pathol 1973; 12: 195–211.
hemodynamics, SMABF or PSS. When RIO was given to BDL rats with 2. Satake M, Tateishi U, Kobayashi T, Murata S and Kumazaki T.
advanced disease, PP (15.5  1.6 vs. 11.9  2.1 mm Hg; p ¼ 0.002), HP content Percutaneous transhepatic portal vein embolization: effectiveness of absolute
(354  169 vs. 233  45mg/g; p ¼ 0.044) and CAB area (29.9  2.2 vs. 19.3  5.7%; ethanol infusion with balloon catheter in a pig model. Acta Radiol 2005; 46:
p 5 0.001) all significantly improved. Further, in BDL-RIO animals, hepatic 344–52.
eNOS and iNOS content increased, while TNF expression was significantly 3. Duncan JR, Hicks ME, Cai SR, Brunt EM and Ponder KP. Embolization of
reduced. In early CCl4-rats, RIO treatment reduced CAB area (33.5  4.9 vs. portal vein branches induces hepatocyte replication in swine: a potential step
25.8  2.8%; p ¼ 0.028) while the reduction in HP was not significant. The in hepatic gene therapy. Radiology 1999; 210: 467–77.
increase in PP (8.13  1.31 vs. 6.43  0.40 mm Hg; p ¼ 0.042) and SMABF 4. Harada H, Imamura H, Miyagawa S and Kawasaki S. Fate of the human
(52  5 vs. 42  4 mL/min; p ¼ 0.010) observed in early CCl4 cirrhosis was sig- liver after hemihepatic portal vein embolization: cell kinetic and morpho-
nificantly blunted in RIO treated animals. In advanced CCl4 rats only a SMABF metric study. Hepatology 1997; 26: 1162–70.
reduction (75  11 vs. 43  6 mL/min; p ¼ 0.036) and a trend towards lower CAB 5. Komori K, Nagino M and Nimura Y. Hepatocyte morphology and kinetics
area (43.8  6.1 vs. 28.9  7.5%; p ¼ 0.056) was notable. RIO had no effects in after portal vein embolization. Br J Surg 2006; 93: 745–51.
control animals (SO and OO rats).
Conclusion: RIO treatment significantly reduced liver fibrosis and portal pressure
in early biliary and toxic cirrhosis. Even in advanced biliary cirrhosis, RIO
treatment ameliorated liver fibrosis and portal hypertension. OP140 EFFECT OF CHRONIC THIOACETAMIDE TREATMENT ON
Disclosure of Interest: P. Schwabl: payments for lectures from Roche and HEPATIC HEMODYNAMIC PARAMETERS IN RATS:
Böhringer Ingelheim; and travel support from AbbVie, Gilead, Janssen and EVALUATION BY MAGNETIC RESONANCE IMAGING
Roche D. Schaffner1, D. Elverfeldt2, P. Deibert1, A. Lazaro1, I. Merfort3, L. Lutz4, M.
T. Reiberger: received payments for lectures from Roche, as well as travel sup- W. Baumstark1, W. Kreisel5, W. Reichardt2
port from Gilead, MSD, and Roche 1
Institute For Exercise- Und Occupational Medicine, Center For Medicine,
M. Trauner: received grants from MSD, honoraria for consulting from AbbVie, Medical Center – University of Freiburg, Faculty of Medicine, University of
Gilead, Janssen, and MSD, payments for lectures from Gilead, MSD, and Freiburg, Freiburg/Germany
Roche, as well as travel support from Gilead 2
Department Of Radiology, Medical Center – University of Freiburg, Faculty of
M. Peck-Radosavljevic: grants from Gilead, MSD, and Roche, honoraria from Medicine, University of Freiburg, Freiburg/Germany
AbbVie, Boehringer Ingelheim, Bristol-Myers Squibb, Gilead, Janssen, and 3
Department Of Pharmaceutical Biology and Biotechnology, University of
MSD, payment-lectures from AbbVie, Boehringer Ingelheim, Bristol-Myers Freiburg, Freiburg/Germany
Squibb, Gilead, Janssen, MSD, and Roche. 4
Institute Of Clinical Pathology, Medical Center – University of Freiburg, Faculty
All other authors have declared no conflicts of interest. of Medicine, University of Freiburg, Freiburg/Germany
5
References Department Of Internal Medicine, Medical Center – University of Freiburg,
Faculty of Medicine, University of Freiburg, Freiburg, Germany, Freiburg/
1. Xie G. et al. Gastroenterology 2012;142(4):918–27.
Germany
2. Knorr, A. et al. Arzneimittelforschung 2008;58:71–80.
Contact E-mail Address: [email protected]
Introduction: For the investigation of hepatic hemodynamics in animal models
invasive methods are conventionally used. This study seeks to evaluate a non-
OP139 MECHANISM OF LIVER ATROPHY DUE TO PORTAL VEIN invasive Magnetic Resonance Imaging (MRI) method as a reliable diagnostic
EMBOLIZATION - ASSOCIATION WITH AUTOPHAGY AND tool in the widely used model of Thioacetamide (TAA)-induced liver injury.
APOPTOSIS Aims & Methods: (1) To quantitatively assess hepatic hemodynamic parameters
Y. Iwao1, H. Ojima2, M. Tanabe1 (portal vein area, portal blood flow velocity and portal blood flow volume) and
1
Hepatobiliary and Pancreatic Surgery, Tokyo Medical and Dental University, aortal blood flow volume using MRI technique in rats; (2) To investigate the
Tokyo/Japan influence of the hepatotoxic agent TAA on these hemodynamic parameters. 54
2
Pathology, Keio University School of Medicine, Tokyo/Japan male Wistar rats were studied. 15 of which were left untreated and 39 received
TAA in their drinking water (0.03g TAA / 100 ml H2O). The TAA dosage was
Contact E-mail Address: [email protected] adjusted weekly based on the body weight changes. From the 39 treated rats 15
Introduction: The mechanism of liver atrophy due to portal vein embolization received TAA for 12 weeks and 24 for 16 weeks. The following parameters were
was still unclear. With regard to the liver, autophagy has been reported to be measured by a 9.4 Tesla preclinical MR scanner: portal vein area, portal blood
caused by starvation and related to hepatocellular atrophy1. Using pig models of flow velocity, portal blood flow volume and aortal blood flow volume.
percutaneous transhepatic portal vein embolization (PTPE) with absolute etha- Specifically gradient-echo fast phase contrast sequences were used with both
nol, we have previously observed temporary elevation of serum levels of liver cardiac and respiratory gating. All MRI measurements were performed under
enzymes immediately after ethanol injection and macroscopic liver atrophy continuous Isoflurane anesthesia. The degree of liver injury was estimated by
accompanied by an increased future liver remnant /total estimated liver volume standard histological criteria. Histological evaluation was performed in all 54 rats
ratio 2 weeks after PTPE2. The other literature have reported that the relative while hemodynamic measurements could be evaluated in 50 rats. For statistical
lobule size in the embolized lobe of the pig had gradually decreased to 23% of the analysis Kruskal-Wallis test was used.
normal pig liver at 12 days after PTPE with a combination of coils and polyvinyl Results: From the rats which received TAA for 12 weeks 100% (15/15) developed
alcohol particles; thereafter, the size did not change3. Therefore, in order to liver fibrosis with a Desmet score of 1–3 (group 12w/fib). From the rats which
A58 United European Gastroenterology Journal 4(5S)
received TAA for 16 weeks, 46% (11/24) developed liver fibrosis with a Desmet
Reference
score of 1–3 (group 16w/fib) and 54% (13/24) had liver cirrhosis with a Desmet
score of 4 (group 16w/cir). The untreated rats (15/54) served as control group 1. Vande Casteele N, et al. Trough concentrations of infliximab guide dosing
(group con). Mean portal vein area showed no significant differences among all for patients with inflammatory bowel disease. Gastroenterology 2015.
groups. However mean portal flow velocity was reduced by 15% in group 12w/
fib, 19% in group 16w/fib and 12% in group 16w/cir compared to group con. In
group 16w/cir mean weight was significantly lower than that of group con. Thus
flow volumes were adjusted according to the body weight in order to eliminate OP142 FREQUENCY AND CHARACTERISTICS OF INFUSION
weight-induced changes in hemodynamics. Mean aortal flow volume per body REACTIONS DURING BIOSIMILAR INFLIXIMAB TREATMENT IN
weight showed no significant differences among all groups. In contrast mean INFLAMMATORY BOWEL DISEASES: RESULTS FROM CENTRAL
portal flow volume per body weight was significantly reduced in group 12w/fib EUROPEAN NATIONWIDE COHORT
by 23% compared to group con. On the other hand, in group 16w/fib and group A. Balint1, M. Rutka1, Z. Vegh2, Z. Kurti2, K.B. Gecse2, J. Banai3, L. Bene4,
16w/cir there was no further reduction of mean portal flow volume per body B. Gasztonyi5, T. Kristof6, L. Lakatos7, P. Miheller8, K. Palatka9, A. Patai10,
weight. These results indicate that in the model of TAA-induced liver injury the A. Salamon11, T. Szamosi3, Z. Szepes1, G.T. Toth12, A. Vincze13, R. Bor1,
development of fibrosis is sufficient to cause a significant decrease in portal flow A. Milassin1, F. Nagy1, M. Kolar14, M. Bortlik14, D. Duricova15, V. Hruba14,
volume. There were no significant differences between group 12w/fib and 16w/fib M. Lukas14, K. Mitrova14, K. Malickova16, M. Lukas14, P.L. Lakatos2,
in terms of all parameters, in particular portal flow volume. T. Molnar17, K. Farkas17
Conclusion: In conclusion the non-invasive MRI technique can be a reliable 1
First Department Of Medicine, University of Szeged, Szeged/Hungary
diagnostic tool to investigate the hepatic hemodynamics in different experimental 2
1st Department Of Medicine, Semmelweis University Faculty of Medicine 1st
models of liver injury. In this particular animal model even the TAA-induced Dept. of Medicine, Budapest/Hungary
liver fibrosis led to a significantly reduced portal liver perfusion. The molecular 3
Military Hospital – State Health Centre, Budapest/Hungary
mechanisms of this finding need to be further investigated. 4
Peterfy Hospital, Budapest/Hungary
Disclosure of Interest: All authors have declared no conflicts of interest. 5
Zala County Hospital, Zalaegerszeg/Hungary
6
B-A-Z County and University Teaching Hospital, Miskolc/Hungary
7
TUESDAY, OCTOBER 18, 2016 08:30–10:00 Csolnoky Ferenc Regional Hospital, Veszprem/Hungary
8
OPTIMISING ANTI-TNF THERAPY – ROOM G_____________________ Second Department of Internal Medicine, Budapest/Hungary
9
Department Of Internal Medicine, Division Of Gastroenterology, University of
Debrecen, Faculty of Medicine, Debrecen/Hungary
OP141 CORRELATION OF ENDOSCOPIC FINDINGS WITH SERUM 10
Markusovszky Hospital, Szombathely/Hungary
DRUG CONCENTRATIONS AND NEED FOR RESCUE THERAPY: 11
Tolna County Teaching Hospital, Szekszard/Hungary
SUBANALYSIS OF THE TROUGH CONCENTRATION ADAPTED 12
Janos Hospital, Budapest/Hungary
INFLIXIMAB TREATMENT (TAXIT) TRIAL 13
University of Pecs, Pecs/Hungary
14
L. Pouillon, M. Ferrante, G. Van Assche, M. Noman, A. Gils, S. Vermeire IBD Clinical and Research Centre, Iscarea.s., Prague/Czech Republic
15
Department Of Gastroenterology and Hepatology, University Hospitals Leuven, Isicare, A.s., PharmaSwiss Ceska Republika, Praha /Czech Republic
16
Leuven/Belgium 19Institute of Medical Biochemistry and Laboratory Diagnostics, 1st Medical
Faculty and General Teaching Hospital, Charles University, Prague/Czech
Contact E-mail Address: [email protected] Republic
Introduction: The Trough Concentration Adapted Infliximab Treatment 17
First Department Of Internal Medicine, University of Szeged, Szeged/Hungary
(TAXIT) randomized controlled trial [1] showed that targeting patients’ inflix-
imab trough concentrations to a 3–7 mg/mL window resulted in a more efficient Contact E-mail Address: [email protected]
use of the drug in patients with inflammatory bowel disease. Following dose Introduction: Safety data of the immunogenicity coming from the ‘real life’ use of
optimization, continued concentration-based dosing was not superior to clini- CT-P13, the first biosimilar to infliximab, in inflammatory bowel disease (IBD)
cally-based dosing for achieving clinical and biochemical remission (primary are still lacking.
endpoint) after 1 year maintenance treatment. This subanalysis of TAXIT Aims & Methods: Our aim was to assess the frequency and characteristics of
aimed to explore the correlation between drug level-based dosing and endoscopic infusion reactions during CT-P13 therapy in 13 Hungarian and 1 Czech IBD
healing. centres. Demographic data were collected and a harmonized monitoring strategy
Aims & Methods: This was a retrospective analysis of all endoscopies performed was applied. Trough level (TL) and anti-drug antibody (ADA) concentration
at the end of TAXIT. For Crohn’s disease (CD), mucosal healing was defined as were regularly measured by ELISA at baseline and before every subsequent
absence of ulcerations (complete mucosal healing) or clear improvement in CT-P13 therapy in the Hungarian cohort. Predictors, characteristics, therapy
ulcerations (partial mucosal healing) when compared to baseline. For ulcerative and outcomes of infusion reactions were prospectively evaluated.
colitis (UC), healing was defined as a Mayo endoscopic subscore of 0 or 1. Rates Results: 384 consecutive IBD patients were included in the present cohort.
of mucosal healing were compared for both arms in TAXIT (clinically-based arm Twenty-eight Hungarian IBD patients (9.6%) developed infusion reaction
1 and concentration-based dosing arm 2) and infliximab trough concentrations during the treatment. Infusion reaction did not occur in the Czech population
were correlated to the degree of healing. thus predictors were assessed only in the Hungarian patients. Infusion reaction
Results: Of the 226 patients completing the TAXIT maintenance phase, 125 occurred most frequently during the 2nd and 3rd infusion. The most frequent
(55%) underwent endoscopy after one year (n ¼ 55 in arm 1 and n ¼ 70 in arm symptoms of infusion reactions were flushing, dyspnoea and chest pain. CT-
2). In the clinically-based dosing arm 1, 50/55 (91%) patients had mucosal heal- P13 therapy had to be stopped in 78.6% of the cases and was switched to
ing at the end of the study, as compared to 63/70 (90%) patients in the concen- adalimumab in 42.8% of the patients. However in 21.4% CT-P13 therapy was
tration-based dosing arm 2 (p ¼ 1). The rates of mucosal healing were also continued with the use of supplementary intervention. Previous anti-TNF expo-
comparable between both arms in CD patients (35/38 in arm 1 vs. 49/52 in sure and ADA positivity during the induction therapy were predictive factor for
arm 2; p ¼ 0.69) and in UC patients separately (15/17 in arm 1 vs. 14/18 patients infusion reaction. Concomitant azathioprine therapy showed borderline protec-
in arm 2; p ¼ 0.66). Patients who reached the primary endpoint of TAXIT more tive effect on infusion reaction.
frequently had complete mucosal healing (73/84 or 87%) compared to patients Conclusion: Patients with previous exposure to anti-TNFs and ADA positivity
who did not reach the primary endpoint (28/41 or 68%) (p ¼ 0.02). Numerically during the induction therapy were more likely to develop infusion reactions. CT-
more patients who needed rescue therapy during maintenance phase of TAXIT P13 biosimilar is safe with low rate of infusion reaction.
had not achieved mucosal healing (3/12 or 25%) compared to patients who did Disclosure of Interest: All authors have declared no conflicts of interest.
not need rescue therapy (9/113 or 8%) (p ¼ 0.09). The mean serum trough con-
centrations during the maintenance phase of TAXIT were 5.31 mg/mL in patients
with mucosal healing and 4.26 mg/mL in patients without mucosal healing
(p ¼ 0.07). OP143 AZATHIOPRINE DOSE REDUCTION INFLAMMATORY BOWEL
Conclusion: The primary endpoint of TAXIT, clinical and biochemical remission, DISEASE PATIENTS ON COMBINATION THERAPY: A
correlated with endoscopic mucosal healing. Similar rates of mucosal healing PROSPECTIVE STUDY
were observed in patients after clinically-based dosing compared to concentra- E. Del Tedesco1, S. Paul2, H. Marotte3, N. Williet4, J.M. Phelip1, L. Peyrin-
tion-based dosing. A trend towards less mucosal healing was seen if rescue ther- Biroulet5, J. Colombel6, X. Roblin1
apy was needed during TAXIT. Mean serum trough concentrations during the 1
University of St. Etienne Dept. de Gastroenterologie, Saint Etienne/France
maintenance phase of TAXIT were higher in patients with mucosal healing. 2
Hôpital Nord, Saint Etienne/France
Disclosure of Interest: M. Ferrante: Financial support for research from Janssen, 3
university of saint etienne, saint etienne/France
Takeda. Lecture fees from Tillotts, Ferring, Boehringer-Ingelheim, Janssen, 4
CHU, Saint Priest en Jarez/France
Chiesi, Falk, Zeria, Mitsubishi Tanabe, MSD, Takeda, Abbvie. Consultancy 5
Department Of Gastroenterology, Nancy University Hospital, Vandoeuvre les
for Abbvie, Ferring, MSD, Boehringer-Ingelheim, Janssen. Nancy/France
G. Van Assche: Financial support for research from Abbvie, MSD. Lecture fees 6
Icahn Scholl of Medicine at Mount Sinai, New York/United States of America
from Janssen, Takeda, Ferring, MSD, Abbvie. Consultancy for Abbvie, MSD,
Takeda. Contact E-mail Address: [email protected]
A. Gils: Lecture fees from MSD, Janssen Biologicals, Abbvie, Pfizer, Takeda. Introduction: Combination therapy with infliximab (IFX) and azathioprine (A) is
Consultancy for UCB. Conflict with license of infliximab, anti-infliximab and the most effective strategy in patients with Crohn’s disease (CD) and ulcerative
adalimumab ELISA from Institution to apDia and with lateral flow infliximab to colitis (UC) naive to both therapies. However the optimal dose of AZA which is
R-Biopharm AG. needed is still controversial. We assessed the impact of AZA dose reduction on
S. Vermeire: Grant/research support from Takeda, MSD, Abbvie. Consultancy/ the risk of clinical relapse and pharmacokinetics of IFX in inflammatory bowel
speaker’s fees from Abbvie, MSD, Takeda, Pfizer, Galapagos, Genentech/Roche, disease (IBD) patients on combination therapy.
Mundipharma, Celgene, Hospira, Second Genome. Aims & Methods: This prospective study included three cohorts of IBD patients
All other authors have declared no conflicts of interest. treated for at least one year with IFX-AZA and being in deep remission (clinical
United European Gastroenterology Journal 4(5S) A59

Table (OP144): Clinical and serological evolution after dose de-escalation

T-1 (n ¼ 33) T0 (n ¼ 43) T1 (n ¼ 43) T2 (n ¼ 26)

Median (IQR) time from T0 18.0 weeks (13.5–26.1) 14.0 weeks (12.3–19.0) 30.5 weeks (26.8–34.5)

Median (IQR) ADA serum level 11.6 mg/mL (9.1–15.1) 11.5 mg/mL (9.3–14.3) 7.5 mg/mL (5.8–9.8) p 5 0.001 7.2 mg/mL (5.4–8.6) p 5 0.001

Median (IQR) C-reactive protein 1.6 mg/L (0.4–4.9) 1.4 mg/L (0.6–3.3) 1.3 mg/L (0.6–5.1) p ¼ 0.217 1.7 mg/L (0.6–4.1) p ¼ 0.139

Median (IQR) serum albumin 44.5 g/L (42.6–47.0) 44.1 g/L (42.2–47.0) 43.7 g/L (41.6–47.2) p ¼ 0.893 42.4 g/L (40.9–45.0) p ¼ 0.330

Median (IQR) PRO2 UC 0.0 (0.0–0.0) 0.0 (0.0–0.0) 0.0 (0.0–0.0) p ¼ 1.000

Median (IQR) PRO2 CD 0.0 (0.0–7.0) 0.0 (0.0–6.0) 2.0 (0.0–9.0) p ¼ 0.048 4.5 (0.0–9.8) p ¼ 0.021

p-values: relative to T0, Wilcoxon Signed Rank test; IQR: interquartile range During a median follow-up of 24 months, 39% of patients needed dose escalation to ADM
40 mg every other week due to clinical relapse (23%), ADM serum levels 53 mg/mL (7%) or both (9%). The only independent factor associated with dose escalation
free survival was a baseline CRP 5 3 mg/L [Odds ratio 3.76 (1.41–10.05), p ¼ 0.008]. We were not able to define a minimal ADM serum level at T0 or T1 to consider or
maintain dose de-escalation. In 52% of patients dose de-escalation was associated with a complete disappearance of AE and this after a median of 4 months (8/17 skin
manifestation, 3/7 arthralgia, 2/7 recurrent infections).

and endoscopic and/or biomarkers remission) for at least 6 months. All patients kit (R-biopharm AG). In addition, patient reported outcome (PRO2), C-reactive
had an IFX trough level over 2 mg/mL and were on stable doses of AZA (2 to 2.5 protein (CRP) and serum albumin were collected for each time-point. Other
mg/ kg/d) and IFX (5 mg/ kg every 8 weeks). In cohort A, AZA and IFX were baseline variables included disease behavior, disease location, smoking behavior,
continued unchanged; In cohort B, the dose of AZA was halved, with a minimum concomitant therapy, body weight, and body mass index. Mann-Whitney U,
dose of 50 mg/d; in cohort C, AZA was stopped and IFX continued as mono- Wilcoxon Signed Rank test, and Cox regression were performed using SPSS 23.0.
therapy. Primary endpoint was failure defined as a clinical relapse (CDAI 4 220 Results: We identified 43 patients with dose de-escalation to ADM 40 mg ETW
with fecal calprotectin 4 450 mg/g stools) and/or need to change the original (32 male, 39 CD, 4 UC, median age 37 years). All patients received monotherapy
therapeutic regimen because of adverse events. Trough levels of IFX (TRI) and with ADM every other week, which was initiated a median of 28 months prior to
antibodies (ATI) were measured before each infusion. dose de-escalation. Median PRO2 was 0, and median CRP level 1.4 mg/L.
Results: 81 patients (45 CD and 36 CD, mean age: 29.7 years, mean disease Reasons for dose de-escalation were ADM associated adverse events (AE,
duration: 24 months)were included (28 in Cohort A; 27 in Cohort B; 26 in n ¼ 1), serum levels above 7 mg/mL (n ¼ 9), or a combination of both (n ¼ 33).
Cohort C). The clinical characteristics, duration of combination therapy, bio- Most frequently reported AE were skin manifestations (52%), arthralgia (24%)
markers levels and TRI were similar in the three cohorts at the time of inclusion. and recurrent infections (21%). While ADM serum level dropped significantly 4
Five patients (17.8%) in Cohort A, three in Cohort B (11.5%), and 8 in Cohort C and 8 months after dose de-escalation, CRP levels remained stable (Table). In
(30.7%) experienced failure at one year (p ¼ 0.1 across group). Three patients in patients with CD a significant increase in PRO2 was observed.
Cohort A had to stop AZA or to reduce the dose due to myelotoxicity or Conclusion: In this retrospective cohort analysis, 61% of patients were able to
digestive intolerance. In cohort A, The mean TRI concentrations were similar continue ADM therapy at a dose of 40 mg ETW. Furthermore, in half of the
at the time of inclusion (3.65 vs 3.45 mg/ml, respectively). In Cohort B, the mean patients who experienced ADM related AE at baseline, the AE disappeared
TRI remained stable after the reduction of AZA dose (3.95 vs 3.6 mg/mL, respec- completely. Regardless of ADM serum levels, disease remission should be objec-
tively) while there was a significant reduction in the mean 6-TGN levels (310 tively assessed prior to dose de-escalation, since an elevated baseline CRP pre-
pmoles vs 128 pmoles, respectively; p ¼ 0 .03) at one year whereas in cohort C, dicted the relapse following de-escalation with subsequent need for increase of
there was a significant reduction in TRI (4.2 vs 2.1 mg/mL; p ¼ 0.02). Four ADM dose.
patients (14.2%) in Cohort A, four patients in Cohort B (14.8%), and 11 in Disclosure of Interest: S. Vermeire: Grants from MSD, Takeda and Abbvie,
Cohort C (42.3%) experienced an unfavourable evolution of IFX pharmacoki- lecture fees from Abbvie, MSD, Falk, Tillotts, Ferring, Centocor, Takeda,
netic defined by a decrease of TRI 5 1 mg/mL or undetectable TRI with positive Hospira; consultancy for Ferring, Abbvie, Shire, Genentech/Roche, Celgene,
ATI (p ¼ 0.022 between A and C, p ¼ 0.039 between B and C, p ¼ 0.87 between A Janssen, MSD, Takeda, Galapagos, Hospira, Mundipharma, Pfizer.
and B). By ROC analysis (AUROC: O.93), a threshold of 6-TGN 5 105 pmoles G. Van Assche: Gert Van Assche receives financial support for research from
was associated with an unfavourable evolution of IFX pharmacokinetic (sensi- Abbvie and MSD, lecture fees from Janssen, Takeda, Ferring, MSD, and Abbvie
tivity: 67%; specificity: 92%; Likelihood ratio: 7.67). and does consultancy for Abbvie, MSD, and Takeda.
Conclusion: AZA dose reduction in IBD patients on combination therapy is as A. Gils: Ann Gils has been a consultant for Merck, Janssen Biologics, and
effective as the maintenance of AZA at the same dose and may improve AZA Abbvie
safety profile. A threshold of 6-TGN 5 105pmoles was associated with an unfa- M. Ferrante: Research grant from Janssen Takeda, lecture fees from Tillotts,
vourable evolution of IFX pharmacokinetics. Ferring, Boehringer-Ingelheim, Janssen, Chiesi, Falk, Zeria, Mitsubishi Tanabe,
Disclosure of Interest: E. Del Tedesco: MSD MSD, Takeda, and Abbvie and does consultancy for Abbvie, Ferring, MSD,
S. Paul: Theradiag, MSD Boehringer-Ingelheim and Janssen.
X. Roblin: MSD, Theradiag, HAC Pharma All other authors have declared no conflicts of interest.
All other authors have declared no conflicts of interest.

OP145 EFFICACY AND SAFETY OF BIOSIMILAR INFLIXIMAB AFTER

OP144 DOSE DE-ESCALATION TO ADALIMUMAB 40 MG EVERY ONE-YEAR: RESULTS FROM A PROSPECTIVE NATIONWIDE
THREE WEEKS IN PATIENTS WITH INFLAMMATORY BOWEL COHORT
DISEASE: A RETROSPECTIVE COHORT ANALYSIS K.B. Gecse1, Z. Vegh1, Z. Kurti1, M. Rutka2, K. Farkas2, J. Banai3, L. Bene4,
S. Van Steenbergen1, S. Bian2, V. Ballet1, S. Vermeire1, G. Van Assche1, A. Gils2, B. Gasztonyi5, P.A. Golovics1, B.D. Lovasz1, T. Kristof6, L. Lakatos7,
M. Ferrante1 P. Miheller8, F. Nagy9, K. Palatka10, M. Papp11, L. Lakner12, A. Patai12,
1
Department Of Gastroenterology and Hepatology, University Hospitals Leuven, A. Salamon13, T. Szamosi3, Z. Szepes9, B. Szalay14, G.T. Toth15, A. Vincze16,
Leuven/Belgium T. Molnar2, P.L. Lakatos1
2 1
Laboratory For Therapeutic and Diagnostic Antibodies, KU Leuven, Leuven/ 1st Department Of Medicine, Semmelweis University Faculty of Medicine 1st
Belgium Dept. of Medicine, Budapest/Hungary
2
First Department Of Internal Medicine, University of Szeged, Szeged/Hungary
Contact E-mail Address: [email protected] 3
Military Hospital – State Health Centre, Budapest/Hungary
Introduction: Although dose escalation is widely used to optimize biological ther- 4
Peterfy Hospital, Budapest/Hungary
apy in case of clinical relapse, less is known about possibilities to de-escalate 5
Zala County Hospital, Zalaegerszeg/Hungary
therapy in patients with inflammatory bowel disease (IBD) who are in clinical 6
B-A-Z County and University Teaching Hospital, Miskolc/Hungary
remission. Dose de-escalation may not only have beneficial economic repercus- 7
Csolnoky Ferenc Regional Hospital, Veszprem/Hungary
sions, it may possibly also decrease the occurrence of adverse events. 8
Second Department of Internal Medicine, Budapest/Hungary
Aims & Methods: In this retrospective cohort analysis, the outcome of dose de- 9
University of Szeged, Szeged/Hungary
escalation to adalimumab (ADM) 40 mg every three weeks (ETW) in patients 10
Department Of Internal Medicine, Division Of Gastroenterology, University of
with IBD was studied. Out of 898 patients treated with ADM for Crohn’s disease Debrecen, Faculty of Medicine, Debrecen/Hungary
(CD) or ulcerative colitis (UC) in a tertiary referral center, we selected all patients 11
Department Of Gastroenterology, University of Debrecen, MHSC Institute of
who had received maintenance therapy with ADM 40 mg ETW with serum levels Medicine, Debrecen/Hungary
available before and after dose de-escalation. Serum was collected 4 months prior 12
Markusovszky Hospital, Szombathely/Hungary
to dose de-escalation (T-1, n ¼ 33), at dose de-escalation (T0, n ¼ 43), 4 months 13
Tolna County Teaching Hospital, Szekszard/Hungary
after dose de-escalation (T1, n ¼ 43) and 8 months after dose de-escalation (T2,
n ¼ 26). ADM serum levels were measured using RIDASCREENÕ monitoring
A60 United European Gastroenterology Journal 4(5S)
14
Department Of Laboratory Medicine, Semmelweis University, Budapest/ results were most sensitive to changes in the perspective of the analysis, utility
Hungary values and time horizon (10-year).
15
Janos Hospital, Budapest/Hungary Conclusion: Biosimilar infliximab is a cost-effective alternative to the originator
16
University of Pecs, Pecs/Hungary product for the treatment of adults with luminal CD, and it may contribute to
increasing the affordability of biological treatments throughout Europe.
Contact E-mail Address: [email protected] Disclosure of Interest: F. Rencz: F Rencz received funding from Hospira Pfizer.
Introduction: Biosimilar infliximab CT-P13 received positive CHMP recommen- V. Brodszky: V Brodszky received funding and support for research on biosimi-
dation in June 2013 for all indications of the originator product. It has been lars from EGIS Pharma, and Hospira Pfizer.
previously shown that CT-P13 is effective and safe in inducing remission in P. Baji: P Baji received funding and support for research on biosimilars from
inflammatory bowel diseases (IBD). However, prospective, long-term data on EGIS Pharma, and Hospira Pfizer.
the efficacy and safety of the biosimilar infliximab in IBD are lacking. M. Pentek: M Pentek received funding and support for research on biosimilars
Aims & Methods: A prospective, nationwide, multicentre, observational cohort from EGIS Pharma, and Hospira Pfizer.
was designed to examine the efficacy and safety of CT-P13 infliximab biosimilar L. Gulacsi: L Gulácsi has been paid as a consultant by Celltrion and received
in the induction and maintenance treatment of Crohn’s disease (CD) and ulcera- funding, and support for research on biosimilars from EGIS Pharma and
tive colitis (UC). Demographic data were collected and a harmonized monitoring Hospira Pfizer.
strategy was applied. Clinical remission, response and biochemical response was K.B. Gecse: KB Gecse has served as a consultant for Pfizer/Hospira and Sandoz
evaluated at week 14, 30 and 54. None of the patients had received infliximab and received speaker’s honoraria from Pfizer/Hospira.
within 12 months prior to initiation of the biosimilar infliximab. Safety data was P.L. Lakatos: PL Lakatos has served as a consultant for Celltrion, EGIS and
registered. Pfizer/Hospira and received speaker’s honoraria from Celltrion, EGIS and
Results: 291 consecutive IBD (184 CD and 107 UC) patients were included in the Pfizer/Hospira and unrestricted research funding from Pfier/Hospira.
present cohort, of which 100 patients reached the week 54 endpoint. The age at All other authors have declared no conflicts of interest.
disease onset was 23/28 years (median, IQR: 19–34 and 22–39) in CD and UC
patients, respectively. 32/49% of CD patients had colonic/ileocolonic disease
location, 41% had complicated disease behaviour, 35% had perianal disease TUESDAY, OCTOBER 18, 2016 08:30–10:00
and 23% had gone through previous surgery. 8/33/59% of UC patients had DRUG-INDUCED UPER GI BLEEDING – ROOM K_____________________
proctitis/left-sided colitis/extensive colitis. 25/14% of patients had received pre-
vious anti-TNF therapy in CD and UC, respectively. 60/52% of CD/UC patients OP147 IDARUCIZUMAB FOR EMERGENT REVERSAL OF
received concomitant immunosuppressives at baseline. 55, 57 and 47% of CD DABIGATRAN-RELATED ANTICOAGULATION DURING SEVERE
patients reached clinical remission by week 14, 30 and 54. Clinical response was GASTROINTESTINAL HEMORRHAGE: INTERIM RESULTS
83, 77 and 58%, respectively. 59, 46 and 53% of UC patients reached clinical (N ¼ 123) FROM THE REVERSE-ADTM STUDY
remission by week 14, 30 and 54. Clinical response was 78, 69 and 64%, respec- J. Aisenberg1, P. Chatterjee2, P. Reilly3, F. Gruenenfelder4, E. Kleine5,
tively. Previous anti-TNF exposure was associated with lower response and S. Glund5, J. Van Ryn6, C. V. Pollack7
remission rates in both CD (p 5 0.001/0.01, p ¼ 0.014/0.05 and p ¼ 0.002/0.04) 1
Department Of Medicine, Icahn School of Medicine at Mount Sinai, New York/
and UC (p ¼ NS/0.06, p ¼ 0.1/0.1 and p ¼ 0.048/0.03) at weeks 14, 30 and 54. United States of America
Mean CRP decreased significantly both in CD and UC patients by week 14, 2
Department Of Medicine, Icahn School of Medicine at Mount Sinai, New York/
which was maintained throughout the 1-year follow-up. (CRP level decreased United States of America
from 20.5 to W14: 8, W30: 8.7 and W54: 12.1 mg/ L in CD and from 29.5 to W14: 3
Boehringer Ingelheim Pharmaceuticals, Ridgefield/United States of America
8.5, W30: 13 and W54: 12.3 mg/L in UC). 21 (6.6%) patients had infusion 4
Boehringer Ingelheim Pharma GmbH & Co. KG, Ingelheim am Rhein/Germany
reactions, 23 (7.9%) patients had infections and 1 death occurred. 5
Boehringer Ingelheim Pharma GmbH & Co. KG, Ingelheim/Germany
Conclusion: This prospective nationwide cohort shows that CT-P13 is effective 6
4. Boehringer Ingelheim Pharma GmbH & Co KG, Biberach an der Riß/Germany
and safe in inducing and maintaining remission in both CD and UC. Efficacy was 7
Thomas Jefferson University, Philadelphia/United States of America
influenced by previous anti-TNF exposure.
Disclosure of Interest: All authors have declared no conflicts of interest. Contact E-mail Address: [email protected]
Introduction: Gastrointestinal bleeding (GIB) is a feared complication of antic-
oagulation therapy. Idarucizumab (IDA) is a rapid-onset specific reversal agent
for the direct thrombin inhibitor dabigatran. IDA should benefit management of
OP146 COST-UTILITY OF BIOSIMILAR INFLIXIMAB (INFLECTRAß) dabigatran users experiencing severe GIB.
FOR THE TREATMENT OF LUMINAL CROHN’S DISEASE IN Aims & Methods: The on-going REVERSE-ADTM study evaluates the safety and
NINE EUROPEAN COUNTRIES efficacy of IDA 5 grams intravenously in dabigatran users with (A) life-threaten-
F. Rencz1, V. Brodszky1, P. Baji1, M. Pentek1, L. Gulacsi1, P.A. Golovics2, ing haemorrhage or (B) requirement for emergency surgery. Here, we analyze the
Z. Vegh2, K.B. Gecse2, S. Danese3, P. Irving4, P.L. Lakatos2 clinical characteristics and outcomes of REVERSE-ADTM enrolees presenting
1
Department Of Health Economics, Covinus University of Budapest, Budapest/ with severe GIB. Our study is performed on an interim analysis cohort of 123
Hungary patients; centralized laboratory coagulation data are available for 90/123 (20/27
2
1st Department Of Medicine, Semmelweis University Faculty of Medicine 1st patients with major GIB).
Dept. of Medicine, Budapest/Hungary Results: Of the 66 patients enrolled in REVERSE-ADTM due to severe bleeding,
3
Istituto Clinico Humanitas-irccs In Gastroenterology, Istituto Clinico Humanitas 27 (41%) bled in the GI tract. The mean age of GIB patients was 77.5 years
IBD Center, Rozzano/Italy (range, 60–93), 15 (56%) were male, and renal impairment was present in 22 of
4
Guy’s and St Thomas’ Hospital Dept. of Gastroenterology, London/United the 23 patients with creatinine clearance measurements (96%). Atrial fibrillation
Kingdom was the indication for anticoagulation in 93%; 74% took their most recent
dabigatran dose 524 hours before presentation. Ten patients (37%) bled from
Contact E-mail Address: [email protected] the upper GI tract, 8 (30%) from the lower GI tract, and 9 (33%) from an
Introduction: Biosimilar infliximab (Inflectraß) has been approved by the unknown level of the GI tract. IDA achieved immediate reversal of dabiga-
European Medicines Agency for the treatment of luminal Crohn’s disease tran-related anticoagulation, and its effect lasted for up to 24 hours in the major-
(CD) since 2013. Currently biosimilars offer a massive price reduction in most ity of patients. Hospital admission was required for 25 patients (93%, median
European countries. Nevertheless, no study has yet compared the cost-effective- length of stay ¼ 6.0 nights); 8 patients required 1 day in intensive care unit
ness of originator and biosimilar agents in luminal CD patients. (Furthermore, (ICU) (30%, median length of ICU stay ¼ 3.5 days). Patients with lower GI
there are no published studies reporting between-biologicals cost-effectiveness for bleeding had shorter time to cessation of bleeding (median 1.5 hours vs. 7.3
luminal CD in European countries.) hours). No adverse events attributable to IDA were reported. A total of 24
Aims & Methods: We aim to compare cost-effectiveness of adalimumab, inflix- patients received 1 unit packed red cells (mean 4.5 units); 9 received fresh
imab, vedolizumab and biosimilar infliximab for the treatment of luminal CD in frozen plasma (mean 2.6 units); 2 received platelets (mean 1.5 units); and 1
nine European countries (Belgium, France, Germany, Hungary, Italy, the received prothrombin complex concentrate prior to IDA treatment. There were
Netherlands, Spain, Sweden and the UK). A probabilistic Markov model was 3 deaths by 90 days, but none directly attributable to GIB. Antithrombotic
developed to analyse the cost-effectiveness of selected biological treatment therapy was resumed in 20 patients (74%) prior to study termination, within a
sequences compared to the standard care or to other biological sequences in median of 6.1 days (range 0–41 days) after IDA administration. Dabigatran was
patients with moderate to severely active luminal CD unresponsive to conven- resumed in 6 patients (22%).
tional treatment. Transition probabilities of moving between health states were Conclusion: The GI tract is the most common site of anticoagulant-associated
estimated based on randomised controlled trials and cohorts. Country-specific haemorrhage meeting clinical criteria for emergent reversal. IDA achieves
unit costs, including drugs, monitoring, administration, hospitalization and sur- immediate reversal of dabigatran-induced anticoagulation, an effect that is sus-
gical costs were considered. The model applied a third-party payer perspective tained for up to 1 day in the majority of patients. Overall, GIB outcomes in this
and a five-year time horizon. Discount rates for both costs and benefits complied setting are favourable; antithrombotic therapy can be resumed promptly in most
with the national pharmacoeconomic guidelines. patients.
Results: The incremental cost-utility ratio (ICUR) of the biosimilar infliximab- Disclosure of Interest: J. Aisenberg: James has provided consultancy to
standard care treatment sequence vs. standard care varied between E35,170/ Boehringer Ingelheim.
QALY (Hungary) and E71,624/QALY (Sweden). Over the five years, the average P. Reilly: Paul Reilly is an employee of Boehringer Ingelheim Pharmaceuticals
undiscounted health gain was 0.3 QALY per patient. In all countries, biosimilar F. Gruenenfelder: Fredrik Gruenenfelder is an employee of Boehringer Ingelheim
infliximab was dominant relative to originator infliximab-standard care strategy. Pharmaceuticals
The inclusion of additional biologicals to the treatment sequence resulted in a E. Kleine: Eva Kleine is an employee of Boehringer Ingelheim Pharma GmbH &
higher cost-utility ratio. ICURs of biosimilar infliximab-adalimumab-vedolizu- Co. KG
mab sequences ranged from E77,305/QALY to E125,643/QALY compared to S. Glund: Stephan Glund Pharma is an employee of Boehringer Ingelheim
the standard care. The biosimilar infliximab-adalimumab-vedolizumab sequence GmbH & Co. KG
dominated the originator infliximab-adalimumab-vedolizumab sequence. The
United European Gastroenterology Journal 4(5S) A61
J. van Ryn: Joanne van Ryn is an employee of Boehringer Ingelheim GmbH & major GIB (upper or lower) event. To compare these risks depending on the
Co. KG treatment adopted after the GIB event. Methods: Retrospective long-term obser-
C.V. Pollack: BI, Bristol-Myers Squibb (BMS)/Pfizer, Daiichi Sankyo (DS), vational cohort study of patients who developed GIB while on AP and/or AC
Janssen, AstraZeneca (AZ). treatment from March 2008 to August 2013. Drug use information was prospec-
All other authors have declared no conflicts of interest. tively collected during the GIB event. Data concerning the follow-up period,
which ended on December 31st 2013 were obtained from databases from 2 dif-
ferent Spanish Health care areas. Primary outcomes were vascular event, GI
rebleeding and death from any cause. Statistical analyses were performed using
OP148 ROLE OF MELATONIN RECEPTORS, SURVIVIN, INSULIN SPSS software version 22.0.
GROWTH FACTOR-1 AND ITS RECEPTOR IN PROTECTIVE Results: 774 patients were included (mean age 78.7  8.9; 56.6% males); 52.8%
ACTION OF MELATONIN AGAINST INDOMETHACIN DAMAGE OF (409/774), 38.5% (298/774), 8.7% (67/774) were on AP, AC or APþAC therapy
GASTRIC EPITHELIAL CELLS respectively. 22.6% of patients presented rebleeding, 17.1% ischemic event and
I. Brzozowska1, A. Ahluwalia2, M. K. Jones3, A.S. Tarnawski4, T. Brzozowski5 26.0% death during the follow up (median 23 months). Following the index GIB,
1
Anatomy, Jagiellonian University Medical College, Krakow/Poland therapy was interrupted in 92.2% (714/774) of patients, although 80.1% (572/
2
Valbhs & Scire, University of California, Long Beach/United States of America/ 714) resumed afterwards (median time 6 days (1–370). Resumption of therapy
CA was associated with higher risk of rebleeding (3.5% vs 24%;p 5 0.001) but lower
3
University of California-Irvine, Long Beach, CA/United States of America risk of death (43.7% vs 19.9%;p 5 0.001). Early resumption of therapy (7 days)
4
VA Long Beach Healthcare System and Uci, University of California, Long vs delayed (47) was associated with a higher rate of ischemic events (13% vs
Beach/United States of America 20.4%;p ¼ 0.020), with no statistical differences in GI events. AC users had
5
Physiology, Jagiellonian University Collegium Medicum, Krakow/Poland higher death risk (OR 1.5; 95%CI: 1.1–2.2) compared to AP users. Dual AP
users had higher risk of ischemic events (OR 2.1; 95%CI: 1.1–3.7). Rebleeding
Contact E-mail Address: [email protected] event rates were 85 and 120 events per 1000 pt-year with AP and AC users
Introduction: Melatonin is a major pineal gland hormone involved in the control respectively. The corresponding event rates were 71 and 82 per 1000 pt-year
of sleep and circadian rhythm but present also in large quantities in the gut. for vascular events, and 93 and 144 respectively for deaths.
This indoleamine is a potent free radical scavenger and exerts protective action Conclusion: Nearly 40% of patients presented a new adverse event related with
against mucosal injury induced by gastric corrosive substances (ethanol, bile) and AP/AC treatment during the follow-up. The risk of death is higher in patients on
stress but the possibility that melatonin directly protects in vitro gastric epithelial AC therapy compared with AP users. Resumption of AC/AP therapy is asso-
cells (cytoprotection) against injury under conditions independent of systemic ciated with higher risk of rebleeding and lower risk of death without any influ-
(e.g. neural, vascular) factors has not been explored before. Likewise, the expres- ence on ischemic events. Resumption of AP or AC agents later than 7 days is
sion of melatonin receptors (MT1 & MT2) in gastric epithelial cells; and, their associated with significant higher risk of ischemic events.
spatial relation to factors promoting cell survival such as survivin, insulin like Disclosure of Interest: A. Lanas: Professor Lanas has been advisor for Astra-
growth factor (IGF-1) and its receptor 1 b (IGFR-1b) has not been so far Zeneca, Bayer and Pfizer.
elucidated. All other authors have declared no conflicts of interest.
Aims & Methods: We studied whether the pretreatment with melatonin results in
protection of cultured rat gastric epithelial cells against indomethacin-induced
gastric mucosal injury and whether it affects the expression of MT1 and -2,
survivin, IGF-1 and IGFR-1b in these cells. In in vitro study, the cultured OP150 NOVEL 4-THIAZOLIDINONE DERIVATIVES AS
normal rat gastric mucosal epithelial cells (RGM1) were pretreated with vehicle CYTOPROTECTIVE AGENTS AGAINST NSAID-INDUCED INJURY
or melatonin (10 mM) for 24 hrs and then exposed to either: medium alone I. Ilkiv1, R. Lesyk2, O. Sklyarov3
(controls), or indomethacin (IND–0.25 mM) for 4 hrs. In these cells the following 1
Biochemistry, Lviv National Medical University, Lviv/Ukraine
were assessed: 1) cell injury under confocal microscopy, 2) survival and apoptosis 2
Pharmaceutical, Organic and Bioorganic Chemistry, Danylo Halytsky Lviv
using Calcein AM live cell tracking dye and MTT assay; 3) cell proliferation National Medical University, Lviv/Ukraine
using BrdU assay; 4) quantitatively expression of MT1 & 2, and survivin, 3
Biochemistry, Danylo Halytsky Lviv National Medical University, Lviv/Ukraine
IGF-1 and IGFR-1b by Western blotting and immunostaining. For comparison,
the quantitative expression of MT1 and MT2 in gastric epithelial and submucosal Contact E-mail Address: [email protected]
structures from full thickness wall specimens of a normal rat stomach was Introduction: Hydrogen sulfide (H2S) and prostaglandins are an important med-
evaluated. iator of mucosal defense and suppression of its synthesis by NSAIDs leads to
Results: Rat gastric mucosa expressed both MT1 and MT2 (1.8-fold more MT1 increased susceptibility to enteropathy. H2S also exerts a number of anti-inflam-
than MT2; p 5 0.01) in gastric epithelial progenitor cells, endothelial cells of matory effects. Thus, the ability of H2S to promote the healing of the damage
blood vessels, and in enteric neural elements. RGM1 cells expressed both MT1 tissue and to resolution of inflammatory response has been exploited in the
and MT2, which were co-localized with survivin, IGF-1 and IGFR-1b. IND development of novel therapeutic agents.
treatment produced extensive cell injury and reduced RGM1 cell viability by Aims & Methods: The purpose of our study was to investigate the role of
3.8-fold (p 5 0.001 vs. control). In cells pretreated with melatonin, IND-induced 4-thiazolidinone derivatives (compounds Les-5054 [5-(3,5-Di-tert-butyl-4-
cell injury and death was dramatically reduced by 82  4% (p 5 0.001) reflecting hydroxy-benzylidene)-2-thioxo-thiazolidin-4-one] and Les-5055 [3-(3,5-Di-tert-
a direct protective action of melatonin. butyl-4-hydroxy-phenyl)-2-mercapto-acrylic acid]) as a novel H2S donors in
Conclusion: 1) Melatonin directly protects the gastric mucosal epithelial cells promoting the resolution of inflammation and injury in small intestine. The
against IND- induced injury and this effect is independent of systemic and studies were conducted on 40 white rats weighing 180–250 g according to the
neural factors, 2) rat gastric epithelial RGM1 cells express melatonin receptors ethical requirements concerning the work with the laboratory animals. Animals
MT1 and MT2 that are co-localized with survivin, IGF-1 and IGFR-1b indicat- were divided into 4 groups: I – control; II – small intestinal injury produced by
ing local autocrine interactions, and 3) besides the systemic hormonal action of indomethacin (IM) in the ulcerogenic dose (35 mg/ kg, subcutaneously) per 72 h;
melatonin derived from pineal gland, this indoleamine can protect the gastric III, IV – compounds Les-5054 and Les-5055 were administered three times per 72
epithelial cells possibly due to its local autocrine and paracrine actions and h intragastrically at a single dose 10 mgkg-1 on the background of NSAID-
interactions with survivin, IGF-1 and its receptor. induced injury. Then the rats were sacrificed and in small intestinal mucosa
Disclosure of Interest: All authors have declared no conflicts of interest. were measured the NOS and arginase activity, concentration of nitrite anion
and MDA, activity of enzymes of the antioxidant protection system (SOD and
catalase) and MPO activity; the concentration of L-arginine and H2S in blood
plasma.
OP149 RISK OF REBLEEDING, VASCULAR EVENTS AND DEATH Results: IM injection manifested by erosions and hemorrhages and leads to the
AFTER GASTROINTESTINAL BLEEDING IN ANTICOAGULANT following changes: the activity of iNOS increased more than threefold (P 5 0.01)
AND/OR ANTIPLATELET USERS as well as the content of nitrite enhanced in two times while arginase activity
B. Marcén1, C. Sostres2, V. Laredo1, L. Ruiz3, E. Alfaro1, P. Camo3, P. Carrera4, decrease more than 4 fold (P 5 0.01); enhanced activity of lipid peroxidation
A. Lanas5 processes manifested by a steep rise of MDA concentration – by 56%
1
Gastroenterology, Universitary Hospital Lozano Blesa, Zaragoza/Spain (P 5 0.01), MPO activity enhanced more than 4 fold (P 5 0.01) and catalase
2
Patologı´a Digestiva, Instituto de Investigación Biosanitaria de Aragón (IIS), activity – by 32% (P 5 0.01). Compound Les-5054 displayed significant cytopro-
Zaragoza/Spain tective effect and decreased the total area of hemorrhagic lesions for 63%
3
Gastroenterology, Universitary Hospital Miguel Servet, Zaragoza/Spain (p 5 0.05). The administration of Les-5054 on the background of IM decrease
4
CIBEREHD, Zaragoza/Spain the activity of iNOS for 35% (P 5 0.01), and activity of eNOS increased for 52%
5
Dept. Medicine & Gastroenterology, University of Zaragoza University Hospital (P 5 0.01), MDA concentration declined for 32% (P 5 0.01), H2S concentration
Dept. of Medicine-Gastroenterology, Zaragoza/Spain increased for 24% (P 5 0.05) as compared with indices of the second group.
Compound Les-5055 decreased the total area of hemorrhagic lesions for 37%
Contact E-mail Address: [email protected] (p 5 0.05) as compared with independent action of indomethacin. Parameters of
Introduction: Patients who develop gastrointestinal (GI) bleeding during antic- NO-synthase system in Les-5055-treated group showed the same tendency as
oagulant (AC) and/or antiplatelet (AP) therapy represent a clinical challenge. under the effect of Les-5054.
Clinical decisión of either long-term interruption or short-term resumption of Conclusion: Administration of 4-thiazolidinone derivatives on the background of
these treatments will have important clinical implications concerning the risk of indomethacin induced injury reduce the activity of iNOS, myeloperoxidase,
vascular, GI bleeding and death events. Differences on the risks between AP or intensity of lipid peroxidation and increase generation of H2S, that may be
AC users after drug resumption are not well established. linked with the structure of this compounds. However compound Les-5054
Aims & Methods: We aimed to determine the rate of rebleeding, vascular events showed more efficacious effect and antioxidant properties than compound
and death in a cohort of patients treated with AP or AC agents who developed a Les-5055. Thus, the novel 4-thiazolidinone derivatives, particularly compound
A62 United European Gastroenterology Journal 4(5S)
Les-5054 demonstrated a remarkable anti-inflammatory and cytoprotective abil- effective in reducing the incidence of colorectal cancers (CRC) in many previous
ity against experimentally NSAID-induced damage in small intestine. studies. However, gastrointestinal (GI) bleeding is the most frequently reported
Disclosure of Interest: All authors have declared no conflicts of interest. serious adverse events for the long term use of aspirin.
Aims & Methods: The objective of this study is to investigate whether the risk of
aspirin usage on increasing ulcer bleeding would outweigh its benefit on the
prevention of CRC. The present study investigated the electronic medical records
OP151 BACTERICIDAL/PERMEABILITY INCREASING FOLD- from 42 publically funded hospitals, which serves a 7 million population in Hong
CONTAINING FAMILY B MEMBER 4 (BPIFB4) ASSOCIATED Kong. All hospital admissions from 2000 to 2004 and their outcome in the
WITH NSAID-INDUCED SMALL INTESTINAL MUCOSAL INJURY follow-up period were extracted until 2014. Aspirin users were matched with
S. Fujimori1, K. Fukunaga2, M. Taisei2, M. Kubo2, R. Hanada3, M. Hayashida4, age and gender in a ratio of 1:2 to non-aspirin users in the study period.
T. Sakurai5, K. Mitsui1, K. Iwakiri1, C. Sakamoto1 Incidences of CRC and GI bleeding were the primary outcomes. Logistic regres-
1
Department Of Gastroenterology, Nippon Medical School, Graduate School of sion was used to compare incidence rates and Cox-proportional hazard regres-
Medicine, Tokyo/Japan sion model was used to compare the mortality rates. Subgroup analyses were
2
RIKEN Center for Integrative Medical Sciences, Yokohama/Japan performed for those with ulcer bleeding, or for those with regular aspirin
3
Medical Co. LTA Sumida Hospital, Tokyo/Japan prescribed.
4
The Third Department Of Internal Medicine, Kyorin University School of Results: A total of 4,564,100 subjects were identified in the system between year
Medicine, Tokyo/Japan 2000 and 2004, and 254,887 of them (5.6%) were prescribed aspirin for at least
5
Department Of Gastroenterology and Hepatology, National Center for Global one month. Among the subjects who were never prescribed aspirin, 491,852
Health and Medicine, Tokyo/Japan subjects (10.8%) were identified in the system. The total sample size of this
study was 746,739. The baseline characteristics of aspirin and non-aspirin users
Contact E-mail Address: [email protected] are described in Table 1. The mean ages of aspirin users and non-aspirin users
Introduction: There was considerable individual variability in NSAID-induced were 68.4 (SD ¼ 13.1) and 66.4 (SD ¼ 13.2) respectively. In the aspirin group,
small intestinal injury in previous studies on healthy subjects. Several studies 78,316 patients (30.7%) had aspirin prescribed for 10 years or more, and 54,011
reported that several single nucleotide polymorphisms (SNPs) were associated of them (69.0%) were routinely prescription during the years of clinic visits.
with gastrointestinal bleeding and/or ulceration. However, the studies investi- Median dose of aspirin used among the patients were 80 mg with interquartile
gated only a few candidate SNPs in the enzymes of metabolizing NSAIDs and range from 80 mg to 100 mg. Average duration of aspirin prescribed was 6.3
arachidonic acid cascade. Therefore, a comprehensive analysis was necessary to years. Patients in aspirin group showed significantly lower incidence of CRC
identify other unknown SNPs having a stronger effect on NSAID-induced small (OR ¼ 0.82; 95% CI ¼ 0.80 to 0.85), and showed significant reduction in overall
intestinal injury than the reported SNPs. mortality (HR ¼ 0.89; 95% CI ¼ 0.86 to 0.92). Whereas, patients in aspirin group
Aims & Methods: The aim of the study was to identify the SNP most signifi- showed significantly higher incidence of GI bleeding (OR ¼ 1.77; 95% CI ¼ 1.74
cantly involved with NSAID-induced small intestinal mucosal injury. One- to 1.80), and showed marginally significant higher mortality among those diag-
hundred fifty healthy subjects were enrolled from an RCT which compared nosed with GI bleeding (HR ¼ 1.03; 95% CI ¼ 1.02 to 1.05). The results remained
small intestinal mucosal breaks after 14-day treatment between celecoxib mono- consistent in the subgroup analyses.
therapy and concomitant treatment with loxoprofen and lansoprazole. Details Conclusion: This is a population-based study to concurrently compare the risk
of the RCT were reported by Fujimori S et al (1). After the RCT, subjects were and benefit of long-term use of aspirin. We concluded that long-term use of low-
divided into three groups on the basis of numbers of increasing small intestinal dose aspirin will increase the incidence of GI bleeding, and moderate increase the
mucosal breaks after NSAIDs treatment with zero (No injury group), one to overall mortality among the patients with GI bleeding. On the other hand, the
four (Mild injury group), and five and more mucosal breaks (Severe injury long-term use of aspirin showed benefit to reduce CRC on both incidence and
group). A genome-wide association study (GWAS) was conducted among the overall mortality.
three groups to detect the SNP which was the most associated with NSAID Disclosure of Interest: All authors have declared no conflicts of interest.
enteropathy.
Results: After RCT and GWAS analysis, 70 subjects receiving the loxoprofen
treatment and 69 subjects receiving the celecoxib treatment were determined to TUESDAY, OCTOBER 18, 2016 08:30–10:00
eligible for analysis. The minimum p-value was detected in the analysis between OUTCOMES IN PERORAL ENDOSCOPIC MYOTOMY (POEM) – ROOM
16 cases with five or more mucosal breaks (severe injury group) and 123 controls M_____________________
with zero to four mucosal breaks (no injury group combined with mild injury
group). In the GWAS, five SNPs in bactericidal/permeability-increasing fold- OP153 COMPREHENSIVE ANALYSIS OF ADVERSE EVENTS
containing family B member 4 (BPIFB4) gene showed the lowest p-value ASSOCIATED WITH PER ORAL ENDOSCOPIC MYOTOMY
(p ¼ 2.69 x 107 with an odds ratio of 40.91). Among the five SNPs, four (POEM) IN 1826 PATIENTS: AN INTERNATIONAL MULTICENTER
were nonsynonymous SNPs (rs2070325: V268I, rs2889732: T320N, rs11699009: STUDY
F527L, rs11696307: T533I, rs11696310: intronic). Y. Haito Chavez1, H. Inoue2, K. W. Beard3, P. V. Draganov4, M. Ujiki5, B.
Conclusion: Although SNPs that surpassed the genome-wide significance level H.a. Rahden6, P. Desai7, A. Repici8, M. Pioche9, B. Hayee10, P. Saxena11,
(p 5 5 x 108) could not be identified through GWAS, results seemed to indicate K. Reavis3, M. Onimaru12, V. Balassone12, J. Nakamura12, Y. Hata12,
that the SNPs of BPIFB4 were associated with NSAID-induced small intestinal D. Yang13, D. Pannu14, A. Abbas4, Y. Perbtani4, L. Patel5, J. Filser6,
mucosal injury. (UMIN: 000007936: The GWAS was financially supported by R. Maselli15, S. Roman16, J. Rivory9, F. Mion17, T. Ponchon18, S. Perretta19,
grants from the Project for Development of Innovative Research on Cancer S. Ngamruengphong1, Y. Chen1, M. Bukhari1, G. Hajiyeva1, A. Ismail1,
Therapeutics and from the Tailor-made Medical Treatment Program (BioBank V. Kumbhari1, M. Khashab1
Japan) funded by Ministry of Education, Culture, Sports, Science and 1
Gastroenterology and Hepatology, John Hopkins Hospital, Baltimore/United
Technology of Japan.) States of America/MD
Disclosure of Interest: S. Fujimori: Dr. Fujimori has received grant/research 2
Digestive Disease Center, Showa University Koto Toyosu Hospital, Tokyo/Japan
support from Astellas Pharma Inc., Covidien Co, Ltd., Daiich-Sankyo Co. 3
The Oregon Clinic, Oregon/United States of America/OR
Ltd., Eisai Co., Ltd., Otsuka Pharmaceutical Co., Ltd., Pfizer Japan Inc., and, 4
Division Of Gastroenterology and Hepatology, University of Florida, College of
Zeria Co., Ltd. Medicine, Gainesville/United States of America/FL
K. Iwakiri: Dr. Iwakiri has received grant/research support from Astellas 5
Department Of Surgery, Evanston Hospital, Evanston/United States of America/
Pharma Inc., Daiich-Sankyo Co. Ltd., Eisai Co., Ltd., Otsuka Pharmaceutical IL
Co., Ltd., Takeda Co., Ltd., and, Zeria Co., Ltd. 6
Surgery, University of Wuerzburg, Wuerzburg/Germany
C. Sakamoto: Dr. Choitsu Sakamoto has received speaker fees from Pfizer, 7
Surat Institute of Digestive Sciences, Surat/India
Astellas, and AstraZeneca. 8
Digestive Endoscopy Unit, Humanitas Research Hospital, Rozzano/Italy
All other authors have declared no conflicts of interest. 9
Gastroenterology and Endoscopy Unit, Digestive Disease Department, H Pavillon-
Reference Edouard Herriot Hospital, Lyon/France
10
Gastroenterology, Kings College Hospital, London/United Kingdom
1. Fujimori S, Hanada R, Hayashida M, et al. Celecoxib Monotherapy 11
Royal Prince Alfred Hospital, Camperdown/Australia/NSW
Maintained Small Intestinal Mucosa Better Compared With Loxoprofen 12
Digestive Diseases Center, Showa University, Koto-Toyosu Hospital, Tokyo/
Plus Lansoprazole Treatment: A Double-blind, Randomized, Controlled
Japan
Trial. J Clin Gastroenterol 2016; 50: 218–226. 13
University Of Florida College Of Medicine, Division of Gastroenterology and
Hepatology, Gainesville/United States of America/FL
14
Division Of Gastroenterology and Hepatology, University of Florida College of
Medicine, Gainesville/United States of America/FL
OP152 RISK OF GASTROINTESTINAL BLEEDING AND BENEFIT 15
Humanitas Research Hospital, Milan/Italy
FROM COLORECTAL CANCER REDUCTION. A 10-YEAR 16
Digestive Physiology, Hôpital Edouard Herriot Dept. of Digestive Physiology,
POPULATION-BASED STUDY FOR LONG-TERM USE OF LOW Lyon/France
DOSE ASPIRIN 17
Digestive Physiology, Hôpital Edouard Herriot Dept. of Dig, Lyon/France
J.J.Y. Sung1, K.K. Tsoi2 18
Dept. Of Digestive Diseases, Herriot University Hospital Dept. de Hepato-gas-
1
Department Of Medicine & Therapeutics, The Chinese University of Hong Kong, troenterologie, Lyon/France
19
Hong Kong/China Department Of Gastrointestinal and Endocrine Surgery, University of
2
Jockey Club School Of Public Health and Primary Care, The Chinese University Strasbourg, Strasbourg/France
of Hong Kong, na/Hong Kong Prc
Contact E-mail Address: [email protected]
Contact E-mail Address: [email protected] Introduction: POEM was introduced as a minimally invasive and effective ther-
Introduction: Aspirin is a potent anti-platelet agent used for the prevention of apeutic modality for the treatment of achalasia and spastic esophageal disorders
cardiovascular and cerebro-vascular diseases. It has also been proven to be (SEDs). Data largely from single-center studies and small case series suggest
United European Gastroenterology Journal 4(5S) A63
POEM as a safe alternative to Heller Myotomy. However, the safety of POEM is 19. Eleftheriadis N, Inoue H, Ikeda H, Onimaru M, Maselli R and Santi G.
still debated since comprehensive analysis of adverse events (AEs) associated with Submucosal tunnel endoscopy: Peroral endoscopic myotomy and peroral
POEM in large cohort studies has not been performed. endoscopic tumor resection. World J Gastrointest Endosc 2016; 8(2): 86–103.
Aims & Methods: We aimed to study (1) the rate of AEs and (2) factors asso- 20. Swanstrom LL, Rieder E and Dunst CM. A stepwise approach and early
ciated with occurrence of AEs in patients undergoing POEM. Methods: Patients clinical experience in peroral endoscopic myotomy for the treatment of acha-
who underwent POEM performed for the treatment of achalasia and SEDs at 12 lasia and esophageal motility disorders. J Am Coll Surg 2011; 213(6): 751–6.
tertiary-care centers (5 US, 4 Europe, 2 Asia and 1 Australia) between 2011 and 21. Disibeyaz S, Koksal AS, Parlak E, Torun S and Sasmaz N. Endoscopic
2015 were used in a case-control study. Cases were defined by the occurrence of closure of gastrointestinal defects with an over-the-scope clip device. A
any AEs related to POEM procedure. Control patients were selected for each AE case series and review of the literature. Clinics and Research in Hepatology
case by matching for age, gender, disease classification (type I&II vs. type III/ and Gastroenterology 2012; 36(6): 614–21.
SEDs). All pertinent data including AEs were collected and their severity was 22. Hagel AF, Naegel A, Lindner AS, Kessler H, Matzel K, Dauth W, et al.
graded according to the ASGE lexicon’s severity grading system. Over-the-scope clip application yields a high rate of closure in gastrointest-
Results: A total of 1826 patients underwent POEM during the study period. inal perforations and may reduce emergency surgery. Journal of
Overall, 153 AEs occurred in 137 patients (7.5%). A total of 48 inadvertent Gastrointestinal Surgery: Official Journal of the Society for Surgery of the
mucosotomies occurred and represented the most common AE of POEM Alimentary Tract 2012; 16(11): 2132–8.
(31% of all AEs, overall incidence 2.8%). Mild, moderate and severe AEs 23. Baron TH, Song LM, Ross A, Tokar JL, Irani S and Kozarek RA. Use of an
occurred in 102 (74.5%), 26 (19%) and 9 (6.5%) patients, respectively. Among over-the-scope clipping device: multicenter retrospective results of the first
the 9 severe AEs, 2 were esophageal leaks, 1 perforation, 1 aspiration pneumonia, U.S. experience (with videos). Gastrointestinal Endoscopy 2012; 76(1): 202–8.
1 empyema, 1 pneumomediastinum, 1 cardiac arrhythmia and 2 delayed bleed- 24. Kirschniak A, Subotova N, Zieker D, Konigsrainer A and Kratt T. The
ing). There were no deaths related to POEM. When patients with AEs were Over-The-Scope Clip (OTSC) for the treatment of gastrointestinal bleeding,
compared with a control group (case-control analysis), there was no difference perforations, and fistulas. Surgical Endoscopy 2011; 25(9): 2901–5.
between the 2 groups in terms of Charlson comorbidity index/ASA class, prior
therapy, sigmoid esophagus, operator specialty, direction of myotomy (anterior
vs. posterior), type of knife used, extent and length of myotomy, and operator
experience. However, time of procedure was significantly longer in cases as com- OP154 LONG TERM OUTCOMES OF PERORAL ENDOSCOPIC
pared to controls (123 min  49 vs. 103 min  38, p ¼ 0.002). Length of stay was MYOTOMY (POEM) IN ACHALASIA PATIENTS WITH A
significantly higher in patients who experienced AEs (4.9d vs. 2.7d, p 5 0.001). MINIMUM FOLLOW-UP OF 2 YEARS: AN INTERNATIONAL
Conclusion: This is the largest study that comprehensively assessed safety of MULTICENTER STUDY
POEM. It highly suggests POEM as a safe therapeutic modality with an overall S. Ngamruengphong1, H. Inoue2, A. Bapaye3, M. Ujiki4, L. Patel4, P. Desai5,
7.5% incidence of AEs. Severe AEs are rare. AEs result in prolongation of B. Hayee6, A. Haji7, V. Wong8, S. Perretta9, S. Dorwat3, M. Pioche10,
hospital stay. Longer procedural times (indicative of technically complex proce- S. Roman11, J. Rivory10, F. Mion12, T. Ponchon13, A. Garros10, J. Nakamura14,
dures) are associated with increases occurrence of AEs. Y. Hata14, V. Balassone14, M. Onimaru14, G. Hajiyeva1, A. Ismail1, Y. Chen1,
Disclosure of Interest: M. Khashab: Consultant of Boston Scientific and M. Bukhari1, Y. H. Chavez1, V. Kumbhari1, R. Maselli15, A. Repici16,
Xlumena M. Khashab1
All other authors have declared no conflicts of interest. 1
Dept. Of Gastroenterology, Johns Hopkins University, Baltimore/United States of
America
2
References Digestive Disease Center, Showa University Koto Toyosu Hospital, Tokyo/Japan
3
Shivanand Desai Center For Digestive Disorders, Deenanath Mangeshkar
1. Achem SR, Crittenden J, Kolts B and Burton L. Long-term clinical and Hospital Digestive Diseases & Endoscopy, Pune/India
manometric follow-up of patients with nonspecific esophageal motor disor- 4
Department Of Surgery, Evanston Hospital, Evanston/United States of America/
ders. Am J Gastroenterol 1992; 87(7): 825–30. IL
2. Stuart RC and Walsh TN. Esophageal peristalsis and achalasia. Am J 5
Surat Institute of Digestive Sciences, Surat/India
Gastroenterol 1995; 90(5): 691–2. 6
Gastroenterology, Kings College Hospital, London/United Kingdom
3. Eckardt VF. Clinical presentations and complications of achalasia. 7
King’s College Hospital, London/United Kingdom
Gastrointest Endosc Clin N Am 2001; 11(2): 281–92, vi. 8
Prince of Wales Hospital, The Chinese University of Hong Kong, Hong Kong/
4. Fisichella PM, Raz D, Palazzo F, Niponmick I and Patti MG. Clinical, Hong Kong PRC
radiological, and manometric profile in 145 patients with untreated achala- 9
Department Of Gastrointestinal and Endocrine Surgery, University of Strasbourg,
sia. World J Surg 2008; 32(9): 1974–9. Strasbourg/France
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5. Wen ZH, Gardener E, Wang YP. Nitrates for achalasia. Cochrane Database Gastroenterology and Endoscopy Unit, Digestive Disease Department, H
Syst Rev. 2004(1):CD002299. Pavillon- Edouard Herriot Hospital, Lyon/France
11
6. Abir F, Modlin I, Kidd M and Bell R. Surgical treatment of achalasia: Digestive Physiology, Hôpital Edouard Herriot Dept. of Digestive Physiology,
current status and controversies. Dig Surg 2004; 21(3): 165–76. Lyon/France
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7. Bansal R, Nostrant TT, Scheiman JM, Koshy S, Barnett JL, Elta GH, et al. Digestive Physiology, Hospices Civils de Lyon, Lyon/France
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Intrasphincteric botulinum toxin versus pneumatic balloon dilation for treat- Dept. Of Digestive Diseases, Herriot University Hospital Dept. de Hepato-gas-
ment of primary achalasia. J Clin Gastroenterol 2003; 36(3): 209–14. troenterologie, Lyon/France
14
8. Cuilliere C, Ducrotte P, Zerbib F, Metman EH, de Looze D, Guillemot F, Digestive Diseases Center, Showa University, Koto-Toyosu Hospital, Tokyo/
et al. Achalasia: outcome of patients treated with intrasphincteric injection of Japan
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botulinum toxin. Gut 1997; 41(1): 87–92. Humanitas Research Hospital, Milan/Italy
16
9. Kroupa R, Hep A, Dolina J, Valek V, Matyasova Z, Prokesova J, et al. Dept. Of Gastroenterology, Ist. Clinico Humanitas Rozzano Dept. of
Combined treatment of achalasia - botulinum toxin injection followed by Gastroenterology, Milano/Italy
pneumatic dilatation: long-term results. Dis Esophagus 2010; 23(2): 100–5.
Contact E-mail Address: [email protected]
10. Campos GM, Vittinghoff E, Rabl C, Takata M, Gadenstatter M, Lin F,
Introduction: Peroral endoscopic myotomy (POEM) aims to palliate symptoms of
et al. Endoscopic and surgical treatments for achalasia: a systematic review
achalasia by reducing pressure at the lower esophageal sphincter (LES). Current
and meta-analysis. Ann Surg 2009; 249(1): 45–57.
data demonstrates high short-term clinical response in 82–100% of patients.
11. Inoue H, Minami H, Kobayashi Y, Sato Y, Kaga M, Suzuki M, et al. However, long term data is very limited.
Peroral endoscopic myotomy (POEM) for esophageal achalasia. Endoscopy Aims & Methods: We aimed to study (1) clinical outcome of patients with a
2010; 42(4): 265–71. minimum post-POEM follow-up of 2 years and (2) factors associated with
12. Pasricha PJ, Hawari R, Ahmed I, Chen J, Cotton PB, Hawes RH, et al. long term clinical failure after POEM. Methods: We conducted a retrospective
Submucosal endoscopic esophageal myotomy: a novel experimental review of consecutive patients with achalasia who underwent POEM with a
approach for the treatment of achalasia. Endoscopy 2007; 39(9): 761–4. minimum follow-up of 2 years at 10 tertiary-care centers (3 US, 4 Europe, 3
13. Inoue H, Sato H, Ikeda H, Onimaru M, Sato C, Minami H, et al. Per-Oral Asia). Clinical response was defined by decrease in Eckardt score to 3.
Endoscopic Myotomy: A Series of 500 Patients. J Am Coll Surg 2015; 221(2): Results: A total of 179 patients (82 males (45.8%); mean age 49 yr) underwent
256–64. POEM for the treatment of achalasia (type I 11, type II 51, type III 6, unspecified
14. Costamagna G, Marchese M, Familiari P, Tringali A, Inoue H and Perri V. type 111). Of these, 16 patients (8.9%) had prior Heller myotomy, 65 (36%) had
Peroral endoscopic myotomy (POEM) for oesophageal achalasia: prelimin- prior pneumatic dilatation (PD) and 6 (3%) had prior botulinum injection.
ary results in humans. Dig Liver Dis 2012; 44(10): 827–32. POEM was successfully completed in all patients. A total of 18 adverse events
15. Ling TS, Guo HM, Yang T, Peng CY, Zou XP and Shi RH. Effectiveness of occurred in 8 (4.4%) patients (8 mucosotomies, 1 delayed bleeding, 1 esophageal
peroral endoscopic myotomy in the treatment of achalasia: a pilot trial in leak, 2 DVT/PE, 1 pneumothorax, 2 symptomatic pleural effusion, 2 aspiration
Chinese Han population with a minimum of one-year follow-up. J Dig Dis pneumonia, and 1 mediastinitis). The median follow-up was 30 months (IQR 26–
2014; 15(7): 352–8. 37). Clinical success was achieved in 97.5% (159/163), 99.8% (124/125), 90%
16. Shiwaku H, Inoue H, Yamashita K, Ohmiya T, Beppu R, Nakashima R, (161/179) in patients with follow-up within 6 months, at 12 months, and 24
et al. Peroral endoscopic myotomy for esophageal achalasia: outcomes of the months, respectively. Of 159 patients with clinical response at 6 months, 11 (7%)
first over 100 patients with short-term follow-up. Surg Endosc. 2016. experienced recurrent symptoms at 2 years. Mean Eckardt score decreased from
17. Khashab MA, El Zein M, Kumbhari V, Besharati S, Ngamruengphong S, 6.7  2.2 before POEM to 1.5  1.4 at the time of last follow-up (p 5 0.001) and
Messallam A, et al. Comprehensive analysis of efficacy and safety of peroral 4sIRP pressure improved, 23.3  8.7 to 7.1  4.4 mmHg (p 5 0.001). As com-
endoscopic myotomy performed by a gastroenterologist in the endoscopy pared to patients with clinical response, the non responders were more likely to
unit: a single-center experience. Gastrointest Endosc 2016; 83(1): 117–25. be younger (44  8 vs 49  16 yr, p 0.03) and had history of prior PD (11 (61%)
18. Cotton PB, Eisen GM, Aabakken L, Baron TH, Hutter MM, Jacobson BC, vs 54 (33%), p 0.03). In a multivariate analysis, history of prior PD was inde-
et al. A lexicon for endoscopic adverse events: report of an ASGE workshop. pendently associated with long-term treatment failure (OR 2.99; 95%CI 1.09–
Gastrointest Endosc 2010; 71(3): 446–54. 8.22, p 0.03). Three patients with clinical failure underwent treatment with repeat
A64 United European Gastroenterology Journal 4(5S)

Table (OP154)

Aspirin Group (n ¼ 254,887) Non-Aspirin Group (n ¼ 491,852)

Age 5 50 50–64 65–79 4 ¼ 80 24,067 (9.4%) 59,289 (23.3%) 121,671 57,690 (11.7%) 129,196 (26.3%) 232,319
(47.7%) 49,860 (19.6%) (47.2%) 72,647 (14.8%)
Sex – Male 136,534 (53.8%) 260,933 (53.1%)
Duration of Aspirin Prescribed 1 month 48,591 (19.1%) 44,516 (17.5%) 34,013 NA*
to 5 6 months 6 months to 5 3 (13.3%) 49,451 (19.4%) 78,316
years 3 years to 5 5 years 5 years to (30.7%)
5 10 years 10 years or more

*Not Applicable for the Patients in Non-Aspirin Group.

POEM (n ¼ 1) and Heller myotomy (n ¼ 2) and clinical response was noted in 2 OP156 MAJOR PERI-OPERATIVE ADVERSE EVENTS OF PERORAL
of them. Of 171 patients with available data, 24% patients reported reflux symp- ENDOSCOPIC MYOTOMY (POEM): 5 YEARS’ EXPERIENCE, 1680
toms after POEM. Reflux esophagitis was noted in 26 patients of 144 (18%) who PATIENTS
had EGD after POEM. 15% of asymptomatic patients had reflux esophagitis. Q. Li1, X. Zhang2, P. Zhou1
Conclusion: POEM is safe and provides high initial clinical success and excellent 1
Endoscopy Center and Endoscopy Research Institute, Zhongshan Hospital, Fudan
long-term outcomes. Less than 10% of patients who had clinical response at 6 University, Shanghai, China, Shanghai/China
months had recurrent symptoms at 2 years. History of prior pneumatic dilatation 2
Endoscopy Center and Endoscopy Research Institute, Zhongshan Hospital, Fudan
is associated with clinical failure. Post-POEM symptomatic reflux occurs in University, Shanghai/China
quarter of patients and esophagitis is found in 15% of asymptomatic patients.
Disclosure of Interest: S. Roman: Sabine Roman is a consultant for Medtronic Contact E-mail Address: [email protected]
and Sandhill Scientific Introduction: Peroral endoscopic myotomy (POEM) is now a widely used treat-
F. Mion: Francois Mion is a consultant for Medtronic ment for esophageal achalasia, supported by several large cohort studies.
M. Khashab: Mouen Khashab is a consultant for Boston Scientific Although major perioperative adverse events (mAE) are rare, in-depth investiga-
All other authors have declared no conflicts of interest. tions of related risks and preventive measures are lacking.
Aims & Methods: Hence, mAE during POEM were systematically assessed in
terms of incidence, risks, prevention, and management. This retrospective
single-center analysis included all patients (N ¼ 1680) undergoing POEM
OP155 A 5-YEAR LONG POEM EXPERIENCE. IS IT TIME TO DRAW between August, 2010 and July, 2015 at our facility. Major adverse events
CONCLUSIONS? were defined as follows: vital-sign instability, required ICU stay, hospital read-
P. Familiari1, A. Calı̀1, R. Landi1, G. Gigante1, A. Tringali1, I. Boskoski1, mission, conversion to open surgery, invasive postoperative procedure, blood
V. Bove1, V. Perri1, F. Borrelli De Andreis1, G. Costamagna2 transfusion, or hospitalization 45 days due to functional impairment.
1
Digestive Endoscopy Unit, Catholic University - Gemelli University Hospital, Results: A total of 55 patients (3.3%, 95% confidence interval [CI] 2.5–4.2%)
Roma/Italy suffered mAE, distributed as follows: delayed mucosal barrier failure, 13 (0.8%,
2
IHU, USIAS Strasbourg University, Strasbourg, France, Strasbourg/France 95% CI 0.4–1.3%); delayed bleeding, 3 (0.2%, 95% CI 0.04–0.5%); hydrothorax,
8 (0.5%, 95% CI 0.2–0.9%); pneumothorax, 25 (1.5%, 95% CI 1.0–2.2%); and
Contact E-mail Address: [email protected] miscellaneous, 6 (0.4%, 95% CI 0.1–0.8%). Four patients (0.2%) required ICU
Introduction: Peroral Endoscopic Myotomy (POEM) has been recently developed admissions. No surgical conversions occurred, and 30-day mortality was zero. In
for the treatment of achalasia and other esophageal motility disorders. Despite stepwise multivariate regression, experience 51 year (OR ¼ 3.85, 95% CI 1.49–
being widely used in many centers, data on the long-term efficacy of POEM are 9.95), air insufflation (OR ¼ 3.41, 95% CI 1.37–8.50), and mucosal edema
still lacking. We report on a large consecutive series of patients treated with (OR ¼ 2.01, 95% CI 1.14–3.53) were identified as related risk factors. After
POEM, with mid- and long-term follow-up. introducing CO2 insufflation, mAE rate declined to 1.9% (95% CI 1.2–2.7%)
Aims & Methods: All the patients who underwent POEM between May 2011 and and seemed to plateau after 3.5 years at 1%.
April 2016 at our endoscopy unit were retrospectively identified on a prospec- Conclusion: In general, POEM is a safe procedure. Major adverse events are rare
tively collected database. Analyzed data included demographics, clinical history, and usually may be prevented or anticipated and conservatively managed.
previous treatments, manometry and procedure data, complications and clinical Disclosure of Interest: All authors have declared no conflicts of interest.
outcomes. Follow-up visits were scheduled at 3, 6, 12, 24, 36, 48 and 60 months References
after POEM. EGD, manometry and barium swallow were regularly performed
during follow-up. pH-monitoring study was performed once, usually between the 1. Stavropoulos SN, Modayil RJ, Friedel D, et al. The International Per Oral
6- and 12-month follow-up visit. Clinical success was defined by an Eckardt score Endoscopic Myotomy Survey (IPOEMS): a snapshot of the global POEM
 3. experience. Surg Endosc 2013; 27: 3322–3338.
Results: A total of 347 patients underwent POEM (mean age 47 years, 48% 2. Ren Z, Zhong Y, Zhou P, et al. Perioperative management and treatment for
males). Seventy-eight patients (22.5%) had type I achalasia, 174 type II complications during and after peroral endoscopic myotomy (POEM) for
(50.1%), 40 type III (11.5%), 2 Jackhammer esophagus (0.6%), 4 distal esopha- esophageal achalasia (EA) (data from 119 cases). Surg Endosc 2012; 26:
geal spasm (1.1%), 1 nutcracker esophagus (0.3%); in 48 patients (13.8%) acha- 3267–3272.
lasia type was not classified (ie: standard manometry or incomplete examination).
Before POEM, 52 patients had undergo pneumatic dilation (PD), 8 surgical
myotomy, 8 botulinum toxin injection. The procedure was effectively completed
in 338 cases (97%). Mild complications occurred in 3 patients (0.8%): a delayed OP157 COMPARATIVE EVALUATION OF PERORAL ENDOSCOPIC
bleeding, a covered esophageal perforation, and a esophageal stricture following MYOTOMY (POEM) FOR THE TREATMENT OF ACHALASIA IN
a large ulceration. All the above mentioned complications were treated conser- PATIENTS WITH FAILED HELLER MYOTOMY VS PATIENTS
vatively. Four patients were lost at follow-up. A minimum 6-month follow-up WITHOUT A HISTORY OF SURGICAL MYOTOMY: A
was available for 274 patients (mean follow-up 19 months). Clinical success was MULTICENTER RETROSPECTIVE COHORT STUDY
achieved in 95% of patients. Thirteen patients had symptoms recurrence: 7 S. Ngamruengphong1, H. Inoue2, M. Ujiki3, A. Bapaye4, P. Desai5, T. Ponchon6,
underwent successful PD, 3 surgery, 3 received no treatment because of mild S. Dorwat4, P. V. Draganov7, Y. Perbtani7, A. Abbas7, D. Pannu8, D. Yang9,
symptoms. Clinical success slightly decreased with time, being 97%, 97%, S. Perretta10, J. Romanelli11, D. Desilets11, B. Hayee12, L. Patel3, M. Pioche13,
93%, 85%, 72% and 67% after 6, 12, 24, 36, 48 and 60 months, respectively. S. Roman14, J. Rivory13, F. Mion15, A. Garros13, J. Nakamura16, Y. Hata16,
However, almost 50% of recurrences (6/13) occurred during the first 25 cases V. Balassone16, M. Onimaru16, G. Hajiyeva1, A. Ismail1, Y. Chen1, M. Bukhari1,
(learning curve). No associations were found between preoperative manometric Y. H. Chavez1, V. Kumbhari1, R. Maselli17, A. Repici18, M. Khashab1
pattern and clinical outcomes: the success rate of POEM was similar in patients 1
Dept. Of Gastroenterology, Johns Hopkins University, Baltimore/United States of
with type I, type II and type III achalasia (94%, 96% and 91%, respectively. America
p40.05). A total reflux time 4 5% was diagnosed in 50% of the patients (111/ 2
Digestive Disease Center, Showa University Northern Yokohama Hospital,
223) who underwent pH-study. Esophagitis was seen in 28% of patients, 22% of Yokohama/Japan
patients receive PPI because of heartburn. Esophagitis healed completely with 3
Department Of Surgery, Evanston Hospital, Evanston/United States of America/
proton pump inhibitors (PPI) in all the patients. GERD symptoms were effec- IL
tively controlled with PPI in all the patients but 2 who complained with heart- 4
Shivanand Desai Center For Digestive Disorders, Deenanath Mangeshkar
burn and regurgitations. Hospital Digestive Diseases & Endoscopy, Pune/India
Conclusion: Our mid-term and long-term follow-up analysis confirms the safety 5
Surat Institute of Digestive Sciences, Surat/India
and efficacy of POEM for the management of achalasia and other motility dis- 6
Dept. Of Digestive Diseases, Herriot University Hospital Dept. de Hepato-gas-
orders. The vast majority of initial clinical failure can be solved with endoscopic troenterologie, Lyon/France
re-treatment. Iatrogenic GERD-rate remains the only possible drawback of the 7
Division Of Gastroenterology and Hepatology, University of Florida, College of
procedure. Medicine, Gainesville/United States of America/FL
Disclosure of Interest: All authors have declared no conflicts of interest. 8
Division Of Gastroenterology and Hepatology, University of Florida College of
Medicine, Gainesville/United States of America/FL
United European Gastroenterology Journal 4(5S) A65
9
University Of Florida College Of Medicine, Division of Gastroenterology and one month and 3 months, the efficacy based on GCSI score and gastroparesis
Hepatology, Gainesville/United States of America/FL symptoms (vomiting, nausea, abdominal pain and gastric fullness), and the
10
Department Of Gastrointestinal and Endocrine Surgery, University of improvement of quality of life (visual analogic scale /5), The secondary objectives
Strasbourg, Strasbourg/France were to document the GES evolution at 2 months and the procedure
11
Department Of Surgery, Baystate Medical Center, Tufts University School of complications.
Medicine, Springfield/United States of America/MA Results: The procedure was completed on all the patients. We observed a sig-
12
Gastroenterology, Kings College Hospital, London/United Kingdom nificant improvement of GCSI score at POD 5, 1 month and 3 months (3.5  0.8
13
Gastroenterology and Endoscopy Unit, Digestive Disease Department, H vs. 0.8  0.8; 0.9  0.9; 1.1  1.5; p 5 0.001). Regarding the severity of symptoms
Pavillon- Edouard Herriot Hospital, Lyon/France analyzed separately, it was observed a significant improvement of each of them,
14
Digestive Physiology, Hôpital Edouard Herriot Dept. of Digestive Physiology, except anorexia. The overall clinical efficacy was 80%, with a mean overall
Lyon/France quality of life improvement 4 65%. The GES normalized in 75% of cases,
15
Digestive Physiology, Hospices Civils de Lyon, Lyon/France showing a significant improvement of the mean half emptying time (222  90
16
Digestive Diseases Center, Showa University, Koto-Toyosu Hospital, Tokyo/ min vs. 133  90; p ¼ 0.03) and of retention at 2 hours (76  20% vs.
Japan 44  26%; p ¼ 0.009). Two patients underwent complications related to the pro-
17
Gastroenterology, Humanitas Clinical and Research Hospital, Rozzano/Italy cedure: one was a bleeding due to an ulceration along the tunnel path (coagula-
18
Dept. Of Gastroenterology, Ist. Clinico Humanitas Rozzano Dept. of tion necrosis) treated by endoscopy, who then worsened a renal insufficiency and
Gastroenterology, Milano/Italy was transferred to intensive care unit; the second had a secondary perforation of
an unseen fundic ulcer, which was managed endoscopically by a naso-cystic drain
Contact E-mail Address: [email protected] and fasting, with excellent outcomes. All the other patients could be reefed at
Introduction: In patients with persistent symptoms after Heller myotomy (HM), POD2–3, and discharged at POD5–6, with PPI treatment.
treatment options include repeat HM, pneumatic dilation (PD) or peroral endo- Conclusion: Per-oral endoscopic pyloromyotomy seems to be an effective
scopic myotomy (POEM). The data on efficacy and safety of POEM for patients approach for treating patients with documented severe refractory gastroparesis.
who failed prior HM are limited to small series. This procedure is also highly reproducible, when applying some tips to increase
Aims & Methods: We aimed to compare technical success, clinical response and the technical success rate, and safe with complication that could be managed
safety of POEM in achalasia patients with and without prior HM. Methods: We endoscopically. It could be a new hope for a many patients whom have a poor
conducted a retrospective review of achalasia patients who underwent POEM at quality of life. More data, especially in prospective studies are needed to confirm
11 tertiary centers (4 US, 4 Europe, 3 Asia). Patients were divided into two these very promising results.
groups: (1) patients who had prior HM (HM group) and (2) those without Disclosure of Interest: All authors have declared no conflicts of interest.
prior HM (control group). Control patients were selected for each HM case by References
matching for age, achalasia subtypes (type I&II vs type III), and baseline Eckardt
scores (ES) [Stage II (ES 4–6) or Stage III (ES 4 6)]. Clinical response was 1. Khashab MA, Stein E, Clarke JO, Saxena P, Kumbhari V, Chander Roland
defined by decrease in ES to 3. Adverse events (AEs) were graded according B, et al. Gastric peroral endoscopic myotomy for refractory gastroparesis:
to the ASGE lexicon. Technical success, clinical success and AEs were compared first human endoscopic pyloromyotomy (with video). Gastrointest Endosc
between the two groups. 2013 Nov; 78(5): 764–8.
Results: A total of 181 patients (91 HM, 90 controls) were included. There was no 2. Gonzalez J-M, Vanbiervliet G, Vitton V, Benezech A, Lestelle V, Grimaud J-
difference between the groups in baseline demographics, ES and 4sIRP. The HM C, et al. First European human gastric peroral endoscopic myotomy, for
group had higher proportion of patients with prior PD (44% vs 26%; p 0.01). treatment of refractory gastroparesis. Endoscopy 2015 Jan; 47(Suppl
The length of myotomy was similar between the two groups. Technical success 1E135–6.
rates were comparable between HM group (89/91; 98%; 2 failures due to exten- 3. Shlomovitz E, Pescarus R, Cassera MA, Sharata AM, Reavis KM, Dunst
sive submucosal fibrosis) and control group (100%) in control group (p 0.49). CM, et al. Early human experience with per-oral endoscopic pyloromyotomy
Procedure time was similar between the two groups. The mean follow-up was 8.5 (POP). Surg Endosc 2015 Mar; 29(3): 543–51.
months (IQR 3.2–14.7) and was similar in both groups. 20 AEs occurred in 19
patients [7 (8%) in HM group and 12 (13%) in control group, p 0.23]. For HM TUESDAY, OCTOBER 18, 2016 08:30–10:00
and control respectively, the rate of mild (5% vs 10%, p ¼ 0.28) and moderate
(1% vs 3%, p ¼ 0.34) AEs were similar. One severe AE (mediastinitis) occurred in
LIVER FIBROSIS: FROM MECHANISM TO THERAPY – ROOM 1.61/
the HM group. Follow-up data were available in 153 patients. Clinical response 1.62_____________________
was significantly lower in the HM group as compared to the control (80% vs
94%, p 0.02). Mean post-POEM ES was also higher in the HM group (2.09  2.5 OP159 EXPRESSION OF CONSTITUTIVELY ACTIVE IKK2 LEADS TO
vs 1.08  1.2, p 0.002). On univariate analysis, prior HM (OR 3.54, p 0.02) and LIVER FIBROSIS AND INCREASED CARCINOGENESIS IN THE
prior PD (OR 3.36, p 0.01) were significantly associated with clinical failure. BACKGROUND OF LIVER SPECIFIC TRP53 DELETION
Multivariate analysis demonstrated prior HM (adjusted OR 2.91, p 0.05) was M. Svinarenko1, S.F. Katz1, S. Fischer1, H. Maier2, A. Tannapfel3,
marginally associated with clinical failure after POEM. Post-POEM sympto- T. Seufferlein1, A. Lechel1
matic reflux, presence of reflux esophagitis and abnormal pH acid exposure 1
Internal Medicine I, University Hospital Ulm, Ulm/Germany
were similar between the two groups. 2
Institute Of Physiological Chemistry, University of Ulm, Ulm/Germany
Conclusion: In this large multicenter study, POEM was safe and effective for 3
Pathological Institute, Ruhr University Bochum, Bochum/Germany
achalasia patients who failed prior HM. Although rate of clinical success in
patients with prior HM is lower than those without prior HM, the safety profile Contact E-mail Address: [email protected]
of POEM is comparable to that of patients with no prior HM. Introduction: Liver carcinoma is of particular importance, since it is a leading
Disclosure of Interest: S. Roman: Sabine Roman is a consultant for Medtronic cause of cancer-related deaths worldwide. Most frequently liver tumors are aris-
and Sandhill Scientific ing in an inflammatory milieu as a consequence of liver fibrosis and cirrhosis,
F. Mion: Francois Mion is a consultant for Medtronic which primarily develop subsequently due to chronic liver diseases. Another
M. Khashab: Mouen Khashab is a consultant for Boston Scientific circumstance contributing to liver cancer formation is the disruption of the
All other authors have declared no conflicts of interest. p53 signaling pathway. In human liver tumors, p53 mutations are associated
with a poor prognosis. In this study, we analyze the cooperation between loss
of p53 and inflammatory response in the liver.
Aims & Methods: To investigate the sequence of inflammation and Trp53 dele-
OP158 GASTRIC PERORAL ENDOSCOPIC ANTRO-PYLORO- tion, we combined two transgenic mouse models. For modulation of an inflam-
MYOTOMY (G-POEM) FOR THE TREATMENT OF REFRACTORY matory response, we used an inducible mouse model (Tet-Off system) with a
GASTROPARESIS: LARGEST SERIES WITH CLINICAL AND permanent expression of a constitutively active IKK2 isoform (CAIKK2). The
SCINTIGRAPHHIC FOLLOW-UP expression of CAIKK2, starting from birth, leads to a continuous activation of
J. Gonzalez, V. Lestelle, A. Benezech, V. Vitton, M. Barthet the NF-kB pathway, simulating chronic inflammation. For the modulation of a
Dept. De Gastroenterologie, APHM - North Hospital, Marseille/France p53 loss, the inducible Cre-recombinase expressing transgenic mouse line
AlfpCre-ERT2 was crossed with a conditional Trp53 knockout mouse.
Contact E-mail Address: [email protected] Tamoxifen treatment at the age of four weeks induces liver-specific deletion of
Introduction: Gastroparesis is an invalidating motility disorder and the available Trp53.
treatments remain disappointing. Recently, a novel approach has been described Results: Expression of the constitutively active IKK2 isoform leads to liver fibro-
by performing a myotomy of the pylorus after creating a tunnel, with promising sis development, increased proliferation in the liver and elevated expression of
results [1–3]. We report the largest retrospective clinical experience in 23 conse- inflammatory markers independent of the p53 status. During ageing, the
cutive patients treated by gastric peroral endoscopic myotomy (G-POEM). The CAIKK2 expression and the inflammatory response decreased, the liver fibrosis
aim was to evaluate the results of this new technique. was reversible. The tumor incidence at the age of 9–12 month in CAIKK2
Aims & Methods: This is a case consecutive report on 23 patients operated for Trp53
/
mice is significantly higher (67%) compared to CAIKK2 mice with
severe refractory gastroparesis, between January 2014 and April 2016, with a wild-type Trp53 (25%). Mice with induced liver-specific Trp53 deletion did not
rigorous prospectively designed follow-up. The inclusion criteria were patients exhibit liver tumor formation at the same age. The majority of liver tumors in
with a disturbed gastric emptying scintigraphy (GES) and elevated GCSI score 4 CAIKK2 Trp53
/
mice show intrahepatic cholangiocarcinoma (ICC) (81%)
2. The procedures were performed under general anesthesia in an intubated next to hepatocellular carcinoma (2%) and combined HCC/ICC (17%). In con-
patient, with large channel gastroscope using CO2 and the Triangle knife trast, CAIKK2 mice with wild-type Trp53 developed mainly HCC (50%), but
(Olympus, Japan) as dissection device. The steps were: sub-mucosal injection also ICC (25%) and HCC/ICC (25%) at lower level.
and mucosal incision 5 cm upstream the pylorus; submucosal tunnel by dissection Conclusion: The study shows that liver-specific Trp53 deletion in combination
(Swift Coag, 35W, Effect 2) until reaching the pyloric arch, which had a consis- with an inflammatory background results in elevated tumor incidence and leads
tent aspect; retrograde antro-pyloro-myotomy of 3cm length; closure of the to an increased occurrence of ICCs in the liver.
mucosal flap with clips. The primary objective was to document, at 5 days, Disclosure of Interest: All authors have declared no conflicts of interest.
A66 United European Gastroenterology Journal 4(5S)
OP160 EXPRESSION OF CD161 ON CD4þ T CELLS PROMOTES Introduction: Inflammatory bowel diseases (IBD) are the most significant
HEPATITIS B VIRUS RELATED LIVER FIBROSIS THROUGH ACID acquired risk factors of colorectal cancer and therefore surveillance colonoscopy
SPHINGOMYELINASE AND CD161-LECTIN-LIKE TRANSCRIPT-1 is widely endorsed. Conventional forward-viewing colonoscopy (FVC), however,
INTERACTION lacks acceptable sensitivity in IBD dysplasia identification and the addition of
L. Cheng, S. Wang, W. Jiang dye-based chromoendoscopy is recommended. Full Spectrum Endoscopy
Gastroenterology, Zhongshan Hospital of Fudan University, Shanghai/China (FUSE) is a novel colonoscope that incorporates 2 additional cameras to the
forward camera and provides 330- degree panoramic view of the colonic mucosa.
Contact E-mail Address: [email protected] Whether FUSE can decrease dysplasia miss rate in IBD surveillance has never
Introduction: Hepatitis B virus (HBV)-related liver fibrosis always progresses been tested previously.
from inflammation to fibrosis. CD4þ T cell immune responses play a pivotal Aims & Methods: This study aims to assess FUSE versus FVC in dysplasia
role in the process. Recently, CD161 is considered to be a costimulatory molecule surveillance in an IBD population. The dysplasia yield of targetted versus
on T cells and an important phenotypic marker of human Th17 cells. random colonic biopsies will also be assessed. Methods: A prospective, single-
Aims & Methods: This study was designed to investigate the roles of CD161 in the center, randomized-order, back-to-back crossover tandem colonoscopy study
pathogenesis of HBV-related liver fibrosis. Methods: A total of 54 CHB patients was conducted comparing FVC versus FUSE in an IBD- surveillance population.
who underwent liver biopsy and 20 healthy controls (HC) were enrolled. CHB Crohn’s disease (CD) and ulcerative colitis (UC) subjects were recruited from the
patients were further categorized according to the disease phase: immune-toler- IBD Sydney Cohort population-based database, all of whom met the inclusion
ant (IT, n ¼ 12), immune-active (IA, n ¼ 30), or inactive CHB (n ¼ 12). Peripheral criteria of published IBD surveillance guidelines. Subjects not due their surveil-
blood mononuclear cells (PBMCs) and flow cytometry sorted CD4þCD161þ and lance colonoscopy were excluded. The primary outcome was the per-lesion dys-
CD4þCD161- T cells were prepared for further flow cytometric and real-time plasia miss rate of the first colonoscopy identified by the second colonoscopy
PCR analyses. Flow cytometry sorted CD4þCD161þ and CD4þCD161- T cells with chromoendoscopy. Secondary outcomes were per-subject dysplasia miss
were also cultured alone or co-culture with primary hepatic stellate cells (HSCs) rate, mean dysplasia lesions found, procedural times, and dysplasia yield of
in in vitro experiments. targeted- versus random colonic biopsies. The trial was registered with the
Results: Compared to HC, the percentage of CD4þCD161þ T cells significantly Australia New Zealand Clinical Trials Registry (ACTRN12616000047493).
increased among IA patients while dramatically decreased among IT patients, Results: In total 104 tandem (52-paired) colonoscopies were conducted with 27
but there was no significant difference between inactive CHB patients and HC. subjects randomized to FVC first and 25 to FUSE first. Both arms were not
Besides, CD161 showed a positive correlation with histological inflammation statistically significantly different for age, IBD duration, CD versus UC, and
grades and advanced histological fibrosis stages. In the PBMCs of CHB patients, additional dysplasia risk factors. The dysplasia prevalence rate of the cohort
CD4þCD161þ T cells exhibited a CD45ROþ memory phenotype and secreted was 30.8%. The dysplasia miss rates for FVC and FUSE were 71.4% versus
more IFN-gamma, TNF-alpha, IL-17, IL-21 and IL-4 whereas produced less IL- 25.0% respectively (P ¼ 0.0001). On per-subject analysis, the dysplasia miss
10 and IL-22 than CD4þCD161- T cells. In comparison with CD4þCD161- T rate was 75.0% using FVC and 25.0% using FUSE (P ¼ 0.046). FUSE identified
cells, in vitro culture of CD4þCD161þ T cells revealed that CD161 expression a mean of 0.37 dysplastic lesions versus 0.12 for FVC (P ¼ 0.007). Targeted
increased the activity of acid Sphingomyelinase (aSM) and subsequent PI3K/ biopsies increased dysplasia identification (26/163, 16.0%) versus random biop-
Akt, MAPK and mTOR pathways of CD4þ T cells. Both knocking down of sies (2/687, 0.3%, P 5 0.0001). Chromoendoscopy identified 10/28 (35.7%) of
CD161 and using imipramine to inhibit aSM could down-regulate CD4þ T cell- dysplastic lesions. The total colonoscopy times were similar (21.2 minutes versus
proliferation and production of IFN-gamma and IL-17, especially for IL-17. 19.1 minutes, P ¼ 0.32) but colonoscope withdrawal time was significantly longer
HSCs express lectin-like transcript-1 (LLT1), the only ligand of human (15.8 minutes versus 12.0 minutes, P ¼ 0.03) for FUSE and FVC respectively.
CD161. HBcAg-stimulated HSCs upregulated LLT1 expression. In the co-cul- Conclusion: Full Spectrum Endoscopy outperformed conventional forward view-
ture system of HSCs and CD4þCD161þ T cells, CD161-LLT1 interaction not ing colonoscopy in inflammatory bowel disease subjects undergoing dysplasia
only promoted the proliferation and activation of HSCs, but increased IL-17 and surveillance. A high dysplasia prevalence was identified most likely due to multi-
IFN-gamma production of CD4þCD161þ T cells as well. Knocking down of ple colonoscopy passes and the use of multiple advanced imaging modalities
CD161 on CD4þ T cells or LLT1 on HSCs could partly reverse the aforemen- comprising of high-definition white-light colonoscopy, FUSE and chromoendo-
tioned effects. In HSCs-CD4þCD161- T cells co-culture system, expression of scopy. Improved dysplasia identification rates may reduce colorectal cancer mor-
pro-fibrotic genes in HSCs were inhibited. However, when CD161 was overex- tality and increase interval colonoscopies. Improved dysplasia yield of targetted
pressed on CD4þCD161- T cells, we detected a reactivated HSCs phenotype. biopsies versus random colonic biopsies was confirmed.
Conclusion: Our data revealed that the expression of CD161 on CD4þ T cells Disclosure of Interest: R.W. Leong: Endochoice USA investigator-initiated grant
might promote HBV-related liver fibrosis through CD161-LLT1 interaction to All other authors have declared no conflicts of interest.
activate HSCs and through raising aSM to enhance the proinflammatory func-
tions of CD4þ T cells.
Disclosure of Interest: All authors have declared no conflicts of interest.
References OP162 THE ACCURACY OF WAVSTAT VERSION 4 OPTICAL BIOPSY
FORCEPS IN CHARACTERIZING COLORECTAL POLYPS LESS 10
1. Takahashi T, Dejbakhsh-Jones S and Strober S. Expression of CD161 MM: A PROSPECTIVE BLINDED STUDY
(NKR-P1A) defines subsets of human CD4 and CD8 T cells with different
N. Mohammed1, R. Sood2, S.V. Venkatachalapathy1, F. Abid1, N. Burr1,
functional activities. J Immunol 2006; 1: 211–216.
P. Luthra1, J. Meadows1, J. Carboneli1, O. Rotimi1, V. Subramanian1
2. Li J, Qiu SJ, She WM, Wang FP, Gao H, Li L, Tu CT, Wang JY, Shen XZ 1
Gastroenterology, St James’s University Hospital NHS Trust, Leeds/United
and Jiang W. Significance of the balance between regulatory T (Treg) and T
Kingdom
helper 17 (Th17) cells during hepatitis B virus related liver fibrosis. PLoS One 2
University Of Leeds, Leeds Institute of Biomedical and Clinical Sciences, Leeds/
2012; 6: e39307.
United Kingdom

TUESDAY, OCTOBER 18, 2016 08:30–10:00 Contact E-mail Address: [email protected]

Introduction: Optical biopsies of colonic polyps 5 10 mm in size could poten-
FREE PAPER SESSION: NOVEL DIAGNOSTIC TOOLS: GOING DEEPER AND DEEPER tially replace standard histological assessment. WavSTAT version 4 is a novel
INTO THE BOWEL – ROOM N1_____________________ optical biopsy system designed by Spectrascience Inc, San Diego, California,
USA. for prediction of histology based on laser induced autofluorescence
OP161 FULL SPECTRUM ENDOSCOPY (FUSE) IN THE DETECTION spectroscopy.
OF INFLAMMATORY BOWEL DISEASE NEOPLASIA (FUSION): A Aims & Methods: The primary aim of this study was to demonstrate the accuracy
RANDOMIZED CROSSOVER TANDEM STUDY VERSUS of WavSTAT version 4 in characterizing colorectal polyps 510 mm that can be
CONVENTIONAL COLONOSCOPY resected and discarded (or left in-situ) without adverse clinical impact. The sec-
R. W. Leong, M. Ooi, C. Corte, Y. Yau, M. Kermeen, A. Alswaifi, P. Katelaris, ondary aim was to compare the real time diagnostic performance of WavSTAT
C. Mcdonald, M. Ngu version 4 with NBI and a combination of endoscopic and WavSTAT assess-
Gastroenterology and Liver Services, Concord Hospital, Sydney/Australia/NSW ments. Patients attending the endoscopy unit for lower gastrointestinal endo-
scopy as requested by their responsible physician were approached to
Contact E-mail Address: [email protected] participate in the study. Adult patients aged above 18 years were included.

Table (OP162): Diagnostic performance of Wavstat4, Endosocpic assessment and combined alogithmic assessment for characterization fo colorectal poylps less than
10 mm in size and prediction of surveillance intervals

WLEþNBI Combination of WavSTAT þ endoscopic

WavSTAT alone assessment assessment (algorithmic approach)

Sensitivity 97.6% (95% CI 0.88–0.95) 85.0% (95% CI 0.77–0.89) 95.8% (95%CI 0.89–0.96)
Specificity 46.9% (95%CI 0.44–0.98) 77.2% (95%CI 0.61–0.82) 78% (95%CI 0.66–0.79)
NPV 96.8% (95%CI 0.85–0.91 91% (95%CI 0.73–0.84) 98.5% (95% CI 0.89–0.95)
PPV 54.7% (95%CI 0.28–0.77) 66% (95%CI 0.44–0.79) 89.3% (95%CI 0.76–0.92)
Surveillance interval (% of patients 81.2% 97% 100%
coded correctly)
Surveillance interval (% of patients 18.8% 3% 0%
called earlier)
United European Gastroenterology Journal 4(5S) A67
Patients known to have inflammatory bowel disease or colorectal cancer were OP164 A ROLE FOR T CELL CLONAL EXPANSIONS IN THE POST-
excluded from the study. Polyps sized 510 mm were assessed in real time by high OPERATIVE RECURRENCE IN CROHN’S DISEASE: A STUDY
definition white light, NBI and WavSTAT version4 optical biopsy forceps. FROM THE REMIND GROUP
Standard techniques were used for polypectomy. Histopathological specimens M. Allez1, M. Ngollo1, C. Stefanescu2, C. Auzolle1, S. Nancey3, F. Djenidi1,
were read separately by two expert GI pathologists blinded to the results of M. Nachury4, A. Buisson5, H. Sokol6, X. Treton7, N. Barnich8, P. Seksik9, L. Le
the NBI and WavSTAT assessments. The primary outcome measure was the Bourhis1
negative predictive value in distinguishing adenomatous from non-adenomatous 1
, Gastroenterology, Hopital Saint-Louis, APHP, INSERM U1160, Universite´
colorectal polyps. The secondary outcome measure was the accuracy of on-site Denis Diderot, Paris/France
recommended surveillance intervals. 2
Service De Gastroenterologie Et Assistance Nutritive, Beujon Hospital, Clichy,
Results: 156 polyps (146 were 510 mm and 10 were 410 mm) were found in 70 Clichy/France
patients (Males-44, females-27). Average age of the patients was 65 years (range 3
Dept. De Gastroenterologie, Hospices de Lyon, Pierre Benite/France
29–95 years). 16 polyps were not included in the final analysis due to discrepancy 4
Gastroenterology, Claude Huriez hospital, University of Lille 2, Lille/France
in histological analysis between two pathologists. We failed to retrieve 5 polyps. 5
Dept. Of Gastroenterology, CHU Estaing Clermont-Ferrand, Clermont-ferrand/
26 patients were excluded from the study (No polyps seen in 17 patients, polyps France
510 mm were not seen in 3 patients, and device failure in 4 patients). A total of 6
Avenir Team Gut Microbiota, INSERM U1157/UMR CNRS 7203, UPMC,
126 polyps 510 mm were included in final analysis. The diagnostic performance Paris/France
for WavStat version 4 and endoscopic assessment is detailed in the table. 7
Hopital Beaujon, Clichy/France
Wavstat4 had a NPV of 96.8% but lacked specificity. Endoscopic assessment 8
UMR 1071 Inserm/University of Auvergne, Clermont-Ferrand/France
had a NPV of 91% and was more specific. Since the specificity of WavSTAT was 9
Department Of Gastroenterology, AP-HP, Hôpital Saint-Antoine, Paris/France
poor mainly for hyperplastic recto-sigmoid polyps we evaluated an algorithmic
approach where we classified the polyps according to the WavSTAT4 result when Contact E-mail Address: [email protected]
proximal to the recto-sigmoid junction. We classed them according to the endo- Introduction: Operative resection in Crohn’s disease is not curative. Indeed, a
scopic classification only if Wavstat4 prediction was as as an adenomatous polyp majority of CD patients undergoing ileocecal resection have an endoscopic recur-
in the recto-sigmoid area. This combined algorithmic approach met the PIVI rence in the neo-terminal ileum as soon as six months after surgery. T cells are
thresholds and had a NPV of 95.8% and predicted 100% of surveillance intervals major players in the intestinal immune response. We previously demonstrated the
correctly. persistence of T cell clonal expansions over time in the inflamed mucosa of CD
Conclusion: WavSTAT version 4 has a high NPV for characterizing colorectal patients (1). The presence of T cell clonal expansions at time of surgery could play
polyps less than 10 mm in size but only predicts surveillance intervals correctly in an important role in the post-operative recurrence.
81.2% of patients.. An algorithmic approach combining Wavstat4 and endo- Aims & Methods: The aims of the study were to explore the impact of the pre-
scopic assessment had a high NPV with accurate prediction of surveillance sence of T cell clonal expansions in the inflamed tissue at time of surgery on the
intervals. risk of post-operative endoscopic recurrence, and to analyse the correlation
Disclosure of Interest: All authors have declared no conflicts of interest. between the persistence of these T cell clones in the neoterminal ileum and
inflammation. The REMIND Post-OPerative study has been performed in 9
centers, collecting data at time of surgery (M0) and of endoscopy (performed
at M6), associated with an extensive bio-banking. Clinical, biological and endo-
OP163 DEEPER AND DEEPER INTO THE SMALL BOWEL IN scopic parameters were collected at month 6. Endoscopic recurrence was defined
PEDIATRIC CROHN’S DISEASE: PROSPECTIVE COMPARATIVE by a Rutgeerts score1. Biopsies of ileal mucosa were collected on surgical speci-
STUDY BETWEEN SMALL INTESTINE CONTRAST men and by endoscopy six months after surgery. T cell Receptor (TCR) analysis
ULTRASONOGRAPHY (SICUS) AND MAGNETIC RESONANCE was performed on DNA extracted from biopsies by next generation sequencing
IMAGING (Adaptive Biotechnology Inc., Seattle, Washington, USA). The TCR repertoire
F. Civitelli1, F. Maccioni2, S. Oliva1, F. Viola1, A. Dilillo1, M. Aloi1, was analyzed in biopsies obtained on the surgical specimen and during the con-
S. Cucchiara1 trol endoscopy at six months. Sequences, numbers, frequencies and clonality
1
Dept. Pediatrics, Gastroenterology and Liver Unit, Sapienza University of Rome, indexes were assessed; and further analyzed to determine TOP100 clone frequen-
Rome/Italy cies and persistent clonal expansions present at both M0 and M6 in each patient.
2
Radiology, Sapienza University, rome/Italy Results: Fifty-seven patients from the REMIND cohort were analyzed: 33 (58%)
were male; median age at surgery was 38 years old (14). We found that the TCR
Contact E-mail Address: [email protected] repertoire in biopsies from CD patients display a large number of unique TCR
Introduction: Small bowel (SB) assessment is essential for the proper management sequences (mean 10000 unique sequences) suggesting a high variety of T cell
of pediatric Crohn’s disease (CD). Magnetic resonance imaging (MRI) is con- specificities. However, measures of diversity of the TCR repertoire showed an
sidered the gold-standard for the evaluation of small bowel (SB). However, MRI important range of clonality within the cohort (0.001 to 0.5). Importantly, the
is expensive, it requires a strong compliance and a considerable amount of oral frequency of the 100 most represented clones in the tissue at M0 was significantly
contrast to adequately distend the intestinal lumen. Small intestine contrast increased in patients with endoscopic recurrence (Rutgeerts score1) at M6,
ultrasonography (SICUS) is non-invasive, low cost and generally well-tolerated showing that increased clonality at time of surgery was predictive of disease
by pediatric patients (pts). recurrence. Furthermore, the presence and frequency of persistent clones (present
Aims & Methods: We aimed to compare the diagnostic accuracy of SICUS and at M0 and M6) was significantly increased in patients who had an endoscopic
MRI in detecting presence, site and extension of SB disease and in assessing recurrence. High or low proportion of persistent clones could define two sub-
strictures in pediatric CD. Children with suspected CD or relapse of a known groups of patients with endoscopic recurrence in regard to their TCR repertoire.
CD were prospectively enrolled. All underwent SICUS, MRI and ileo-colono- Interestingly, expanded clones could be found in different T cell subsets.
scopy, performed by different operators blinded to other results. The SB was Conclusion: T cell clonal expansions in the inflamed tissue at time of surgery and
subdivided into: jejunum, ileum, terminal ileum (TI). The concordance (k) their persistence in the neoterminal ileum after surgery are both associated with
between the two techniques for presence and site of lesions was calculated post-operative endoscopic recurrence in Crohn’s disease.
according to Landis and Koch criteria*. For the TI, sensitivity (SE) and speci- Disclosure of Interest: M. Allez: I received honoraria from MSD, Abbvie,
ficity (SP) were also assessed, with ileo-colonoscopy as reference standard. One- Janssen, Novo Nordisk, Novartis, Takeda, Genentech, UCB, Pfizer, Ferring
way ANOVA with Kruskal-Wallis post-test was applied to compare the exten- All other authors have declared no conflicts of interest.
sion (cm) of disease in the different segments. Reference
Results: 66 pts (median age 13; range 7–18), 23 suspected, 43 known CD were
included. The overall concordance (k) between SICUS and MRI for presence of 1. Camus M, et al. Mucosal Immunol. 2014 Mar;7(2):325–34. doi: 10.1038/
SB lesions was 0.94 (ES 0.06; 95%CI 0.8–1). The k for segments was: jejunum mi.2013.51.
0.67 (ES 0.1, 95%CI 0.4–0.8), ileum 0.91 (ES 0.06, 95% CI 0.76–1), TI 0.91 (ES
0.06; 95%CI 0.8–1). SE and SP (%) of SICUS and MRI for TI lesions were 98,
100 and 93, 92, respectively. There was no difference in the assessment of disease
extension between SICUS and MRI (p ns). The overall k for strictures was 0.62 OP165 TARGETED CHEMICAL ANALYSIS OF THE COLON CANCER
(ES 0.1, 95% CI 0.4–0.8). SE and SP(%) of SICUS and MRI for TI strictures MICROBIOME USING DESORPTION ELECTROSPRAY
were 100, 100 and 92, 87, respectively. MRI provided 7 false positive results, not IONISATION MASS SPECTROMETRY IMAGING (DESI-MSI)
detected at SICUS nor confirmed at endoscopy. J. Alexander1, A. Mroz1, A. Perdones-Monteiro2, A. Scott1, L. Gildea3,
Conclusion: The diagnostic performance of SICUS is comparable to that of MRI S. Cameron3, F. Bolt3, F. Rosini3, R. Goldin1, J. Mckenzie2, A. Burke3,
in pediatric CD. SICUS is useful in assessing SB strictures, probably with higher N. Strittmatter3, N. Koundouros4, K. Veselkov1, A. Darzi1, G. Poulogiannis4,
accuracy than MRI. SICUS might represent a first-line tool in pediatric CD, able D. Cunningham5, J. Nicholson2, J. Marchesi6, Z. Takats1, J. Kinross1, J. Teare3
to reduce costs and to post-pone or even avoid more invasive and expensive 1
, Imperial College London, London/United Kingdom
investigations. 2
Computational & Systems Medicine, Imperial College London, London/United
Disclosure of Interest: All authors have declared no conflicts of interest. Kingdom
3
Reference Surgery & Cancer, Imperial College London, London/United Kingdom
4
Institute for Cancer Research, London/United Kingdom
1. Kramer SM, et al. Clinical biostatistics: the biostatistics of concordance. Clin 5
Royal Marden Hospital, London/United Kingdom
Pharmacol Ther 1981; 29: 111–123. 6
Centre For Gut Health, Imperial College London, London/United Kingdom
Contact E-mail Address: [email protected]
Introduction: The gut microbiome is an important modulator of colorectal (CRC)
cancer risk. Here we describe a novel methodology for the targeted analysis of the
A68 United European Gastroenterology Journal 4(5S)
colon cancer microbiome using mass spectrometry imaging in a prospective Disclosure of Interest: C. Monast: Employee of Janssen Research and
cohort of CRC patients. Development, LLC
Aims & Methods: A prospective, multi centre observational study was performed A. Stojmirovic: Employee of Janssen Research and Development, LLC
on patients undergoing elective resections for colorectal cancer at Imperial R. Dobrin: Employee of Janssen Research and Development, LLC
Healthcare NHS Trust and the Royal Marsden Hospital. Fresh mucosal tissue C. Brodmerkel: Employee of Janssen Research and Development, LLC
was sampled under aseptic conditions from cancers and adjacent normal tissue F. Baribaud: Employee of Janssen Research and Development, LLC
and frozen at –80 C. Using 16S rRNA sequencing analysis of corresponding
tissue samples (performed in Mothur and Stamp), target bacteria including
Fusobacterium spp, E.Coli and Bifidobacteria were identified. A chemical data-
base of these bacteria was created using Rapid Evaporative Ionisation Mass OP167 COMPREHENSIVE CIRCULATORY TRANSCRIPTOME AND
Spectrometry (REIMS) from pure cultures of the target microbes. Desorption PROTEOMIC PROFILING IN NEWLY DIAGNOSED
Electrospray Ionisation Imaging Mass Spectrometry (DESI-MSI) was then per- INFLAMMATORY BOWEL DISEASES: A MULTI-CENTRE COHORT
formed to provide a spatially resolved map of the mucosal microbial lipidome. STUDY
Taxon specific data were mapped onto these images using chemical spectra iden- R. Kalla1, A. T. Adams1, J. Lindstrom2, Ibd Character Consortium1,
tified by REIMS. Candidate microbial lipids were validated using cell co-culture M.H. Vatn3, J. Jahnsen4, P. Ricanek5, D. Bergemalm6, J.D. Söderholm7,
experiments and analysis with REIMS. Multivariate analysis was performed M.J. Pierik8, F. Gomollon9, M. D’Amato10, J. Halfvarson11, J. Satsangi1
using Matlab (Mathworks) and R. Both unsupervised Principle Component 1
Centre For Genomics and Experimental Medicine, University of Edinburgh,
Analysis and supervised Linear Disciminant Analysis were performed. Edinburgh/United Kingdom
ANOVA was used to perform statistical analysis of single lipid species. 2
Deparment Of Gastroenterology, University of Oslo, Oslo/Norway
Results: 26 patients with sporadic colorectal cancer were recruited (17 women, 3
Inst. Of Clinical Medicine, University of Oslo, Oslo/Norway
median age 68, range 35–84, median BMI 27 kg/m2). Eight tumours were right 4
Deparment Of Gastroenterology, Akershus University Hospital, Lorenskog/
sided, eleven were left sided and seven were rectal. Two patients had neo-adju- Norway
vant chemoradiotherapy. Histology showed six adenomas, one T1, six T2, ten T3 5
Department Of Gastroenterology, Oslo University Hospital, Oslo/Norway
and three T4 cancers. Using DESI-MSI it was possible to geographically identify 6
Deparment Of Gastroenterology, Örebro University, Örebro/Sweden
distinct anatomical regions based on co-registration of the chemical data with 7
University Hospital, Linköping University, Linköping/Sweden
independently validated HþE stained tissue. Using leave one patient out cross 8
Dept Of Gastroenterology and Hepatology, Maastrich University Medical Center
validation, DESI-MSI was able to diagnose cancer from normal colonic mucosa Dept. of Gastroenterology, Maastricht/Netherlands
with ROC AUC ¼ 97.5. Increased long chain fatty acids were seen in malignant 9
Servicio De Aparato Digestivo, Hospital Clı´nico Universitario Lozano Blesa,
tissue and increased glycerophospholipids were seen in healthy mucosa (both Zaragoza/Spain
p 5 0.001). Target spectra just specific to the mucosa were then extracted for 10
Unit Of Molecular Genetics Of Digestive Diseases, BioCruces Health Research
analysis. This revealed 102 lipid species that differentiated colon cancer from Institute, Bilbao/Spain
normal adjacent mucosa, including 24 attributable to taxon-specific markers 11
Dep. Of Internal Medicine, Örebro University Hospital, Örebro/Sweden
for Bacteroidetes, Bifidobacteriales and Enterobacteriales. These were positively
validated using cell culture REIMS. Contact E-mail Address: [email protected]
Conclusion: Chemical mapping of the colonic lipidome permits spatially resolved Introduction: There is an unmet need to gain functional insights into pathways
analysis of the cancer microbiome and its metabolic functions, and this has that are relevant in Inflammatory Bowel Diseases (IBD). By performing tran-
diagnostic value. DESI-MSI provides a completely novel methodology for study- scriptome and proteome profiling in newly diagnosed IBD, we can gain an under-
ing microbial-host interactions critical to the aetiology of inflammation and standing into the molecular mechanisms that may be relevant in disease.
cancer. Aims & Methods: Gene expression patterns from whole blood RNA and proteo-
Disclosure of Interest: All authors have declared no conflicts of interest. mic profiles from serum were assessed from patients using targeted RNA-seq
(Ion AmpliSeq Transcriptome Human Gene Expression platform) and Olink
multiplex protein panels (Olink Proteomics). Treatment-naı̈ve newly diagnosed
IBD and healthy symptomatic controls were included in the study. Phenotypic
OP166 UNSUPERVISED, TRANSCRIPTOMICS-BASED CLUSTERING data were captured including demographics and disease classification. Statistical
OF ULCERATIVE COLITIS PATIENTS REVEALS MARKED analysis was performed using R. Differentially expressed transcriptomes were
HETEROGENEITY THAT RELATES TO ANTI-TNF TREATMENT correlated with serum protein expression to obtain a circulating profile at
RESPONSE diagnosis.
C. Monast, A. Stojmirovic, R. Dobrin, C. Brodmerkel, F. Baribaud Results: RNA expression profiles were available in 639 patients (351 IBD, 288
Immunology, Janssen Research and Development, LLC, Spring House/United controls). A total of 5678 genes were differentially expressed between IBD and
States of America/PA controls. Using hsCRP to adjust for inflammatory status, 1440 remained signifi-
cant. The most differentially expressed genes were CD-177 (Bonferroni corrected
Contact E-mail Address: [email protected] p ¼ 2.31036), VBP1 (p ¼ 2.901032) and S100 proteins (S100A9,
Introduction: Heterogeneity in IBD patient populations is widely cited as the p ¼ 3.31026 and S100A12, p ¼ 6.81026). Proteomic profiles were available
main barrier to efficient clinical trials and development of therapies with high in 635 patients (152 CD, 159 UC, 26 IBD-U, 298 non-IBD) Multivariable ana-
clinical efficacy. We and others hypothesize that phenotypic heterogeneity is a lysis identified 59 protein markers that were significantly associated with IBD.
direct result of molecular heterogeneity in disease-driving molecular pathways. The top significant proteins upregulated in IBD included MMP12 (Holm-
We present an approach not extensively explored for defining molecular hetero- adjusted p ¼ 4.11026) and CXCL9 (p ¼ 1.71020). Matched serum protein
geneity in a manner independent of known biology. profiles were available and correlated with RNA expression. 39 proteins
Aims & Methods: Whole-genome transcriptomic data was generated for colonic showed significant correlation with gene expression including OSM (rho ¼ 0.51,
biopsies from 217 moderately to severely active ulcerative colitis subjects and 21 Holm-adjusted p ¼ 1.41040) and S100A12 (rho ¼ 0.33, p ¼ 3.41014) while
healthy normal controls. Subjects were scored based on enrichment of 113 co- other markers such as CXCL9 show poor correlation (rho ¼ 0.16, p ¼ 0.04). As
expression modules, or lists of correlated genes, derived from colonic biopsies biomarkers, top 2 serum markers were able to discriminate IBD from controls
from both UC and CD biopsies. Scores for each subject and co-expression with a similar area under the receiver operator characteristics curve (AUC) of
module were computed using the gene set variation analysis algorithm. Co- 0.75 and 0.74 respectively. Individually these markers outperformed hsCRP
expression modules were then hierarchically clustered into 4 module clusters (n ¼ 619, AUC 0.64, p for comparison ¼ 2.7x104 vs. MMP12) and albumin
and annotated with pathways using the union of genes within each of the 4 (AUC 0.66, p ¼ 0.004 vs MMP12). 6 proteins differentiated UC from CD includ-
module clusters. Each subject was then reclassified based on the 4 module clusters ing MMP12 (p ¼ 4.6104). In CD, MMP12 levels were lower in those with
by taking the median enrichment score of the modules within each module clus- small bowel involvement(Montreal Classification L1, L3 and L4 vs L2;
ter. IBD subjects and normal controls were then hierarchically clustered into 4 p ¼ 0.009) while in UC, MMP12 levels were significantly higher in extensive
subgroups using the 4 module clusters and assessed for relationship to anti-TNF disease (Paris classification E1 and E2 vs. E3, p ¼ 5.8x107).
response. Conclusion: This is the largest integrative multicentre characterisation of the
Results: The 4 module clusters represented distinct pathway sets which we sum- circulating expression profile studied in IBD at diagnosis. These data identify
marized as inflammation/monocytes, mucosa/pro-regulatory, T cells/metabolism key pathways that may be relevant in IBD pathogenesis and demonstrate the
and mitochondria/metabolism. Patients belonging to the subgroup characterized translational potential of these markers in diagnosing and classifying IBD.
by the highest enrichment for the inflammation/monocyte module cluster trended Disclosure of Interest: R. Kalla: Funded by IBD Character Ferring Speaker Fees
towards lower response rates to anti-TNF therapy. Conversely, the highest J. Jahnsen: JJ has served as a speaker, a consultant and a advisory board member
response rates to anti-TNF therapy were observed in the subgroup characterized for MSD, Tillot, Ferring, AbbVie, Celltrion, Orion Pharma, Takeda, Napp
by the lowest enrichment for the inflammation/monocyte module cluster. These Pharm, Meda, AstroPharma, Hikma and Pfizer.
subgroups also contained normal healthy controls. Enrichment values for the F. Gomollon: Advisor: Grifols, Abbvie, MSD. Travel Grants: Abbvie, MSD.
mucosa/pro-regulatory module cluster anti-correlated (r ¼ 0.49) with enrich- Research funding (Department) MSD
ment values for the inflammation/monocyte module cluster. J. Satsangi: JS has served as a speaker, a consultant and an advisory board
Conclusion: We find that there is pronounced molecular heterogeneity in the member for MSD, Ferring Abbvie and Shire, consultant with Takeda, speaking
pathways present in colonic biopsies from UC patients. We also show that this fees from MSD and has received research funding from Abbvie
heterogeneity may be related to the ability of patients to respond to anti-TNF All other authors have declared no conflicts of interest.
therapy. This suggests that molecular stratification may be a key step towards
designing smaller clinical trials and identifying meaningful personalized medicine
approaches for IBD patients.
United European Gastroenterology Journal 4(5S) A69

Table 1 (OP168): Demographics, procedural outcomes, bowel cleanliness and adenoma detection.

P value

Demographics WE N ¼ 408 WI N ¼ 408 AI N ¼ 408 WE vs WI WE vs AI WI vs AI ANOVA

Females, n (%) 184 (45.1) 185 (45.3) 183 (44.9)

Males, n (%) 224 (54.9) 223 (54.7) 225 (55.1) 1y 1y 0.888y 0.990
Age, mean (SD) 61.4 (6.2) 61.0 (6.3) 60.9 (6.2) 0.261z 0.173z 0.822z 0.350
Body Mass Index, mean (SD) 26.4 (4.1) 26.4 (4.4) 26.6 (4.4) 0.751z 0.473z 0.696z 0.775
Indications for colonoscopy, n (%)
Screening FITþ 242 (59.3) 242 (59.3) 222 (54.4) 1y 0.157y 0.157y 0.263
Screening FOBTþ 18 (4.4) 19 (4.7) 19 (4.7) 0.863y 0.863y 1y 0.982
Family history of colorectal cancer 47 (11.5) 47 (11.5) 45 (11.0) 1y 0.823y 0.823y 0.968
Primary colonoscopy 101 (24.8) 100 (24.5) 122 (29.9) 0.920y 0.099y 0.084y 0.143
Procedural outcomes
Cecal intubation rate (final), n (%) 402 (98.5) 400 (98.0) 399 (97.8) 0.590y 0.435y 0.807y 0.734
Cecal intubation time, mean (SD), min 10.1 (5.4) 9.4 (5.7) 9.7 (6.7) 0.050z 0.364z 0.390z 0.188
Withdrawal time without polypectomy, mean (SD), min 9.5 (3.2) 9.5 (3.6) 8.9 (3.1) 0.870z 0.074z 0.128z 0.084
Total procedure time, mean (SD), min 24.8 (11.7) 24.6 (12.0) 23.3 (11.0) 0.842z 0.059z 0.098z 0.128
Withdrawal endoscopists’ correct guesses of insertion method 119 (29.2) 135 (33.1) 116 (28.4) -- -- -- --
Overall Boston Bowel Preparation Scale (BBPS) score, mean (SD) 7.9 (1.5) 7.4 (1.6) 7.5 (1.7) 50.0005z 50.0005z 0.924z 50.0005
Right colon BBPS score (SD) 2.6 (0.6) 2.4 (0.6) 2.4 (0.7) 50.0005z 50.0005z 0.815z 50.0005
Infused water during insertion, median (range), mL 550 (50–6500) 400 (50–2000) 0 (0–1000) -- -- -- --
Aspirated water during insertion, median (range), mL 500 (0–6500) 50 (0–1000) 100 (0–900) -- -- -- --
Adenoma detection
Overall ADR, n (%) 201 (49.3) 177 (43.4) 165 (40.4) 0.395y 0.011y 0.092y 0.036
Overall advanced adenoma detection rate, n (%) 79 (19.4) 70 (17.2) 58 (14.2) 0.4137y 0.049y 0.249y 0.145
Right colon ADR, n (%) 98 (24.0) 78 (19.1) 69 (16.9) 0.089y 0.012y 0.413y 0.034
MAPþ, mean (SD) 1.79 (1.2) 1.98 (1.9) 1.79 (1.3) 0.265z 0.981z 0.245z 0.365
At BBPS 9–8 (entire colon) WE n ¼ 275 WI n ¼ 227 AI, n ¼ 227
Adjusted overall ADR, n (%) 148 (53.8) 94 (41.4) 88 (38.8) 50.0005y 50.0005y 0.566y 0.001
At BBPS 3 (right colon) WE n ¼ 243 WI n ¼ 186 AI n ¼ 190
Adjusted right colon ADR, n (%) 63 (25.9) 32 (17.2) 26 (13.7) 0.0007y 50.0005y 0.346y 0.004

SD, standard deviation; FITþ, positive at fecal immunochemical testing; FOBTþ, fecal occult (guaiac-based) blood testing; Advanced adenomas: adenomas 10 mm
in diameter, or high grade dysplasia, or with 20% villous components. yChi-squared; zt test; ANOVA, analysis of variance.

the withdrawal. To assess adequacy of blinding the withdrawal, the second

TUESDAY, OCTOBER 18, 2016 08:30–10:00 endoscopist was asked to guess the insertion technique.
IMPROVING DETECTION OF POLYPS – ROOM N2_____________________ Results: All results are reported in Table 1. Demographics, clinical features,
indications, cecal intubation rates and procedure times were comparable.
OP168 A RANDOMIZED, CONTROLLED TRIAL COMPARING AIR Compared with AI (40.4%), WE (49.3%) but not WI (43.4%) achieved signifi-
INSUFFLATION, WATER IMMERSION AND WATER EXCHANGE cantly higher overall ADR (p ¼ 0.011 and 0.092, respectively). Compared with AI
FOR ADENOMA DETECTION IN SCREENING COLONOSCOPY (14.2%), WE (19.4%) but not WI (17.2%) achieved significantly higher advanced
PATIENTS ADR (p ¼ 0.049 and 0.249, respectively). In the right colon, WE (24%) but not
S. Cadoni1, P. Falt2, E. Rondonotti3, F. Radaelli3, P. Fojtik4, P. Gallittu1, WI (19.1%) achieved significantly higher ADR than AI (16.9%) (p ¼ 0.012 and
M. Liggi5, A. Amato6, S. Paggi7, V. Smajstrla4, O. Urban2, M. Erriu8, 0.413, respectively). Even after split-dose preparation, WE was associated with
F.W. Leung9 higher overall and right colon BBPS scores. The impact was most notable in
1
Digestive Endoscopy Unit, St. Barbara Hospital, Iglesias/Italy patients with excellent BBPS, adjusted entire and right colon ADR of WE were
2
Digestive Diseases Center, Vitkovice Hospital, Ostrava/Czech Republic significantly higher than those of WI and AI. Multivariate logistic regression
3
Dept. Of Gastroenterology, Ospedale Valduce Gastroenterology Unit, Como/Italy showed that WE, compared with AI, was an independent predictor of adenoma
4
Vitkovice Hospital, Digestive Diseases Center, Ostrava/Czech Republic detection in the entire colon [OR (95% CI), 1.18 (1.03–1.36)] and in the right
5
St. Barbara Hospital, Digestive Endoscopy Unit, Iglesias/Italy colon [1.24 (1.04–1.47)], respectively. Comparable correct guesses of insertion
6
Dept. Of Gastroenterology, Gastroenterology Unit, Ospedale Valduce, Como, method (532%) suggest adequate investigator blinding. Similar withdrawal
Italy, Como/Italy times without polypectomy suggested withdrawal technique was comparable.
7
Gastroenterology Unit, Valduce Hospital, Como/Italy Equal mean adenoma per positive colonoscopy (MAPþ) suggest ADR was not
8
Department Of Surgical Sciences, University of Cagliari, Cagliari/Italy negatively impacted by the one-and-done approach. Volumes of water infused
9
Sepulveda Ambulatory Care Center, VAGLAHS and David Geffen School of and suctioned suggested that WE, WI and AI methods were correctly used.
Medicine at UCLA, Los Angeles/United States of America/CA Conclusion: The current study shows that in European screening patients, WE
increased adenoma detection by 18% in the entire colon and by 24% in the right
Contact E-mail Address: [email protected] colon. Moreover, compared with the two other methods, WE improves the qual-
Introduction: Adenoma detection rate (ADR, proportion of patients with at least ity of colon cleansing. A type II error could account for the absence of statistical
one adenoma) is the primary quality indicator of colonoscopy, due to its correla- significance between unadjusted ADR in the WE and WI groups, further direct
tion with the risk of post-colonoscopy interval cancer and mortality [1,2]. Data comparisons between WE and WI are required.
from U.S. male veterans [3,4], patients in Taiwan [5] and Europe [6], suggest that Disclosure of Interest: S. Cadoni: Recipient of the 2013 ESGE Research Grant
water exchange (WE, infusion of clean water in an airless lumen and removal of All other authors have declared no conflicts of interest.
dirty water during insertion), but not water immersion (WI, infusion of water as References
adjunct to insufflation and removal of residual water during withdrawal) signifi-
cantly increases ADR in the proximal (cecum-splenic flexure) and right (cecum- 1. Rex DK, Gastrointest Endosc 2015;81:31–53.
ascending) colon, when compared with standard air insufflation (AI). 2. Corley DA, N Engl J Med 2014;370:1298–306.
Limitations of these studies were their retrospective analysis and/or investigators 3. Leung FW, Gastrointest Endosc 2012;76:657–666.
unblinded to the insertion method. 4. Leung FW, J Interv Gastroenterol 2011;1(1):8–13.
Aims & Methods: In a prospective, multi-site randomized controlled trial we 5. Hsieh Y-H, Am J Gastroenterol 2014;109(9):1390–400.
tested the hypothesis that WE, but not WI, significantly increases ADR (primary 6. Cadoni S, Dig Liver Dis 2016. First online: 23 March. DOI: 10.1016/
outcome measure) compared with AI. The study population was represented by j.dld.2016.03.004.
50–70 years-old asymptomatic subjects, undergoing colonoscopy as primary
screening test or after positive fecal occult blood test. A total of 1224 (672
males) patients were enrolled at three centers and randomly allocated 1:1:1 to
WE, WI and AI. Split-dose bowel preparation was adopted to ensure optimal
pre-procedure cleansing. To overcome the limitation of previous reports of
unblinded colonoscopist performing withdrawal inspection, after reaching the
cecum another investigator blinded to the insertion technique used performed
A70 United European Gastroenterology Journal 4(5S)
OP169 EFFICACY OF ENDOCUFF-ASSISTED COLONOSCOPY IN THE OP171 FREQUENCY AND PREDICTORS OF ADVANCED HISTOLOGY
DETECTION OF COLORECTAL POLYPS IN LARGE NON-PEDUNCULATED COLORECTAL POLYPS:
Y. Wada1, Y. Wada1, M. Wada1, Y. Fukuma2, M. Fukuda3, K. Ohtsuka3 EXPERIENCE-BASED DATA AT A UNIVERSITY HOSPITAL
1
Department Of Endoscopy, Wada Clinic, Wakayama/Japan H.R. Cheng1, R.M.m. Bogie2, B. Winkens3, H.I. Grabsch4, R. De Ridder2,
2
Tranomon Hospital, Tokyo/Japan J.W.A. Straathof2, A.A. Masclee2, S. Sanduleanu2
3 1
Tokyo Medical and Dental University, Tokyo/Japan Department Of Gastroenterology and Hepatology, Máxima Medical Center,
Veldhoven/Netherlands
Contact E-mail Address: [email protected] 2
Division Of Gastroenterology-hepatology, Department Of Internal Medicine,
Introduction: Colonoscopy is the gold standard for detecting colorectal adenomas Maastricht University Medical Centerþ, Maastricht/Netherlands
and cancers. Endoscopic surveillance has been shown to be effective for prevent- 3
Department Of Methodology and Statistics, Maastricht University Medical
ing colorectal cancer. Although the detection of colorectal polyps at an early Centerþ, Maastricht/Netherlands
stage is important, the endoscopic visualization of early neoplasia can be 4
Grow, School For Oncology and Developmental Biology, Maastricht University
difficult. Medical Centerþ, Maastricht/Netherlands
Aims & Methods: The Endocuff is a new device that can be attached to the tip of
the colonoscope to hold the colonic folds away from the field of view during Contact E-mail Address: [email protected]
withdrawal. The aim of this study was to compare the polyp and adenoma Introduction: Endoscopic resection of large non-pedunculated colorectal polyps
detection rates between Endocuff-assisted colonoscopy and standard colono- (LNPCPs) is challenging, with a significant proportion of them containing malig-
scopy. This randomized prospective study was conducted at two academic endo- nancy. Diagnostic work-up has the potential to improve clinical outcomes. The
scopy departments in Japan. The subjects were 446 patients who underwent a aims of this study were to examine the frequency of LNPCPs in clinical practice,
complete colonoscopic examination from April 2015 to September 2015. The endoscopic and histopathologic features and predictors for advanced histology.
Endocuff group included 239 patients. Cecal intubation rate, insertion time, Aims & Methods: We previously trained all endoscopists (9 faculty and 14 trai-
withdrawal time, pain score, complications, polyp detection rate, and adenoma nees) at Maastricht UMCþ on detection, diagnosis and endoscopic resection of
detection rate were assessed. colorectal neoplasms using a stepwise training program: Phase 1: Training on
Results: There were no differences between the groups in cecal intubation rate, detection and diagnosis of colorectal neoplasms, with special attention for non-
insertion time, withdrawal time, or pain score. Cecal intubation was achieved in polypoid (flat and depressed) colorectal neoplasms using lectures, videos and
235 patients (98.8%) in the Endocuff group. In four patients, the Endocuff- individual feedback. Phase 2: Training in endoscopic resection techniques using
assisted examination had to be stopped in the sigmoid colon due to severe ste- videotraining and hands-on training with experienced colonoscopists. Then, we
nosis caused by diverticula or cancers. These examinations were completed with a embarked in a prospective study of all consecutive colonoscopies performed at
standard colonoscope. Superficial mucosal erosions occurred in 54 patients our institution from February 2008 to February 2012. Quality indicators (cecal
(23.0%) during withdrawal in the Endocuff group but no major complication intubation rate, adenoma and polyp detection and resection rate) were moni-
occurred. The polyp detection rate in patients increased by 12% (62% vs. 50%, tored. We recorded patient characteristics (age, gender) and lesion characteris-
P ¼ 0.013) and the adenoma detection rate increased by 15% (55% vs. 40%, tics, i.e. location, size, shape using Paris classification (including photo
P ¼ 0.001) with the use of Endocuff. The advanced adenoma detection rate documentation) and histopathology. We defined LNPCPs as large (20 mm)
was higher in the Endocuff group but no statistically significant difference was non-pedunculated (i.e. sessile, flat, depressed, combinations) colorectal neo-
found (6.1% vs. 3.2%, P ¼ 0.17). plasms (Rutter et al, Gut 2015). We paid special attention to laterally spreading
Conclusion: Endocuff-assisted colonoscopy enabled a significantly higher polyp tumors (LSTs), defined as superficially growing lesions along the mucosa instead
and adenoma detection rate than standard colonoscopy. This attachment of growing up- or downwards. We conducted a logistic regression analysis to
improved important quality measures used for screening colonoscopy. identify predictors for advanced histopathology, defined as high-grade dysplasia
Disclosure of Interest: All authors have declared no conflicts of interest. or early colorectal cancer (pT1).
Results: A total of 7166 neoplasms were identified in 9353 patients (mean age
58.9 years, 46.0% male), of which 205 (2.9%) in 176 (1.9%) patients (mean age
68.3 years, 56.3% male) were LNPCPs. The majority (65.9%) of LNPCPs were
OP170 DEVELOPMENT AND VALIDATION OF A SIMPLE located in the proximal colon. Mean size was 30 mm (20–100 mm). Ninety-six
CLASSIFICATION SYSTEM FOR IN VIVO DIAGNOSIS OF LNPCPs (46.8%) were sessile and 109 (53.2%) LSTs. LNPCPs contained low-
COLORECTAL POLYPS USING THE NEWLY INTRODUCED grade dysplasia adenoma (29.8%), high-grade dysplasia adenoma (37.1%), early
OPTICAL ENHANCEMENT (OE) TECHNOLOGY colorectal cancer (17.1%), sessile serrated adenoma/polyp (6.6%), hyperplasia
H. Neumann1, M. Vieth2, L. Fry3, G.E. Tontini1, K. Mönkemüller3 (8.8%), and traditional serrated adenoma (0.5%). Sessile-LNPCPs more often
1
Department Of Medicine I, University Hospital Erlangen, Erlangen/Germany contained advanced histopathology than LST-LNPCPs (61.5% vs. 34.9%,
2
Abt. Pathologie, Klinikum Bayreuth Abt. Pathology, Bayreuth/Germany p 5 0.001). After adjusting for age and gender, distal location (OR 3.1, 95%-
3
Basil Hirschowitz Endoscopic Center Of Excellence, University of Alabama at CI 1.6–6.0, p 5 0.001), size of lesion (OR 2.7 for LNPCP 40 mm compared to
Birmingham, Birmingham/United States of America 20–29 mm, 95% CI 1.1–6.2, p ¼ 0.023) and sessile shape (OR 2.3, 95%-CI 1.2–
4.4, p 5 0.001) were all independent predictors for advanced histopathology. The
Contact E-mail Address: [email protected] overall referral rate to surgery (n ¼ 45) decreased from 30.4% in the first half of
Introduction: Optical enhancement (OE) will be introduced at UEGW 2016 as a the study period to 16.7%. Delayed bleeding occurred in 6 (5.6%) cases after
novel endoscopic imaging technique that adjusts emitted light to enhance muco- endoscopic resection, none requiring surgical intervention. No perforations
sal vascular pattern and surface pattern morphology. This study assessed for the occurred.
first time the utility of OE to predict colorectal polyp histology. Conclusion: In this real-life prospective cohort, 1.9% of all patients undergoing a
Aims & Methods: Primary objective was to develop and validate a simple classi- colonoscopy had a LNPCP. Lesion size, sessile shape and distal location were
fication system allowing differentiation of hyperplasic and adenomatous color- independent predictors of advanced histology. Careful case selection which con-
ectal lesions by using OE. In the first phase, the capacity of experienced siders both patient-related factors and endoscopic predictors of advanced histol-
endoscopists to predict the histology of colorectal polyps was assessed. In the ogy is critical to optimize the outcomes of endotherapy for LNPCPs.
second phase, a simplified classification was developed allowing histologic pre- Disclosure of Interest: S. Sanduleanu: Consultancy: Pentax Europe
diction. Thirdly, the validity of the classification was evaluated among inexper- All other authors have declared no conflicts of interest.
ienced raters, including medical students, nurses and GI fellows. At least, a pilot Reference
clinical evaluation was performed during real-time colonoscopy.
Results: A simple classification system for differentiating hyperplasic and adeno- 1. Rutter MD, Chattree A, Barbour JA, et al. British Society of
matous colorectal lesions by using OE was developed and validated. Diagnosis Gastroenterology/Association of Coloproctologists of Great Britain and
was made in 85% to 90% of polyps with high-confidence. Sensitivity ranged Ireland guidelines for the management of large non-pedunculated colorectal
from 92% to 96% and specificity ranged from 86% to 93%, respectively. polyps. Gut 2015 Dec; 64(12): 1847–1873.
During real-time colonoscopy, diagnosis was made with high-confidence in
90% of polyps with sensitivity of 96%, specificity of 92%, and accuracy of
95%. Positive and negative predictive values were 96% and 93%, respectively.
Conclusion: We developed and validated for the first time a simple and effective OP172 HEALTH EFFECTS AND COSTS DUE TO POST-
classification system for differentiating hyperplasic and adenomatous colorectal COLONOSCOPY COLORECTAL CANCER
lesions by using the newly introduced OE-technology during real-time colono- M. Aronsson1, P. Carlsson1, A. Ekbom2, R. Hultcrantz3, A. Forsberg4
scopy. These findings need to be evaluated in future prospective, controlled, and 1
Division Of Health Care Analysis, Department of Medical and Health Sciences,
blinded clinical trials. Linköping/Sweden
Disclosure of Interest: All authors have declared no conflicts of interest. 2
Department Of Medicine, Karolinska Instituet Solna, Stockholm/Sweden
3
Karolinska Institutet, Huddinge Hospital, 4Division of Gastroenterology,
Department of Medicine, Stockholm/Sweden
4
Inst Molecular Medicine and Surgery, Karolinska Institutet, Stockholm/Sweden
Contact E-mail Address: [email protected]
Introduction: Colorectal cancers (CRC) detected shortly after a colonoscopy are
referred to as a post-colonoscopy colorectal cancer (PCCRC), and has been
reported to represent 2–9% of all CRCs, depending on the definition, setting
and methods for estimating its incidence. The delay in detection of the CRC
might imply higher mortality, effect on the quality of life of the diagnosed indi-
viduals, and association with extra costs for health services.
Aims & Methods: The aim of this study was to estimate the loss of health and
health care costs following delay in CRC-diagnosis due to PCCRC in Sweden. A
United European Gastroenterology Journal 4(5S) A71

Table 1 (OP172): Logistic regression model adjusted for age and gender to identify predictors for advanced histopathology in LNPCPs. LGD: low-grade dysplasia;
HGD: high-grade dysplasia; early CRC: early colorectal cancer (pT1).

Histopathology
Feature Total (n ¼ 205) Unadjusted OR (95% CI) Adjusted OR* (95% CI)
LGD (n ¼ 108) HGD or early CRC (n ¼ 97)

Location p 5 0.001 p 5 0.001

Proximal 135 (65.9%) 87 (64.4%) 48 (35.6%) 1.0 1.0
Distal 70 (34.1%) 21 (30.0%) 49 (70%) 4.2 (2.3–7.9) 3.1 (1.6–6.0)
Size p ¼ 0.191 & 0.001 p ¼ 0.131 & 0.023
20–29 mm 109 (53.2%) 67 (61.5%) 42 (38.5%) 1.0 1.0
30–39 mm 57 (27.8%) 29 (50.9%) 28 (49.1%) 1.5 (0.8–2.9) 1.7 (0.9–3.5)
40 mm 39 (19.0%) 12 (30.8%) 27 (69.2%) 3.6 (1.6–7.8) 2.7 (1.1–6.2)
Shape p 5 0.001 p 5 0.001
LST 109 (53.2%) 71 (65.1%) 38 (34.9%) 1.0 1.0
Sessile 96 (46.8%) 37 (38.5%) 59 (61.5%) 3.0 (1.7–5.3) 2.3 (1.2–4.4)

*Logistic regression model adjusted for age and gender

recent register study of colonoscopies in Sweden during 2001–2010 revealed that 2010); of these 15,046 were invited for four rounds of FIT, 8,407 for one-time
18,244 individuals were diagnosed with CRC within 0–36 months after a colono- sigmoidoscopy, and 6,600 for one-time colonoscopy screening. We compared 2
scopy. A CRC was defined as a PCCRC if it was detected within 6–36 months rounds of FIT to one-time sigmoidoscopy and 4 rounds of FIT to one-time
after a colonoscopy in which no cancer was detected. A total of 1,473 (8.1%) colonoscopy. Cumulative (cum.) participation rate, positivity rate, number of
PCCRCs were found in the register study and included in this study. A lifelong colonoscopies, and diagnostic yield were calculated for each method. The DY
mathematical Markov model was employed to calculate the lifelong health effects was calculated relative to eligible invitees and participants. Between-group differ-
and resource usage for PCCRC. The effects were calculated by simulating the ences for participation, number of colonoscopies and DY were evaluated using
hypothetical lives of the individuals diagnosed with PCCRC if their condition multivariable logistic regression analysis adjusted for age and gender.
had instead been diagnosed at the time of colonoscopy. These lives were then Results: In total, 28,515 eligible persons (median age 60 years, IQR 55–66; 50%
compared with simulated lives of individuals diagnosed with PCCRC, in terms of males) were invited. Cum. participation was significantly higher for FIT (77%)
life expectancy, quality of life and costs. The simulation model was constructed than for sigmoidoscopy (31%; p 5 0.001) and colonoscopy (24%; p 5 0.001).
by using Swedish registry data, supplemented with data from the published Number of colonoscopies performed relative to eligible invitees was highest for
scientific literature and databases. colonoscopy (24%) compared to FIT (13%; p 5 0.001) and sigmoidoscopy (3%;
Results: Our simulation indicated that if the CRC of the individuals diagnosed p 5 0.001). For invitees the DY for advanced neoplasia (AN) was significantly
with PCCRC had been diagnosed at the prior colonoscopy, there would have higher after two rounds of FIT compared to one-time sigmoidoscopy (3.1% vs
been a down-staging of the cancer. The proportion of patients at each cancer 2.3%; p 5 0.001) and after four rounds of FIT compared to one-time colono-
stage shifted from 53% in stage I-II, 35% in stage III and 9% in stage IV at the scopy (4.5% vs 2.2%; p 5 0.001). For participants, DY for AN was significantly
time of the index colonoscopy, to; 47% in stage I-II, 31% in stage III and 22% in higher for endoscopic screening; 4.7% for 2 rounds of FIT compared to 7.3% for
stage IV, respectively, when diagnosed as a PCCRC. Additionally, based on our sigmoidoscopy (p 5 0.001), and 6.1% for 4 rounds of FIT compared to 9.1%
simulations 3% of the PCCRC was expected to be at an adenoma stage at the colonoscopy (p 5 0.001).
time of the colonoscopy and were, thus, theoretically able to prevent. The 1,473 Conclusion: In this population-based CRC screening cohort, we demonstrated
PCCRCs were associated with a loss of 1551 life-years or, expressed differently, that multiple rounds of FIT screening detects significantly more advanced neo-
1275 quality-adjusted life-years, compared to being ones detected at colono- plasia per invitee compared to one-time sigmoidoscopy and colonoscopy screen-
scopy. Additionally, the delay in detection was also associated with higher life- ing, and with significantly fewer colonoscopies needed. Colonoscopy detected
time costs due to an increased need of health care services related to CRC. The more advanced neoplasia per participant. However, due to low participation in
cumulative cost was estimated to be E1,922, 000 less if the patients had been colonoscopy screening, FIT seems most effective in population-based CRC
diagnosed at the time of the prior colonoscopy. The extra cost per case is E1305. screening.
Conclusion: Our simulation results imply that false negative colonoscopies cause Disclosure of Interest: All authors have declared no conflicts of interest.
significant loss of life-years and quality of life in the affected individuals. This,
together with higher costs, motivates further efforts to improve the quality of
colonoscopies. TUESDAY, OCTOBER 18, 2016 08:30–10:00
Disclosure of Interest: All authors have declared no conflicts of interest. SURGERY IN IBD – ROOM L7_____________________

OP174 OUTCOMES OF EMERGENCY ADMISSIONS WITH CROHN’S

DISEASE IN ADULTS IN ENGLAND BETWEEN 2004 AND 2014
OP173 COMPARISON OF COLONOSCOPY, SIGMOIDOSCOPY AND J. Rees1, J. Mytton2, F. Evison2, P. Patel3, R. Cooney4, N. Trudgill1
MULTIPLE ROUNDS OF FIT-BASED COLORECTAL CANCER 1
Dept. Gastroenterology, Sandwell General Hospital, West Bromwich/United
SCREENING: LONG-TERM FOLLOW-UP Kingdom
E.J. Grobbee1, M. Van Der Vlugt2, A.J. Van Vuuren1, A.K. Stroobants2, 2
Informatics, University Hospitals Birmingham NHS Foundation Trust,
R.C. Mallant-Hent3, I. Lansdorp-Vogelaar4, P.M. Bossuyt5, E.J. Kuipers6, Birmingham/United Kingdom
E. Dekker7, M.C.w. Spaander8 3
Urology, University Hospitals Birmingham NHS Foundation Trust, Birmingham/
1
Gastroenterology and Hepatology, Erasmus MC University Medical Center, United Kingdom
4
Rotterdam/Netherlands Gastroenterology, University Hospitals Birmingham NHS Foundation Trust,
2
Gastroenterology and Hepatology, Academisch Medisch Centrum, Amsterdam/ Birmingham/United Kingdom
Netherlands
3
Gastroenterology and Hepatology, Flevoziekenhuis, Amsterdam/Netherlands Contact E-mail Address: [email protected]
4
Department Of Public Health, Erasmus University Medical Center, Rotterdam, Introduction: Between 2006 and 2010, the UK national audit of adult inflamma-
Rotterdam/Netherlands tory bowel disease admissions revealed a small but non-significant fall in mor-
5
Clinical Epidemiology, Biostatistics and Bioinformatics, Academic Medical tality in Crohn’s disease (CD) from 1.3 to 0.8%, an increase in the rate of
Centre, Amsterdam/Netherlands prescription of anti-TNF therapy on admission from 3.9 to 8% and a fall in
6
Department Of Gastroenterology and Hepatology, Erasmus MC University surgery from 23 to 18%.
Medical Center, Rotterdam/Netherlands Aims & Methods: Hospital Episode Statistics (HES) is an administrative database
7
Gastroenterology & Hepatology, Academic Medical Centre, Amsterdam/ of data on all elective and emergency care episodes in hospitals in England. Using
Netherlands HES, patients aged between 18 and 60 years coded with a first emergency admis-
8
Gastroenterology and Hepatology, Erasmus MC University Medical Center sion with CD were identified. The influence of demographic factors, comorbidity
Gastroenterology and Hepatology, Rotterdam/Netherlands and infused anti-TNF therapy on mortality, surgery and emergency readmissions
was examined using multivariate logistic regression.
Contact E-mail Address: [email protected] Results: Between 2004 and 2014, 24,830 patients (55% female, mean age of 35
Introduction: Several methods for colorectal cancer (CRC) screening are avail- (IQR 25–44)) were identified. Mortality was 0.22% at 30 days, 0.29% in hospital
able; the most often used include colonoscopy, sigmoidoscopy and fecal immu- and 0.81% within 1 year. During admission, 19.2% of patients underwent sur-
nochemical testing (FIT). To date, comparison between these screenings methods gery (median time to surgery 2 days (IQR 1–6)) and 1.9% received infused anti-
was mainly focused on one-time endoscopic screening to one-time FIT screening. TNF therapy. Surgery during admission rose from 16.1 to 22.9% (OR 1.52 (95%
A fair comparison of diagnostic yield (DY) of FIT would comprise cumulative CI 1.32–1.75), p 5 0.001) between 2004 and 2014, and infused anti-TNF therapy
DY after multiple rounds of FIT screening. The aim of our study is to compare rose from 1.8 to 2.8% between 2006 and 2014. In-hospital and 1-year mortality
the DY of multiple rounds of FIT-screening to one-time screening by sigmoido- fell from 0.51 and 1.03% in 2004 to 0.10 and 0.57% in 2013 (0.18 (95% CI 0.04–
scopy and colonoscopy. 0.77), p ¼ 0.021 and 0.46 (0.23–0.91), p ¼ 0.026 respectively). Patients aged 35–60
Aims & Methods: Demographic data of 30,007 randomly chosen individuals aged had a higher 30-day (3.99 (1.97–8.05), p 5 0.001) and 1-year mortality (4.57
50–74 were obtained from municipal population registers (June 2006 - August (3.14–6.65), p 5 0.001) than those aged 18–34. Increasing comorbidity (15.38
A72 United European Gastroenterology Journal 4(5S)
(7.33–32.23), p 5 0.001) and deprivation (3.14 (1.06–9.31), p ¼ 0.039) was asso- patients who underwent surgery for Crohn’s disease terminal ileitis were enrolled.
ciated with a higher 30-day and 1-year mortality, but not gender. Females were They were interviewed by telephone and responded to the generic Cleveland
less likely to have surgery during their admission (0.71 (0.67–0.76), p 5 0.001) or Global Quality of Life (CGQL) questionnaire and the Body Image
within 1 year (0.82 (0.77–0.97), p 5 0.001) and surgery within 1 year was more Questionnarie (BIQ). Their disease activity was defined as Harvey-Bradshaw
common in younger (35–60 years 0.87 (0.81–0.93), p 5 0.001) and non-white Index (HBI). Comparisons and correlations were carried out with non-para-
patients (1.18 (1.08–1.28), p 5 0.001). Anti-TNF therapy during admission was metric tests. Survival analysis was performed with log rank test.
associated with less surgery immediately (0.39 (0.28–0.54), p 5 0.001) and within Results: In our study group 46 patients had minimally invasive surgery for term-
1 year (0.55 (0.41–0.73), p 5 0.001). Emergency readmissions within 30 days were inal ileum CD while 66 had open surgery for the same indication. Twenty seven
associated with male gender (females 0.74 (0.55–0.98), p 0.039), younger age (35– patients had a recurrent CD. The total CGQL score and its single items (quality
60 years 0.85 (0.79–0.91), p 5 0.001), non-white ethnicity (1.25 (1.13–1.38), of health, quality of life and energy levels) were significantly higher (and thus,
p 5 0.001) and not having anti-TNF therapy during admission (0.74 (0.55– better) in the laparoscopy group patients. Similarly, all the BIQ items were sig-
0.98), p0.039). nificantly better in patients who had a minimally invasive surgery compared to
Conclusion: For patients with a first emergency admission for CD, in-hospital those who had open surgery. At univariate analysis, total CGQL score was
and 1-year mortality fell considerably over the study period. Surgery and anti- directly correlated with minimally invasive surgery (rho ¼ 0.40, p 5 0.001) and
TNF therapy during admission has increased between 2004 and 2014. Surgery inversely correlated with disease activity at the moment of the interview
during admission was associated with men and at 1 year with men, younger age (rho ¼ 0.44, p ¼ 0.001), the use of steroids (rho ¼ 0.20, p ¼ 0.02) and recurrent
and non-white ethnicity. CD as indication for surgery (rho ¼ 0.19, p ¼ 0.05). At multivariate analysis, only
Disclosure of Interest: J. Rees: Received a grant of £10,000 from Merck Sharp minimally invasive surgery and disease activity at the moment of the interview
and Dohme (MSD) to contribute to access to HES data. Abstract also accepted revealed to be independent predictors of quality of life. Finally, minimally inva-
as a poster presentation at BSG Liverpool June 2016 sive surgery tended to be associate to a less frequently CD recurrence (p ¼ 0.08)
All other authors have declared no conflicts of interest. Conclusion: Minimally invasive surgery was associated to a better quality of life
and body image perception. This results is probably due in part to the beneficial
effect of minimally invasive surgery on body image but also by the less severe
disease of these patients (less recurrent Cd as indication for surgery or simpler
OP175 IS THE ‘RESET’ SURGERY EFFECTIVE FOR CROHN’S DISEASE surgery). Quality of life is essentially predicted by current disease activity and
PATIENTS REFRACTORY TO ANTI-TNFA THERAPY? minimally invasive surgery. Finally, minimally invasive surgery tended to be
S. Takashima1, S. Hiraoka1, Y. Kondo2, T. Inokuchi1, D. Takei1, A. Nakarai1, associate to a less frequent CD recurrence.
Y. Sugihara1, M. Takahara1, K. Harada1, H. Okada1 Disclosure of Interest: All authors have declared no conflicts of interest.
1
Department Of Gastroenterology and Hepatology, Okayama University Graduate
School of Medicine, Dentistry and Pharmaceutical Sciences, Okayama/Japan
2
Department Of Gastroenterological Surgery, Okayama University Graduate
School of Medicine, Dentistry and Pharmaceutical Sciences, Okayama/Japan OP177 CLOSE RECTAL DISSECTION VERSUS TOTAL MESORECTAL
EXCISION IN PATIENTS WITH INFLAMMATORY BOWEL DISEASE
Contact E-mail Address: [email protected] UNDERGOING PROCTECTOMY
Introduction: Anti TNF-alpha agents (anti-TNF) are currently the most effec- J. De Groof1, O. Van Ruler2, M. Wildenberg3, J. De Bruyn3, P. Tanis4, G.R. Van
tive therapeutics for Crohn’s disease (CD). Some of CD patients under anti- Den Brink5, W. A. Bemelman6, C.J. Buskens7
TNF therapy, however, need surgery because of disease progression. Surgical 1
Surgery and Gastroenterology & Hepatology, AMC, Amsterdam/Netherlands
resection (‘Reset’) usually leads to the elimination of the intestinal regions with 2
Surgery, Academic Medical Center, Amsterdam/Netherlands
the most severe activity. However, little is known about whether retreatment with 3
Tytgat Institute For Liver and Intestinal Research & Gastroenterology &
anti-TNF is effective for patients who underwent ‘Reset’ surgery. The aim of Hepatology, Academic Medical Center, Amsterdam/Netherlands
this study was to evaluate the efficacy of anti-TNF therapy for CD patients who 4
Dept. Of Surgery, Academic Medical Center Dept. of Surgery, Amsterdam/
underwent surgery due to the refractoriness to previous anti-TNF. Netherlands
Aims & Methods: From July 2005 to November 2015, 65 CD patients underwent 5
Dept. Of Gastroenterology, Academisch Medisch Centrum, Amsterdam/
intestinal resection at Okayama University Hospital. Of these, 34 patients Netherlands
received anti-TNF therapy after surgery: 19 refractory to preoperative anti- 6
Department Of Surgery, Academisch Medisch centrum Dept. of Surgery,
TNF (TNF-refractory group), and 15 anti-TNF naı̈ve (TNF-naı̈ve Amsterdam/Netherlands
group). The efficacy of post-surgical treatment with anti-TNF was compared 7
Colorectal Surgery, Academic Medical Center, Amsterdam/Netherlands
according to the status of pre-operative anti-TNF therapy. In addition, clinical
factors predicting relapse in patients with anti-TNF retreatment after precedent Contact E-mail Address: [email protected]
surgery were evaluated. The evaluated factors were clinical backgrounds, dura- Introduction: Proctocolectomy or completion proctectomy in inflammatory
tion of TNF therapy, concomitant medications before and after surgery, labora- bowel disease patients is frequently complicated by disturbed perineal wound
tory data before surgery, and the residual of the affected intestine after surgery, healing and presacral abscess formation. Close rectal dissection (CRD) has
etc. The relapse was defined as intensification of medical therapy, hospitalization, been regarded as an improved surgical technique for benign conditions that
or surgery due to worsening of abdominal symptoms, CRP elevation with the could reduce this complication by leaving the rectal mesentery in situ to minimize
evidence of endoscopic recurrence. dead space cavity compared to total mesorectal excision (TME).
Results: Patients of the TNF-refractory group showed significantly higher rate Aims & Methods: The aim of this study was to compare perineal wound healing
of relapse than those of the TNF-naı̈ve group (12/19 (63%) vs. 3/15 (20%), in ulcerative colitis (UC) and Crohn’s disease (CD) patients undergoing TME or
p 5 0.05). In the evaluation of factors predicting relapse in patients with retreat- CRD. Since it has been suggested that Crohn’s mesenteric adipose tissue is
ment of anti-TNF after surgery, only the residual of the affected intestine after involved in CD pathology with reduced regulatory potential of wound healing
surgery is the significant predictor of relapse (patients with vs. without residual macrophages, differences in macrophage populations between UC and CD
the affected intestine: 11/12 (92%) vs. 3/7(43%), p 5 0.05). patients were assessed. Adult patients undergoing proctocolectomy or comple-
Conclusion: The ‘Reset’ surgery was not so effective for CD patients refractory to tion proctectomy without reconstruction for UC or CD (2005–2015) were
anti-TNF therapy. In particular, patients with the residual of the affected intes- included. Endpoints were postoperative perineal complications, and healing at
tine after surgery had higher risk of relapse despite retreatment with anti-TNF 6 and 12 months. Rectal mesentery was cultured and walk-out cells were analysed
after surgery. Those patients may need additional treatment besides anti-TNF by flow cytometry. CD45þ immune cells were identified, with phenotyping of
therapy or increase in the dosage amount of the anti-TNF agent. wound healing macrophages by regulatory markers CD206 and CD14.
Disclosure of Interest: All authors have declared no conflicts of interest. Results: Fifty-nine patients (17 UC/42 CD) were included (46.4% male, mean age
45.5 (14.5)). CRD was performed in 8 UC (47.1%) and 32 CD patients
(76.2%). In UC, significantly less perineal complications (17.6% versus 47.6%,
p ¼ 0.033) and a higher healing rate at 6 months (87.5% versus 64.3%, p ¼ 0.066)
OP176 IMPACT OF MINIMALLY INVASIVE SURGERY ON QUALITY were seen. No significant differences in outcome between the techniques in UC.
OF LIFE AFTER SURGERY FOR CROHN’S DISEASE TERMINAL Perineal complications occurred less frequently in CD patients who underwent
ILEITIS TME compared to CRD, (20.0% versus 56.3%, p ¼ 0.045), with higher healing
I. Angriman1, O. Zini1, R. D’Inca2, G.C. Sturniolo3, R. Bardini4, M. Scarpa5 rates at 6 months after TME (90.0% versus 53.3%, p ¼ 0.052). Perineal healing
1
Dept. Of General Surgery, University of Padova, Padova/Italy rate at 12 months was 87.5% in the TME group versus 65.5% in the CRD group
2
Division of Gastroenterology, Padova/Italy (p ¼ 0.443). Analysis of rectal mesentery showed an enhanced infiltration of
3
Gastroenterology, Padua University Hospital, Padua/Italy CD45þ immune cells in CD patients with the balance between CD3þ lymphoid
4
Department Of Surgery, Oncology and Gastroenterology, University Of Padua, T cells and CD14þ myeloid cells skewed significantly towards the myeloid popu-
School Of Medicine, Chirurgia Generale, Padova/Italy lation (UC vs CD median 24% versus 53%, p 5 0.01 In addition, macrophages
5
Esophageal and Digestive Tract Surgical Unit, Regional Centre For Esophageal in CD patients showed significantly less expression of the wound healing marker
Disease, Veneto Institute of Oncology (IOV-IRCCS), Padova/Italy CD206, in line with a more pro-inflammatory and less wound healing profile of
CD rectal mesentery. Strikingly, these alterations were maintained in patients
Contact E-mail Address: [email protected] with a defunctioning stoma.
Introduction: Crohn’s disease (CD) is a chronic illness that interferes with the Conclusion: In UC, significantly less perineal complications were seen after proc-
daily life of those affected. Surgical treatment is required in about 70% of CD tocolectomy or completion proctectomy, compared to CD with higher healing
patients during the course of disease and risk of surgery is among the highest rates. 450% of CD patients had perineal complications and impaired healing,
rated concerns among them. Quality of life is often worsened by intestinal which was seen more frequently after CRD. These findings can probably be
surgery. explained by the increased pro-inflammatory myeloid cell population with
Aims & Methods: The aim of the study is to assess the impact of minimally decreased wound healing macrophages, irrespective of the presence of a
invasive surgery on quality of life after surgery for Crohn’s disease terminal
ileitis. From June 2010 to December 2015, one hundred twelve consecutive CD
United European Gastroenterology Journal 4(5S) A73
defunctioning stoma. These findings suggest that excision of the mesorectum is of point. Improvement in IBDQ was defined as an increase of 420 points. Failure
crucial importance in CD. was defined as when patients underwent colectomy or prescribed trial medication
Disclosure of Interest: All authors have declared no conflicts of interest. (eg. Vedolizumab, Etrolizumab).
Results: In total, 30 patients (57% female) with a median age of 40 (IQR, 33–47)
underwent appendectomy with a mean preoperative total Mayo score of 9 (SD
2). The mean baseline IBDQ was 125 (SD 34). After 3 months, clinical response
OP178 LONG-TERM FOLLOW-UP AFTER ILEORECTAL was seen in 16 (53%) patients of whom 7 (30%) were in remission (7 patients
ANASTOMOSIS IN ULCERATIVE COLITIS (UC): A GETAID/ refused endoscopy at this time point). Improvement in IBDQ was seen in 14
GETAID CHIRURGIE MULTICENTER RETROSPECTIVE COHORT (47%) patients with a mean of 120 (SD 29) that increased to 168 (SD 29).
OF 343 PATIENTS After 12 months, 11 patients failed (7 colectomy, 4 trial medication) and 5 did
M. Uzzan1, J. Cosnes2, N. Gault3, A. Amiot4, J. Gornet5, P. Seksik6, S. Nancey7, not yet reach the endpoint. In the remaining 14 patients, 9 (36%) had lasting
D. Laharie8, M. Allez9, M. Nachury10, A.L. Pelletier11, V. Abitbol12, clinical response of whom 5 (23%) were in remission (3 patients refused
M. Fumery13, A. Buisson14, R. Altwegg15, Y. Panis3, X. Treton16 endoscopy).
1
Gastroenteroogy, Hôpital Beaujon, APHP, PARIS/France Conclusion: Appendectomy was effective in at least 30% of therapy-refractory
2
Gastroenterology, Hopital St Antoine Gastroenterology GETAID, Paris/France UC patients. These early results suggests that UC patients may benefit from
3
Beaujon Hospital, Clichy/France appendectomy and that this effect is maintained for a longer period of time.
4
Dept. Of Gastroenterology, Henri Mondor Hospital, APHP Dept. of However, follow up of at least 2 years is warranted to exclude a possible placebo
Gastroenterology, Creteil/France effect.
5
Hôpital Saint-Louis Gastroente´rologie, Paris Cedex /France Disclosure of Interest: All authors have declared no conflicts of interest.
6
Saint-antoine Hospital, Gastroenterology & Nutrition Department, Paris Cedex /
France TUESDAY, OCTOBER 18, 2016 08:30–10:00
7
Dept. De Gastroenterologie, Hospices de Lyon, Pierre Benite/France GI INFECTIONS FROM MECHANISMS TO TREATMENT – ROOM L8_____________________
8
CHU de Bordeaux Hopital Haut-Leveque Dept. de Gastroenterologie, Pessac
cedex/France
9
Gastroenterology, Hopital Saint-Louis APHP, Universite´ Denis Diderot Paris 7, OP180 THE RISK OF CLOSTRIDIUM DIFFICILE INFECTION IN
Paris/France PATIENTS WITH PERNICIOUS ANAEMIA: A RETROSPECTIVE
10
Gastroenterology, Claude Huriez hospital, University of Lille 2, Lille/France COHORT STUDY USING PRIMARY CARE DATABASE
11
Bichat Hospital, Paris/France F. Othman, C. J. Crooks, T. Card
12
Hopital Cochin Gastroente´rologie, Paris Cedex/France City Hospital Campus, University Of Nottingham, Nottingham/United Kingdom
13
Amiens University Hospital, Amiens/France
14
Dept. Of Gastroenterology, CHU Estaing Clermont-Ferrand, Clermont-ferrand/ Contact E-mail Address: [email protected]
France Introduction: Previous studies have shown an association between proton pump
15
Hopital Saint Eloi Hepatologie Gastro enterologie, Montpellier cedex /France inhibitor use and Clostridium difficile infection1. One suggested mechanism of
16
Hopital Beaujon, Clichy/France this association is the very low stomach acid levels caused by these drugs, since
gastric acidity is an important host defence against ingested pathogens. If acid
Contact E-mail Address: [email protected] suppression is the true cause of Clostridium difficile infection in patients receiving
Introduction: Colectomy is frequently performed in ulcerative colitis (UC) proton pump inhibitors, then this effect should be manifested in patients with
patients. Although ileal pouch-anal anastomosis is recommended after colect- achlorhydia (no acid production), a condition associated with pernicious anae-
omy, ileorectal anastomosis (IRA) is still performed. The main objective of our mia. Elucidating this association would provide a clear understating of the acid-
study was to determine the cumulative incidence of IRA failure and its prognos- suppression hypothesis underlying the increased risk of infection in patients who
tic factors. have received gastric acid suppressive therapy.
Aims & Methods: This was a multicenter retrospective cohort study, which Aims & Methods: The aim of this study was to determine the risk of Clostridium
included patients with IRA for UC performed between 1960 and 2014. IRA difficile infection in patients with pernicious anaemia. We conducted a popula-
failure was defined as secondary proctectomy and/or rectal cancer occurrence. tion based cohort study using English linked primary (Clinical Practice Research
Uni- and multivariate survival analyses were performed using a Cox-propor- Datalink) and secondary (Hospital Episode Statistics) care records (1998–2012).
tional hazards model. The exposed group consisted of patients with a diagnosis of pernicious anaemia
Results: 343 patients from 13 French centers were included. Median follow-up who had been treated with vitamin B12 therapy. Each exposed patient was
after IRA was 10.6 years. IRA failure rates were estimated at 27.0% (95CI [22– matched by age (within 5 years), gender and general practice to non-pernicious
32]) and 40.0% (95CI [33–47]) at 10 and 20 years, respectively. Median survival anaemia patients, with the follow-up start date of the control being as their
time without IRA failure was estimated at 26.8 years. Two-thirds of secondary matched exposed patient. Cox regression analysis was used to estimate the
proctectomies were performed for refractory proctitis, and 20% for rectal neo- hazard ratio (HR) and 95% confidence interval for the association between
plasia. Univariate analysis identified factors associated with IRA failure: IRA Clostridium difficile infection and pernicious anaemia, adjusted for potential
performed after 2004, a longer duration of disease at the time of IRA and having confounders.
received immunomodulative agents prior to IRA. In multivariate analysis, treat- Results: We identified 20,058 patients with pernicious anaemia receiving vitamin
ment with both immunosuppressant (IS) and anti-TNF before colectomy was B12 therapy and 196,895 controls. The crude incidence rate of Clostridium diffi-
independently associated with IRA failure (HR ¼ 2.9, 95CI [1.21–7.10]). cile was 3.3/1000 person-years for those with pernicious anaemia while it was 1.7/
Conversely, colectomy for severe acute colitis was associated with decreased 1000 person-years for controls. Patients with pernicious anaemia had a greater
risk of IRA failure (HR ¼ 0.6, 95CI [0.41–0.97]). risk of Clostridium difficile infection than controls (adjusted HR 1.52, 95% con-
Conclusion: Patients with UC have a high risk of IRA failure, particularly when fidence interval 1.33 to 1.73).
performed for refractory disease. However, IRA could be discussed after colect- Conclusion: Individuals with pernicious anaemia have an increased risk of
omy for severe acute colitis, in patients naive to both IS and anti-TNF. Clostridium difficile infection. This study supports severe hypochlorhydria as
Disclosure of Interest: All authors have declared no conflicts of interest. the mechanism for the increased Clostridium difficile infection in people who
have received long-term acid suppression medication.
Disclosure of Interest: F. Othman: This study has been carried out as part of my
PhD program at University of Nottingham-UK, funded by Scholarship Award
OP179 THERAPY REFRACTORY UC PATIENTS MAY BENEFIT FROM from King Saud bin Abdulaziz University for Health Sciences Saudi Arabia.
APPENDECTOMY; EARLY RESULT FROM THE PASSION STUDY There is no other potential conflicts of interest
S. Sahami1, C.J. Buskens2, D.C. Winter3, S. Martin3, G. R.a.m. D’Haens4, W. All other authors have declared no conflicts of interest.
A. Bemelman5 Reference
1
Surgery, Academic Medical Center Dept. of Surgery, Amsterdam/Netherlands
2 1. Dial S, Delaney JAC, Barkun AN and Suissa S. Use of gastric acid-suppres-
Colorectal Surgery, Academic Medical Center, Amsterdam/Netherlands
3 sive agents and the risk of community-acquired Clostridium difficile-asso-
Surgery, St Vincent’s University Hospital, Dublin/Ireland
4 ciated disease. JAMA. American Medical Association 2005 Dec 21; 294(23):
Gastroenterology & Hepatology, Academic Medical Center, Amsterdam/
2989–95.
Netherlands
5
Department Of Surgery, Academisch Medisch centrum Dept. of Surgery,
Amsterdam/Netherlands
Contact E-mail Address: [email protected] OP181 CONSISTENT AND REPRODUCIBLE PRODUCTION OF A
Introduction: Evidence has been accumulating indicating that the appendix has an MICROBIOTA-BASED DRUG FOR RECURRENT C. DIFFICILE
immunomodulatory role in patients with ulcerative colitis (UC) potentially redu- INFECTION: APPLICATION OF A NOVEL DIAGNOSTIC FOR
cing the need for medication and colectomy. However, prospective data are DYSBIOSIS
limited and the therapeutic mechanism is not yet understood. The objective of C. Jones
this study was to examine the effect of an appendectomy to modulate the disease Rebiotix Inc., Roseville/United States of America/MN
course of therapy refractory UC patients.
Aims & Methods: Patients with therapy refractory UC, and referred for procto- Contact E-mail Address: [email protected]
colectomy were invited to undergo laparoscopic appendectomy first. The primary Introduction: Antibiotics are the first-line treatment for C. difficile infection
endpoint was clinical response at 3 months and after 12 months. Secondary (CDI). However, the most commonly prescribed antibiotics for CDI are asso-
endpoints were remission, improvement in IBDQ score and failure. Results ciated with high recurrence rates. Antibiotics have been shown to disrupt the
were measured by the Mayo score (partial clinical 0–9 and endoscopic 0–3) intestinal microbiota. Restoration of the intestinal microbiota to its pre-disease
and IBDQ score (32 to 224). Clinical response was defined as a decrease in the state protects against recurrence. There is an unmet need for a standardised,
partial Mayo of 3 points. Remission was defined as an endoscopic Mayo 1 reproducible microbiota-based therapy for recurrent CDI. RBX2600, a
A74 United European Gastroenterology Journal 4(5S)
microbiota-based drug candidate targeted at recurrent CDI, is sourced from on microbiota composition, on DNA methylation and on genes expression
human-derived microbes from extensively screened donors and manufactured with a specific focus on CEACAM6.
using standardised, quality controlled processes. Aims & Methods: CEABAC10 female mice were fed a HMD (supplemented in
Aims & Methods: To compare the bacterial abundance in the source material for folate, biotin, B12 vitamin, zinc, methionine) for 2 weeks before pregnancy. After
RBX2660 (DS) with the bacterial abundance in the finished drug product (DP) weaning, the colonic epithelial cells from offspring were purified using EDTA.
used in the Phase 2B PUNCH CD 2 study. A total of 70 DS samples sourced We analyzed different physiological parameters such as the lipocalin-2 in stools.
from 17 unrelated donors (mean age 27; range 18 to 57 years; 94% male) from E. coli population was quantified using a qPCR approach. DNA methylation
August 2014 to February 2016 were compared with 70 matched DP samples was measured at a global level and on the CEACAM6 promoter using bisulfite-
using the GA-map Dysbiosis Test (GA-test), Genetic Analysis AS, Oslo, sequencing. qPCR was used to quantify CEACAM6 mRNA. RNA-seq was also
Norway. The GA-test uses 54 probes targeting V3 to V7 of the bacterial 16s used to highlight transcriptomic changes in colonic cells in the both conditions
rRNA gene to characterise and identify bacteria present. Approximately 300–400 tested.
bacteria at different taxonomic levels are covered, providing for an assessment of Results: We observed that mice fed a HMD show a significant decrease in basal
the microbial community using multiple variable regions. The GA- test enables lipocalin-2 level in stools compared to mice receiving a conventional diet suggest-
serial assessment of the faecal bacterial abundance profile as well as potentially ing a beneficial effect on global intestinal inflammation. No significant changes
clinically relevant alterations in the microbiome over time. These capabilities of were observed on histological sections following HMD. Microbiota analysis
the GA-test were used to assess the production processes for RBX2660. The revealed a 1000-fold decrease in E. coli population in mice fed HMD compared
differences in bacterial abundance between the DP and DS were calculated to mice receiving a conventional diet. As expected, global DNA methylation
from log10 of the probe values (DP-DS); averaging the differences. analysis revealed a global increase in cytosine methylation in mice fed a HMD
Results: The GA-test found that the bacterial abundance in the RBX2660 DP compared to mice fed a conventional diet. Bisulfite sequencing revealed a hyper-
was lower than in the DS in 38 of the 54 probes; equal in number in 6 of the methylation of the CEACAM6 promoter, especially on the HRE sites. This
probes; and higher in 10. More specifically, Firmicutes and Actinobacterium hypermethylation of the promoter was associated with a significant decrease in
showed reduced signal strength in the DP compared with the DS. CEACAM6 expression as measured by qPCR and Western-blot. RNA-seq data
Bacteroidetes showed increased signal strength in the DP compared with the confirmed the decrease in CEACAM6 expression and highlighted many mis-
DS, while Proteobacteria demonstrated equal signal strength in both samples. regulated genes following HMD, among them, many genes involved in adaptive
The comparative abundance in the DP vs. the DS is shown in Table 1. Accuracy immunity.
was as high as 83.4% at cross-validation. Principal component analysis found Conclusion: This work shows that the addition of a few vitamins and oligo-ele-
that the bacterial profiles in the RBX2660 DP, though lower than in the donor ments to the diet could interfere with the DNA-methylation metabolism leading
source material, were largely kept intact during the production process for all 17 to changes in genes expression such as a decrease in CEACAM6 and modify
donors. microbiota composition leading to eradication of the E. coli population in the
intestine. A diet-based strategy could help decreasing AIEC colonization in CD
Table 1: Comparative Signal Strength of Bacteria patients by modulating CEACAM6 expression.
Disclosure of Interest: All authors have declared no conflicts of interest.
Signal Strength
Bacteria in DP vs. DS Mean Difference (95% CIM)

Bacteroidetes OP183 COMPARATIVE GENOMICS AND SINGLE NUCLEOTIDE

Bacteroides fragilis Increased 0.07 (0.03, 0.11) POLYMORPHISM DISTRIBUTION BETWEEN ADHERENT-
Parabacteroides Increased 0.12 (0.07, 0.17) INVASIVE ESCHERICHIA COLI (AIEC) AND NON-AIEC STRAINS
FROM THE HUMAN INTESTINE
Alistipes Increased 0.17 (0.11, 0.23)
C. Camprubı́, M. Lopez-Siles, M. Ferrer-Guixeras, L. Niubo-Carulla, C. Abellà-
Firmicutes
Ametller, J. Garcia-Gil, M. Martinez-Medina
Lachnospirae Decreased 0.13 (0.15, 0.11) Biology, University of Girona, Girona/Spain
Streptococcus Decreased 0.16 (0.20, 0.13
Contact E-mail Address: [email protected]
Negativicutes Increased 0.03 (0.01, 0.06) Introduction: The molecular basis of Adherent-invasive Escherichia coli (AIEC)
Clostridia Decreased 0.18 (0.20, 0.16) pathogenicity, a pathotype associated with Crohn’s disease, still needs to be well
Actinobacteria resolved. Nowadays the identification of the pathotype is performed with time-
Bifidobacterium Decreased 0.33 (0.38, 0.28) consuming techniques based in phenotypic screening of cultured bacteria; obtain-
ing new molecular tools would therefore be of great significance.
DP ¼ drug product DS ¼ drug source CIM ¼ confidence interval of mean Aims & Methods: Our aim was to identify putative genetic elements involved in
AIEC phenotype to gain insight into the mechanisms of its pathogenicity and to
find molecular targets for its identification. To achieve this objective we per-
Conclusion: GA-test analysis confirmed that RBX2660 can be manufactured in a formed comparative genomics of three E. coli strain pairs consisting in one
consistent and reliable manner with the preservation of key bacterial diversity AIEC and one non-AIEC of identical pulsed field gel electrophoresis fingerprint.
believed critical for protection from recurrent CDI. Each pair belonged to a distinct phylogroup. This approach was designed in
Disclosure of Interest: C. Jones: Employee of Rebiotix Inc., Roseville, MN USA order to increase the chance of finding sequences AIEC-specific and not strain-
References specific. The six strains’ genomes were sequenced de novo by combining paired-
end libraries of HiSeq Illumina and PacBio. Two different approaches for com-
1. Kelly CP and Lamont JT. Clostridium difficile- More difficult than ever. N parative genomics were used: i) assembly with Velvet and genome comparison
Engl J. Med 2008; 359: 1932–40. between pairs with Differences software, ii) SPAdes for assembly and compara-
2. Casén C, Vebø HC, Sekelja M, et al. Deviations human gut microbiota: A tive genomics between pairs in relation to a genome of reference (AIEC UM146)
novel diagnostic test for determining dysbiosis in patients with IBS or IBD. with Mauve. Only non-synonymous Single Nucleotide Polymorphisms (SNPs) in
Aliment Pharmacol Ther 2015; 42: 71–83. coding regions were selected. Sanger sequencing was performed to confirm the
presence of SNPs and to evaluate the distribution of the SNPs in a collection of
22 AIEC and 29 non-AIEC isolates. Nucleotides for each SNP were analysed
taking into account AIEC phenotype, adhesion and invasion indices of isolates
OP182 A METHYL DONOR MOLECULES-SUPPLEMENTED DIET by 2 test or ANOVA as required.
ERADICATES E. COLI POPULATION AND METHYLATES Results: Genome sizes of Velvet assemblies for AIEC strains ONT:HNT-D,
CEACAM6 PROMOTER DECREASING ITS EXPRESSION IN O6:H1-B2 and O22:H7-B1 were 4.86, 5.16 and 4.79Mb respectively. When
COLONIC EPITHELIAL CELLS IN MICE SPAdes was used, they presented þ95,362bp, þ47,933bp and þ30,178bp respec-
E. Gimier1, A. Agus2, N. Barnich2, J. Denizot3 tively. Comparative genomics of the first approach reported 114, 80 and 31
1
M2iSH UdA/Inserm U1070, Clermont-ferrand/France SNPs, whereas the second resulted in 19, 27 and 31 SNPs respectively. Six
2
M2ish, Umr 1071 Inserm/university Of Auvergne Inra Usc 2018, University of SNPs were found with both strategies. From all, 23 SNPs were confirmed by
Clermont Auvergne, Clermont-Ferrand/France Sanger and analysed among the study collection. These SNPs were comprised in
3
Clermont Universite´, M2iSH, UMR 1071 INSERM/Universite´ d’Auvergne, 14 genes from which 3 were involved in metabolic processes, 2 in stress tolerance
Clermont-Ferrand, France Unite´ Sous Contrat 2018 Institut National de la and 3 in adhesion and invasion pathways. Most of the SNPs were strain-specific,
Recherche Agronomique, Clermont-Ferrand/France except from one found in a gene putatively implicated in adhesion/invasion, that
was differentially distributed among AIEC and non-AIEC strains (p ¼ 0.029).
Contact E-mail Address: [email protected] Interestingly, this SNP plus 3 other SNPs positions located in the same gene
Introduction: Adherent-invasive E. coli are clearly involved in triggering and were associated with invasion (p 5 0.024) and one of them also with adhesion
maintaining ileal CD. AIEC bacteria adhere to the enterocytes through high (p ¼ 0.04).
affinity interaction between their variant type one pili and abnormally expressed Conclusion: To conclude, we have detected SNP variations in a single gene that
CEACAM6 protein on host cells. We previously reported an original mechanism could be associated with AIEC phenotype. However, further studies with site-
of CEACAM6 regulation depending on DNA methylation of transcription specific mutations are needed to confirm the implication of this gene in the AIEC
factor HIF-1 binding site (HRE, Hypoxia responsive element) in the promoter pathogenicity and the SNP effects. Our study indicates that there is not an AIEC-
of the gene. We observed that an unmethylated HRE site allows HIF-1 to bind specific genetic marker and widely distributed in all AIEC.
the promoter and to induce CEACAM6 expression in intestinal epithelial cells Disclosure of Interest: All authors have declared no conflicts of interest.
(IEC). Decreasing CEACAM6 expression in CD intestinal cells is one strategy
that could prevent AIEC bacteria colonization of the intestinal mucosa and
subsequent inflammation. This work aims at studying the effect of a methyl-
donor enriched diet (HMD: High Methyl Diet) on the intestinal physiology,
United European Gastroenterology Journal 4(5S) A75
OP184 ENTEROHEMORRHAGIC ESCHERICHIA COLI TROPISM TO female. Patients with CDI had higher mortality rate (adjusted odds Ratio
PEYER’S PATCHES: ROLE OF LONG POLAR FIMBRIAE AND (OR):5.84, 95% confidence interval (CI):1.79–19.07, p 5 0.01) compared with
INHIBITION BY A PROBIOTIC YEAST patients without CDI. Looking at morbidity, patients with CDI had similar a
C. Cordonnier1, J. Ramboz1, J. Thévenot1, L. Etienne-Mesmin1, A. Rougeron1, colectomy rate (OR:1.16, CI: 0.75–1.77, p ¼ 0.5), ICU admission rate (OR: 2.77,
S. Renier1, N. Barnich1, S. Blanquet-Diot2, V. Livrelli1 CI: 0.93–8.29, p ¼ 0.07) and shock rate (OR: 3.06, CI: 0.94–9.97, p ¼ 0.06) but a
1
Universite´ d’Auvergne, M2iSH, « Microbes, Intestin, Inflammation et lower intestinal resection rate (OR: 0.26, CI: 0.08–0.82, p ¼ 0.02) compared with
Susceptibilite´ de l’Hôte » UMR-Inserm/Universite´ d’Auvergne U1071, USC-INRA patients without CDI. When resource utilization was examined, patients with
2018, Clermont-Ferrand/France CDI had longer LOS (adjusted mean (mean): 2.54 days, CI: 1.78–3.30 days,
2
EA CIDAM, Clermont-Ferrand/France p 5 0.01), higher TPN use (OR: 2.71, CI: 1.92–3.82, p ¼ 0.02), higher total hos-
pitalization charges (mean: $14,250, CI: $8,473–$20,026, p 5 0.01) and similar
Contact E-mail Address: [email protected] abdominal CT scan use (OR: 1.41, CI: 0.78–2.59, p ¼ 0.25) compared with
Introduction: Enterohemorrhagic Escherichia coli (EHEC) are food-borne patho- patients without CDI.
gens associated with diarrhea, hemorrhagic colitis and life-threatening complica- Conclusion: Current or past CDI is associated with increased mortality among
tions such as hemolytic-uremic syndrome. EHEC interact with the Follicule- hospitalized patients with Crohn’s disease. However, patients with CDI have
Associated Epithelium (FAE) of Peyer’s patches of the distal ileum in humans similar colectomy rates, shock or ICU admission rate compared with patients
and translocate across the intestinal epithelium via M cells. Molecular mechan- without CDI. Finally, CDI has a profound effect on resource utilization with
isms are still unknown but Long Polar Fimbriae (Lpf), which contribute to longer length of stay, increased TPN use and substantially higher total hospita-
intestinal colonization, may be involved. Currently no specific treatment is avail- lization charges.
able in EHEC infections and use of antibiotics remains controversial. Probiotic Disclosure of Interest: All authors have declared no conflicts of interest.
could be an alternative strategy.
Aims & Methods: The objectives of the study were to investigate the role of Lpf in
EHEC tropism to Peyer’s patches, and to explore the influence of probiotic TUESDAY, OCTOBER 18, 2016 08:30–10:00
yeasts on EHEC interactions with intestinal mucosa. The expression of lpf COLON CANCER: FROM SCREENING TO PALLIATION – ROOM 1.86_____________________
genes (encoded by two lpf operons) of EHEC O157:H7 strain EDL933 was
analyzed using in vitro models of the human upper gastrointestinal tract and OP186 SELF-EXPANDABLE METALLIC STENT AS BRIDGE TO
large intestine. To investigate the involvement of Lpf in the ability of EDL933 to SURGERY IS MORE SUPERIOR THAN TRANSANAL DRAINAGE
target Peyer’s patches, we generated the DlpfA1, DlpfA2, DlpfA1-DlpfA2 iso- TUBE AT QUALITY OF LIFE FOR THE PATIENTS WITH PRIMARY
genic mutants and trans-complemented them with lpf genes. Lpf interaction with MALIGNANT COLORECTAL OBSTRUCTION
M-like cells was investigated using an in vitro model of specialized M cells. K. Kojima1, N. Toda1, S. Kurosaki1, K. Funato2, S. Kawamura1, Y. Karasawa1,
In vivo interactions of EHEC with murine Peyer’s patches were analyzed in S. Maeshima1, T. Ohki1, M. Seki1, K. Tagawa1
ileal loop assays. Mice were infected with a mixture of two bacterial strains, 1
Gastroenterology, Mitsui Memorial Hospital, Tokyo/Japan
and the numbers of Peyer’s patches-interacting bacteria were determined using 2
Mitsui Memorial Hospital, Tokyo/Japan
a competitive index analysis. To investigate the effect of probiotic yeasts, mice
were given the probiotic for 7 days before ileal loops assays were conducted with Contact E-mail Address: [email protected]
O157:H7 wild type. Introduction: Self-expandable metallic stent (SEMS) or transanal drainage tube
Results: Lpf isogenic mutants (i) were not able to interact with ileal biopsies (TDT) is endoscopic decompression for malignant colorectal obstruction. SEMS
containing Peyer’s patches compared to the wild type strain in competitive colo- is said to be superior to TDT at quality of life (QOL) for the patients, but the
nization assays and (ii) translocated across M cells at levels significantly lower comparison between SEMS and TDT for malignant colorectal obstruction was
than those observed for the wild type strain. Trans-complementation of the few reported include the clinical efficiency, safety and prognosis.
mutants with the cloned lpf genes restored their ability to interact with Peyer’s Aims & Methods: The aim of this study is to evaluate QOLs, clinical efficiency
patches and M cells, indicating that expression of lpfA1 or/and lpfA2 genes is and safety between SEMS and TDT for the patients with malignant colorectal
required for interactions with Peyer’s patches. Bloodshot Peyer’s patches were obstruction. We retrospectively analyzed 69 patients who underwent SEMS or
macroscopically observed following EHEC infection of murine ileal loops. We TDT insertion for malignant colorectal obstruction from April 2009 to March
showed that or pre-treatment with yeasts significantly inhibited O157:H7 inter- 2016 on the basis of single-center experience in Japan. SEMS was inserted for
actions with Peyer’s patches and reduced the number of hemorrhagic Peyer’s bridge to surgery (BTS) or palliation, and TDT was inserted for BTS or bridge to
patches in murine ileal loops. Since yeast cell surface is rich in mannose, the SEMS insertion.
role of carbohydrates in EHEC interactions with Peyer’s patches was investi- Results: There were 27 patients in SEMS group (male 37.0%, median age
gated. Among the carbohydrates tested, only mannose specifically limited the 73  17.0years) and 42 patients in TDT group (male 54.8%, median age
interactions of EHEC with Peyer’s Patches. 65  15.2 years). Technical success rate was 100% of SEMS group and 95.2%
Conclusion: We conclude that Lpf are involved in the interactions of EHEC with of TDT group (p ¼ 0.15). The endoscopic decompression as BTS for primary
murine Peyer’s patches and are needed for an active translocation across M cell colorectal cancer was performed in 57.1% of SEMS group and 85.7% of TDT
monolayer. Tropism of EHEC to Peyer’s patches can be limited by probiotic group (p ¼ 0.02). Among these patients, the duration for surgery after decom-
yeasts and by specific carbohydrates. pression was longer in SEMS group (14.9  7.0 days vs 10.5  6.6 days, p ¼ 0.04),
Disclosure of Interest: All authors have declared no conflicts of interest. because the rate of temporary discharge was significantly higher in SEMS group
(41.7% vs 0.0%, p 5 0.001). No significant difference was shown about the
hospitalization in both group (36.1  23.5 days vs 46.4  36.0 days, p ¼ 0.36).
The rate of oral intake (at least soft solids) was significantly higher in SEMS
OP185 CURRENT OR PAST CLOSTRIDIUM DIFFICILE INFECTION IS group (88.9% vs 25.0%, p 5 0.001). The Colonic Stent Safe Procedure Research
ASSOCIATED WITH INCREASED MORTALITY, MORBIDITY AND Group ColoRectal Obstruction Scoring System (CROSS) score before decom-
RESOURCE UTILIZATION AMONG PATIENTS HOSPITALIZED pression had no significant difference in both group (1.1  0.9 vs 1.2  0.7,
FOR CROHNS’ DISEASE: RESULTS OF A NATIONWIDE ANALYSIS p ¼ 0.49), but CROSS score after decompression was significantly improved in
P. Kroner1, M. S. Abougergi2 SEMS group (3.7  0.8 vs 2.3  0.5, p 5 0.001). The complications after proce-
1
Medicine, Mt. Sinai St. Luke’s / West Hospitals, New York/United States of dure, such as perforation, migration, re-obstruction, had no significant difference
America/NY in both group.
2
Catalyst Medical Consulting, Baltimore/United States of America/MD
Table: Patients characteristics and results
Contact E-mail Address: [email protected]
Introduction: Multiple factors have been associated with an acute flare of Crohn’s SEMS (n ¼ 27) TDT (n ¼ 42) p value
disease, including cigarette smoking and non-steroidal anti-inflammatory drug
use. Recently, Clostridium difficile infection (CDI) has been added to this list. Sex (male) 10 (37.0%) 23 (54.8%) N.S.
CDI can become chronic or recurrent in 20% of patients. To date, the impact of Age (median, years) 73  17.0 65  15.2 N.S.
CDI on patients’ mortality and other outcomes among patients with Crohn’s -Age4 ¼ 85years 9 (33.3%) 3 (7.1%) p ¼ 0.005
disease has not been investigated.
Aims & Methods: The aim of this study is to explore the impact of past or current Obstructed location (left side) 23 (85.2%) 38 (90.5%) N.S.
CDI on mortality, morbidity and resource utilization among patients hospita- Primary colorectal cancer 21 (77.8%) 28 (70.0%) N.S.
lized for Crohn’s disease. This was a retrospective cohort study using the 2012 -BTS 12 24 p ¼ 0.02
National inpatient sample, the largest publically available inpatient database in -Bridge to SEMS insertion - 2
the United States. The inclusion criteria were: 1- a principal diagnosis of Crohn’s
disease 2- A principal diagnosis of intestinal hemorrhage, obstruction, fistula, or -Palliation 7 -
abdominal abscess with a secondary diagnosis of Crohn’s disease. There were no -Emergent surgery 2 1
exclusion criteria. The primary outcome was in-hospital mortality. The second- Metastatic colorectal cancer 6 (22.2%) 12 (30.0%) N.S.
ary outcomes were morbidity as measured by shock, intensive care unit (ICU) -BTS 0 5
admission, colectomy or intestinal resection rate and resource utilization as mea-
sured by length of hospital stay (LOS), abdominal CT scan, total parenteral -Bridge to SEMS insertion - 2
nutrition (TPN) use and total hospitalization charges. Odds ratios and means -Palliation 5 -
were adjusted for the following confounders using multivariate regression ana- -Emergent surgery 1 1
lyses: age, sex, race, median income in the patient’s zip code, Charlson -Technical Success 27 (100%) 40 (95.2%) N.S.
Comorbidity Index, hospital region, rural location, size and hospital teaching
status. Complications
Results: 74,515 patients with Crohn’s disease were included in the study, 1,465 -Perforation 2 (7.4%) 6 (14.3%) N.S.
(2%) of whom had CDI. The mean age was 43 years and 42% of patients were (continued)
A76 United European Gastroenterology Journal 4(5S)
Table Continued I. Maetani: Lecture fee: Century medical inc., Boston Scientific Japan., Piolax M
edical Device, MC Medical
SEMS (n ¼ 27) TDT (n ¼ 42) p value Y. Saida: grants and personal fees:Century Medical Inc., Boston Scientific Japan,
Olympus Medical System
-Re-obstruction 5 (18.5%) 1 (2.4%) N.S. All other authors have declared no conflicts of interest.
-Migration 2 (7.4%) 2 (4.8%) N.S. Reference
QOLs
1. Matsuzawa T, et al. Gastrointest Endosc 2015;82:697–707.
-Temporary discharge 5/12 (41.7%) 0/24 (0.0%) p 5 0.001
-Duration for surgery (days) 14.9  7.0 10.5  6.6 N.S.
-Hospitalization (days) 36.1  23.5 46.4  36.0 p ¼ 0.36
-Oral intake (at least soft solids) 11/12 (88.9%) 6/24 (25.0%) p 5 0.001 OP188 17 YEARS OF SINGLE CENTER EXPERIENCE WITH SELF-
EXPANDABLE METAL STENTS IN COLONIC OBSTRUCTION
-CROSS score (before procedure) 1.1  0.9 1.2  0.7 N.S.
-CROSS score (after procedure) 3.7  0.8 2.3  0.5 p 5 0.001 T. Bjerke, M. Rasmussen, S. Meisner
Digestive Disease Center, Bispebjerg Hospital, Copenhagen/Denmark
Contact E-mail Address: [email protected]
Conclusion: SEMS has the equivalent safety, clinical efficiency and is more super- Introduction: Since 1991, self-expandable metal stents (SEMS) has been used in
ior at QOLs for the patients with malignant colorectal obstruction, comparing the treatment of malignant colonic obstruction (1). In 1997, Bispebjerg Hospital
TDT. was the first hospital in Denmark to initiate the use of SEMS in the treatment of
Disclosure of Interest: All authors have declared no conflicts of interest. malignant colonic obstruction. This study represents the largest material from a
single centre ever published.
Aims & Methods: This is a prospective registration of all patients who underwent
SEMS at our institution, in the period from January 1st 1997 to October 1st 2014.
OP187 EVALUATION OF CLINICAL FACTORS ASSOCIATED WITH No patients were excluded. The indications were predominantly malignant, but a
THE TECHNICAL DIFFICULTY OF SELF-EXPANDABLE few were performed at benign indications. All procedures were performed with a
METALLIC STENT PLACEMENT FOR MALIGNANT COLONIC combined endoscopic and fluoroscopic technique. Relevant patient characteris-
OBSTRUCTION tics, the postoperative course, complications and follow-up data, were gathered
M. Shimada1, T. Kuwai2, A. Kanazawa3, S. Yoshida4, H. Isayama4, by retrospective patient chart review.
T. Matsuzawa4, T. Yamada4, S. Saito4, N. Hirata4, T. Sasaki4, K. Koizumi4, Results: In the period, 521 SEMS procedures was performed in 455 patients, 402
K. Tominaga4, I. Maetani4, Y. Saida5 of these had colorectal cancer. Mean age was 74  13 years, and 50.3% were
1
Surgery, Toyonakamidorigaoka Hospital, toyonaka/Japan male. The indications for SEMS placement were malignant colonic obstruction in
2
Gastroenterology, Kure Medical Center and Chugoku Cancer Center, Kure/Japan 418 patients, including 158 as bridge to surgery (BTS), 237 as palliation, three
3
Surgery, Toyonakamidorigaoka Hospital, Toyonaka/Japan with malignant anastomotic stricture and 20 patients with obstruction due to
4
Japan Colonic Stent Safe Procedure Research Group, Tokyo/Japan external tumor compression. The benign indications in 37 patients were respec-
5
Dept. Of Surgery, Toho University Ohashi Medical Center, Tokyo/Japan tively diverticulitis stricture in 15, diverticulitis fistula in two and benign anasto-
motic stricture in 20. Two hundred and seventy-seven patients had manifested
Contact E-mail Address: [email protected] total colonic obstruction and 121 had small bowel dilatation at the time of the
Introduction: In January 2012, the National Health Insurance began covering procedure. The placement of the SEMS was 111 in rectum, 221 in sigmoid colon,
endoscopic self-expandable metallic stent (SEMS) placement for malignant colo- 52 in descending colon, 30 in splenic flexure, 30 in transverse colon, 6 in hepatic
nic obstruction, and now this procedure is widely used in Japan. However, the flexure and 5 in ascending colon. Mean length of stenosis was 4.5  1.9 cm and
clinical factors affecting the technical difficulty of SEMS placement are unclear. mean days of obstruction was 5.2  3.4 days. There was an overall technical
Aims & Methods: This study aimed to clarify the clinical factors associated with success rate at 90.3% and clinical success rate of 87.7%. Stent procedure related
the technical difficulty of SEMS placement for malignant colonic obstruction. complications was 4.2%, mainly guidewire perforations, and none of these
We established the Colonic Stent Safe Procedure Research Group to provide patients died within 30 days. A second stent intervention was performed in
instructions on how to safety perform SEMS placement, and we then conducted 5.9% in the BTS group, 11.9% in the palliative group and in 27.3% in the
tis prospective, observational, single-arm, multicenter clinical trial between group of benign indications, external tumor compression and malignant anasto-
March 2012 and October 2013 in Japan. Forty-six facilities participated in this motic stricture. Very few patients required additional re-interventions. The over-
study. An uncovered WallFlex Enteral Colonic Stent (Boston Scientific all 30-day mortality rate was 13.4%, 5.8% for BTS group and 17% for palliative
Corporation) was placed in each patient. Technically difficult cases of SEMS group. Follow up time for BTS group was mean 79  70 months and at last
placement were defined as those that had a procedure time longer than 45 min follow up 35.3% (36/102) showed clinical signs of recurrence. 5-year survival
(i.e., 1.5-fold longer than the median procedure time). We evaluated the clinical in BTS group was 32.3% and 2.5% in the palliative group.
data and extracted risk factors associated with the technical difficulty of SEMS Conclusion: Our data shows that routine use of SEMS insertion is a safe and
placement by using univariate and multivariate analyses. effective technique for colonic decompression in the setting of malignant large
Results: A total of 518 consecutive patients were enrolled in this study. Seven bowel obstruction, as either a palliative measure or as a bridge to subsequent
patients were excluded and the remaining 511 patients constituted the per-pro- resection. SEMS for benign conditions is feasible but with less favourable
tocol cohort. Of these, 289 were men (57%), and the mean age was 70.6 years. outcome.
Three hundred eleven patients (61%) underwent stenting as a bridge to surgery, Disclosure of Interest: All authors have declared no conflicts of interest.
and 200 (39%) underwent stenting for palliation. Technical success was achieved Reference
in 501 patients (98%). The median (range) procedure time in the cohort with
technical success was 30 min (4–170 min). One hundred thirty-six patients (27%) 1. Dohomoto M. Endoscopic implantation of rectal stents in palliative treat-
were defined as technically difficult cases of SEMS placement. Clinical risk fac- ment of malignant stenosis. Endosc Dig 1991; 3(11): 1507–1512.
tors independently associated with the technical difficulty in SEMS placement
were metastasis of peritoneal carcinomatosis (odds ratio [OR], 2.24; 95% con-
fidence interval [CI], 1.26–3.96; p 5 0.01), a Colorectal Obstruction Scoring
System (CROSS) 1score of 0 before SEMS placement (OR, 2.00; 95% CI, OP189 LONG-TERM SURVIVAL AFTER ENDOSCOPIC STENTING AS
1.18–3.40; p 5 0.01), tumor site in the right colon (OR, 3.33; 95% CI, 2.06– A BRIDGE TO SURGERY IN OBSTRUCTIVE COLON CANCER: A
5.42; p 5 0.001), stricture length 45 cm (OR, 1.65; 95% CI, 1.01–2.70; SINGLE CENTER STUDY
p ¼ 0.04), the placement of 41 stent (OR, 5.96; 95% CI, 1.39–29.72; p ¼ 0.02), B. Verstockt1, A. Van Driessche2, M. De Man2, P. Van Der Spek1,
and a length of 46 cm for the first stent (OR, 2.21; 95% CI, 1.38–3.56; p 5 0.01). K. Hendrickx1, V. Casneuf1, P. Dobbels1, Y. Van Molhem3, J. Vandervoort1
However, the clinical risk factors independently negatively associated with tech- 1
Dept. Gastroenterology, OLV Hospitals Aalst/Asse/Ninove, Aalst/Belgium
nical difficulty were a history of chemotherapy before SEMS placement (OR, 2
Dept. Gastroenterology, UZ Gent, Gent/Belgium
0.47; 95% CI, 0.22–0.98; p ¼ 0.04), digestive tract decompression (OR, 0.45; 95% 3
Dept. Abdominal Surgery, OLV Hospitals Aalst/Asse/Ninove, Aalst/Belgium
CI, 0.25–0.81; p 5 0.01), and a diameter of 25 mm for the first placed stent (OR,
0.32; 95% CI, 0.12–0.76; p ¼ 0.02). Contact E-mail Address: [email protected]
Conclusion: This large study demonstrated the high technical success rate of Introduction: Self-expandable metallic stents are increasingly used in the treat-
SEMS placement for malignant colorectal obstruction. However, clinicians ment of obstructive colorectal cancer. Although endoscopic stenting is widely
should perform this procedure very carefully in cases with metastasis of perito- accepted in a palliative setting, disagreement exists about its role in a curative
neal carcinomatosis, severe stenosis with a CROSS score of 0, and/or long stric- setting (1). The main advantage of this approach is the elective, and thereby less
tures treated with a long stent. invasive, character of the surgical resection. It offers the opportunity for an
Disclosure of Interest: M. Shimada: personal fees:Century Medical Inc., Boston adequate pre-operative assessment of the patient and a good preparation of
Scientific Japan the colon (2).
T. Kuwai: personal fees: Boston Scientific Japan Aims & Methods: This study aims to describe the long-term survival data in a
S. Yoshida: personal fees: Century Medical Inc., Boston Scientific Japan, ZEON large patient group, treated with a stent as a bridge to surgery (BTS) for colon
H. Isayama: Donation & Lecture fees:Century Medical Inc. Boston Scientific cancer. Ninety-seven patients, who presented in a Belgian secondary hospital
Corp., Taewoong Medical Co, Ltd between June 1998 and November 2013 with a large bowel obstruction due to
T. Matsuzawa: personal fees: Boston Scientific Japan colon cancer, were included. All patients underwent endoscopic stenting as a BTS
S. Saito: personal fees:Century Medical Inc., Boston Scientific Japan in a potentially curable disease. Procedure-related complications and long-term
T. Sasaki: personal fees: Boston Scientific Japan., Piolax Medical Device follow-up survival data were collected and compared with the colon cancer mor-
K. Koizumi: Lecture fee: Century medical inc.personal fees: Olympus Medical tality in Belgium in the same era (3).
Syste ms
United European Gastroenterology Journal 4(5S) A77
Results: Overall survival in this observational cohort did not differ significantly OP191 SCREENING COLONOSCOPIES IN SENIORS OVER 70 YEARS
from survival in all Belgian colon cancer patients in the same period (p ¼ 0.14). OF AGE
One-, five- and ten-year survival was not statitiscally different in both groups I. Mikoviny Kajzrlikova1, P. Vitek2, J. Chalupa1, J. Kuchar1, J. Platos1, P. Reha1
(95.9% vs 79.0%; 54.7% vs 51.2%; 41.0% vs 35.6% respectively). Additionally, 1
Beskydy Gastrocentre, Internal Department, Hospital Frydek Mistek Internat
for tumour stage II, III and IV no statistical differences between both cohorts Dept., Frydek Mistek/Czech Republic
were found (p ¼ 0.21, p ¼ 0.58, p ¼ 0.10 respectively). Technical success rate was 2
Beskydy Gastrocentre, Internal Department, Hospital Frydek Mistek Internat
94.8%. Seventy patients did not experience any complication. Stent migration Dept., Faculty of Medicine, University of Ostrava, Frydek Mistek/Czech Republic
occurred in 9 patients, whereas stent-related micro- and macro perforations were
observed in 14 patients, without influencing survival. Incidence rates of perito- Contact E-mail Address: [email protected]
neal metastases did not differ significantly between patients with and without any Introduction: The recomended age for colonoscopy screening in average risk
type of perforation (22.2% vs 15.2% respectively, p ¼ 0.47). On average, surgery population is 50–55 years, but there is no upper age limit. Many patients are
took place 16.6 days after colonic stenting, ranging from an operation on the addressed for screening in advanced age. Although the prevalence of neoplastic
same day as the endoscopic procedure, to an interval of maximal 124 days. In lesions increases with age, life expectancy decreases. The aim of or study was to
82.5% of the cases a laparoscopic resection of the tumor was performed. Five evaluate the outcomes of screening colonoscopies in population over 70 years of
point two per cent of the patients got primarily open surgery. In 5.2% of the age.
patients a laparoscopic procedure was converted to laparotomy, because of adhe- Aims & Methods: The data from all screening colonoscopies performed in one
sions or peritonitis. Stoma rates were low (5.2%). non-university gastroenterology center from january 2012 to december 2015 were
Conclusion: These data indicate that stenting before surgery is effective and safe recorded to database in MS Excel. The main parts of the database comprise of
in the treatment with curative intent of patients with obstructive colon cancer and epidemiologic data about the patient, data about examination, histologic results
reinforce the debate on stenting as a BTS. and complications. The data of population aged 70 years and over and under 70
Disclosure of Interest: All authors have declared no conflicts of interest. years were compared, the chi-square and Student t test were used to compare
References dichotomous and continous variables considering level od significance of .05.
Results: 1677 screening colonoscopies were performed in total, 333 in group 70
1. van Hooft JE, van Halsema EE, Vanbiervliet G, Beets-Tan RG, DeWitt JM, years and more, 1344 in group under 70 years. Polyp detection rate (PDR) and
Donnellan F, et al. Self-expandable metal stents for obstructing colonic and and quality of bowel preparation in both groups were comparable. There were
extracolonic cancer: European Society of Gastrointestinal Endoscopy significantly more neoplasias (ADR), advanced neoplasias (advanced adenoma
(ESGE) Clinical Guideline. Endoscopy 2014; 46(11): 990–1053. and carcinoma) and carcinomas in older group and also adenoma per colono-
2. Lee JM and Byeon JS. Colorectal Stents: Current Status. Clin Endosc 2015; scopy rate (APCR) was higher in seniors. Caecal intubation rate was significantly
48(3): 194–200. lower. The numer of colonoscopies after positive FOBT was significantly higher
3. Belgian Cancer Registry. Cancer in Belgium, 2013. Brussels. than primary colonoscopies in seniors. See the table. There were no bleeding
complications or perforations during screening examinations in both groups.

OP190 IMPACT OF MORTALITY FROM SURGICAL ADENOMA 70 years (333) 570 years (1344) p
REMOVAL ON THE EFFECTIVENESS OF COLORECTAL CANCER
SCREENING Men 160 (48%) 706 (53%) 0.139
M. Buskermolen1, M.P. Van Der Meulen1, E. Toes-Zoutendijk1, M. Van FOBT/primary col. 213/120 660/684 50.005
Leerdam2, M.C.w. Spaander3, H. De Koning4, I. Lansdorp-Vogelaar5 PDR 237 (71%) 911 (68%) 0.240
1
Public Health, Erasmus MC, Rotterdam/Netherlands
2 ADR 174 (52%) 616 (46%) 0.037
Dept. Of Gastroenterology, Netherlands Cancer Institute, Amstelveen/
Netherlands Advanced ADR 74 (22%) 200 (15%) 0.001
3
Gastroenterology & Hepatology, Erasmus Medical Center Gastroenterology and Carcinoma 10 (3%) 17 (1%) 0.024
Hepatology, Rotterdam/Netherlands APCR 1.102 0.875 0.006
4
Erasmus MC, Rotterdam/Netherlands
5 Caecal intubation 313 (94%) 1304 (97%) 0.006
Department Of Public Health, Erasmus University Medical Center, Rotterdam,
Rotterdam/Netherlands Inadequate preparation 24 (7%) 74 (5%) 0.237

Contact E-mail Address: [email protected]

Introduction: Implementation of colorectal cancer (CRC) screening programs
results in an increase in the number of adenoma diagnoses. Some of the advanced Conclusion: Screening colonoscopies in population over 70 years of age in our
adenomas (AADs) cannot be endoscopically removed and patients may then be study were safe, with higher detection of neoplasias, but with lower completion
referred for surgery. However these surgical resections have an associated mor- rate. There was higher number of colonoscopies after positive FOBT than pri-
tality risk and will have a negative impact on the effectiveness of CRC screening. mary colonoscopies among seniors.
So far, the size of this impact is unknown. Therefore the objective of this study is Disclosure of Interest: All authors have declared no conflicts of interest.
to estimate the size of this perioperative mortality in relation to AAD removal on
the effectiveness of CRC screening.
Aims & Methods: We used the MISCAN-Colon microsimulation model to simu- TUESDAY, OCTOBER 18, 2016 10:30–12:00
late the Dutch population, aged 50 years and older in 2013 and followed them COMPLICATIONS IN IBD – ROOM F2_____________________
lifetime. The population was offered biennial FIT (FOB-Gold at a cut-off of 46
mg/g feces) screening between ages 55 and 75. Gradual roll-out was simulated OP192 THE OCCURENCE OF ANAEMIA AND ANAEMIA SUBTYPES
from 2014 to 2020 according to implementation. To assess the impact of perio- DURING THE FIRST YEAR OF DISEASE IN AN EAST-WEST
perative mortality in relation to AAD removal, we simulated a scenario with and EUROPEAN INCEPTION COHORT – AN ECCO-EPICOM COHORT
without perioperative mortality within the screening program. In the scenario STUDY
with perioperative mortality, we assumed that 3.9% of all AADs diagnosed J. Burisch1, L. U. Gerdes2, S. Almer3, S. Cukovic Cavka4, S. Sebastian5,
during diagnostic colonoscopy need to be surgically removed, based on findings I. Kaimakliotis6, D. Duricova7, N. Pedersen8, R. Salupere9, K.R. Nielsen10,
in Dutch pilot studies. The perioperative mortality rate is estimated at 2.1%, P. M. Oksanen11, K.H. Katsanos12, S. Odes13, V. Andersen14, D. Valpiani15,
based on reports of Dutch surgeons. This leads to an overall mortality risk of L. Kupcinskas16, S. Turcan17, F. Magro18, A. Goldis19, K. Kofod Vinding20,
0.08% for every AAD diagnosis. The primary outcomes were the size of perio- E. Belousova21, K. Ladefoged22, Y. Bailey23, V. Hernandez24, J. Halfvarson25,
perative mortality per year, the number of prevented CRC deaths, life years O. Shonová26, N. Arebi27, M.L. Hoivik28, B. Moum28, E. Langholz29,
gained (LYG), quality adjusted life years (QALYs) and costs. Sensitivity analyses P.L. Lakatos30, P. Munkholm1, J.F. Dahlerup31
were performed with a mortality risk of 0.05% and 0.11%. 1
Department Of Gastroenterology, North Zealand University Hospital,
Results: During the roll out of the Dutch screening program between 2014 and Frederikssund/Denmark
2020, perioperative mortality caused up to 18 deaths every year. After 2020 the 2
Center For Quality, Region of Southern Denmark, Odense/Denmark
number of AAD screen detected decreased and thus perioperative mortality 3
Division Of Gastroenterology and Hepatology, Karolinska Institutet, Stockholm/
decreased gradually through approximately 11 per year in 2033. Between 2014 Sweden
and 2033, a total of 251 individuals died from perioperative complications. This 4
Division Of Gastroenterology and Hepatology, University Hospital Center
corresponded with a decrease in prevented CRC deaths of 1.5% (22135 without Zagreb, University of Zagreb School of Medicine, Zagreb/Croatia
operation mortality vs 21928 with), a decrease in LYG from screening of 2.5% 5
Hull and East Riding NHS Trust, Hull/United Kingdom
and in QALY’s of 1.0%. The impact on costs of the screening program was 6
Nicosia private practice, Nicosia/Cyprus
negligible. With higher and lower perioperative mortality assumptions, the out- 7
Ibd Center Iscare, Charles University, Prague/Czech Republic
comes altered proportionally. 8
Gastroenterology Department, Slagelse Hospital, Slagelse/Denmark
Conclusion: Mortality due to surgical AAD resection has a negative impact on 9
Division Of Endocrinology and Gastroenterology, Tartu University Hospital,
the effectiveness of CRC screening, although the impact is modest. Benefits of Tartu/Estonia
CRC screening as a whole are maintained. However, deaths due to surgical AAD 10
Medical Department, National Hospital of the Faroe Islands, Torshavn/Faroer
resection are an order of magnitude larger than deaths due to complications of Islands
colonoscopy. Future studies into the effectiveness of CRC screening should 11
Department Of Gastroenterology and Alimentary Tract Surgery, Tampere
therefore incorporate the harms of surgical AAD removal. University Hospital, Tampere/Finland
Disclosure of Interest: All authors have declared no conflicts of interest. 12
Division Of Internal Medicine, Medical School of Ioannina, Ioannina/Greece
13
Department Of Gastroenterology and Hepatology, Ben-Gurion University of the
Negev Beersheba, Beer Sheva/Israel
A78 United European Gastroenterology Journal 4(5S)
14
Medical Department, Viborg Regional Hospital, Viborg/Denmark variations in the use of biological therapy might contribute to the observed
15
On behalf of the EpiCom Northern Italy center based in Florence, Forlı`, and differences in anaemia frequency.
Padova, Northern Italy/Italy Disclosure of Interest: All authors have declared no conflicts of interest.
16
Institute For Digestive Research, Lithuanian University of Health Sciences, References
Kaunas/Lithuania
17 1. Burisch J, et al. East-West gradient in the incidence of inflammatory bowel
Department Of Gastroenterology, State University of Medicine and Pharmacy of
the Republic of Moldova, Chisinau/Moldova disease in Europe: the ECCO-EpiCom inception cohort. Gut 2014.
18 2. Burisch J, et al. Initial disease course and treatment in an inflammatory
Hospital de São João, Porto; Institute of Pharmacology and Therapeutics,
Oporto Medical School and Institute for molecular and cell biology, University of bowel disease inception cohort in Europe: the ECCO-EpiCom cohort.
Porto, Porto/Portugal Inflamm Bowel Dis 2014.
19
Clinic Of Gastroenterology, University of Medicine ‘Victor Babes’, Timisoara/
Romania
20
Medical Department, Amager & Hvidvore Hospital, Amager/Denmark
21
Department Of Gastroenterology, Moscow Regional Research Clinical Institute, OP193 INCIDENCE AND RISK FACTORS OF SERIOUS VIRAL
Moscow/Russian Federation INFECTIONS IN INFLAMMATORY BOWEL DISEASE
22
Medical Department, Dronning Ingrids Hospital, Nuuk/Greenland A. Wisniewski1, J. Kirchgesner2, C. Landman2, A. Bourrier2, I. Nion Larmurier2,
23
Department Of Gastroenterology, Adelaide and Meath Hospital, Trinity College H. Sokol2, P. Seksik2, J. Cosnes2, L. Beaugerie2
of Dublin, Dublin/Ireland 1
Gastroente´rologie Et Nutrition, Hopital Saint Antoine, Paris/France
24
Gastroenterology Department, Complexo Hospitalario Universitario de Vigo, 2
Department Of Gastroenterology, AP-HP, Hôpital Saint-Antoine, Paris/France
Vigo/Spain
25
Dep. Of Internal Medicine, Örebro University Hospital, Örebro/Sweden Contact E-mail Address: [email protected]
26
Gastroenterology Department, Hospital Ceske´ Budejovice, Ceske´ Budejovice/ Introduction: Use of immunosuppressants in IBD is associated with an increased
Czech Republic risk of serious infections that varies considerably according to infection and
27
St. Mark’s Hospital, Imperial College London, London/United Kingdom immunosuppressant subtypes. This study aimed to determine the incidence rate
28
Dept. Of Gastroenterology, Oslo University Hospital, Oslo/Norway and risk factors for serious viral infection (SVI) according to drug exposure and
29
Gentofte Hospital, Hellerup/Denmark IBD activity in patients with IBD.
30
1st Department Of Medicine, Semmelweis University, Budapest/Hungary Aims & Methods: Using MICISTA registry, a prospective observational cohort
31
Department Of Hepato-gastroenterology V, Aarhus University Hospital, Aarhus/ of IBD patients treated at our tertiary care hospital, we identified between Jan
Denmark 2005 and Dec 2014 patients who developed SVI as defined by need for hospita-
lization, definite organ damage or disabling sequelae. Cases of CMV colitis with-
Contact E-mail Address: [email protected] out systemic manifestations were excluded. We first estimated incidence rates of
Introduction: The EpiCom-cohort is a European prospective population-based SVI, overall and according to maximal yearly treatment. Additionally, we per-
cohort of unselected patients uniformly diagnosed with inflammatory bowel dis- formed a case-control study (4 controls for 1 case matched for age, gender, IBD
ease (IBD) in 2010 in 31 Western and Eastern European centres1. Previously, this subtype and duration) assessing risk of SVI according to IBD drug use and IBD
cohort has demonstrated differences in the treatment strategy of IBD patients clinical activity in the 3 months preceding the SVI (data extracted from individual
between Eastern and Western European centre including that significantly more health records).
patients in Western Europe receive biological therapy2. Despite these differences Results: We identified 31 patients with SVI among 2645 patients, followed for a
in treatment no differences regarding disease outcomes including surgery and median period of 6.2 years and a total observational time of 16922 patient-years.
hospitalization rates and quality of life between the two regions have been We identified 13 cases of CMV systemic infection (primary infection (n ¼ 6),
found. Anaemia is a common systemic complication and/or extra-intestinal man- reactivation (n ¼ 7)), 10 cases of EBV infection (primary infection (n ¼ 6) includ-
ifestation to IBD as well as an indicator of the level of global IBD care and ing 2 haemophagocytic syndromes, reactivation (n ¼ 4)), 5 cases of VZV infection
inflammation control. (varicella (n ¼ 3), shingles (n ¼ 2)) and 3 cases of HSV infection (severe esopha-
Aims & Methods: The aim of the current study was to investigate the occurrence gitis, facial nerve paralysis, severe refractory cutaneous manifestation). Most
of anaemia as well as differences between Eastern and Western Europe during the patients required hospitalization (94%) and received IV anti-viral therapy
first year of disease. Incident patients were followed prospectively from the time (52%), while no death occurred. The incidence rate of SVI in patients with
of diagnosis. Clinical data on surgery, medical treatment, hospitalization, and IBD was 1.83 per 1000 patients-years. Table 1 shows the incidence rate of SVI
blood samples were captured throughout the follow-up period. Anaemia and its according to the maximal treatment received during the year. In the case control
subtypes were defined according to the World Health Organisation and ECCO study, risk of SVI was associated with exposure to thiopurine (adjusted odds-
guideline. ratio (aOR), 5.1; 95% CI, 1.9–13.4; p ¼ 0.001) and methotrexate (aOR, 4.1;
Results: A total of 827 patients aged 15 years or older from 29 centres (20 95%CI, 1.0–16.8; p ¼ 0.05), and active clinical disease (aOR, 3.2; 95% CI, 1.3–
Western, 9 Eastern European) were eligible for analysis of whom 433 (52%) 8.1; p ¼ 0.02). Odds-ratios for corticosteroids and anti-TNF did not reach statis-
had ulcerative colitis (UC), 300 (37%) had Crohn’s disease (CD), and 94 tical significance (1.1 and 1.2, respectively).
(11%) had IBD unclassified (IBDU). The proportion of patients with anaemia
and its subtypes at diagnosis and follow-up is shown in table 1. Overall, anaemia Exposure to Incidence rate 95%
was more frequent in Eastern than in Western European patients for both CD medication for SVI (per 1000 Confidence
and UC. After 1 year of follow-up significantly more patients in Eastern Europe (patients-years) patients-years) P value interval
who were anaemic at diagnosis remained anaemic (23% UC, 24% CD) compared
to Western Europe (8% UC 9% CD), while a similar proportion in both regions No treatment or 5ASA 7922 0.50 ref 0.01–1.00
changed from the anaemic state to normal (20% UC and 35% CD in both
regions) during follow-up. More IBD patients receiving biological therapy Steroids 1582 0.63 0.68 0–1.87
during the first year of disease changed status from anaemia at diagnosis to no Immunomodulators 6236 3.2 0.0002 1.80–4.61
anaemia at follow-up (83%) compared to patients not having received biological Anti-TNF  5173 1.16 0.31 0.23–2.09
therapy (70%), while fewer patients receiving biological therapy remained anae- immunomodulators
mic during follow-up (17% vs 30%). These differences did, however, not reach
statistical significance (p ¼ 0.09). Conclusion: SVI are rare events in patients with IBD who do not receive immu-
nosuppressants. Exposure to thiopurines or methotrexate, and IBD clinical activ-
Table 1: Prevalence of anemia at diagnosis and at 1-year follow up. ity increases substantially the risk. Among 100 patients treated with thiopurines
for 10 years, 3 will develop SVI.
Ulcerative colitis Crohn’s disease Disclosure of Interest: All authors have declared no conflicts of interest.
Eastern Europe Western Europe Eastern Europe Western Europe

Follow- Follow- Follow- Follow-

Diagnosis up Diagnosis up Diagnosis up Diagnosis up OP194 COLORECTAL CANCER RISK IN A NATIONWIDE
INFLAMMATORY BOWEL DISEASE COHORT WITH LOW GRADE
Anaemia - overall 43% 26% 29% 13% 58% 25% 45% 12% DYSPLASIA
Iron deficiency 6% 3% 3% 2% 7% 4% 1% 0% L. Derikx1, S. V. Tilburg2, I.D. Nagtegaal3, L. Nissen1, F. Hoentjen4
1
Anaemia of 9% 3% 3% 1% 13% 0% 12% 1% Gastroenterology and Hepatology, Jeroen Bosch Hospital’s, Hertogenbosch/
chronic disease Netherlands
2
Mixed anaemia 6% 1% 1% 1% 24% 7% 17% 1% Gastroenterology and Hepatology, Radboud university medical centre, Nijmegen/
Other anaemia 6% 4% 4% 2% 2% 0% 6% 2% Netherlands
3
Unclassified 14% 16% 16% 6% 13% 15% 10% 9% Pathology, Radboud University Nijmegen Medical Center Dept. of Pathology,
Nijmegen/Netherlands
4
Gastroenterology and Hepatology, Radboud University Medical Center Nijmegen,
Nijmegen/Netherlands
Conclusion: In this unselected, population-based inception cohort the frequency
of anaemia was high at the time of diagnosis, especially for CD, but decreased Contact E-mail Address: [email protected]
during the first year of follow-up. More Eastern than Western European patients Introduction: Patients with long-standing colonic inflammatory bowel disease
remained anaemic after 1 year of follow-up. These geographic differences could (IBD) bear an increased colorectal cancer (CRC) risk. Endoscopic surveillance
be caused by differences in awareness of anaemia or they might reflect differences allows early detection and removal of precancerous lesions such as low-grade
in global care and inflammation control of IBD patients in Europe. Geographic dysplasia (LGD), and may subsequently prevent CRC. However, the long-term
outcome after LGD and the subsequent risk to develop CRC remains uncertain,
United European Gastroenterology Journal 4(5S) A79
since most available studies are small and cover a relatively short follow-up OP196 PREDICTORS OF FIRST COLONIC EPITHELIAL NEOPLASIA
period. To this end, we established a nationwide cohort of IBD patients with a IN PATIENTS WITH INFLAMMATORY BOWEL DISEASE
history of LGD to 1) determine the cumulative CRC incidence, and 2) identify UNDERGOING COLONOSCOPIC SURVEILLANCE
risk factors for developing CRC. J. Kirchgesner1, M. Svrcek2, C. Landman1, A. Bourrier1, I. Nion Larmurier1,
Aims & Methods: Using the Dutch National Pathology Registry (PALGA) we N. Hoyeau3, H. Sokol1, P. Seksik1, J. Cosnes1, J. Fléjou2, L. Beaugerie1
identified all IBD patients diagnosed with LGD between 1991 and 2005 in the 1
Department Of Gastroenterology, AP-HP, Hôpital Saint-Antoine, Paris/France
Netherlands. Subsequently, follow-up data were extracted until 2016. We deter- 2
Department Of Pathology, AP-HP, Hôpital Saint-Antoine, Paris/France
mined the cumulative CRC incidence with Kaplan Meier curves censuring 3
Department Of Pathology, AP-HP, Hôpital Saint-Antoine, Paris, France, Paris/
patients at the end of colorectal surveillance or colectomy. A case control France
study, comparing IBD patients with LGD who developed CRC (cases) versus
patients who did not develop CRC (controls), was performed to identify risk Contact E-mail Address: [email protected]
factors for developing CRC. Demographic data, including gender, IBD type, age Introduction: Patients with inflammatory bowel disease (IBD) are at increased
and duration, and LGD age and recurrence, were extracted from PALGA. risk for developing colorectal neoplasia (CRN). Little is known about risk factors
Subsequently univariable and multivariable Cox regression analyses with back- of first CRN in IBD patients after a surveillance colonoscopy negative for
ward elimination were used to identify independent risk factors. neoplasia.
Results: We identified 1177 IBD patients with colonic LGD with a median Aims & Methods: The aim of our study was to identify predictive factors of first
follow-up time of 9.8 years per patient after LGD diagnosis (total follow-up CRN in IBD patients after a surveillance colonoscopy negative for neoplasia. All
time: 11741 patient years). 825 (70.1%) patients had ulcerative colitis, 216 consecutive patients who underwent at least two colonoscopies at Saint-Antoine
(18.4%) Crohn’s disease and 136 (11.6%) indeterminate colitis. Hundred nine Hospital between 01/01/1996 and 01/03/2015 and whose first procedure was a
out of 1177 (9.3%) patients underwent colectomy. CRC developed in 86 out of surveillance colonoscopy were included. A nested case-control study was per-
1177 patients resulting in a cumulative incidence of 2.9%, 5.8%, 11.1%, and formed to assess risk factors of CRN in inflamed mucosa. Information on treat-
18.7% after respectively 5, 10, 15 and 20 years. Patients with an IBD duration ments, endoscopic and histologic inflammation was collected. The identified
of more than 5 years before LGD development had a significantly higher cumu- CRN risk factors were used to build a predictive score that was then tested in
lative CRC incidence (14.7% after 15 years) compared to those with a shorter the whole study population.
IBD duration (9.4% after 15 years; log rank p ¼ 0.001). Furthermore, patients Results: Among 404 patients who underwent 1236 colonoscopies, 38 patients who
with recurrent LGD had a higher CRC risk compared to patients with single developed CRN in inflamed mucosa and 92 matched controls were included in a
LGD (10.5% after 15 years versus 4.5% after 15 years; log rank p ¼ 0.026). nested case-control study. Independent factors significantly associated with CRN
Multivariable Cox regression identified both a longer IBD duration (hazard were primary sclerosing cholangitis (PSC) (Odds ratio (OR), 6.26; CI 95% 1.07–
ratio 2.5, 95% confidence interval 1.5–4.3) and recurrent LGD (hazard ratio 36.8, p ¼ 0.04), presence of neutrophils, crypt abscess or histological ulcerations
1.9, 95% confidence interval 1.1–3.4) as independent factors associated with (OR, 8.77; CI 95% 1.71–45, p ¼ 0.009) and presence of crypt architectural irre-
increased CRC risk. gularities without neutrophils or ulcerations (OR, 8.09; CI 95% 1.21–54.3,
Conclusion: We showed a cumulative CRC risk of 18.7% after 20 years in a large p ¼ 0.03) on more than half of procedures during follow-up, exposure to thio-
nationwide cohort of IBD patients with a history of LGD. Both a longer IBD purines (OR, 0.18; CI 95% 0.047–0.698, p ¼ 0.01) and 5-aminosalicylates (OR,
duration and recurrent LGD were identified as independent risk factors for CRC 0.27; CI 95% 0.084–0.876, p ¼ 0.03) at the time of neoplasia or last colonoscopy.
development following LGD. These findings may aid in risk stratification follow- We developed a score based on these five items at the time of the surveillance
ing a diagnosis of LGD in IBD patients. colonoscopy negative for neoplasia. Among patients with a score of 0, the nega-
Disclosure of Interest: All authors have declared no conflicts of interest. tive predictive value in predicting any CRN was 100% in patients with colonos-
copies performed 1 and 3 years after the first surveillance colonoscopy.
Conclusion: In IBD patients undergoing endoscopic surveillance, the risk of first
CRN is increased in case of PSC, persistence of histological acute inflammation
OP195 ROLE OF DIFFUSION-WEIGHTED IMAGING (DWI) IN MRI- and quiescent disease, and decreased by concurrent treatment with thiopurines
ENTEROGRAPHY FOR THE EVALUATION OF SURGICAL RISK IN and 5-aminosalicylates. The use of a predictive score derived from these factors
PATIENTS WITH CROHN’S DISEASE could be considered for making decisions on optimal intervals between two
A. Testa1, A. Rispo1, P. P. Mainenti2, D. Musto1, N. Imperatore1, M. Rea1, surveillance colonoscopies.
O. M. Nardone1, N. Caporaso1, F. Castiglione1 Disclosure of Interest: A. Bourrier: Anne Bourrier has received lecture fees from
1
Gastroenterology, Department of Clinical Medicine and Surgery, School of UCB
Medicine "Federico II" of Naples, Naples, Italy, Naples/Italy H. Sokol: Harry Sokol received consulting fees from Enterome, Astellas, Roche,
2
Radiology, Department of Clinical Medicine and Surgery, School of Medicine Merck, Maat and Danone.
"Federico II" of Naples, Naples, Italy, Naples/Italy P. Seksik: Philippe Seksik had consulting fees from Abbvie, Merck-MSD and
Biocodex and grants from Biocodex.
Contact E-mail Address: [email protected] J. Cosnes: Jacques Cosnes has received lecture fees from Abbvie, consulting fees
Introduction: In Crohn’s disease (CD) it’s useful to discriminate inflammatory from Vifor Pharma
from fibrotic lesions. MRI-Diffusion Weighted Imaging (DWI) is able to identify L. Beaugerie: Laurent Beaugerie has received consulting fees from Abbott, lec-
active inflammation in most pathological tissues. ture fees from Abbott, Abbvie, MSD, Ferring Pharmaceuticals, Janssen, and
Aims & Methods: We aimed to define the role of DWI in evaluating the risk of research support from Abbott, Biocodex and Ferring Pharmaceuticals.
surgery in CD. We performed an observational prospective study including all All other authors have declared no conflicts of interest.
consecutive CD patients with active CD undergone MRI. MRI study included:
measurement of bowel wall thickness (BWT), CD extension, enhancement pat-
tern, pre-stenotic dilation, presence of oedema and/or comb-sign, presence of TUESDAY, OCTOBER 18, 2016 10:30–12:00
fistulas/abscesses, T2 and T2 sequences. Furthermore, all patients were studied COLORECTAL CANCER SCREENING: STATE-OF-THE-ART – ROOM
by DWI sequences defining: visual analysis of iperintensity and analysis of K_____________________
Apparent Diffusion Coefficient (ADC) maps. Statistical analysis was performed
dividing all patients in 2 groups (operated vs not operated) using T-student and OP198 PREDICTORS AND TRENDS IN FECAL HEMOGLOBIN
X-square test when indicated. To identify the variables associated to surgical risk, CONCENTRATION: LONG-TERM FOLLOW-UP OF FIT-NEGATIVE
we performed a logistic multiple regression expressing the risk in terms of Odd SCREENEES IN POPULATION-BASED COLORECTAL CANCER
Ratio. Finally, the diagnostic accuracy was tested by a ROC curve. SCREENING
Results: 110 patients were enrolled and 127 bowel segments resulted pathologic at E.J. Grobbee1, E. H Schreuders1, B. Hansen2, M.J. Bruno3, I. Lansdorp-
MRI. 26 patients (23.6%) and 31 segments were resected during the follow-up Vogelaar4, M.C.w. Spaander5, E.J. Kuipers6
period. At all pathological segments, the iperintensity in DWI sequences, the 1
Gastroenterology And Hepatology, Erasmus MC University Medical Center,
reduction of ADC max, ADC medium and the presence of fistulas/abscesses Rotterdam/Netherlands
were significantly associated with a subsequent surgical intervention (p 5 0.05). 2
Erasmus MC, University Medical Center Rotterdam, Rotterdam/Netherlands
In particular, the presence of CD complication was the variable with the highest 3
Department Of Gastroenterology & Hepatology, University Medical Center
risk of surgery (p ¼ 0.008; OR 3.9; 95% CI 1.4–10.7). When excluding the Rotterdam, Rotterdam/Netherlands
patients with complications, we reported a significant correlation of DWI iper- 4
Department Of Public Health, Erasmus University Medical Center, Rotterdam,
intensity, ADC max and medium with surgical intervention. The reduction of Rotterdam/Netherlands
ADC medium was the variable with the highest risk of surgery (p ¼ 0.03; OR 2.0; 5
Gastroenterology & Hepatology, Erasmus Medical Center Gastroenterology and
95% CI 0.79–0.92). The cut-off value for discriminating patients at risk of sur- Hepatology, Rotterdam/Netherlands
gery was 1.081x10–3 mm2/s (sensibility 55.6%, specificity 70.3%, PPV 33.3%, 6
Department Of Gastroenterology and Hepatology, Erasmus MC University
NPV 85%). Medical Center, Rotterdam/Netherlands
Conclusion: The presence of fistulas/abscesses remains the variable most asso-
ciated with surgical risk in CD. In not complicated CD, DWI sequences at MRI- Contact E-mail Address: [email protected]
Enterography correlates with the need of surgery. High value of ADC medium Introduction: Quantitative fecal immunochemical tests (FITs) are invariably used
shows high NPV for surgery in CD patients. in a qualitative manner using pre-specified cut-offs in colorectal cancer (CRC)
Disclosure of Interest: All authors have declared no conflicts of interest. screening. To optimize FIT-based screening programs, it makes sense to explore
if participants with a negative FIT result at first participation and subsequent
participations can be categorized according to fecal Hb (fHb) concentration to
predict risk of developing future colorectal advanced neoplasia (AN).
Aims & Methods: In this population based screening cohort, average-risk subjects
aged 50–74 years, were invited for four rounds of FIT screening (cut-off of 10 mg
Hb/g, corresponding to 50 ng Hb/ml buffer). For this study all subjects with a
negative FIT at first participation were included. Baseline fHb was divided into 3
A80 United European Gastroenterology Journal 4(5S)
categories (0 mg Hb/g, 40–5 mg Hb/g and, 45–10 mg Hb/g) to calculate cumu- colitis that occurred after FS (incidence rate, 0.0082%). There were no cases of
lative incidence of AN. To identify factors associated with AN a Cox propor- perforation after endoscopy.
tional hazard regression analysis was performed to calculate hazard ratios (HRs). Conclusion: Although there are some problems in introducing FS into mass
Consecutive FIT results were analyzed using logistic regression analyses to cal- screening for CRC, (i.e. cost-effectiveness, speed of examinations and lack of
culate relative risks of AN. Risks were visualized by generating heat plots for manpower), FS is easier to prepare and it is a shorter and safer procedure
men and women. than colonoscopy. The findings suggest that using FIT in combination with FS
Results: A total of 13,566 subjects were invited for screening of whom 9,561 is effective for detecting CRC in first-time subjects that are 50 years of age and
(70%) participated at least once. Of those, 7,663 (92%) had a negative FIT at older. However, this same procedure provides limited benefit for those who are
first screen. Median follow-up was 4.7 years (IQR 2.0–6.1 years). Screenees with below 50 years of age.
a baseline fHb of more than 5 mg Hb/g had a 23% higher cumulative incidence of Disclosure of Interest: All authors have declared no conflicts of interest.
AN than those with a baseline fHb of 0 mg Hb/g (p 5 0.001). In multivariate Cox
regression analysis HRs increased from 1.7 (95% CI 1.2–2.2) to 6.0 (95% CI 4.0–
9.0) for a fHb concentration of more than 0 to 5 mg Hb/g and more than 5 up to
10, respectively (p 5 0.0001; Table 1). In logistic regression analysis of two con- OP200 GASTROINTESTINAL EVENTS AFTER A NORMAL
secutive negative FIT results, RRs increased with fHb concentration, with up to a COLONOSCOPY IN FIT-POSITIVE PARTICIPANTS IN AN
14-fold risk increase for two consecutive FITs with both a fHb concentration of 8 ORGANIZED, POPULATION-BASED COLORECTAL CANCER
mg Hb/g feces compared to twice a fHb concentration of 0 mgHb/g (p 5 0.001). SCREENING PROGRAM
L. Rivero Sánchez1, M. Pellise2, M. Lopez-Ceron1, J. Grau1, A. Pozo1,
Table 1: Time-dependent cox-regression analysis of baseline FIT of advanced A. Serradesanferm1, M. Diaz1, C. Rodriguez De Miguel1, J.M. Auge1, L. Llovet1,
neoplasia. A. Castells3
1
Advanced neoplasia Hospital Clinic of Barcelona, Barcelona/Spain
2
Univariate Multivariate Hospital Clinic i Provincial de Barcelona, Barcelona/Spain
3
HR 95% CI p-value 95%CI p-value Gastroenterology, Hospital Clinic, Barcelona/Spain

Gender (male) 1.7 1.3–2.3 50.001 1.6 1.2–2.1 50.001 Contact E-mail Address: [email protected]
Introduction: Positive fecal immunochemical test (FIT) is associated to colorectal
Age (years) 1.1 1.0–1.1 50.001 1.1 1.0–1.1 50.001
neoplasia and/or bleeding from non-neoplastic lesions. However, a considerable
Baseline fHb conc.
proportion of individuals with a positive FIT have a normal colonoscopy.
0 mg Hb/g Ref. 50.001 Ref. Aims & Methods: We aimed 1) to identify possible causes of positive-FIT result in
40–5 mg Hb/g 1.8 1.3–2.4 1.7 1.2–2.2 50.001 subjects with normal colonoscopy 2) to ascertain the rate of post-colonoscopy
45–10 mg Hb/g 7.0 4.6–10.5 6.0 4.0–9.0 colorectal cancer (CRC) in this cohort. Methods: All individuals from the first
Socioeconomic status round of the Barcelona’s CRC Screening Program (January 2010–December
High Ref. 0.08 2012) with a positive FIT(20 mg/g) and complete negative colonoscopy (i.e.
Average 1.0 0.7–1.3 no neoplastic lesion) were included. Subsequent gastrointestinal events that
implied a medical consultation and/or procedure were recorded at the National
Low 0.6 0.4–1.0
Health Service electronic database. Attribution of causality for positive FIT was
ascertained according to time of presentation of the event: certain (at baseline
colonoscopy), probable (6 months after colonoscopy), possible (6–12 months
Conclusion: Among FIT negative screenees, baseline fHb concentration is an after colonoscopy), uncertain (412 months after colonoscopy). Post-colono-
independent predictor for the risk of future AN. Moreover, fHb concentrations scopy CRC were defined as any invasive CRC detected after colonoscopy until
of two consecutive negative FITs are a strong predictor of the risk of AN with up the end of follow-up (median, 50.6 months [range, 36–69]).
to a 14-fold risk increase. These findings suggest a role for fHb in personalized Results: From 2659 individuals who underwent colonoscopy after a positive FIT,
screening strategies in population-based screening policies. In addition, the use of 811 (30.5%; age 59.1  0.4 years; 60.7% women) had a negative colonoscopy. In
fHb of negative FITs may permit alteration of screening intervals. Such strategies 102 (12.6%) individuals a cause of positive FIT was identified at the colonoscopy
could decrease unnecessary burden for screenee and optimize the use of program (angiodisplasia, 50; inflammatory lesions, 52). Of those 709 individuals with a
related resources. normal colonoscopy, 32 (4.5%) had subsequent gastrointestinal events classified
Disclosure of Interest: All authors have declared no conflicts of interest. as probable cause in 2 (gastric adenocarcinoma and Los Angeles’ grade D eso-
phagitis), possible cause in 4 (invasive CRC, small bowel lymphoma, diverticular
hemorrhage, and gastric antral vascular ectasia), and uncertain cause in 26 (2
invasive CRC, 4 advanced adenomas, 2 non-advanced adenomas, 15 inflamma-
OP199 MASS SCREENING FOR COLORECTAL CANCER BY USING A tory lesions, and 3 anorectal disorders). Age, sex, FIT levels, comorbidities
FECAL IMMUNOCHEMICAL TEST IN COMBINATION WITH (hepatic, renal, coagulopathy) or chronic antiplatelet/anticoagulant/NSAID
FEXIBLE SIMOIDOSCOPY treatments were not associated with a higher prevalence of gastrointestinal
R. Nozaki, K. Yamada, M. Takano events. On the other hand, 3 (0.36%) post-colonoscopy CRC were detected
Gastroenterology, Coloproctology Center, Takano Hospital, Kumamoto City/ (age, 56.3  7.5 years; 66% men; TNM stage: 2 were IIIA and 1 was IIIB)
Japan within 11–28 months after screening. There were no significant differences
regarding age, sex and FIT level among subjects with or without post-colono-
Contact E-mail Address: [email protected] scopy CRC.
Introduction: To date, there have only been a few large-scale community-based Conclusion: Most individuals (83%) with a positive FIT and negative colono-
studies that examined the efficacy of using a fecal immunochemical test (FIT) in scopy do not have any lesion that may explain this result. Of these, 96% do not
combination with flexible sigmoidoscopy (FS) for colorectal cancer (CRC) present subsequent gastrointestinal events. Importantly, the rate of post-colono-
screening. Since 1983, we have been conducting community-based mass screening scopy CRC in these subjects is very low (0.36%).
for CRC using fecal occult blood testing in combination with FS in Kyushu, Disclosure of Interest: All authors have declared no conflicts of interest.
Japan. In 1988, we designed special buses with the necessary equipment to per- References
form FS mass screening in order to test as many people as possible. The two-day
FIT method combined with small caliber electronic endoscopes for FS have been 1. Brenner H, Chang-Claude J, Seiler CM, et al. Long-term risk of colorectal
in use since 1992.The aim of this study was to investigate the efficacy of combin- cancer after negative colonoscopy. J Clin Oncol 2011; 29: 3761–7.
ing FIT with FS to detect CRC and then analyze the CRC detection rates. 2. Hardcastle JD, Chamberlain JO, Robinson MH, et al. Randomised con-
Aims & Methods: A large sample of 1,597,734 subjects that underwent the FIT trolled trial of faecal-occult-blood screening for colorectal cancer. Lancet
procedure to detect CRC and who exhibited a cut-off value of 100 ng/ml were 1996; 348: 1472–7.
enrolled in this study from 1992 to 2014. Colorectal cancers that were detected 3. Quintero E, Castells A, Bujanda L, et al. Colonoscopy versus fecal immu-
using FIT in conjunction with follow-up examinations were classified as two-day nochemical testing in colorectal-cancer screening. N Engl J Med 2012; 366:
FIT-detected cancers. When lesions (i.e. polyps) were found using FS despite a 697–706.
negative two-day FIT outcome or when CRC was detected using colonoscopy the 4. Faivre J, Dancourt V, Lejeune C, et al. Reduction in colorectal cancer mor-
cancers were classified as FIT-negative and FS-detected, respectively. Out of the tality by fecal occult blood screening in a French controlled study.
cases with a negative two-day FIT outcome, 180,779 of them underwent FS. Gastroenterology 2004; 126: 1674–80.
Results: The positive rate for the negative two-day FIT and FS cases was 8.6% 5. Steele RJC, McClements P, Watling C, et al. Interval cancers in a FOBT-
and 90.9% of them underwent work-up examinations. The work-up examina- based colorectal cancer population screening programme: implications for
tions resulted in a CRC detection rate of 0.15% (mucosal cancer, 0.12%; invasive stage, gender and tumour site. Gut 2012; 61: 576–81.
cancer, 0.03%). In first-time negative two-day FIT and FS cases (33,469), the 6. Farrar WD, Sawhney MS, Nelson DB, et al. Colorectal cancers found after a
cancer detection rates were as high as 0.27% (mucosal cancer, 0.22%; invasive complete colonoscopy. Clin Gastroenterol Hepatol 2006; 4: 1259–64.
cancer, 0.05%). On the other hand, 7.1% of all the subjects were detected as
positive using only the two-day FIT procedure and 78.0% of them underwent
work-up examinations. This resulted in a detection rate of 0.16% (mucosal
cancer, 0.07%; invasive cancer, 0.09%). Among first-time subjects (417,352),
the cancer detection rate using only the two-day FIT procedure was 0.32%
(mucosal cancer, 0.14%; invasive cancer, 0.17%). The CRC detection rate was
significantly higher in males than in females and the rates increased with age in
both genders. Moreover, the detection rates were significantly higher in males
that were 50 years of age or older. Adverse events included 15 cases of ischemic
United European Gastroenterology Journal 4(5S) A81

Table (OP202)

Colonoscopy
Screen-detected cancer FIT interval cancer interval cancer CRC in non-participants p-value

Total CRCs 116 27 13 109

Age diagnosis (%(n))50– 24.1 (28) 43.1 (50) 32.8 (38) 22.2 (6) 40.7 (11) 37 (10) 7.7 (1) 61.5 (8) 30.8 (4) 19.3 (21) 45 (49) 35.8 (39) p ¼ 0.803
5960–69–470
Sex (male;%(n)) 62.9 (73) 59.3 (16) 53.8 (7) 63.3 (69) p ¼ 0.904
SES (%(n))–Low–Average– 11.2 (13) 70.7 (82) 18.1 (21) 7.4 (2) 77.8 (21) 14.8 (4) 15.4 (2) 76.9 (10) 7.7 (1) — p ¼ 0.814
High
Tumor location (%(n))– 29.3 (34) 70.7 (82) 0 (0) 37 (10) 63 (17) 0 (0) 69.2 (9) 23.1 (3) 7.7 (1) 34.9 (38) 61.5 (67) 3.6 (4) p ¼ 0.010
Proximal–Distal–
Unknown
Stage–I–II–III–IV–Missing 51.7 (60) 13.8 (16) 31.9 (37) 29.6 (8) 22.2 (6) 33.4 (9) 14.8 38.5(5) 7.7(1) 7.7(1) 38.5(5) 15.6 (17) 28.5 (31) 33.0 (36) p 5 0.001
2.6 (3) 0 (0) (4) 0 (0) 7.7(1) 21.1 (23) 1.8 (2)
Survival (% (n)) 88 (102) 81.5 (22) 61.5 (8) 59.6 (65) p 5 0.001

OP201 CHANGES IN HEALTH BEHAVIOUR ONE-YEAR AFTER programs based on guaiac fecal occult blood testing are available in literature,
TESTING NEGATIVE AT COLORECTAL CANCER SCREENING – A few data exist on cancers in FIT-screening programs.
RANDOMIZED CONTROLLED STUDY Aims & Methods: The aim of our study was to compare patient demographics,
M. D. Knudsen1, A. Hjartåker2, G. Hoff3, T. De Lange4, T. Bernklev5, tumor site, stage and survival between patients with screen-detected CRCs (SD-
P. Berstad1 CRC) and non-screen-detected CRCs (non-SD-CRC). Between 2006 and 2014,
1
Department Of Bowel Cancer Screening, Cancer Registry of Norway, Oslo/ asymptomatic persons aged 50 to 74 were invited to take part in four consecutive
Norway biennial FIT-screening rounds. CRC cases were identified through linkage with
2
Department Of Nutrition, Institute Of Basic Medical Sciences, University of Oslo, the Netherlands Cancer Registry and were classified into four groups: SD-CRC,
Oslo/Norway FIT interval cancers (diagnosed between screening rounds after negative FIT),
3
Department Of Research And Development, Telemark Hospital, Skien/Norway colonoscopy interval cancers (diagnosed after negative colonoscopy after a posi-
4
Cancer Registry of Norway, Oslo/Norway tive FIT) and CRC in non-participants (the latter three representing non-SD-
5
Research And Development, Vestfold Hospital, Tønsberg/Norway CRC). Information on gender, age, socioeconomic status (SES), tumor site, stage
and survival were collected and compared between patients in the four CRC
Contact E-mail Address: [email protected] groups using Chi-square-test.
Introduction: Nine out of ten participants in colorectal cancer (CRC) screening Result: A total of 27,340 people were invited for FIT-screening, of whom 18,752
have a negative screening test result. It has been hypothesized that getting a (68,6%) participated at least once. Median follow-up time was 46,4 months (IQR
negative screening test result may reduce incentives to strive for a healthy 18.5–72.4). Among participants, 3,009 (16%) had a positive FIT in one of the 4
lifestyle. screening rounds. In total, 265 patients were diagnosed with CRC: 116 were SD-
Aims & Methods: The aim of the present study was to investigate potential CRCs, 27 FIT interval CRCs, 13 colonoscopy interval CRCs and 109 CRCs
differences in changes of health behavior at one-year follow-up between detected in non-participants. There were no differences between the groups
screen-negative attendees to two different screening modalities and controls regarding age, gender and SES distribution. Screen-detected CRCs, FIT interval
not invited to screening. Participants of both gender, aged 50–74, were invited cancers and CRCs in non-participants were mostly located in the distal colon
to complete a self-reported lifestyle questionnaire (LSQ) on smoking, body (70.7%, 63%, 61.5% of cases, respectively), whereas colonoscopy interval CRCs
weight, physical activity, alcohol intake and selected dietary items at baseline were mainly located in the proximal colon (69.2%)(p ¼ 0.010). Stage distribution
and at one-year follow-up. Participants were randomly assigned to five biennial was significantly different between the four groups, with more favorable stages in
rounds of fecal immunochemical test (FIT), one round flexible sigmoidoscopy patients with SD-CRCs (p 5 0.001). Stage distribution in patients with FIT
(FS) or no screening (controls). In total, 1809 and 1327 individuals with a nega- interval CRC and CRCs in non-participants was similar (p ¼ 0.361). Survival-
tive screening test result in the FIT and FS group, respectively, completed the rates were significantly higher among patients with SD-CRCs and FIT interval
LSQ, as did 1029 controls. ANCOVA and logistic regression were used to cal- cancers compared to non-participants and patients with colonoscopy interval
culate differences in changes of health behavior (and 95% confidence intervals CRCs.
(CI)) between the arms at follow-up. Conclusion: In this population-based CRC screening cohort, 0.14% of all parti-
Result: Participants with a negative CRC screening test result in the first round of cipants were diagnosed with a FIT interval CRC during follow-up. The patients
the FIT arm reduced their alcohol consumption significantly more than controls with SD-CRCs had the most favorable stages and highest survival rates. Our
(0.29 glass/week, (95%CI; 0.54 to 0.04)) during one-year follow-up. Body results support the effectiveness of FIT-screening programs.
weight decreased more in participant with a negative screening test result in the Disclosure of Interest: All authors have declared no conflicts of interest.
FS arm than in the FIT arm during the one-year follow-up (0.31 kg, (95%CI;
0.55 to 0.08)).
Conclusion: The present study does not suggest unfavorable short-term conse-
quences in health behavior after getting a negative CRC screening test result OP203 THE ADDED BENEFIT OF SURVEILLANCE IN COLORECTAL
whether this is from once only FS or first round of FIT screening. CANCER SCREENING
Disclosure of Interest: All authors have declared no conflicts of interest. M. J.E. Greuter1, E. Dekker2, G.A. Meijer3, V.M.h. Coupé4
1
Epidemiology And Biostatistics, VU University Medical Center, Amsterdam/
Netherlands
2
Gastroenterology & Hepatology, AMC, Amsterdam/Netherlands
OP202 SCREEN-DETECTED AND NON-SCREEN-DETECTED 3
Department Of Pathology, The Netherlands Cancer Institute, Amsterdam/
COLORECTAL CANCERS AFTER FOUR ROUNDS OF FECAL Netherlands
IMMUNOCHEMICAL TEST-BASED COLORECTAL CANCER 4
Epidemiology And Biostatistics, VU Medical Center Epidemiology and
SCREENING Biostatistics, Amsterdam/Netherlands
M. Van Der Vlugt1, E.J. Grobbee2, P.M. Bossuyt3, A. Bos4, I. Lansdorp-
Vogelaar5, M.C.w. Spaander6, E. Dekker7 Contact E-mail Address: [email protected]
1
Dept. Of Gastroenterology, Academisch Medidisch Centrum Gastroenterology & Introduction: Although the impact of colorectal cancer (CRC) screening on CRC
Hepatolog, Amsterdam/Netherlands burden is well studied, the added benefit of surveillance in the context of an
2
Gastroenterology & Hepatology, Erasmus MC University Medical Center, implemented screening programme is unclear.
Rotterdam/Netherlands Aims & Methods: Using the Adenoma and Serrated pathway to Colorectal
3
Clinical Epidemiology, Biostatistics And Bioinformatics, Academic Medical CAncer model, we simulated the Dutch faecal immunochemical test (FIT) -
Centre, Amsterdam/Netherlands based screening programme and combined this with a colonoscopy surveillance
4
Department Of Research, Netherlands Comprehensive Cancer Organisation, strategy based on the Dutch guideline. In this strategy, individuals considered at
Utrecht/Netherlands low risk return to screening after ten years whereas surveillance with a three or
5
Department Of Public Health, Erasmus University Medical Center, Rotterdam, five-year interval is recommended for high- and intermediate-risk individuals,
Rotterdam/Netherlands respectively. Furthermore, we evaluated three strategies in which the surveillance
6
Gastroenterology & Hepatology, Erasmus Medical Center Gastroenterology and intervals as recommended in the Dutch guideline were prolonged to a) five years
Hepatology, Rotterdam/Netherlands for all individuals at increased risk, b) five and ten years for respectively high-
7
Gastroenterology & Hepatology, AMC, Amsterdam/Netherlands and intermediate-risk individuals and c) ten years for all individuals at increased
risk. The comparator strategy was no screening and no surveillance. In addition,
Contact E-mail Address: [email protected] we simulated a screening only strategy without surveillance. Outcomes were CRC
Introduction: Fecal immunochemical test (FIT)-based colorectal cancer (CRC) incidence and mortality, number of colonoscopies per detected CRC, life-years
screening aims to detect CRC in an early stage, thereby reducing morbidity and lived and costs per individual in the lifetime of 20,000,000 individuals.
mortality from this disease. Whereas data on interval CRCs in screening
A82 United European Gastroenterology Journal 4(5S)
Result: FIT screening without a surveillance programme reduced CRC incidence Disclosure of Interest: M. Mandorfer: M.M. received honoraria for consulting
and mortality with respectively 25.4% and 39.0% compared to a no screening from Janssen, payments for lectures from Boehringer Ingelheim, Bristol-Myers
and no surveillance strategy. CRC incidence and mortality reductions increased Squibb, Janssen and Roche, as well as travel support from AbbVie, Gilead, MSD
to 28.1% and 40.8% when surveillance based on the Dutch guideline was added and Roche.
to FIT screening. Prolonging surveillance intervals slightly reduced surveillance K. Kozbial: K.K. received travel support from AbbVie, Bristol-Myers Squibb
effectiveness (incidence reductions 26.6%–27.2%, mortality reductions 39.6%– and Gilead.
40.8% compared to no screening and no surveillance). In screening, 21 diagnostic P. Schwabl: P.S. received payments for lectures from Roche and travel support
colonoscopies were required to detect one CRC. The burden of surveillance was from Janssen and Roche.
considerably higher; in the Dutch guideline strategy, 572 colonoscopies were C. Freissmuth: C.F. received travel support from Gilead and Janssen.
required to detect one CRC by surveillance. Prolonging surveillance intervals R. Stern: R.ST. received travel support from AbbVie.
decreased this burden to 129–366 colonoscopies per surveillance-detected CRC. A.F. Stättermayer: A.F.S. received honoraria for consulting from Gilead, pay-
All screening plus surveillance strategies were equally or more effective (0–0.0011 ments for lectures from Boehringer Ingelheim, Janssen and Roche, as well as
life-years gained) and less costly (E2.45-E8.24) than screening only. The travel support from Gilead, Bristol-Myers Squibb, Janssen and Roche.
strategy in which all surveillance intervals were set at five years dominated all T. Reiberger: T.R. received payments for lectures from Roche, as well as travel
other screening plus surveillance strategies. support from Gilead, MSD and Roche.
Conclusion: Adding surveillance to FIT screening reduces CRC burden and is S. Beinhardt: S.B. received honoraria for consulting from AbbVie, payments for
cost-effective compared to screening without surveillance. However, the colono- lectures from Bristol-Myers Squibb, as well as travel support from Gilead, MSD
scopy burden in surveillance is markedly higher than this burden in a screening and Roche.
programme. Through modelling, we showed that this burden can be substantially M. Trauner: M.T. received grants from MSD, honoraria for consulting from
lowered, without substantial loss of effectiveness, if surveillance intervals are AbbVie, Gilead, Janssen and MSD, payments for lectures from Gilead, MSD
lengthened to five years. and Roche, as well as travel support from Gilead.
Disclosure of Interest: All authors have declared no conflicts of interest. H. Hofer: H.H. received payments for lectures from AbbVie, Gilead, Janssen,
MSD and Roche.
A. Ferlitsch: A.F. received grants from Janssen and payments for lectures from
TUESDAY, OCTOBER 18, 2016 10:30–12:00 Gilead, MSD and Roche.
VIRAL HEPATITIS: NATURAL HISTORY AND TREATMENT – ROOM P. Ferenci: P.F. received grants from Gilead, MSD, and Roche, as well as hon-
M_____________________ oraria for board membership and consulting from AbbVie, Boehringer
Ingelheim, Bristol-Myers Squibb, Gilead, Janssen, Idenix, MSD and Roche.
OP204 SUSTAINED VIROLOGIC RESPONSE TO INTERFERON-FREE M. Peck-Radosavljevic: M.P. received grants from Gilead, MSD and Roche,
THERAPIES AMELIORATES HCV-INDUCED PORTAL honoraria for board membership and consulting from AbbVie, Boehringer
HYPERTENSION Ingelheim, Bristol-Myers Squibb, Gilead, Janssen and MSD, as well as payments
M. Mandorfer, K. Kozbial, P. Schwabl, C. Freissmuth, R. Schwarzer, R. Stern, for lectures from AbbVie, Boehringer Ingelheim.
D. Chromy, A. F. Stättermayer, T. Reiberger, S. Beinhardt, W. Sieghart, All other authors have declared no conflicts of interest.
M. Trauner, H. Hofer, A. Ferlitsch, P. Ferenci, M. Peck-Radosavljevic
Division Of Gastroenterology And Hepatology, Department Of Internal Medicine
Iii, Medical University of Vienna, Vienna/Austria
OP206 RISK OF AND PREDICTORS FOR CLINICAL EVENTS
Contact E-mail Address: [email protected] FOLLOWING VIROLOGICAL RELAPSE IN CHRONIC HEPATITIS
Introduction: Portal pressure, assessed by hepatic venous pressure gradient B PATIENTS AFTER CESSATION OF NUCLEOS(T)IDE ANALOGUE
(HVPG) measurement, drives the development of liver-related complications THERAPY
and mortality in patients advanced chronic liver disease. Since a decrease in Y. Hsu1, C. Wu2, C. Chang3, J. Lin4
HVPG translates into a clinically meaningful benefit, it is an acceptable surrogate 1
Center For Database Research, E-Da Hospital/I-Shou University, Kaohsiung/
endpoint. Taiwan
Aims & Methods: We aimed to investigate the impact of sustained virologic 2
Division Of Gastroenterology, Taichung Veterans General Hospital, Taichung/
response (SVR) to interferon (IFN)-free therapies on portal hypertension in Taiwan
patients with paired HVPG measurements. One hundred and four patients 3
Division Of Gastroenterology And Hepatology, E-Da Hospital, Kaohsiung/
with portal hypertension (HVPG  6 mmHg) who underwent HVPG and transi- Taiwan
ent elastography (TE) before IFN-free therapy (baseline [BL]) were retrospec- 4
School of Medicine, Fu Jen Catholic University, New Taipei City/Taiwan
tively studied. The effect of SVR on portal pressure was investigated in patients
with SVR who also underwent follow-up (FU)-HVPG and TE after IFN-free Contact E-mail Address: [email protected]
therapy (group A; n ¼ 60). To demonstrate the generalizability of our results, we Introduction: Clinical hepatitis may follow virological relapse in chronic hepatitis
included a second group (group B; n ¼ 40), comprising all patients who achieved B (CHB) patients after discontinuing nucleos(t)ide analogue (NAs), but the inci-
SVR, but did not undergo FU-HVPG measurement. In these patients, only dence and risk predictors remained elusive.
information on FU-TE was available. Moreover, we also included 4 patients Aims & Methods: Between July 1, 2011 and July 1, 2015, this multicenter study
who did not achieve SVR. prospectively enrolled 140 consecutive CHB patients with negative HBeAg and
Result: SVR to IFN-free therapies significantly decreased HVPG across all BL- undetectable viral DNA at the cessation of NAs after a minimum of 3 years on
HVPG strata: 6–9 mmHg (BL:7.37  0.28 vs. FU: 5.11  0.38 mmHg; therapy. In those who experienced virological relapse (viral DNA 42,000 IU/
2.26  0.42 mmHg; P 5 0.001), 10–15 mmHg (BL:12.2  0.4 vs. mL), the incidences of clinical relapse (virological relapse plus ALT 480 IU/mL)
FU:8.91  0.62 mmHg; 3.29  0.59 mmHg; P 5 0.001) and  16 mmHg and persistent/severe hepatitis (clinical relapse lasting for 3 months or accompa-
(BL:19.4  0.73 vs. FU:17.1  1.21 mmHg; 2.3  0.89 mmHg; P ¼ 0.018). In nied with jaundice) were estimated by the Kaplan Meier method. Predictors were
the subgroup of patients with BL-HVPG of 6–9 mmHg, portal hypertension explored by the Cox proportional hazard modelling.
resolved in 63%(12/19), while no patient had an increase in HVPG at FU. Result: Following virological relapse that took place in 94 patients, clinical
Among patients with a BL-HVPG of 10–15 mmHg, portal hypertension resolved relapse and persistent/severe hepatitis occurred in 49 and 34 patients, respec-
in 14%(3/21), 29%(6/21) had a FU-HVPG of 6–9 mmHg, while no patient tively. The 2-year cumulative incidences were 61.5% (95% CI, 50.1  73.0%)
showed a progression of portal hypertension at FU. Finally, in the subgroup and 56.2% (95% CI, 42.2  71.2%), respectively. Multivariate-adjusted analyses
of patients with a BL-HVPG  16 mmHg, 5%(1/20) and 35%(7/20) of patients revealed clinical relapse was associated with serum concentration of viral DNA
had a regression to a FU-HVPG of 6–9 mmHg or a FU-HVPG of 10–15 mmHg, (hazard ratio [HR], 1.26 per log/mL; 95% CI, 1.04  1.53) and alanine amino-
respectively. However, portal hypertension did not resolve in any patient and transferase (ALT) at virological relapse (HR, 1.003 per IU/L; 95% CI,
20%(4/20) of patients showed an increase in HVPG at FU. Patients with Child- 1.0  1.004), as well as ALT at NA cessation (HR, 1.008; 95% CI,
Pugh stage B were less likely to have a HVPG-decrease (HR:0.103; 95%CI:0.02– 1.002  1.01), whereas persistent/severe hepatitis was associated with viral
0.514; P ¼ 0.006), when compared to Child-Pugh A patients. In the subgroup of DNA (HR, 1.41; 95% CI, 1.16  1.71), ALT (HR, 1.004; 95% CI,
patients with a BL-HVPG  10 mmHg, the relative change in liver stiffness (per 1.001  1.01), and -fetoprotein (HR, 1.13 per ng/ml; 95% CI, 1.02  1.26) at
%; HR:0.972; 95%CI:0.945–0.999; P ¼ 0.044) was a predictor of a HVPG- virological relapse.
decrease 10%. The area under the receiver operating characteristic curve for Conclusion: Clinical hepatitis frequently occurs following virological relapse in
the diagnosis of FU-HVPG 10 mmHg by FU liver stiffness was CHB patients after NA cessation, and may be predicted by serum viral load,
0.931(95%CI:0.865–0.997). The liver stiffness values at FU for ruling-in and ALT, and -fetoprotein at the viral resurgence.
ruling-out FU-HVPG  10 mmHg were 12.4 (negative predictive value:100%) Disclosure of Interest: All authors have declared no conflicts of interest.
and 25.3 kPa (positive predictive value:94%), respectively. Changes in liver stiff- Reference
ness, platelet count, and liver function tests were comparable between patients
with (group A) and without FU-HVPG measurement (group B), providing an 1. Hsu YC, Mo LR, Chang CY, Wu MS, Kao JH, Wang WL, Yang TH, Wang
argument for the generalizability of our results. Among the 4 patients without CS, Chiang MF, Chen CC, Fang YJ, Hung HW, Wu CY, Lin JT.
SVR, one patient underwent FU-HVPG and TE (HVPG increased from 18 to Association Between Serum Level of Hepatitis B Surface Antigen at End
20 mmHg; liver stiffness increased from 45 to 75 kPa), while 3 patients only of Entecavir Therapy and Risk of Relapse in e Antigen-negative Patients.
underwent FU-TE (16.5 to 14.8 kPa, 72 to 72 kPa and 10.2 to 10.5 kPa). Clin Gastroenterol Hepatol. 2016 Mar 24. pii:S1542–3565(16)00330-X. doi:
Conclusion: SVR to IFN-free therapies ameliorates portal hypertension across all 10.1016/j.cgh.2016.03.024.
BL-HVPG strata. However, amelioration of portal hypertension was less likely in
patients with more advanced liver dysfunction. TE might be useful for the non-
invasive evaluation of portal hypertension after SVR. In contrast, patients who
did not achieve SVR showed either no significant improvement or even worsen-
ing of liver disease.
United European Gastroenterology Journal 4(5S) A83
OP207 COMBINATION THERAPY WITH DACLATASVIR AND 83.9  15.4  103 cell/ul, creatinine 1.3  0.2 mg/dl, AST 77.4  22.4 IU/dl, ALT
ASUNAPREVIR IN CIRRHOTIC AND NON-CIRRHOTIC PATIENTS 66.5  15.2 IU/dl, AFP 29.8  10.8 ug/dl, MELD score 22.6  2, Child Turcotte
WITH HEPATITIS C VIRUS GENOTYPE 1B IN JAPAN Pugh (CTP) score 9  0.9. After six months of therapy; all the patients were
A. Tamori, M. Enomoto, S. Kobayashi-Uchida, H. Hai, Y. Teranishi, compliant, with no reported major complications. Mean platelet count was sig-
H. Motoyama, R. Kozuka, E. Kawamura, A. Hagihara, Y. Murakami, nificantly increased after treatment (88.6  13.9  103 cell/ul, p ¼ 0.000), with
N. Kawada significant improvement in serum albumin (2.7  0.02 gm/dl, p ¼ 0.000), total
Hepatology, Osaka City University Medical School, Osaka, Japan, Osaka/Japan bilirubin (1.4  0.2 mg/dl, p ¼ 0.000), AFP (16.3  0.9 ug/dl, p ¼ 0.000), CTP
score (8.4  0.5, p ¼ 0.002) and MELD score (21.2  1.04, p ¼ 0.000). After treat-
Contact E-mail Address: [email protected] ment a significant reduction in the episodes of HE was noted; only 8/29 still
Introduction: Combination therapy with daclatasvir (DCV; NS5A inhibitor) and experiencing HE (2 4 14.312, p ¼ 0.0002, 1.4  0.2 episodes/2 months). SVR
asunaprevir (ASV; second-generation HCV-NS3/NS4A protease inhibitor) was was achieved in 36 patients (90%). Ascites became completely controlled in 10
approved for patients with HCV genotype 1 in Japan since September 2014. patients (25%) and partially controlled in 23 patients (57.5%) and not changed in
Now, elderly patients and those with advanced hepatic fibrosis including chronic 7 patients (17.5%)
liver cancer were administered IFN-free therapy. Our objective was to assess the Conclusion: Treatment of decompensated cirrhotic patients with a 6-month low
efficacy and tolerability of DCV/ASV combination therapy in patients with dose DAA had led to SVR in 90% with improvement in CTP, MELD scores and
hepatic cirrhosis. a significant reduction in hepatic encephalopathy episodes with better control of
Aims & Methods: In total, 153 consecutive patients with HCV 1 b initiating DCV/ ascites.
ASV therapy were enrolled. The cohort comprised 52 patients with compensated Disclosure of Interest: All authors have declared no conflicts of interest.
cirrhosis and 101 patients without cirrhosis (67 males and 86 females; median References
age, 71 years; 9 patients were 480 years old). NS5A resistance-associated var-
iants (RAV) were examined using direct sequencing. The patients were treated 1. Mohd Hanafiah K, Groeger J, Flaxman AD and Wiersma ST. Global epi-
with 60 mg of DCV once daily and 100 mg of ASV twice per day for 24 weeks. demiology of hepatitis C virus infection: new estimates of age-specific anti-
Clinical, biological, and virological data, including adverse effects, were recorded body to HCV seroprevalence. Hepatology 2013; 57(4): 1333–42.
at baseline and during follow-up. 2. Shiratori Y, Imazeki F, Moriyama M, Yano M, Arakawa Y, Yokosuka O,
Result: Only 10 (6.5%) patients had L31M or Y93H RAVs. There was no sta- et al. Histologic improvement of fibrosis in patients with hepatitis C who
tistically significant difference in age, sex, IL28B genotypes, HCV viral load at have sustained response to interferon therapy. Ann Intern Med 2000; 132(7):
baseline, ALT level, creatinine level, or NS5A RAVs between patients with and 517–24.
without cirrhosis. On the other hand, those with cirrhosis showed significantly 3. Roberts S, Gordon A, McLean C, Pedersen J, Bowden S, Thomson K, et al.
lower levels of platelets, white blood cells, and hemoglobin and higher levels of Effect of sustained viral response on hepatic venous pressure gradient in
alpha fetoprotein. The rapid viral response rate (HCV-RNA 5 25 IU/ml at week hepatitis C-related cirrhosis. Clin Gastroenterol Hepatol 2007; 5(8): 932–7.
4) was the same between patients with and without cirrhosis (80% and 84%, 4. Flamm SL, Everson GT, Charlton M, Denning JM, Arterburn S and
respectively). One of 52 patients with cirrhosis, and two of 101 patients without Brandt-Sarif T. Ledipasvir/sofosbuvir with ribavirin for the treatment of
cirrhosis who did not have NS5A RAVs at baseline developed viral break- HCV in patients with decompensated cirrhosis: preliminary results of a pro-
through. The rate of SVR12 was 94% (49/52) in patients with cirrhosis and spective, multicenter study. Hepatology 2014; 60(Suppl1S320A).
97% (96/99) in patients without cirrhosis. Grade 3/4 complications frequently
occurred in 21% of patients with cirrhosis (p ¼ 0.04), of whom two had an
elevated ALT level, two progressed to decompensated cirrhosis without ALT
elevation, one developed interstitial pneumonia, one had severe bronchitis, one OP209 INTERFERON-FREE DAA TREATMENS DECREASE PORTAL
had arterial fibrillation, two had gastrointestinal bleeding, and two developed PRESSURE AND HALT HISTOLOGICAL NECROINFLAMMATION
edema. Of the patients without cirrhosis (9%), ALT elevation was observed in IN HIV/HCV - COINFECTED PATIENTS WITH PORTAL
five patients, coagulation abnormality developed in two patients, gastrointestinal HYPERTENSION
bleeding occurred in one, and high fever occurred in one patient. After DCV/ P. Schwabl1, M. Mandorfer1, S. Steiner1, B. Scheiner1, T. Bucsics1,
ASV therapy, HCC developed in two cirrhotic patients, and one non-cirrhotic K. Grabmeier-Pfistershammer2, M. Aichelburg2, W. Sieghart1, A. Ferlitsch1,
patient. M. Trauner1, M. Peck-Radosavljevic1, T. Reiberger1
Conclusion: DCV/ASV therapy achieved a high anti-HCV effect in patients both 1
Div. Of Gastroenterology And Hepatology; Department Of Internal Medicine Iii,
with and without cirrhosis. However, careful management is necessary in patients Medical University of Vienna, Vienna/Austria
with cirrhosis. 2
Div. Of Immunology, Allergy And Infectious Diseases, Department Of
Disclosure of Interest: A. Tamori: I have received research funding from Chugai Dermatology, Medical University of Vienna, Vienna/Austria
Pharmaceutical Co., Ltd., MSD K.K., and Bristol-Myers Squibb.
N. Kawada: Dr. Norifumi Kawada has received research funding from MSD Contact E-mail Address: [email protected]
K.K., Chugai Pharmaceutical Co., Ltd. Bristol-Myers Squibb, and a lecturer’s Introduction: Patients with HIV/HCV confection show increased fibrosis progres-
fee from Janssen Pharmaceutical K.K. sion and are at risk for complications of portal hypertension (PHT). We mea-
All other authors have declared no conflicts of interest. sured changes in liver stiffness and portal pressure and evaluated liver histology
after successful interferon (IFN)-free DAA therapy.
Aims & Methods: HIV/HCV patients undergoing IFN-free DAA treatment and
had paired hepatic venous pressure gradient (HVPG) and liver stiffness (LS)
OP208 EXPERIENCE IN THE MANAGEMENT OF DECOMPENSATED measurements at baseline and three months after end of treatment (SVR12)
HCV CIRRHOTIC PATIENTS WITH LOW DOSE SOFOSBUVIR AND were included. LS and HVPG were measured in a fasted, non-sedated state.
RIBAVIRIN COMBINED WITH DACLATASVIR Concomitant beta-blocker treatment was stopped for all measurements. Post-
A. S. Hanafy treatment liver biopsies were assessed by METAVIR score.
Internal Medicine, Zagazig University, Zagazig/Egypt Result: Of 19 patients (56% male, age: 53.4  6.7 years, 95% concomitant anti-
retroviral therapy), 16 received SOF/DCV, 2 SOF/ RBV, and 1 SOF/LDV. Seven
Contact E-mail Address: [email protected] (37%) patients were treatment experienced and HCV genotype (GT) distribution
Introduction: With the introduction of oral direct-acting antiviral (DAA) therapy was: GT-1a: 12, GT-1b: 2 and GT-3a: 5. All patients had portal hypertension
in the management of chronic active HCV, sustained response rates occurred in (HVPG 4 5 mmHg) and 14 patients (74%) presented with liver cirrhosis
more than 95% of patients with compensated liver disease with improvement in (LS 4 12 kPa). DAA treatment resulted in 100% SVR12. LS decreased signifi-
their survival and the risk of decompensation that necessitates liver transplanta- cantly from 23.0  16.5 to 16.9  16.1 kPa (mean change (
): 6.1  5.2 kPa;
tion. The postulated explanation of reduced rates of sustained virological p 5 0.001). Also, HVPG decreased from 10.4  4.0 to 7.6  4.3 mmHg (
:
response in decompensated cirrhosis was explained by extensive portosystemic 2.8  2.4 mmHg; p 5 0.001). In patients with clinically significant portal hyper-
collaterals, advanced fibrotic parenchyma which are difficult to be penetrated, tension (HVPG  10 mmHg, n ¼ 9), HVPG decreased from 13.8  3.0 to
and provide dormant foci for viral reactivation. It was claimed that achieving 10.9  3.8 mmHg (
: 2.9  2.8 mmHg; p ¼ 0.015) – resulting in a hemodynamic
SVR will improve MELD and CPT scores with improvement in clinically sig- response of 10% in 6/9 (66%) patients. In the subgroup of patients with base-
nificant portal hypertension and hepatic venous pressure gradient. line HVPG 5 10 mmHg (n ¼ 10), a reduction from 7.3  1.3 to 4.6  1.8 mmHg
Aims & Methods: Evaluation of the efficacy and safety of managing chronic (
: 2.7  2.2 mmHg; p ¼ 0.003) was noted – resulting in cure of PHT
active HCV in patients with decompensated cirrhosis and if SVR will improve (55 mmHg) in 6/10 (60%). Posttreatment liver biopsies were available in 15
CTP, MELD scores and quality of life of these patients Forty patients with patients, of which the majority (66%) did not show any hepatic necroinflamma-
decompensated cirrhosis with frequent hepatic encephalopathy or difficult to tory activity (METAVIR A0). 8 of 14 (57%) patients with cirrhosis at baseline,
treat ascites were included if they had chronic active HCV proved by the posi- presented a post-treatment histological METAVIR F3. Serum transaminases
tivity of HCV RNA, elevated transaminases. Patients were excluded if they had were normalized after therapy (AST: 66  34 vs. 33  20, p 5 0.001; ALT:
hepatocellular carcinoma, other causes of liver diseases or mixed causes (exces- 60  37 vs. 24  15, p 5 0.001), while hemoglobin, WBC and CD4 cell counts
sive alcohol consumption, autoimmune liver disease), previous liver transplanta- remained stable.
tion. The patients were given sofosbuvir 200 mg, ribavirin 200 mg, and Conclusion: Virological response to IFN-free DAA therapies decreases LS and
daclatasvir 60 mg for 6 months and evaluated for the development of sustained ameliorates portal hypertension. SVR12 seems to abolish histological necroin-
virological response (SVR), the occurrence of complications and the effects of flammatory activity in most HIV/HCV coinfected patients. It remains to be
SVR on the rate of development of hepatic encephalopathy, improvement in explored if these improvements result in decreased liver-related mortality in the
ascites control. setting of HIV/HCV coinfection.
Result: Forty patients (31 males, 9 females) presented with chronic active HCV Disclosure of Interest: P. Schwabl: received payments for lectures from Roche and
were enrolled, all showed difficult to treat cirrhotic ascites. 29 patients showed Böhringer Ingelheim, and travel support from AbbVie, Gilead, Janssen, and
chronic recurrent episodes of hepatic encephalopathy (62.5%, 2.1  0.6 episodes/ Roche
2 months). The mean age was 51.4  6.3 years, albumin 2.3  0.4 gm/dl, total
bilirubin 1.9  0.5 mg/dl, Hemoglobin 9.9  0.9 gm/dl, platelet count
A84 United European Gastroenterology Journal 4(5S)
M. Mandorfer: received honoraria for consulting from Janssen, payments for OP211 DIAGNOSTIC CHARACTERISTICS OF DEPRESSED TYPE
lectures from Boehringer Ingelheim, Bristol- Myers Squibb, Janssen, and Roche, COLORECTAL NEOPLASMS IN MAGNIFYING ENDOSCOPY AND
as well as travel support from AbbVie, Gilead, MSD, and Roche ENDOCYTOSCOPY
B. Scheiner: received travel support from Gilead. S. Kudo1, K. Igarashi1, S. Matsudaira2, Y. Kouyama3, K. Ichimasa2, Y. Mori2,
T. Bucsics: received payments for lectures from Roche and travel support from M. Misawa4, T. Kudo2, T. Hisayuki5, T. Hayashi2, K. Wakamura2, H. Miyachi2,
Bristol-Myers Squibb A. Katagiri2, T. Baba2, F. Ishida2
K. Grabmeier-Pfistershammer: received honoraria for consulting from Gilead, 1
Digestive Disease Center, Showa University Northern Yokohama Hospital,
payments for lectures from Bristol-Myers Squibb and ViiV, as well as travel Yokohama/Japan
support from Bristol-Myers Squibb, Gilead, and GlaxoSmithKline 2
Digestive Disease Center, Showa University Northern Yokohama Hospital
A. Ferlitsch: reveived travel support from AbbVie and Gilead Digestive Disease Center, Yokohama/Japan
M. Trauner: received grants from MSD, honoraria for consulting from AbbVie, 3
Northern Yokohama Hospital, Showa University Northern Yokohama Hospital,
Gilead, Janssen, and MSD, payments for lectures from Gilead, MSD, and Yokohama/Japan,4Northern Yokohama Hospital, Showa University Northern
Roche, as well as travel support from Gilead Yokohama Hospital Digestive Disease Center, Yokohama/Japan
M. Peck-Radosavljevic: received grants from Gilead, MSD, and Roche, honor- 5
Showa University Northern Yokohama Hospital Digestive Disease Center,
aria from AbbVie, Boehringer Ingelheim, Bristol-Myers Squibb, Gilead, Janssen, Yokohama/Japan
and MSD, and payments for lectures from AbbVie, Boehringer Ingelheim,
Bristol-Myers Squibb, Gilead, Janssen, MSD, and Roche Contact E-mail Address: [email protected]
T. Reiberger: received payments for lectures from Roche, as well as travel sup- Introduction: Colorectal cancers are generally recognized to develop from‘‘po-
port from Gilead, MSD, and Roche. lyps’’. This ‘‘adenoma-carcinoma sequence’’ theory has been in the mainstream
All other authors have declared no conflicts of interest. of development of colorectal cancers. But recently the existence of many
depressed-type cancers has been revealed, which are considered to emerge
directly from normal epithelium, not through the adenomatous stage. This
TUESDAY, OCTOBER 18, 2016 10:30–12:00 theory is called ‘‘de novo’’ pathway. Now, it is possible to presume the histology
IMPROVING DETECTION AND TREATMENT OF COLONIC POLYPS – ROOM of colorectal lesions using magnifying endoscopy (pit pattern classification) and
N2_____________________ endocytoscopy (EC).We can observe not only the structural atypia but also the
cellular atypia in living colorectal lesions. The aim is to clarify the diagnostic
OP210 RANDOMIZED, BACK-TO-BACK TRIAL OF NEW GENERATION characteristics of depressed-type colorectal neoplasms, demonstrating the valid-
OF NBI (HQ 290) FOR THE DETECTION OF COLORECTAL POLYPS ity of pit pattern diagnosis and EC classification.
H.J. Goong1, B.M. Ko2, S.R. Jeon1, H.G. Kim1, S.J. Hong1, J. Kim1, M.S. Lee1 Aims & Methods: A total of 27599 colorectal neoplasms excluding advanced
1
Digestive Disease Centerand Research Institute, Department Of Internal cancers were resected endoscopically or surgically in our unit from April 2001
Medicine, SoonChunHyang University School of Medicine, Bucheon and Seoul, to December 2015. Of these, 16075 lesions were low-grade dysplasia, 5241 were
Korea, Bucheon and Seoul/Korea, Republic of high-grade dysplasia and 1097 were submucosally invasive (T1) carcinomas.
2
Department Of Internal Medicine, SoonChunHyang University School of According to the developmental morphology classification, they were divided
Medicine, Bucheon/Korea, Republic of into 3 types: depressed, flat and protruded type. We investigated the rate of T1
carcinomas and the characteristics of depressed-type neoplasms concerning pit
Contact E-mail Address: [email protected] pattern and EC classification.
Introduction: The benefits of narrow band imaging (NBI) for improving the Result: The rate of T1 carcinomas in depressed-type lesions reached to 62.1%,
detection of colorectal polyps remain questionable. The newly available second meanwhile that in flat-type and protruded-type lesions was 3.3% and 2.8%,
generation of NBI using 290 system (290-NBI) privides an at least two folds respectively. Within less than 5 mm in diameter, that was 10.6%, 0% and 0%,
brighter image compared with the previous version. respectively. Most (90.1% and 91.5%) of the flat-type and protruded-type lesions
Aims & Methods: The aim of this study was to compare polyp miss rates between showed type IIIL or IV pit pattern corresponding to adenomas, whereas 94.6% of
290-NBI and high-resolution white light endoscopy (HR-WLE). Methods: From the depressed-type lesions were characterized by type IIIS, VI or VN pit pattern
June 2015 to September 2015, 102 patients were randomized to undergo either corresponding to carcinomas. As for endocytoscopy, most of the flat-and pro-
HD-WLE or 290-NBI colonoscopy. In HD-WLE group, we performed colono- truded-type lesions showed EC2 corresponding to adenomas. In contrast, the
scopic examination as first inspection with HR-WLE followed by a second depressed-type lesions were observed as EC3a (38.9%) and EC3b (58.0%) cor-
inspection with NBI. In 290-NBI group, colonoscopic examination were per- responding to invasive carcinomas.
formed first inspection with NBI followed by a second inspection with HR- Conclusion: This study revealed the diagnostic characteristics of depressed-type
WLE. The primary outcomes were polyp miss rates. lesions. They show typically type IIIS,VI or VN pit patterns in magnifying endo-
Result: A total of 127 polyps of 102 patients were detected. In HD-WLE group, scopy and type EC3a or EC3b in endocytoscopy. These lesions tend to invade the
39 polyps were detected during the first inspection. A second inspection with NBI submucosal layer even when they are small. Therefore, it is important to consider
added 20 polyps, resulting in polyp miss rate of 33.9% with HR-WLE. In the deeply and examine the developmental morphology of colorectal neoplasms.
NBI group, 54 polyps were detected during the first inspection. Subsequent Disclosure of Interest: All authors have declared no conflicts of interest.
inspection with HR-WLE added 14 polyps, resulting in polyp miss rate of NBI
of 20.6% (33.9% vs 20.6%, p ¼ 0.068). In subgroup analysis, the polyp miss rates
of flat type of HR-WLE and NBI showed significant difference (18.6% vs. 5.9%,
p ¼ 0.029). OP212 ASSOCIATION OF CHROMOSOMAL INSTABILITY AND
Conclusion: New generation of NBI (HQ290) may reduce polyp miss rates and be MICROSATELLITE INSTABILITY PATHWAYS WITH
more effective in reducing polyp miss rates of flat type. POSTCOLONOSCOPY COLORECTAL CANCER IN A
Disclosure of Interest: All authors have declared no conflicts of interest. RETROSPECTIVE COHORT STUDY
References R.M. m. Bogie1, C. M. c. Le Clercq1, Q.J. m. Voorham2, M. Cordes3, D. Sie3, E.
Van Den Broek2, S. D. j. De Vries3, N. C. t. Van Grieken3, B. Ylstra3, R.
1. Narrow-band imaging international colorectal endoscopic classification to
G. Riedl4, M. Van Engeland4, G.A. Meijer2, A. A. m. Masclee1, B. Carvalho2,
predict polyp histology: REDEFINE (with videos). Gastrointest Endosc.
S. Sanduleanu5
2016:S0016–5107. 1
Division Of Gastroenterology And Hepatology, Maastricht University Medical
2. Real-time characterization of diminutive colorectal polyp histology using
Center, Maastricht/Netherlands
narrow-band imaging: implications for the resect and discard strategy. 2
Department Of Pathology, The Netherlands Cancer Institute, Amsterdam/
Gastroenterology. 2016;150:406–18.
Netherlands
3. Narrow-band imaging in the prediction of surveillance intervals after poly- 3
Department Of Pathology, VU Medical Center Amsterdam, Amsterdam/
pectomy in community practice. Endoscopy. 2015;47:808–14.
Netherlands
4. Narrow-band imaging versus white light for the detection of proximal colon 4
Department Of Pathology, Maastricht University Medical Center, Maastricht/
serrated lesions: a randomized, controlled trial. Gastointest endosc.
Netherlands
2016;83:166–71. 5
Grow, School For Oncology And Developmental Biology, Maastricht University
5. Investigating endoscopic features of sessile serrated adenomas/polyps by
Medical Centerþ, Maastricht/Netherlands
using narrow-band imaging with optical magnification. Gastrointest endosc.
2015;82:108–17. Contact E-mail Address: [email protected]
6. Real-time optical diagnosis for diminutive colorectal polyps using narrow- Introduction: Over 50% of the postcolonoscopy colorectal cancers (PCCRCs)
band imaging: the VALID randomised clinical trial. Gut. 2015;64:1569–77. (i.e. CRC diagnosed after a colonoscopy that excluded cancer) originate from
7. Accuracy of in vivo colorectal polyp discrimination by using dual-focus high missed precursor lesions, in particular the subtle appearing non-polypoid (flat
definition narrow-band imaging colonoscopy. Gastrointest endosc. and depressed) adenomas and sessile serrated lesions. The biologic pathway of
2014;80:1072–87. these lesions is unclear. We hypothesized that PCCRCs and subtle appearing
8. Detection of colorectal adenoma by narrow band imaging (HQ190) vs. high- precursors may share molecular features. In a retrospective, cohort study, we
definition white light colonoscopy: a randomized controlled trial. Am J examined the occurrence of chromosomal instability (CIN), microsatellite
Gastroenterol. 2014;109:855–63. instability (MSI), and CpG island methylator phenotype (CIMP) in PCCRCs
and prevalent CRCs.
Aims & Methods: We identified all PCCRCs diagnosed from 2001 to 2010 in a
large gastroenterology practice from the Netherlands (le Clercq et al, Gut 2014).
PCCRCs were defined as cancers occurring within 5 years after a complete index
colonoscopy, which excluded CRC. We applied a clinical algorithm to assign the
most likely explanation of PCCRC (incomplete colonoscopy/ insufficient bowel
preparation, missed lesion, incompletely resected lesion or new cancer). PCCRCs
attributable to technical factors (insufficient bowel preparation/ incomplete
United European Gastroenterology Journal 4(5S) A85

Table 1. (OP213)

Point of
ASA Insertion Procedure Deepest Final
Subject # Age Sex Indication(s) BMI Grade Time (min) Time (min) Insertion Complications Diagnosis

1 24 M Abdominal pain; video 40 III 33 41 Distal Jejunum None None

capsule findings of
ulcerated mucosa in mid
small bowel
2 22 M CT scan finding of 21 II 32 43 Cecum None None
intussusception
3 61 F Gastrointestinal bleeding; 27 III 61 94 Cecum None None
video capsule finding of
angioectasia
4 58 F Iron deficiency anemia; 23 II 47 70 Distal Ileum None None
video capsule finding of
angioectasia
5 67 F Iron deficiency anemia 23 II 48 66 Cecum None None
6 33 M Gastrintestinal bleeding 28 III 59 78 Cecum Bleeding Meckel’s diverticulum
7 29 M Suspected crohn’s; video 28 II 49 72 Cecum None Crohn’s
capsule findings of a
bleeding angioectasia
and a small bowel polyp

colonoscopy or incomplete resection) were excluded. We reviewed clinical and endotracheal anesthesia, the motorized spiral enteroscope (SIF-Y0019,
pathological records. Whole-genome DNA copy number changes and mutation Olympus, Japan) is inserted through the mouth. The rotational advancement
status of genes commonly affected in CRC (APC, KRAS, BRAF, FBXW7, and withdrawal is controlled by the endoscopist using a foot pedal. The primary
PIK3CA, NRAS, SMAD4 and TP53) were examined by shallow whole- outcome of the study was the depth of insertion of the enteroscope.
genome sequencing and targeted sequencing, respectively, using Illumina next Result: Demographics of the study patients are summarized in Table 1. Of the
generation sequencing platforms. MSI and CIMP status were examined using first 7 completed procedures, we were able to accomplish complete enteroscopy
the pentaplex marker panel from Promega and the Weisenberger CIMP panel in 5 (71%) patients. In the other two instances, the distal jejunum and distal
using methylation-specific PCR, respectively. ileum were reached. The average insertion time was 47 minutes [range: 32–61]
Result: In total, 120 PCCRCs and 100 prevalent CRCs were examined. with an average total procedure time of 66 minutes [range: 41–94]. A bleeding
Regarding clinicopathological features, PCCRCs are more often located proxi- event requiring hospitalization occurred within 7 days of one of the procedures
mally in the colon (p 5 0.001), non-polypoid appearing (p ¼ 0.001), early stage but that was due to the underlying lesion rather than a complication of the
tumors (p ¼ 0.008), and poorly differentiated (p ¼ 0.001) compared to prevalent procedure. No other significant adverse events were reported.
CRCs. Regarding DNA copy number alterations, PCCRCs contain less often Conclusion: We present our initial experience of a safety and efficacy data trial for
17p (p ¼ 0.002) and 18q (p ¼ 0.003) deletions than prevalent CRCs. Furthermore, the motorized spiral enteroscope. We were able to safely accomplish full entero-
PCCRCs contain less frequently APC (p ¼ 0.04), NRAS (p ¼ 0.03), and TP53 scopy in 71% of cases with a single antegrade deep enteroscopy using the motor-
mutations (p ¼ 0.03) than prevalent CRCs. In contrast, MSI (p ¼ 0.004), CIMP ized spiral enteroscope. This percent achievement of complete enteroscopy in a
(p ¼ 0.02) and BRAF mutations (p ¼ 0.04) are more frequent in PCCRCs than time typically reported for unidirectional deep enteroscopy suggests that this
prevalent CRCs. device is a significant development in design of small bowel enteroscopes. One
Conclusion: Both CIN and MSI pathways are associated with the occurrence of patient experienced bleeding requiring hospitalization within 7 days of the pro-
PCCRC. PCCRCs contain less often deletions of chromosomes 17p and 18q, cedure. This was a significant adverse event (SAE) by protocol. However on
APC, NRAS and TP53 mutations and more often MSI, CIMP and BRAF further review it was determined that the patient bled from a Meckel’s diverti-
mutations than prevalent cancers. Such molecular profiles are similar to those culum, identified during deep enteroscopy. Subsequent surgery was curative.
previously described in non-polypoid (flat and depressed) adenomas and sessile Disclosure of Interest: K. Bhattacharya: Consulting for Olympus
serrated lesions. Taken together, our results support the hypothesis that non- D. Cave: Consulting and receipt of research funds from Olympus. Consulting for
polypoid adenomas and sessile serrated lesions are in the origin of PCCRCs. Medtronics.
Disclosure of Interest: S. Sanduleanu: Consultancy: Pentax Medical Systems D. Demarco: Consulting for Spirus
Europe All other authors have declared no conflicts of interest.
All other authors have declared no conflicts of interest.
Reference
1. le Clercq CM, Bouwens MW, Rondagh EJ, Bakker CM, Keulen ET, de OP214 THE AER-O-SCOPE COLONOSCOPE PROVIDES SUCCESSFUL
Ridder RJ, Winkens B, Masclee AA and Sanduleanu S. Postcolonoscopy ENDOSCOPIC THERAPY IN AN EX VIVO SWINE COLON MODEL
colorectal cancers are preventable: a population-based study. Gut 2014 Jun;
S. Bezobchuk, I.M. Gralnek
63(6): 957–63. PubMed PMID: 23744612.
Institute Of Gastroenterology, Ha’Emek Medical Center, Afula/Israel
Contact E-mail Address: [email protected]
Introduction: The Aer-O-Scope Colonoscope System (GI View Ltd., Ramat Gan,
OP213 MOTORIZED SPIRAL ENTEROSCOPY: A NEW TECHNIQUE Israel) is a self-propelled, joystick controlled, disposable colonoscope that pro-
FOR ONE-STAGE COMPLETE ENTEROSCOPY vides panoramic (360 ) endoscopic visualization of the colon and includes two
E. Belkin1, K. Bhattacharya1, E. Odstrcil2, D. Cave3, P. V. Draganov4, working channels compatible with standard endoscopic tools [1,2].
D. Demarco2 Aims & Methods: We aimed to demonstrate the success of the self-propelled Aer-
1
Gastroenterology, University of Massachusetts Medical School, Worcester/United O-Scope colonoscope in providing endoscopic therapeutic access. Therapeutic
States of America/MA endoscopic access was a priori defined as the ability to reach a pre-defined
2
Gastroenterology, Baylor University Medical Center, Dallas/United States of target of interest, a pseudo-polyp, within an ex vivo swine colon and deliver
America/TX "simulated" endoscopic therapy including: polypectomy with snare or biopsy
3
Medicine-gastroenterology, University of Massachusetts Medical School, forceps, submucosal injection, or thermal coagulation using argon plasma coa-
Worcester/United States of America/MA,4Division Of Gastroenterology And gulation (APC). This was a prospective cohort study (n ¼ 12 ex vivo swine colons
Hepatology, University of Florida, College of Medicine, Gainesville/United States each housed in four different models that simulated variants of a human colon).
of America/FL Varying sized pseudo-polyps (n ¼ 8 in each ex vivo swine colon) were created
using colored thread and were randomly distributed throughout each ex vivo
Contact E-mail Address: [email protected] swine colon. Thus, n ¼ 96 pseudopolyps in total were created: 1 mm–5mm
Introduction: Three different platforms have been developed to perform deep (n ¼ 77, 80%); 6 mm–9mm (n ¼ 13, 14%); 10 mm (n ¼ 6, 6%). Following one
enteroscopy; namely, single balloon, double balloon, and spiral enteroscopy. day of Aer-O-Scope training for joystick utilization and endoscopic therapeutic
None of these devices permits routine evaluation of the entire small intestine, access, two endoscopists (IMG and SB) performed all the colonoscopies (n ¼ 12
even with a combination of antegrade and retrograde enteroscopy. We report our colonoscopies per each endoscopist) on three separate procedure dates, in
early clinical experience with a motorized spiral enteroscope, which may provide random order, and blinded to the type of colon model. The study’s primary
a modality for one-stage complete enteroscopy. endpoint was a success rate of at least 90% in providing simulated endoscopic
Aims & Methods: We report early experience with a prospective multi-center therapy and the study’s secondary endpoint was endoscopist-perceived usability
efficacy and safety trial. The study was approved by the institutional review of the Aer-O-Scope for endoscopic therapy. We planned on performing a total of
boards of each of the participating centers. Patients referred for evaluation of 240 simulated endoscopic therapies (n ¼ 192 biopsy forceps, snare polypectomy,
small bowel disease at one of the three participating centers requiring antegrade or combination injection/snare polypectomy and n ¼ 48 APC applications). This
enteroscopy were offered participation in the study, and then screened for exclu- sample size allowed up to a 10% pseudo-polyp miss rate with a two-sided
sion criteria. If enrolled, informed consent was obtained. Under general
A86 United European Gastroenterology Journal 4(5S)
statistical precision of 5%. This study protocol was reviewed and approved by an TUESDAY, OCTOBER 18, 2016 10:30–12:00
animal ethics committee. BARRET’S ASSOCIATED NEOPLASIA – ROOM L7_____________________
Result: There were 5 (5.2%) pseudo-polyps dislodged, thus 235 simulated endo-
scopic therapies were able to be attempted. The success rate of the Aer-O-Scope OP216 DEVELOPMENT AND VALIDATION OF A CLASSIFICATION
colonoscope simulated endoscopic therapy was: 234/235 ¼ 99.6% (95%CI 0.976– SYSTEM TO IDENTIFY BARRETT’S NEOPLASIA USING ACETIC
1.00). The overall success rate was 234/240 97.6% (p 5 0.001). The below Table ACID CHROMOENDOSCOPY: THE PREDICT CLASSIFICATION
shows the number of successful simulated endoscopic therapies per endoscopic K. Kandiah1, F.J. q., J. Chedgy2, G. Longcroft-Wheaton3, O. Pech4, P. Bhandari1
tool. All endoscopic tools had a success rate 495%. There were only 2 failures, 1
Gastroenterology, Queen Alexandra Hospital, Portsmouth/United Kingdom
both during use of a polypectomy snare. Endoscopist-rated subjective usability of 2
Endoscopy, Queen Alexandra Hospital, Portsmouth/United Kingdom
the Aer-O-Scope for simulated endoscopic therapy (easy to perform or only 3
Gastroenterology, Portsmouth Hospitals NHS trust, Hampshire/United Kingdom
slightly complicated to perform) was very high (98%–100%) for all endoscopic 4
Klinik Für Gastroenterologie Und, Krankenhaus Barmherzige Brüder Klinik für
tools. Gastroenterologie und Interventionelle Endoskopie, Regensburg/Germany

Endoscopic Tool n Therapeutic Successes 95%CI Contact E-mail Address: [email protected]

Introduction: Neoplasia in Barrett’s can be very subtle and difficult to identify.
Snare 140 138 (98.6%) 0.95–1.00 Acetic acid chromoendoscopy (AAC) has been demonstrated to highlight neo-
plastic areas allowing for earlier treatment. Although the technique of AAC is
Biopsy Forceps 47 47 (100%) 0.92–1.00 very simple, lesion recognition with acetic acid (AA) remains a challenge and
Injection Needle 60 60 (100%) 0.94–1.00 therefore hampering its widespread usage.
APC 48 48 (100%) 0.93–1.00 Aims & Methods: We aim to develop a simple and easy to use classification
system for AAC to allow easy identification of Barrett’s neoplasia. Three
Conclusion: In an ex vivo swine colon model, the Aer-O-Scope Colonoscope expert AAC endoscopists (PB, GLW, OP) formed a working group to identify
System demonstrated the ability to easily provide simulated endoscopic thera- AAC component criteria of non-dysplastic and dysplastic Barrett’s using a mod-
peutic access using standard endoscopic tools while having very high usability ified Delphi Method. Following this, a panel of 7 advanced endoscopists assessed
ratings. the performance of each individual criterion by reviewing a bespoke online data-
Disclosure of Interest: S. Bezobchuk: I am a consultant for GI View Ltd. base of 40 images and 40 videos of non-dysplastic and dysplastic Barrett’s
I.M. Gralnek: I am a consultant for GI View Ltd. lesions. Finally, we assessed the diagnostic reproducibility of the validated cri-
References teria by asking 13 non-AAC expert endoscopists to complete an assessment tool
of 40 images and 20 videos using this newly developed classification system.
1. Gluck N et al. Endoscopy Intl Open 2015. Result: The component criteria identified by the expert AAC endoscopists were
2. Gluck N et al. Gastrointest Endosc 2015. as follows: - Early focal loss of acetowhitening - Present: Indicates presence of
neoplasia - Absent: Indicates the absence of neoplasia - Surface pattern - Normal
(Large uniformly distributed pits): Indicates non-neoplastic Barrett’s - Abnormal
(Compact, irregular or absent pits): Indicates neoplasia A total of 560 observa-
OP215 OUTCOME OF ENDOSCOPIC MUCOSAL RESECTION OF 424 tions were undertaken to validate these criteria. The sensitivity, specificity, nega-
LARGE SESSILE COLONIC POLYPS (20MM) OVER A 9 YEAR tive predictive value (NPV) and positive predictive value (PPV) is shown in Table
PERIOD: A SINGLE CENTRE EXPERIENCE AND ANALYSIS OF 1.
CHANGE WITH TIME
D.N.F. N.F. Lim1, R. J. Robinson1, A. Moore1, J. De Caestecker2, P. Wurm1 Table 1: Validation results of the classification criteria
1
Digestive Disease Centre, University Hospital of Leicester, Leicester/United Criteria Sensitivity Specificity NPV PPV
Kingdom
2
Digestive Disease Centre, University Hospital of Leicester, Leicester/United Loss of 96.2% 93.8% 90.9% 97.5%
Kingdom acetowhitening (93.4–97.9%) (88.9–96.9%) (85.5–94.8%) (95.4–98.8%)
Surface pattern 77.0% 99.0% 91.4% 96.9%
Contact E-mail Address: [email protected]
Normal (69.7–83.3%) (97.5–99.7%) (88.4–93.9%) (92.2–99.1%)
Introduction: Endoscopic mucosal resection (EMR) has become the standard Abnormal 99% 77.0% 96.9% 91.4%
technique for resection of large sessile and flat colonic polyps. We aimed to (97.5–99.7%) (69.7–83.3%) (92.2–99.1%) (88.4–93.9%)
assess the clinical outcome of colonic EMR of polyps 2 cm and greater in size
at University Hospital of Leicester NHS Trust and to assess changes over a 9-
year period.
Aims & Methods: Data was collected for all sessile colonic polyps 20 mm When the AAC validated criteria are applied by the 13 endoscopists, the sensi-
removed by EMR between 2006 and 2014 by 3 endoscopists (PW, JDC, RJR). tivity, specificity, NPV and PPV of detecting neoplastic Barrett’s are 98.5%,
Patient demographics, resection technique, completeness of initial resection, 64.0%, 97.5% and 72.5% respectively.
recurrence rate at first surveillance (SC1), polyp eradication at 2nd surveillance Conclusion: We have developed and established the validity of a simple classifica-
after at least 1 year (SC2) and complication rates were analysed. tion system to identify Barrett’s neoplasia using AAC. When non-AAC trained
Result: 564 patients were assessed for EMR, among which there were 424 com- endoscopists apply these criteria, the sensitivity and NPV meet the recommended
pleted EMRs (BCSP 138, Symptomatic 286) by three operators. Of the 140 not PIVI threshold.
proceeding to complete EMR, in 65 EMR was not attempted and patients were Disclosure of Interest: All authors have declared no conflicts of interest.
referred for surgical resection (cancer 31, technical difficulty 34). In a further 32,
EMR was attempted but abandoned; all were referred for surgery (cancer 18,
benign polyp 14). Finally, 43 had no intervention (13 declined, 22 non-adenoma-
tous or pseudo polyps, 8 moved away). The mean age was 68.7 years (range 25– OP217 STEPWISE DEVELOPMENT OF A VOLUMETRIC LASER
93), male 226 (53%), female 198 (47%). Mean polyp size was 33 mm (median ENDOMICROSCOPY PREDICTION SCORE FOR BARRETT’S
30 mm). Site of polyp was right colon 27%, transverse colon 5%, left colon 68% NEOPLASIA USING MATCHED VLE-HISTOLOGY IMAGES OF
(rectum 58%, sigmoid 4%, descending 6%). Piecemeal EMR was done in 381 ENDOSCOPIC RESECTION SPECIMENS
(90%), and ‘en bloc’ in 43 (10%). Of those who have undergone surveillance so A. Swager1, M.G. h. Van Oijen2, G.J. Tearney3, C. L. Leggett4, S.L. Meijer5,
far, recurrence was found in 56/284 (19.7%) at initial SC1 (mean 7 month; range W.L. Curvers6, J.J. Bergman7
2–36) and was endoscopically treated in 53/56 (94.6%); 3/56 (5.4%) referred for 1
Gastroenterology And Hepatology, Academic Medical Center, Amsterdam/
surgical resection (2 cancer, 1 non lifting). Complete eradication after one year Netherlands
SC2 (mean 16 months, range 5–51) 211/234 (90.2%) with recurrence in 23 (9.8%) 2
Medical Oncology, Academic Medical Center, Amsterdam/Netherlands
– but in 22/23 this was endoscopically resected. Overall complication rate 17/424 3
Pathology and Wellman Center for Photomedicine, Massachusetts General
(4%): immediate perforation 1/424 (0.2%) post-caecal EMR required conserva- Hospital and Harvard Medical, Boston, Boston/United States of America
tive medical treatment; post polypectomy pain syndrome 14/424 (3.3%) required 4
Gastroenterology And Hepatology, Mayo Clinic, Rochester/United States of
admission for overnight conservative medical treatment. Delayed bleeding 2/424 America/MN
(0.5%) required endoscopic therapy to achieve haemostasis. There were no pro- 5
Pathology, Academic Medical Centre, Amsterdam/Netherlands
cedure-related deaths. For each 3-year period (2006–8, 2009–11, 2012–14), there 6
Gastroenterology And Hepatology, Catharina hospital, Eindhoven/Netherlands
was a consistent reduction in number of polyps not treated endoscopically or 7
Gastroenterology & Hepatology, Academic Medical Centre, Amsterdam/
requiring surgery (overall decrease of 15.7%), incomplete EMR referred for Netherlands
surgical resection (overall decrease of 2.3%) and recurrence rate at first SC1
(overall decrease 16.3%). There were increases in numbers of EMRs performed Contact E-mail Address: [email protected]
annually (overall increase 26%), mean polyp size resected (þ7 mm), level 3 & 4 Introduction: Endoscopic detection of early neoplasia in Barrett’s esophagus (BE)
polypectomies (3.7 and 7%) and complete eradication rate at SC1 (16.3%). is difficult. Volumetric laser endomicroscopy (VLE) is an advanced imaging
Conclusion: This is a large single-centre series of EMR of 424 sessile colonic system incorporating 2nd generation optical coherence tomography in a bal-
polyps 42 cm performed by 3 operators over a 9 year period; almost 20% had loon-based system, providing a 6-cm long circumferential scan of the esophageal
recurrence at initial surveillance, most managed endoscopically, with eradication wall up to 3 mm deep, with near-microscopic resolution. Several VLE features of
rate at 1 year of over 90% (22/23 one year recurrences treated endoscopically). early BE neoplasia have been determined previously (1,2).
Examination of time trends over this period showed progressive reduction in Aims & Methods: Aims of this study were to determine (additional) VLE features
recurrence and a trend for larger, more complex polyps to be resected endosco- of neoplasia, based on precise VLE-histology correlations ex vivo, and to develop
pically, with a corresponding drop in surgical management, demonstrating and validate a VLE prediction score for early BE neoplasia.
improvement in outcome with time. A unique database of VLE images from endoscopic resection specimens and
Disclosure of Interest: All authors have declared no conflicts of interest. corresponding histology from BE patients þ/- neoplasia was used. Precise
United European Gastroenterology Journal 4(5S) A87
VLE-histology correlation methodology has been described previously (3). In the Result: Ten patients were recruited at a single centre. We included in the analysis
orientation phase, 25 VLE-histology images were evaluated in an unblinded 19 EMR specimens with at least one dysplastic gland and 45 punch biopsies, of
manner by a GI pathologist, BE endoscopist and VLE researcher. Features which 16 were dysplastic. In the whole EMR analysis, we found a significantly
potentially predictive for early BE neoplasia were identified and subsequently lower mean fluorescence intensity (MFI) in dysplastic versus non-dysplastic areas
discussed in consensus with 2 VLE experts. In the learning phase, VLE images (P 5 0.0001), in accordance with the reported reduced binding of WGA to neo-
corresponding with neoplasia ((high-grade dysplasia (HGD) or early adenocar- plastic Barrett’s epithelium (1). Similarly, the MFI of punch biopsies taken from
cinoma (EAC); n ¼ 10) and non-dysplastic (ND)BE tissue (n ¼ 10) were scored by dysplastic regions was significant lower compared to that of non-dysplastic areas
the 2 VLE experts – blinded to histology – for presence of neoplasia and VLE (P ¼ 0.0002). Finally, we found that the fluorescent contrast between dysplastic
features identified in the orientation phase. After a consensus meeting, a predic- and non-dysplastic areas was higher in EMRs with wider extent of neoplasia (R2
tion score was created based on multivariable logistic regression analysis using 0.58, p ¼ 0.0002).
learning phase results. This score was validated by expert scoring of 40 additional Conclusion: WGA-based NIR imaging is an effective method for differentiating
VLE images (20 HGD/EAC; 20 NDBE) using area under receiver operating dysplastic from non-dysplastic Barrett’s mucosa ex vivo, which reduces the
characteristic (ROC) curve (AUC) analysis. effects of tissue autofluorescence. In-vivo studies are now required to test the
Result: Four VLE features potentially predictive for BE neoplasia were identi- efficacy of this method for detecting dysplasia during endoscopic surveillance.
fied: 1) lack of layering; 2) higher surface signal than subsurface signal; 3) pre- Disclosure of Interest: All authors have declared no conflicts of interest.
sence of irregular, dilated glands/ducts; 4) homogeneity. In the learning phase, Reference
features 1, 2 and 3 were significantly and independently associated with neopla-
sia. The VLE neoplasia prediction score was developed with: feature 1 (6 points), 1. Bird-Lieberman EL, Neves AA, Lao-Sirieix P, O’Donovan M, Novelli M,
2 (6 or 8 points for equal or higher surface signal) and 3 (5 points). ROC curve of Lovat LB, et al. Molecular imaging using fluorescent lectins permits rapid
this prediction score showed an AUC of 0.83 (95% CI 0.69–0.96) in the learning endoscopic identification of dysplasia in Barrett’s esophagus. Nat Med 2012;
and 0.81 (95% CI 0.71–0.90) in the validation phase. A cut-off value of 8 was 18(2): 315–21.
associated with a sensitivity and specificity of 85% and 68% in the learning and
83% and 71% in the validation phase, respectively.
Conclusion: This study, using high-quality ex vivo VLE-histology correlation,
confirms that the VLE features layering, surface signal, and irregular glands/ OP219 RESULTS OF A PROSPECTIVE MULTICENTER BELGIAN
ducts are independently and significantly associated with early BE neoplasia. REGISTRY OF RADIOFREQUENCY ABLATION FOR BARRETT’S
Using these features, we developed and validated a VLE prediction score for ESOPHAGUS
BE neoplasia, with promising accuracy. J. Vliebergh1, P.H. Deprez2, H. Willekens1, D. De Looze3, H. Orlent4,
Disclosure of Interest: G.J. Tearney: Massachusetts General Hospital has a licen- E. Macken5, P. Christiaens6, F. Mana7, G. De Hertogh1, R. Bisschops1
sing arrangement with NinePoint Medical. Dr. Tearney has the rights to receive 1
Gastroenterology, UZ Leuven, Leuven/Belgium
royalties from this licensing arrangement. 2
Dept. De Hepato-gastroenterologie, Cliniques Universitaire Saint-Luc Universite´
J.J. Bergman: - Researchsupport: Olympus Endoscopy, Fuji-film, Cook Medical, de Louvain, Brussels/Belgium
Boston Scientific, Covidien, Erbe, Ninepoint Medical, C2-therapeutics, 3
UZ Gent, Gent/Belgium
Cernostics, Interpace - Training programs:Covidien, Boston Sc. - Consultancy- 4
AZ Sint-Jan, Brugge/Belgium
speaker: Cook, Boston Sc.,Covidien 5
Uza, Antwerpen/Belgium
All other authors have declared no conflicts of interest. 6
Imelda Bonheiden, Bonheiden/Belgium
7
References UZ Brussel, Brussel/Belgium
1. Evans JA, Poneros JM, Bouma BE, Bressner J, Elkan F, Shishkov M, et al. Contact E-mail Address: [email protected]
Optical Coherence Tomography to Identify Intramucosal Carcinoma and Introduction: Radiofrequency ablation (RFA), combined with endoscopic resec-
High-Grade Dysplasia in Barrett’s Esophagus. Clin Gastroenterol Hepatol tion (ER) of visible lesions, can be used as a primary treatment for low-grade
2006; 4(1): 38–43. dysplasia (LGD), high-grade dysplasia (HGD) and early adenocarcinoma (EAC)
2. Leggett CL, Gorospe EC, Chan DK, Muppa P, Owens V, Smyrk TC, et al. in Barrett’s esophagus. In prospective multicenter controlled trials, high rates of
Comparative diagnostic performance of volumetric laser endomicroscopy complete remission of dysplasia (CR-D) and intestinal metaplasia (CR-IM) has
and confocal laser endomicroscopy in the detection of dysplasia associated been reported.
with Barrett’s esophagus. Gastrointest Endosc. Elsevier, Inc.; 2015. Aims & Methods: The aim of this study is to monitor outcome and efficacy of
3. Swager A, Boerwinkel DF, de Bruin DM, Weusten BL, Faber DJ, Meijer RFA in a setting of absence of reimbursement in a multicenter national prospec-
SL, et al. Volumetric laser endomicroscopy in Barrett’s esophagus: a feasi- tive registry. Between February 2008 and August 2015, data from 7 centers
bility study on histological correlation. Dis Esophagus. 2015 May 8;1–8. performing RFA were collected in the Belgian RFA registry. All procedures
were monitored for indication, treatment before RFA, short/long-term compli-
cations and prospective long-term pathological outcome. Primary endpoint was
CR-D and CR-IM. Secondary endpoints was safety.
OP218 DETECTION OF DYSPLASIA IN BARRETT’S OESOPHAGUS Result: 538 RFA procedures were registered in 279 different patients (mean age
USING LECTIN-BASED NEAR INFRA-RED MOLECULAR 65; 84.5% men). In 60% a previous EMR/ESD was performed. Baseline worst
IMAGING: AN EX-VIVO STUDY ON HUMAN TISSUE histology prior to RFA (including ER) was: 2% SIM (5), 8% LGIN (22), 52%
M. Di Pietro1, A. A. Neves2, M. O’Donovan3, D. J. Waterhouse4, S. HGIN (146), 37% adenocarcinoma (102), 1% unknown (4). At the time of
E. Bohndiek4, K. Brindle2, R.C. Fitzgerald1 analysis 44 patients were still under treatment. In an intention to treat analysis
1
MRC Cancer Unit, University of Cambridge, Cambridge/United Kingdom (ITT), 83% (194/235) patients achieved CR-IM and 87% (204/235) CR-D after a
2
Cambridge Institute, Cancer Research UK, Cambridge/United Kingdom median of 2 RFA sessions. 18 patients discontinued treatment, giving a per
3
Histopathology, Cambridge University Hospitals, Cambridge/United Kingdom protocol(PP) CR-IM in 89% (194/217) and CR-D in 94% (204/217). 185 and
4
Physics, University of Cambridge, Cambridge/United Kingdom 193 patients with CR-IM respectively CR-D entered follow-up. Recurrence of
disease was limited to IM in 38 patients and recurrent neoplasia occurred in 24
Contact E-mail Address: [email protected] patients: 7 LGD, 17 HGIN/Ca. With a median FU time of 735 days, the ITT and
Introduction: Detection of early neoplasia in Barrett’s oesophagus by white-light PP analysis for durability of CR-IM is 63% and 66% respectively. The results of
endoscopy is challenging due to the inconspicuous nature of dysplasia. Molecular durability of CR-D with a median FU time of 670 days in an ITT and PP analysis
imaging using fluorescently labelled wheat-germ agglutinin (WGA) is a promis- are 82% and 87% respectively. Immediate complications occurred in 4% of the
ing tool for detecting dysplasia as this topically applied imaging agent shows procedures in 21 different patients (7.5%): 16 small mucosal lacerations (9 after
lower binding to dysplastic versus non-dysplastic oesophageal glandular sizing), 7 bleedings, no perforations. Late adverse events occurred in 8% of the
mucosa (1). However in an endoscopy setting, the detection of fluorescence in procedures in 42 different patients (15%): 19 stenosis (mean 4 dilatations), 7
the blue/green range is limited by high levels of tissue autofluorescence. This bleedings, 3 poor healing, 9 prolonged hospitalization for general symptoms, 4
limitation can be overcome by using near infra-red (NIR) imaging. fever without prolonged hospitalization, 2 pneumonia. Comparison of the
Aims & Methods: The aim of this study was to assess in an ex-vivo model the Belgian RFA registry with the EURO II trial and with the UK RFA registry
feasibility of WGA-based NIR imaging for detection of dysplasia in Barrett’s. To revealed that there was no significant difference for CR-IM, CR-D and compli-
this end, we studied patients with early Barrett’s-related neoplasia undergoing cation rate. Remarkably, there were significantly more rescue treatments
endoscopic mucosal resection (EMR). Freshly collected EMR specimens were (p 5 0.0001) in Belgium before achieving remission in comparison to the UK.
sprayed with WGA-IR800CW (10 mg/mL; 10 min, room temperature); washed Conclusion: Our data confirm that combined ER- RFA is an efficient treatment
with PBS buffer and then imaged with a high-sensitivity NIR camera for Barrett’s associated neoplasia. In the absence of reimbursement, more escape
(FluobeamTM, Fluoptics). Planar fluorescence images were captured and up to treatments were performed in comparison to published controlled trials. Outside
two punch biopsies (2 mm diameter) were collected from each EMR specimen, clinical trials, meticulous follow-up appears to be even more important to detect
under fluorescence guidance. The EMRs were then formalin fixed and paraffin and treat early recurrence. We suggest a systematic registration of RFA practice
embedded (FFPE), cut every 2 mm and processed for histopathological assess- to monitor long term outcome and efficacy.
ment. Each section was scored by an expert GI pathologist every 1 mm to con- Disclosure of Interest: All authors have declared no conflicts of interest.
struct a pathology grid, which was manually co-registered with the fluorescence
image. Targeted punch biopsies, taken from areas of interest within the EMR
specimen, were also scored by the pathologist. The mean fluorescence intensity
(MFI) of cells in dysplastic and non-dysplastic areas was compared by the
Wilcoxon matched-pairs signed rank test. The MFI of punch biopsies taken
from dysplastic and non-dysplastic areas was compared by Mann-Whitney
test. The correlation between the fluorescent contrast and spatial extent of dys-
plasia was analysed by linear regression.
A88 United European Gastroenterology Journal 4(5S)
OP220 LONG-TERM FOLLOW-UP RESULTS OF STEPWISE RADICAL signaling pathways. SMAD4 mutations or deletions are also found in 10% of
ENDOSCOPIC RESECTION FOR BARRETT’S ESOPHAGUS WITH esophageal adenocarcinoma (EAC) patients and are associated to poor prognosis
EARLY NEOPLASIA (1).
K. Belghazi1, F. G. i. Van Vilsteren1, B.L. a.m. Weusten2, S.L. Meijer3, Aims & Methods: The aim of this project is to elucidate whether BMP4 is
J.J. Bergman4, R.E. Pouw5 involved in malignancy in EAC. We have recently developed unique low mole-
1
Gastroenterology And Hepatology, Academic Medical Centre, Amsterdam/ cular weight Llama derived antibodies that specifically and effectively target
Netherlands BMP4 and therefore present less off-target effects, which renders them more
2
Departement Of Gastroenterology And Hepatology, St Antonius Hospital, apt for clinical purposes (2–3). These antibodies were used to study the effect
Nieuwegein/Netherlands of specific inhibition of BMP4 on both in vitro as well as in vivo models of
3
Pathology, Academic Medical Centre, Amsterdam/Netherlands Esophageal Adenocarcinoma.
4
Gastroenterology & Hepatology, Academic Medical Centre, Amsterdam/ Result: We have found that 70% of EAC tumors express BMP4 at the protein
Netherlands levels. When the analysis was restricted to SMAD4 negative EAC tumors about
5
Gastroenterology & Hepatology, Academic Medical Centre, Amsterdam, 90% of those were BMP4þ. Using an antibody that recognizes the pro-domain
Netherlands, Amsterdam/Netherlands of BMP4, and therefore identifies the cells producing BMP4, we found that
epithelial as well as some stromal cells, produce BMP4. We validated these results
Contact E-mail Address: [email protected] by generating an RNAseq database of 56 EAC biopsies, and confirmed that
Introduction: Stepwise radical endoscopic resection (SRER) allows for complete approximately 80% of those samples expressed BMP4 at the RNA levels. We
endoscopic resection of Barrett’s esophagus (BE) with early neoplasia. This next investigated the correlation of BMP4 expression and found that patients
approach has been shown very effective in reaching complete eradication of with high levels of BMP4 expression tend to have a poorer recurrence-free sur-
high-grade dysplasia (HGD) or early cancer (EC) (CE-neo) in 98% and all vival than patients with low BMP4 expression, which suggests a more aggressive
intestinal metaplasia (CE-IM) in 85% of patients. tumor behavior in BMP4 expressing EAC tumors. Inhibition of BMP4 function
Aims & Methods: The aim of this study was to report the long-term follow-up in SMAD4 negative EAC cells by the anti-BMP4 antibodies leads to an increase
(FU) results after successful SRER for BE with early neoplasia. We screened all in chemosensitivity and a decrease in invasive and migratory capabilities in vitro.
patients treated with SRER in two centers between 2001–2014, for BE 5 cm Analyses of the signaling pathways showed that inhibition of the BMP4-
with HGD/EC, without signs of invasion 4T1sm1, G3/G4 differentiation, mediated non-canonical pathways was responsible for these effects. Next, we
lymph-vascular invasion or irradical deep resection margins in ER specimens. made use of a patient-derived tumor xenograft (PDTX) mouse model of a
All patients who had reached endoscopic and histologically confirmed CE-neo SMAD4 negative EAC tumor (4). Preclinical in vivo studies with these mice
and CE-IM after SRER were included for evaluation of long-term FU. All confirmed that anti-BMP4 antibodies can effectively reduce tumor growth and
information from FU endoscopies and histological outcomes were collected synergistically act with chemotherapy agents.
and entered in a dedicated database. Duration of FU was calculated from last Conclusion: Our studies support a role of BMP4 as a positive regulator of chemo-
treatment till last FU endoscopy. Primary outcomes: recurrence of HGD/EC and resistance and invasiveness in EAC, and suggest that inhibition of BMP4 with
recurrence of IM combined with visible BE islands or tongues. Secondary out- highly specific antibodies has the potential to ameliorate the malignant behavior
comes: Buried Barrett’s (BB) in neosquamous biopsies, and IM in biopsies of aggressive SMAD4 negative esophageal cancers.
obtained distal to the neo-z-line. Disclosure of Interest: All authors have declared no conflicts of interest.
Result: Seventy-three patients were included (64 men, mean age 66 yrs, median References
BE C2M3). Worst baseline pathology: HGD, n ¼ 50; EC, n ¼ 23. Median FU
was 76 months (IQR 55–102) with a median of 6 (IQR 4–8) endoscopies. 1. Singhi AD, Foxwell TJ, Nason K, Cressman KL, McGrath KM, Sun W,
Recurrence of HGD/EC was observed in 1 patient (1.4%) after 129 months Bahary N, Zeh HJ, Levy RM, Luketich JD, Davison JM.Smad4 loss in
FU (T1bN0M0 treated with curative surgery). Recurrence of IM in endoscopi- esophageal adenocarcinoma is associated with an increased propensity for
cally visible BE was observed in 16 patients (of which 2 had LGD) after a median disease recurrence and poor survival. Am J Surg Pathol. 2015 Apr;39(4):
FU of 31 months. In all cases the extent of recurrence was limited to small 487–95.
(51 cm) islands or tongues. Histological recurrence without visible BE was 2. Calpe S, Correia AC, Sancho-Serra MD, Krishnadath KK.Comparison of
found in 25 patients: 3 patients had BB in neosquamous biopsies (4% overall, newly developed anti-bone morphogenetic protein 4 llama-derived antibo-
0.7% per patient year); 24 patients (33%) showed IM in biopsies just distal to a dies with commercially available BMP4 inhibitors. MAbs. 2016 Mar 11:0.
normal appearing neo-z-line. A finding of IM of the neo-Z-line was reproduced 3. Calpe S, Wagner K, Khattabi M El, Rutten L, Zimberlin C, Dolk E, et al.
in 50% of patients and BB in none of the patients. Additional treatment was Effective inhibition of Bone Morphogenetic Protein function by highly spe-
performed in 8 patients: esophagectomy for T1b-cancer, ER of small island with cific llama-derived antibodies. Mol Cancer Ther. 2015.
LGD (n ¼ 1), APC for small islands (n ¼ 5), RFA for LGD in the neo-z-line 4. Read M, Liu D, Duong CP, Cullinane C, Murray WK, Fennell CM, et al.
(n ¼ 1). CE-neo and CE-IM (excluding IM in the neo-z-line) at the last FU Intramuscular Transplantation Improves Engraftment Rates for Esophageal
endoscopy (after additional treatment) was seen in 100% and 96% respectively. Patient-Derived Tumor Xenografts. Ann Surg Oncol. 2015.
Conclusion: This study presents the longest published follow-up data on SRER to
date. The 6-year outcomes show that after successful SRER of BE 5 cm recur- TUESDAY, OCTOBER 18, 2016 10:30–12:00
rence of HGD/EC is rare (1% overall, 0.2% per patient year). Recurrence of
endoscopically visible BE with IM or LGD was found in 22% of patients and ACCURACY IN UPPER GI ENDOSCOPY – ROOM L8_____________________
was generally confined to small islands or tongues. Buried glands were rare (0.7% OP222 PREMEDICATION WITH SIMETHICONE AND N-
per patient year) and just as IM of the neo-z-line (33% of cases) of insignificant ACETYLCYSTEINE IN IMPROVING MUCOSAL VISIBILITY
importance. DURING UPPER ENDOSCOPY – A PROSPECTIVE DOUBLE-
Disclosure of Interest: B.L.A.M. Weusten: Financial support for research: BLINDED RANDOMIZED CONTROLLED TRIAL
Covidien/Medtronic; Erbe Medical; C2Therapeutic, Consultancy: Boston L. Elvas, M. Areia, S. Alves, D. Brito, S. Saraiva, A.T. Cadime
Scientific; C2Therapeutic. Gastroenterology, Portuguese Oncology Institute - Coimbra, Coimbra/Portugal
J.J. Bergman: Financial support for research: Covidien/Medtronic; Olympus
Endoscopy; Cook Medical; Boston scientific; Erbe Medical; C2Therapeutic; Contact E-mail Address: [email protected]
Fuji-film; Ninepoint Medical; Consultancy: Boston Scientific; Cook Medical; Introduction: Upper endoscopy is the most common method for the diagnosis of
Covidien/Medtronic; Boston Scientific upper gastrointestinal tract diseases. Our aim was to determine if pre-medication
All other authors have declared no conflicts of interest. with simethicone or N-Acetylcysteine improves mucosal visualization during
upper endoscopy.
Aims & Methods: Randomized double-blinded, placebo controlled trial of 297
patients scheduled for upper endoscopy, pre-medicated 15–30 minutes before
OP221 SPECIFIC BMP4 INHIBITION AS A POTENTIAL THERAPEUTIC with: A–100 mL of water (placebo); B–water plus 100 mg simethicone; C–water
STRATEGY FOR SMAD4 DEFECTIVE ESOPHAGEAL plus simethicone plus 600 mg N-acetylcysteine. Primary outcome was the quality
ADENOCARCINOMAS of mucosal visualization (score: 1-excellent; 2-adequate; 3-inadequate). Trial
S. Calpe1, M. Read2, S. Hoefnagel3, M.D.C. Sancho Serra3, D. Straub4, registered in http://clinicaltrials.gov (NCT02357303). Statistical analysis with
A. Correia3, N. Clemons5, D. Liu6, W. Phillips5, K.K. Krishnadath3 X2 and one-way ANOVA with Tukey’s correction.
1
Academic Medical Center, Amsterdam/Netherlands Result: Visualization scores between groups B and C (versus A) were significantly
2
Surgical Oncology Research Laboratory, Peter MacCallum Cancer Centre, better in the oesophagus 1.09 and 1.15 vs. 1.31 (p 5 0.05) and stomach 1.26 and
Melbourne/Australia 1.30 vs. 1.67 (p 5 0.01) and better without significance in the duodenum 1.07 and
3
Gastroenterology And Hepatology, AMC, Amsterdam/Netherlands 1.09 vs. 1.20 (p ¼ NS). ‘‘Excellent’’ scores versus others provided similar results
4
Amsterdam Medical Center, Amsterdam/Netherlands (B and C vs. A): oesophagus 91% and 87% vs. 71% (p 5 0.001), stomach 76%
5
Sir Peter Maccallum Department Of Oncology, Peter MacCallum Cancer Centre, and 75% vs. 39% (p 5 0.001) and duodenum 85% and 82% vs. 73% (p ¼ NS).
Melbourne/Australia There were no significant differences in scores between groups B and C or
6
Sir Peter Maccallum Department Of Oncology, Peter MacCallum Cancer Centre, between gastric scores if previous subtotal gastrectomy (B and C vs. A): 1.45
Melbourne/Australia and 1.68 vs. 1.86 (p ¼ NS). The rate of reported lesions was higher in group B
(without statistical significance).
Contact E-mail Address: [email protected] Conclusion: Pre-medication with simethicone leads to better mucosal visibility,
Introduction: BMP4 is a growth factor with a key role in carcinogenesis and might improve diagnostic yield and should be considered standard practice.
metastasis. We previously found that BMP4 is aberrantly expressed in Barret’s Addition of N-acetylcysteine had no benefit over simethicone alone.
esophagus and that together with CDX2 drives the intestinalization of epithelial Disclosure of Interest: All authors have declared no conflicts of interest.
metaplasia. Its role in the progression and development towards esophageal
adenocarcinoma remains uncertain. In colorectal cancers that present mutations
in the canonical transcription factor SMAD4, BMP4 induces tumorigenic char-
acteristics in epithelial cells through activation of its SMAD-independent
United European Gastroenterology Journal 4(5S) A89
OP223 DIAGNOSIS OF TUMOR EXTENT OF EARLY GASTRIC Contact E-mail Address: [email protected]
CANCER BY MAGNIFYING NARROW BAND IMAGING VS. Introduction: Volumetric laser endomicroscopy (VLE) incorporates 2nd genera-
CHROMOENDOSCOPY: A MULTICENTER PROSPECTIVE tion optical coherence tomography technology in a balloon-based system, which
RANDOMIZED CONTROLLED TRIAL is capable of scanning the esophagus circumferentially over 6 cm, up to a depth of
T. Kanesaka1, T. Nagahama2, N. Uedo1, H. Doyama3, K. Uchita4, T. Ueo5, 3 mm with near-microscopic resolution. VLE has the potential to improve detec-
H. Ishikawa6, K. Yao7 tion of early neoplasia in Barrett’s esophagus (BE). However, interpretation of
1
Dept. Of Gastrointestinal Oncology, Osaka Medical Center for Cancer and VLE images is complex due to subtle differences in architecture and gray-scale
Cardiovascular Diseases, Osaka/Japan color and the large amount of images that needs to be scrutinized by the endos-
2
Department Of Endscopy, Fukuoka University Chikushi Hospital, Fukuoka/Japan copist (a 6-cm VLE scan contains 1200 frames). A recently developed clinical
3
Dept. Of Gastroenterology, Ishikawa Prefectural Central Hosp., Kanazawa/Japan prediction model of VLE features for BE neoplasia showed a reasonable accu-
4
Dept. Of Gastroenterology, Kochi Red Cross Hospital, Kochi/Japan racy (AUC of 0.81).
5
Department Of Gastroenterology, Oita Red Cross Hospita, Oita/Japan Aims & Methods: The aim of this study was to investigate the feasibility of a
6
Department Of Molecular-targeting Cancer Prevention, Kyoto Prefectural computer algorithm to identify early BE neoplasia on ex vivo VLE images. Sixty
University of Medicine, Kyoto/Japan VLE images from a database of high-quality one-to-one VLE-histology correla-
7
Department Of Endoscopy, Fukuoka University Chikushi Hospital, Fukuoka/ tions were used (30 non-dysplastic (ND)BE and 30 neoplastic images; high-grade
Japan dysplasia and early adenocarcinoma), consisting of VLE scans from endoscopic
resection specimens of Barrett’s patients þ/- neoplasia. VLE images were normal-
Contact E-mail Address: [email protected] ized to a height of 400 pixels in order to obtain a standardized zoom factor.
Introduction: Accurate diagnosis of lateral extent of early gastric cancer (EGC) is Previously identified VLE features predictive for BE neoplasia served as clinical
important in terms of deciding treatment indication and achieving complete input for the algorithm: 1) higher VLE surface signal than subsurface signal in
resection by endoscopy or surgery. Magnifying narrow band imaging (M-NBI) tissue, 2) lack of layering. From these VLE features an algorithm feature was
has been suggested to increase yield of endoscopic diagnosis for determining developed analyzing both top layers and surface signal. A signal intensity histo-
extent of EGC. gram using 8 intensity categories was calculated over the first 4 layers of 50
Aims & Methods: To compare diagnostic ability of M-NBI for determining lat- pixels, starting at the top of the image. Linear support vector machine was
eral extent of EGC with that of chromoendoscopy (CE). This study was con- used to classify the images according to the used VLE texture features. Leave-
ducted as a multicenter prospective randomized controlled trial including one one-out cross-validation was employed for validation of the algorithm.
university hospital, one cancer referral center and three general hospitals. Result: Using the correlated histology as the reference standard, sensitivity, spe-
Inclusion criteria were patients with EGC sized 1 cm or over who underwent cificity and accuracy for the algorithm to detect BE neoplasia were 93%, 70%
endoscopic or surgical treatment. Exclusion criteria were history of gastric resec- and 82%, respectively. The performance of the algorithm was good, with an area
tion and high risk of bleeding for biopsy. After stratification by institution, under the receiver operating curve (AUC) of 0.91 to detect BE neoplasia in ex
tumor location, and histological type, patients were randomly assigned to M- vivo VLE images. Most distinctive features of the algorithm are the top layers
NBI or CE groups. In each group, tumor extent was firstly evaluated by white and mid-range intensities of the histogram.
light endoscopy according to difference of mucosal height and color, then oral Conclusion: This is the first study in which a computer algorithm for BE neopla-
margin of the tumor was determined by the assigned method. Diagnostic criteria sia was developed based on VLE images with direct histological correlates. The
of M-NBI were 1) demarcation line and 2) irregular microvessel/microsurface algorithm showed good performance to detect BE neoplasia in ex vivo VLE
patterns; and that of CE were 1) abrupt change of mucosal structure of the images (AUC 0.91). Compared to the performance of a recently developed clin-
surrounding mucosa and 2) irregular structure patterns. Biopsy specimens were ical VLE prediction score (AUC 0.81), this study suggests that an automatic
taken from 5-mm-outside and -inside of the oral boundary of the tumor and sent detection algorithm seems to perform at least as good as assessment by VLE
for histological evaluation. When the outside specimen was non-cancer and the experts in detecting early neoplasia on VLE. Future studies on in vivo VLE scans
inside specimen was cancer in histology, it was defined as ‘‘successful delinea- are needed to further validate the algorithm.
tion’’. Primary endpoint was difference of proportion of successful delineation Disclosure of Interest: J.J. Bergman: - Research support: Olympus Endoscopy,
between the two groups. A study protocol was approved by institutional review Fuji-film, Cook Medical, Boston Scientific, Covidien, Erbe, Ninepoint Medical,
board in each institution and written informed consent for study participation C2-therapeutics, Cernostics, Interpace - Training programs: Covidien, Boston Sc.
was obtained from all patients. - Consultancy-speaker: Cook, Boston Sc.,Covidien
Result: A total of 382 patients were enrolled and were assigned to the M-NBI All other authors have declared no conflicts of interest.
group (n ¼ 191) and the CE group (n ¼ 191). Eight patients in the M-NBI group
and 12 in the CE group were excluded remaining 183 in the M-NBI and 179 in
the CE group for analysis. Successful delineation rates (95% CI) in the M-NBI
and CE groups were 86% (81–91%) and 84% (78–89%), respectively (p ¼ 0.498). OP225 OPTICAL ENHANCEMENT SYSTEM TM PLUS OPTICAL
Conclusion: This prospective randomized controlled trial revealed M-NBI and MAGNIFICATION UTILITY IN THE IDENTIFICATION OF
CE were equally accurate for determining extent of EGC, thus both methods are NORMAL GASTRIC MUCOSA, HELICOBACTER PYLORI
adequate to perform in clinical practice (UMIN000014628). ASSOCIATED GASTRITIS, AND GASTRIC ATROPHY
Disclosure of Interest: All authors have declared no conflicts of interest. C. Robles-Medranda1, M. Valero1, M. Puga1, M. Soria2, J. Ospina1,
Reference H. Alvarado1, H. Pitanga Lukashok1
1
Endoscopy, Instituto Ecuatoriano de Enfermedades Digestivas-IECED-University
1. Nagahama T, Yao K, Maki S, et al. Usefulness of magnifying endoscopy
Hospital Omni, Guayaquil/Ecuador
with narrow-band imaging for determining the horizontal extent of early 2
Endoscopy, Instituto Ecuatoriano de Enfermedades Digestivas - IECED,
gastric cancer when there is an unclear margin by chromoendoscopy (with
Guayaquil/Ecuador
video). Gastrointest Endosc 2011; 74: 1259–67.
Contact E-mail Address: [email protected]
Introduction: It has been proposed that high-resolution zoom endoscopes (optical
zoom up to 115 times) could predict gastric pit pattern for gastric pathology.
OP224 FEASIBILITY OF A COMPUTER ALGORITHM FOR Recently an image-enhanced endoscopic technology called Optical Enhancement
DETECTION OF EARLY BARRETT’S NEOPLASIA USING system (OE SystemTM) was introduced, improving visualization of microvessels.
VOLUMETRIC LASER ENDOMICROSCOPY In addition to this, new high-definition zoom scopes called MagniviewTM are
A. Swager1, F. Van Der Sommen2, S. Zinger2, S.L. Meijer3, E.J. Schoon4, available allowing an optical zoom up to 136 times with a better evaluation of the
J.J. Bergman5, P. De With2, W.L. Curvers6 mucosa and superficial vascular aspects.
1
Gastroenterology And Hepatology, Academic Medical Center, Amsterdam/ Aims & Methods: The aim of this study was to evaluate the utility OE SystemTM
Netherlands plus MagniviewTM in the diagnosis of normal gastric mucosa, Helicobacter pylori
2
Electrical Engineering, Eindhoven University of Technology, Eindhoven/ associated gastritis, and gastric atrophy. Methods: Prospective, non-randomized
Netherlands and double blind study. All of the participants enrolled had functional dyspepsia
3
Pathology, Academic Medical Centre, Amsterdam/Netherlands according to the Rome III criteria and were tested for Helicobacter Pylori (HP)
4
Dept. Of Gastroenterology, Catharina Hospital Gastroenterology and using stool antigen test. After this phase two groups were selected, dyspeptic HP
Hepatology, Eindhoven/Netherlands (þ) and dyspeptic HP (-) patients (control group). Finally an upper endoscopy
5
Gastroenterology & Hepatology, Academic Medical Centre, Amsterdam/ using OE systemTM plus MagniviewTM scopes was performed and the gastric
Netherlands body evaluated using a previously described classification of four patterns,
6
Gastroenterology And Hepatology, Catharina hospital, Eindhoven/Netherlands based on the combination of the parameters subepithelial capillary network
(SECN), collecting venules and round pits. Type 1 pattern predicts normal

Table 1. (OP225): Overall accuracy of the four patterns predictions

Sensitivity, % (95% CI) Specificity, % (95% CI) PPV, % (95% CI) NPV, % (95% CI) Accuracy, %

Type Ia 90.00 (55.50–99.75) 79,03 (66.82–88.34) 40.91 (20.70–63.65) 90.00 (89.35–99.95) 80.55
Type II–IIIb 91.43 (76.94–98.20) 78.38 (61.79–90.17) 80.00 (64.35–90.95) 90.62 (74.98–98.02) 84.72
Type IVc 66.67 (9.43–99.16) 88.41 (78.43–94.86) 20.00 (2.52–55.61) 98.39 (91.34–99.96) 87,50

a) Ability to predict normal mucosa. b) Ability to predict Helicobacter pylori infection. c) Ability to predict mucosa atrophy.
A90 United European Gastroenterology Journal 4(5S)
gastric mucosa, types 2 and 3 HP related gastritis and the type 4 gastric atrophy. Disclosure of Interest: B.L.A.M. Weusten: - Research support for IRB approved
(1) Images were photographically recorded and biopsies taken in order to corre- studies: Covidien GI Solutions Erbe Medical C2Therapeutic - Consultancy:
late the images with the histology Boston Scientific C2Therapeutic
Result: A total of 72 patients were included, 35 in the dyspeptic HP (þ) group All other authors have declared no conflicts of interest.
and 37 in the control dyspeptic HP (-) group. The average age was 46.3 (37–58.5)
years old and 69.4% were women. The images were analyzed and classified into
the four patterns after the agreement of three endoscopists. There were 22
(30.6%) patients with type I, 13 (18.1%) with type II, 27 (37.5%) with type III OP227 ROAD MAP FLUOROSCOPY FOR SUCCESSFUL GUIDANCE OF
and 10 (13.9%) with type IV pattern. Almost all patients (90%) with normal ENDOSCOPIC INTERVENTIONS IN THE ESOPHAGUS
mucosa were Type I. Most type II and III patterns had active chronic gastritis, J. Weigt1, W. Obst1, A. Kandulski2, P. Malfertheiner1
which correlates with HP infection. In fact, 32/34 (91.5%) of patients with HP 1
Gastroenterology, Hepatology & Infectious Diseases, Medizin. Universität
(þ) were Type II-III. The 66% of patients with atrophy had Type IV pattern. The Magdeburg Gastroenterologie und Hepatologie, Magdeburg/Germany
Table 1 shows the overall accuracy of the four patterns predictions. Type I 2
Department Of Gastroenterology, Otto-von-Guericke University,
predicts normal mucosa, Type II-III HP infection, and Type IV atrophy with a MAGDEBURG/Germany
sensitivity of 90%, 91% and 66.7% respectively and an accuracy of 80.5%,
84.7% and 87.5% respectively. Finally the intra and inter-observer agreement Contact E-mail Address: [email protected]
was calculated with a kappa value of 0.91 and 0.89 respectively Introduction: Digital subtraction angiography is a method to enhance the contrast
Conclusion: OE chromoendoscopy plus optical magnification has proved to be of anatomic structures after opacification with contrast media. Therefore struc-
useful in the diagnosis of normal gastric mucosa and HP associated gastritis with tures that are not of interest are deleted from the image by subtraction of image
high accuracy, unlike gastric atrophy evaluation information. A variation of this technique is called Road Map Fluoroscopy
Disclosure of Interest: C. Robles-Medranda: Key Opinion Leader for Pentax (RMF) where an image at peak opacification is used as the mask for subsequent
Medical subtraction images. With this technique the advancement of guidewires, stents
All other authors have declared no conflicts of interest. or catheters can be viewed without additional marking or contrast injection.
Reference In summary, the opacification is only performed once but the information remains
on the image throughout the investigation. In this way anatomic structures such as
1. Anagnostopoulos GK, Yao K, Kaye P, et al. High-resolution magnification length or diameter of stenosis can be measured with high accuracy (1–4). Although
endoscopy can reliably identify normal gastric mucosa, Helicobacter pylori- esophageal stent placement has been reported to be safe also without fluoroscopic
associated gastritis, and gastric atrophy. Endoscopy 2007; 39(3): 202–7. guidance most endoscopists prefer to use fluoroscopy during stent deployment
(5–7). Mucosal marking using the injection of lipoidol for stent implantation is
widely used among endoscopists but may no longer be necessary if RMF is used as
guidance of the procedure. The use of RMF has so far not been evaluated for
OP226 FIRST-IN-MAN PILOT STUDY: FEASIBILITY OF LASER endoscopic procedures.
MARKING IN BARRETT’S ESOPHAGUS WITH VOLUMETRIC Aims & Methods: We aimed to evaluate the usefulness of Road Map Fluoroscopy
LASER ENDOMICROSCOPY to guide endoscopic interventions in the esophagus. Patients with esophageal
A. Swager1, A. J. De Groof1, S.L. Meijer2, B.L. a.m. Weusten1, W.L. Curvers3, strictures were consecutively enrolled in a monocentric observational trial.
J.J. Bergman4 After identification of the stenosis, a Road Map (Philips Multidiagnost Eleva,
1
Gastroenterology And Hepatology, Academic Medical Center, Amsterdam/ Philips Healthcare, Netherlands) scan was performed using 20–40 ml of water
Netherlands soluble contrast media that was applied through the working channel of a gas-
2
Pathology, Academic Medical Centre, Amsterdam/Netherlands troscope (Fujifilm EG530NW or Olympus GIF-Q 180). RMF recording requires
3
Gastroenterology And Hepatology, Catharina hospital, Eindhoven/Netherlands stable fluoroscopy of the region of interest to generate a mask for consecutive
4
Gastroenterology & Hepatology, Academic Medical Centre, Amsterdam/ subtraction. Thereafter contrast medium is injected. After RMF application all
Netherlands further fluoroscopy images contain the information of the subtraction as steady
overlay. Directly after the RMF was finished, the complete fluid was removed
Contact E-mail Address: [email protected] from the esophagus to avoid aspiration. Patients were all investigated in recum-
Introduction: Volumetric laser endomicroscopy (VLE) is an advanced imaging bent position under sedation with midazolam or propofol. All further interven-
system that provides a 6-cm long, circumferential scan of the esophageal wall tions and measurements were performed by using the RM images.
subsurface layers with near-microscopic resolution. VLE has the potential to Result: 21 investigations were performed in 18 patients (age:71  13 years male:12
improve the detection of neoplasia during Barrett’s esophagus (BE) surveillance. female:6). Indications for interventions were: balloon dilatation of benign stric-
A new feature of the VLE system is a laser marking tool that enables direct tures: n ¼ 9 including 1 pneumatic balloon dilatation for the treatment of acha-
marking of suspicious areas during VLE scanning, which subsequently can be lasia, bouginage of benign stricture: n ¼ 3 and diagnostic radiography without
targeted for histological sampling. We herein describe the first in human use of intervention: n ¼ 1. In addition 8 stents, 5 partially covered and 3 fully covered,
the VLE laser marking tool in BE patients. were placed using RMF as a guide for exact determination of stent length and
Aims & Methods: The aim is to evaluate visibility and positional accuracy of VLE diameter. Stents were also deployed under RMF guidance (figure). Endoscopic
laser marks in different esophageal tissue types on white light endoscopy (WLE) control revealed desired stent position in all cases. The choice of stent was made
and VLE. BE patients with and without neoplasia were imaged with VLE. In a by measurement of the length of the stenosis as well as diameter of healthy
learning phase protocol refinements were practiced. In the second phase, visibi- esophagus adjacent to the stricture. Available stents that fitted best to the mea-
lity of laser marks (LMs) was assessed by randomly marking 4 quadrants in sured dimensions were implanted. In all procedures RMF successfully guided the
squamous, BE and gastric tissue. LMs were automatically placed in offset intervention. The feeling of resistance during bouginage was exactly matching the
mode; 2 LMs 6 mm apart horizontally. In the third phase, positional accuracy location for RMF projection of the stenosis. With the help of RM imaging
of LMs was tested, whereby previously placed electrocoagulation markers dilatation balloons could easily be centered inside the stenosis to avoid slipping
(ECMs) were targeted on VLE and laser marked (2 ECMs per tissue type). In of the balloon. Complications did not occur.
the final phase, in each patient the most suspicious areas for neoplasia were Conclusion: RMF provides the possibility of permanent radiographic illustration of
identified on VLE, targeted by laser marks and subsequently biopsied. stenosis or anatomic changes throughout the intervention by using contrast medium
Result: In total 17 BE patients were included (15 males, median age 67): 11 only at the beginning of the intervention. RMF is feasible and safe to guide radi-
patients with non-dysplastic (ND)BE, 6 patients with high-grade dysplasia ology based interventions in the esophagus. RMF directs the selection of stents
(HGD) or early esophageal adenocarcinoma (EAC). Median BE length: C2 better than endoscopy because all relevant dimensions can be measured exactly.
(IQR 1–9) M4 (IQR 4–11). In total 222 LMs were placed, of which 207 (93%) Disclosure of Interest: All authors have declared no conflicts of interest.
were visible upon WLE and 192 (86%) on VLE, see table for visibility per tissue
type. In total in 25/33 of targeted ECMs (76%) the LMs were confirmed to be
positioned accurately. Three ECMs were not accurately targeted due to a system TUESDAY, OCTOBER 18, 2016 10:30–12:00
error and 5 due to difficult visualization on VLE. In the final phase (5 patients), SMALL BOWEL DISEASE AND NUTRITIONAL THERAPY – ROOM
18 areas identified on VLE as most suspicious were successfully targeted by LMs 1.86_____________________
(3 areas contained EAC, 3 HGD, 1 LGD and 11 NDBE). Mean VLE procedure
time was 22 minutes (SD 6) – with a mean total endoscopy time of 56 minutes OP228 GASTROINTESTINAL DISEASES IN COMMON VARIABLE
(SD 17). No adverse events were reported. IMMUNODEFICIENCY
S. Pikkarainen1, T. Martelius2, J. Selenius3, M. Seppänen4, M.A. Färkkila1
Visibility of laser marks in esophageal tissue types 1
Dept. Of Gastroenterology, Helsinki University Hospital, Helsinki/Finland
2
Dept Of Infectious Diseases, Helsinki University Hospital, Helsinki/Finland
Gastric Barrett’s Squamous 3
Rare Diseases Center And Dept. Of Infectious Diseases Clinic, Helsinki University
mucosa mucosa mucosa TOTAL
Hospital, Helsinki/Finland
4
Rare Diseases Center, Helsinki University Hospital, Helsinki/Finland
Upon WLE 49/62 (79%) 96/96 (100%) 62/64 (97%) 207/222 (93%)
Upon VLE 43/62 (69%) 88/96 (92%) 61/64 (95%) 192/222 (86%) Contact E-mail Address: [email protected]
Introduction: Common variable immunodeficiency (CVID) is the most common
Conclusion: The first in human use of VLE laser marking in 17 BE patients was symptomatic primary immunodeficiency in adults. CVID is a combination of
found to be feasible and safe. The majority of the LMs was visible upon WLE humoral and cell-mediated deficiency, and the cornerstone of its treatment is
and VLE, although appearance on VLE can be subtle. Targeting VLE areas of intravenous or subcutaneous immunoglobulin therapy. However, while this
interest proved to be highly successful and VLE laser marking may thus improve treatment prevents infections, many CVID patients may still develop a broad
the clinical value of VLE in BE surveillance in the future. spectrum of gastrointestinal disorders including autoimmune and inflammatory
diseases such as atrophic gastritis, small bowel villous atrophy and inflammatory
bowel disease (IBD).
United European Gastroenterology Journal 4(5S) A91
Aims & Methods: Aim of the study: To investigate in detail the gastrointestinal have a physiologically different profile compared to non post-cholecystectomy
phenotype of CVID patients living in southern Finland. Patients and Methods: Type 3a patients, with more severe bile acid malabsorption. This warrants sepa-
Our study cohort consisted of 105 adult CVID patients followed up between rate analysis in future research.
2007–2015 in Helsinki University Hospitaĺs Adult Immunodefiency Unit and Disclosure of Interest: All authors have declared no conflicts of interest.
the respective outpatient clinics of Carea and Eksote. CVID patients were diag- Reference
nosed with the strict vaccine response criteria and lived within these 3 hospital
districts of southern Finland (1.9 million inhabitants). Adult patients of this 1. Summers et al 2016 BMJ Open Gastro., ahead of print.
cohort were diagnosed from the year 1960 to 2015 when recruitment stopped.
We investigated retrospectively their medical records, laboratory results, endo-
scopy (over 300 endoscopies) ja histology reports and data was collected to an
electronic database designed for the study. Of this patient cohort, 12 patients died OP230 EVALUATING THE UTILITY OF AMINO ACID CITRULLINE AS
and 11 were lost to follow up. A METABOLOMIC SIGNATURE IN PREDICTIVE AND FOLLOW UP
Result: Upper endoscopy and ileo-colonoscopy were done at least once to 83 VALUE IN CELIAC DISEASE; SUGGESTING IT TO BE A MARKER
(79%) and 77 (73%) patients, respectively. 1. Gastric: Helicobacter pylori was OF ENTEROCYTE VILLOUS DAMAGE
found in 7 patients, was negative in 74 and unknown in 23 patients. Eradication A. Lomash, S. Kumar, S. K. Polipalli, S. Kapoor
was succesful in all Helicobacter-positive patients. Helicobacter-negative chronic Pediatrics, MAMC & Associated LN Hospital, New-Delhi/India
gastritis without marked atrophy, but ranging from mild to severe inflammatory
activity, was found in 11 patients (11%). In addition, atrophic gastritis was found Contact E-mail Address: [email protected]
in 10 patients (10%). 2. Small bowel: All tested patients were seronegative for Introduction: Amino acid citrulline is a non-essential amino acid which does not
coeliac disease. Of patients with increased intra-epithelial lymphocytes and vil- corporate into proteins and small intestine (gut enterocyte) is the main endogen-
lous atrophy of duodenum, 2 had complete histological and clinical response to ous source of circulating citrulline in blood. Since celiac disease is thought to be a
gluten-free diet and all 4 others were unresponsive but had no enterocyte anti- highly heterogeneous spectrum ranging from classic malabsorptive form to aty-
bodies. 3 of the patients with refractory duodenal villous atrophy and inflamma- pical potential or latent form. It is envisaged that citrulline could be an important
tion had also inflammatory changes in colon as well. 3. Hepatobiliary: Primary metabolomic or proteomic signature to assess silent and potential forms of the
sclerosing cholangitis or CVID-associated cholangitis was diagnosed in 5 disease, compliance of the disease after institution of gluten free diet and it may
patients. 3. Large Bowel: Inflammatory changes of mucosa ranged from unspe- add predictive value for closer surveillance of high risk groups such as first degree
cific colitis and microscopic colitis (including lymphocytic colitis and collagen relatives of CD.
colitis) to crypt-desctructive and/or graft-versus-host like severe inflammation. Aims & Methods: We aimed to evaluate the baseline and six months follow up
Colonic enteropathy included IBD-like phenotypes: colitis ulcerosa was diag- plasma citrulline levels in patients with celiac disease and in their first degree
nosed in 5 patients (2 colectomies) and one patient had stricturing ileocolonic relatives and to establish a correlation between histopathological findings and the
Crohńs disease. Altogether, inflammation of colon was more common than small amino acid levels as a biomarkers for villous atrophy. Materials and Method:
bowel enteropathy and it was found in 20 patients (19%). Prior to ileocolono- The procedure adopted for measuring plasma citrulline was Tendem Mass
scopy, bacterial and parasitic infections were ruled out by standard laboratory Spectrometery (LC-MS/MS) & RP-HPLC. Disease state was confirmed by his-
methods including fecal sample screening. Nodular lymphatic hyperplasia was topathology findings including Marsh score and HLA typing(DQ2 & DQ8) BY
detected from gastric mucosa to rectum, and ranged from asymptomatic SSP-PCR
enhanced ileal nodularity to major changes of the gastric and bowel mucosal Result: Mean plasma citrulline levels in 54 serology positive subjects was
appearance and function. It was relatively common finding and noted in 36 9.0  SD umol/L whereas the mean citrulline levels in 124 serology negative
patients (34%). 4. Mortality and gastrointestinal malignancies: 12 patients died subjects (first degree relatives) was 24.3umol/L. This difference was statistically
during the follow up and in 3 patients it was directly due to metastatic malig- highly significant with p value of 0.0001. Correlations between biopsy grades of
nancies of gastrointestinal tract: 2 patients with gastric adenocarcinoma and one Subjects with their citrulline levels were established & found to be significant. For
patient with adenocarcinoma of the colon. Small bowel enteropathy had been Marsh 3c grade lesions, mean citrulline levels were 5.6  SD umol/L. For Marsh
found also in other 2 patients that died due to the cardiovascular disease. 3b, mean citrulline levels were 15.0  SD umol/L with p value 0.006.
Meanwhile, one patient with unspecific inflammatory nodularity of colon even- Understandably the patients with total villous atrophy had a lower citrulline
tually developed ceacal large B-cell lymphoma which was timely diagnosed, and levels even if they were asymptomatic. All the patients were on stringent six
treated successfully. month follow up and the mean levels were 12.8  SD umol/L. DQ2 heterodimer
Conclusion: Gastrointestinal and hepatobiliary manifestations are common were collectively found in 71.63% high risk subjects. A total of 8.69% subjects
among patients with CVID and the risk malignancies are increased. found negative for HLA DQ2 heterodimer. HLA type DQ8 was not found in any
Disclosure of Interest: All authors have declared no conflicts of interest. of the subject.
Reference Conclusion: Citrulline alone is a very important metabolomic signature of initial
damage of gut enterocytes in celiac disease and also when correlated with Marsh
1. Resnick, Elena S. et al. ‘‘Morbidity and Mortality in Common Variable score. Citrulline estimation on dried blood spots using tandem mass spectrometry
Immune Deficiency over 4 Decades.’’ Blood 119.7 (2012): 1650–1657. is a minimally invasive and promising test in near future which could be trans-
ported from the remotest place in the country to suggest improvement in gut
enterocyte mass. Plasma citrulline estimation assures detection of potential celiac
disease and may be use for monitoring of compliance and recovery in CD which
OP229 BILE ACID DIARRHOEA: EVIDENCE FOR LOWER SEHCAT is likely to be of immense benefit in the diagnosis of celiac disease and analyzing
RETENTION IN TYPE 3 PATIENTS FOLLOWING citrulline on dried blood spot by a highly sensitive technique of liquid chromato-
CHOLECYSTECTOMY graphy mass spectrometry may ease follow up and diagnosis of CD
J. Mclaughlin1, R. Logan2, F. Reid3, J. Summers3 Disclosure of Interest: All authors have declared no conflicts of interest.
1
Gi Centre, University of Manchester Salford Royal Hospital Gastrointestinal
Centre, Manchester/United Kingdom
2
Department Of Gastroenterology, Kings College Hospital, London/United
Kingdom OP231 CELLULAR ZINC IS REQUIRED FOR INTESTINAL
3
Kings College, London/United Kingdom EPITHELIAL BARRIER MAINTENANCE VIA THE REGULATION
OF CLAUDIN-3 AND OCCLUDIN EXPRESSION
Contact E-mail Address: [email protected] T. Suzuki, Y. Miyoshi
Introduction: Bile Acid Diarrhoea (BAD) is an under-recognised cause of chronic Graduate School Fo Biosphere Science, Hiroshima University, Higashi-Hiroshima/
diarrhoea and can be assessed by measuring SeHCAT retention. BAD can relate Japan
to terminal ileal disease or resection (designated as Type 1), be considered as
idiopathic (type 2), or be linked to other underlying conditions (Type 3). Its Contact E-mail Address: [email protected]
prevalence is increased following cholecystectomy, but the clinical profile and Introduction: Intracellular zinc is required for a variety of cell functions. Previous
severity of bile acid malabsorption are poorly characterised. studies suggest that the intracellular zinc has an essential role in the maintenance
Aims & Methods: A prospective study evaluated SeHCAT usage across the of the intestinal tight junction (TJ) barrier, however, the underlying mechanisms
United Kingdom was undertaken, capturing data from 38 centres and 1,036 remain unclear (1, 2). The present study investigated the essential roles of intra-
patients. Aims were to investigate SeHCAT retention rates according to the cellular zinc in the preservation of intestinal TJ integrity and the underlying
type of BAD suspected, and to evaluate centre-defined abnormal results. molecular mechanisms in human intestinal Caco-2 cells and mouse colons.
Result: Of the 1,036 patients, 752 had information on suspected BAD type, of Aims & Methods: Depletion of intracellular zinc in Caco-2 cells and mouse colons
whom 310 had suspected Type 3 BAD (71% female, mean age 49 years). A large was achieved by the application of a cell permeable zinc chelator, N, N,N’,N’-
subset were identified as post-cholecystectomy (n ¼ 98, 82% female, mean age 52 Tetrakis(2-pyridylmethyl)ethylenediamine (TPEN). Caco-2 cells grown in
years) and non post-cholecystectomy (n ¼ 212, 67% female, mean age 48 years). Transwell inserts were incubated with TPEN. The TJ barrier function was
Suspected Type 3 are hereon referred to as BAD Types 3a (all except post- assessed by measuring transepithelial electrical resistance (TER) and dextran
cholecystectomy) and 3b (post-cholecystectomy only). Patients with suspected flux. The TJ proteins expression and distribution (ZO-1, ZO-2, occludin, JAM-
BAM Type 3a had the largest mean retention of 25% (95% CI: 22.3–28.0%, 1, and claudin-1-4) were evaluated by immunoblot, immunofluorescence and
median ¼ 20, while post-cholecystectomy patients (BAD Type 3b) had a mean qPCR analyses. To confirm specificity of the TPEN effects, ZnSO4 was supple-
retention of 15% (95% CI: 11.7–18.3%, median ¼ 9). These compare to mean mented to the culture media in the presence of TPEN. The TPEN-induced pro-
retentions of 9% in suspected Type 1 and 21% in Type 2 (1). Centre-defined teolysis of occluidn was examined by biotinylation of cell surface proteins. To
abnormal results were higher amongst suspected Type 3b patients (56%) than examine the mechanisms underlying for the zinc depletion-induced occludin pro-
Type 3a (30%), with correspondingly higher bile acid sequestrant prescriptions teolysis, selective inhibitors of calpain, proteasomes, autophagy, matrix metallo-
for Type 3b patients (49%) than Type 3a (25%) at the time of the survey. protease and cathepsin were used. The effect of zinc depletion on claudin-3
Conclusion: Subdivision of BAD Type 3 patients suggest (although not conclu- promoter activity was examined by means of a reporter gene assay. Roles of
sively given the limitations of this survey) that post-cholecystectomy patients transcription factors, sp1 and egr1, for the zinc-mediated claudin-3 promoter
A92 United European Gastroenterology Journal 4(5S)
activity were examined by a mutagenesis technique in the promoter assay and poorly. Fatigue was a major limiting symptom. The global QOL numerical
RNA interference technology. The effects of TPEN on occludin and claudin-3 rating was also poor in all groups.
expression in mouse colons were also examined in combination with the calpain Conclusion: As part of the holistic clinical care of patients on HPN, their QOL
inhibitor. should be considered. Results of this study show that the majority of our HPN
Result: Intracellular zinc depletion by TPEN impaired the TJ barrier of intestinal patients experience problems that impair their QOL. It is not possible to establish
Caco-2 cells, indicated by decreased TER and increased dextran flux. The TPEN- how much this relates to the underlying condition or HPN itself. This is an area
induced TJ disruption is associated with downregulation of 2 TJ proteins, occlu- that would benefit from further study.
din and claudin-3. These changes induced by TPEN were completely restored by Disclosure of Interest: All authors have declared no conflicts of interest.
supplemental zinc. Biotinylation of cell surface proteins revealed that the zinc
depletion induced the proteolysis of occludin, but not claudin-3. Occludin pro- Reference
teolysis was sensitive to the inhibition of calpain activity, and increased calpain 1. Baxter JL, Fayers PM and McKinlay AW. The Clinical and Psychometric
activity was observed in the zinc-depleted cells. Although qPCR analysis and Validation of a Questionnaire to Assess the Quality of Life of Adult Patients
promoter reporter assay have demonstrated that the zinc depletion-induced clau- Treated With Long-Term Parenteral Nutrition. JPEN J Parenter Enteral
din-3 downregulation occurred at transcriptional levels, a site-directed mutation Nutr 2010; 34: 131.
in the egr1 binding site in the claudin-3 promoter sequence induced loss of both
the basal promoter activity and the TPEN-induced decreases. Reduced egr1
expression by a specific siRNA also inhibited the claudin-3 expression and bar-
rier maturation in cells. In mouse colons, the calpain inhibitor restored the
TPEN-induced decrease in occludin, but not claudin-3. OP233 EARLY ENTERAL VERSUS TOTAL PARENTERAL NUTRITION
Conclusion: This study shows that intracellular zinc has an essential role in the IN PATIENTS UNDERGOING PANREATICODUODENECTOMY: A
maintenance of the intestinal epithelial TJ barrier through regulation of occludin RANDOMIZED MULTICENTER CONTROLLED TRIAL (NUTRI
proteolysis and claudin-3 transcription. Intracellular zinc seems to physiologi- DPC)
cally suppress occludin proteolysis by robust calpain activity. Further, zinc J. Perinel1, C. Mariette2, B. Dousset3, I. Sielezneff4, A. Gainant5, J. Mabrut6,
finger-containing egr1 was shown to be critical for the transcriptional regulation S. Bin Dorel7, M. El Bechwaty8, M. Pocard9, E. Buc10, A. Sauvanet11, M. Adham
of claudin-3. (Member Efisds)12
1
Disclosure of Interest: All authors have declared no conflicts of interest. Dept. Of Hepato-biliary, hospices civils de lyon, Lyon/France
2
References Department Of Digestive And Oncological Surgery, University Hospital Claude
Huriez, Lille/France
1. Finamore A, Massimi M, Conti Devirgiliis L and Mengheri E. Zinc defi- 3
Department Of Digestive Surgery, Hôpital Cochin – St-Vincent de Paul, PARIS/
ciency induces membrane barrier damage and increases neutrophil transmi- France
gration in Caco-2 cells. J Nutr 2008; 138: 1664–1670. 4
Digestive Surgery Unit, Marseille University Hospital, Marseille, Marseille/
2. Wang X, Valenzano MC, Mercado JM, Zurbach EP and Mullin JM. Zinc France
supplementation modifies tight junctions and alters barrier function of 5
Department Of Digestive Surgery, CHU Dupuytren, Limoges/France
CACO-2 human intestinal epithelial layers. Dig Dis Sci 2013; 58: 77–87. 6
Department Of Digestive Surgery And Liver Transplantation, Croix-Rousse
Hospital, Lyon/France
7
Pole Information Me´dicale Evaluation Recherche, Lyon/France
8
Department Of Hepato-biliary And Pancreatic Surgery, Edouard Herriot
OP232 EVALUATING THE QUALITY OF LIFE OF ADULT PATIENTS Hospital, Lyon/France
9
ON HOME PARENTERAL NUTRITION IN NORTHERN AND Department Of Digestive Surgery, APHP, PARIS/France
10
NORTHEAST ENGLAND Department Of Digestive Pathology, Surgery Unit, CHU Clermont Ferrand
M. Hu, L. Gemmell, H. Cook, H. Leyland, J. Leeds, D. Mansour, N. Thompson, Hôtel Dieu, Clermont ferrand/France
11
C. Mountford Department Of Hepato-biliary And Pancreatic Surgery, Hôpital Beaujon, clichy/
Department Of Gastroenterology, Freeman Hospital, Newcastle-upon-Tyne/United France
12
Kingdom Department Of Hepato-biliary And Pancreatic Surgery, Edouard Herriot
Hospital, LYON/France
Contact E-mail Address: [email protected]
Introduction: Home parenteral nutrition (HPN) is an established treatment for Contact E-mail Address: [email protected]
the management of patients with Type 3 intestinal failure (IF). A Quality of Life Introduction: Current nutritional guidelines recommend the use of enteral over
(QOL) assessment tool (HPN-QOL version 1.0) was developed and validated in parenteral nutrition in patients undergoing gastrointestinal surgery. However,
2009 specifically for this patient population (1). Little data exist in literature on the NJEEN remains controversial in patients undergoing PD.
the QOL of HPN patients. We incorporated this tool into local clinical practice Aims & Methods: To compare nasojejunal early enteral nutrition (NJEEN) with
to evaluate the QOL of our HPN cohort in Northern and Northeast England. total parenteral nutrition (TPN), after pancreaticoduodenectomy (PD), in terms
Aims & Methods: The HPN-QOL was discussed with all patients in clinic and of postoperative complications. Multicenter, randomized, controlled trial was
sent by post with a prepaid return envelope and a letter explaining how informa- conducted between 2011 and 2014. Nine centers in France analyzed 204 patients
tion will be used. Participation was voluntary. Responses were collected between undergoing PD to NJEEN (n ¼ 103) or TPN (n ¼ 101). Primary outcome was the
February and July 2015. Data were anonymised for analysis and reporting. rate of postoperative complications according to Clavien-Dindo classification.
Patients scored themselves in 45 questions relating to 10 domains of function and Successful NJEEN was defined as insertion of a nasojejunal feeding tube, deli-
9 domains of symptoms. 3 further questions asked for a global numerical rating vering at least 50% of nutritional needs on PoD 5, and no TPN for more than
of QOL. A final question allowed free text comments. Scores were computed if at consecutive 48 hours.
least half of the questions in each domain were answered as per the validated Result: Postoperative complications occurred in 77.5% (IC 95% [68.1–85.1])
process in HPN-QOL. Raw patient responses were scaled to a score of 0–100 for patients in the NJEEN group versus 64.4% (IC 95% [54.2–73.6]) in TPN
each domain. The QOL global numerical ratings had a scale of 60 to 65. Based group (p ¼ 0.040). NJEEN was associated with higher frequency of postoperative
on the rating descriptors in the HPN-QOL we interpreted a scaled score of more pancreatic fistula (POPF) (48.1% vs. 27.7%, p ¼ 0.012) and higher severity
than 50 in domains relating to function as good functioning ability. A scaled (grade B/C 29.4% vs. 13.9%; p ¼ 0.007). There was no significant difference in
score exceeding 50 in symptom domains were interpreted as frequent symptoms the incidence of post-pancreatectomy hemorrhage, delayed gastric emptying,
impairing QOL. For the QOL global numerical ratings, a scaled score of 23 or infectious complications, the grade of postoperative complications and the
more was interpreted as good overall QOL. length of postoperative stay. A successful NJEEN was achieved in 63% patients.
Patients were grouped according to the following 4 criteria for further analysis: In TPN group, average energy intake was significantly higher (p 5 0.001) and
gender, age (455 and 55), presence of stoma, and aetiology of IF. Within each patients had an earlier recovery of oral feeding (p ¼ 0.0009).
group, QOL scaled scores were compared in every domain using the Kruskal- Conclusion: In patients undergoing PD, NJEEN was associated with increased
Wallis test. overall postoperative complications rate. The frequency and the severity of
Result: 55 responses were received from 67 patients. Two responses were excluded POPF were also significantly increased after NJEEN. In term of safety and
due to insufficient information to perform any form of analysis. 22 patients feasibility, NJEEN should not be recommended.
(41.5%) were male and 31 female. Median age was 55 years (range 19–85). 27 Disclosure of Interest: All authors have declared no conflicts of interest.
patients (50.9%) were 55 years and younger and 26 patients were older than 55
References
years. The aetiologies of intestinal failure were mesenteric ischaemia, 16 (30.2%);
inflammatory bowel disease (IBD), 15 (28.3%); surgical complications, 8 1. Bozzetti F, Gianotti L, Braga M, et al. Postoperative complications in gas-
(15.1%); motility disorder and radiation enteritis, 5 each (18.9% in total); and trointestinal cancer patients: the joint role of the nutritional status and the
malignancy, 4 (7.5%). 37 patients (69.8%) had a stoma and 16 had no stoma. nutritional support. Clin Nutr 2007; 26: 698–709.
There was no significant difference between patients with and without a stoma in 2. La Torre M, Ziparo V, Nigri G, et al. Malnutrition and Pancreatic Surgery:
all domains except gastrointestinal (GI) symptoms (p ¼ 0.01). This is in keeping Prevalence and Outcomes. J Surg Oncol 2013; 107: 702–8.
with findings by Baxter, et al (1). In gender analysis, males reported better ability 3. Kanda M, Fujii T, Kodera Y, et al. Nutritional predictors of postoperative
to eat and drink (p ¼ 0.027), better perceived support from the MDT (p ¼ 0.027), outcome in pancreatic cancer. Br J Surg 2011; 98: 268–74.
and better sexual function (p ¼ 0.046). However, they also reported more GI 4. Weimann A, Braga M, Harsanyi L, et al. ESPEN guidelines on enteral
symptoms (p ¼ 0.006). In age group analysis, patients over 55 had lower employ- nutrition: surgery including organ transplantation. Clin Nutr 2006; 25:
ment scores (p ¼ 0.004) and more GI symptoms (p ¼ 0.014). The lower employ- 224–44.
ment scores may be confounded by advancing age alone. In analysis of aetiology, 5. Braga M, Ljungqvist O, Soeters P, et al. ESPEN guidelines on parenteral
patients with motility disorders reported significantly reduced ability to eat and nutrition: surgery. Clin Nutr 2009; 28: 378–86.
drink compared to those with other causes of IF except malignancy (p ¼ 0.034). 6. Bozzetti F, Braga M, Gianotti L, et al. Postoperative enteral versus parent-
Regardless of gender, age, or presence of stoma, patients generally rated their eral nutrition in malnourished patients with gastrointestinal cancer: a rando-
ability to travel/holiday, physical function, employment and sexual function mised multicentre trial. Lancet 2001 Nov; 358(9292): 1487–92.
United European Gastroenterology Journal 4(5S) A93
7. Moore FA, Feliciano DV, Andrassy RJ, et al. Early enteral feeding, com- OP235 THE CENTRAL ROLE OF THE GUT MICROBIOTA IN CHRONIC
pared with parenteral, reduces postoperative septic complications. The INTESTINAL PSEUDO-OBSTRUCTION
results of a meta-analysis. Ann Surg 1992; 216: 172–83. S. Sidani1, G. De Palma1, M. Pigrau1, J. Lu1, E.F. Verdu1, N. Causada Calo1, C.
8. Braga M, Gianotti L, Gentilini O, et al. Early postoperative enteral nutrition H. Lee2, S. M. Collins1, P. Bercik1
improves gut oxygenation and reduces costs compared with total parenteral 1
Farncombe Family Digestive Health Research Institute, McMaster University,
nutrition. Crit Care Med 2001; 29: 242–8. Hamilton/Canada/ON
9. . Enteral versus parenteral nutrition after gastrointestinal surgery: a systema- 2
Department Of Microbiology, St. Joseph’s Healthcare Hamilton, Hamilton/
tic review and meta-analysis of randomized controlled trials in the english Canada/ON
literature. J Gastrointest Surg 2008 Apr; 12(4): 739–55MazakiTEbisawaK.
10. Braunschweig CL, Levy P, Sheean PM, et al. Enteral compared with par- Contact E-mail Address: [email protected]
enteral nutrition: a meta-analysis. Am J Clin Nutr 2001 Oct; 74(4): 534–42. Introduction: Chronic Intestinal Pseudo-Obstruction (CIPO) is a chronic severe
11. Di Carlo V, Gianotti L, Balzano G, et al. Complications of pancreatic sur- disorder of gastrointestinal (GI) motility leading to clinical features of intestinal
gery and the role of perioperative nutrition. Dig Surg 1999; 16(4): 320–6. obstruction without mechanical occlusion. The intestinal microbiota is a key
12. Gianotti L, Braga M, Gentilini O, et al. Artificial nutrition after pancreati- factor determining gut motility. We hypothesized that dysbiosis may be found
coduodenectomy. Pancreas 2000; 21(4): 344–51. in CIPO and that it contributes to clinical features of the disease.
13. Yermilov I, Jain S, Sekeris E, et al. Utilization of parenteral nutrition follow- Aims & Methods: 1) To characterize the gut microbiota of patients with CIPO. 2)
ing pancreaticoduodenectomy: is routine jejunostomy tube placement war- To determine whether this microbiota is responsible for clinical features typical
ranted?. Dig Dis Sci 2009; 54: 1582–8. of CIPO using a gnotobiotic mouse model. 3) To evaluate whether faecal micro-
14. Gerritsen A, Besselink MG, Cieslak KP, et al. Efficacy and complications of biota transplantation (FMT) improves symptoms of CIPO. The faecal micro-
nasojejunal, jejunostomy and parenteral feeding after pancreaticoduodenect- biota of 3 patients with CIPO (1 female, median age 38.6  11 years) and 3
omy. J Gastrointest Surg 2012; 16: 1144–51. healthy volunteers (2 females, 39.5  9 years) was analyzed by 16S rRNA
based Illumina sequencing. Stool samples from 1 patient with CIPO and 1
healthy control were used to colonize germ-free NIH Swiss mice (n ¼ 15 mice
TUESDAY, OCTOBER 18, 2016 10:30–12:00 per donor, mixed gender) by oral gavage. GI transit was determined at 2 weeks
ABSTRACTS ON FIRE: GI: ALL ABOUT MICROBIOTA? – HOTSPOT_____________________ using a validated in vivo videofluoroscopic technique1. Caecum and stomach
size, and maximal bowel diameter, were determined using oral contrast-enhanced
OP234 DIETARY EMULSIFIERS DIRECTLY IMPACT THE HUMAN abdominal CT scan. The faecal microbiota of recipient mice was analyzed 48
GUT MICROBIOTA INCREASING ITS PRO-INFLAMMATORY hours and 2 weeks after colonization by Illumina and inferred metagenomic
POTENTIAL profiles were assessed by PICRUSt. The CIPO patient was then treated with
B. Chassaing1, T. Van De Wiele2, A. Gewirtz1 FMT by jejunal infusion from a healthy donor at regular intervals for 20
1
Institute For Biomedical Sciences, Georgia State University, Atlanta/United weeks. GI symptoms, overall health and quality of life were assessed using stan-
States of America dardized questionnaires.
2
Laboratory Of Microbial Ecology And Technology, Ghent University, Ghent/ Result: The microbiota of patients with CIPO exhibited marked dysbiosis with
Belgium predominance of Proteobacteria species, especially Enterobacteriaceae and
Enterococcaceae. In contrast, healthy volunteers showed a predominance of
Contact E-mail Address: [email protected] Firmicutes and Bacteroidetes. Bacterial richness and diversity were lower in
Introduction: We recently demonstrated that, in mice, consumption of dietary CIPO patients. The faecal microbiota profiles of gnotobiotic mice resembled
emulsifiers, detergent-like components of many processed foods, results in a that of human donors. Mice colonized with microbiota from the CIPO patient
disturbed gut microbiota, including alterations in species composition, elevated had a slower GI transit than mice with healthy control microbiota (mean transit
pro-inflammatory potential (i.e. higher levels of bioactive LPS and flagellin) and score 1  2 vs. 12  5, p 5 0.001). Furthermore, CIPO microbiota colonized mice
microbiota encroachment (1). Such disturbance of the microbiota promotes a had a larger caecum size (2.39  0.32 cm3 vs. 1.56  0.22 cm3, p 5 0.001) and a
range of chronic inflammatory diseases including metabolic syndrome and coli- higher maximal bowel diameter (3.3  0.2 mm vs. 2.9  0.2, p ¼ 0.003) compared
tis. However, the underlying mechanism by which emulsifiers induce such effects, to control microbiota colonized mice. Bacterial genes related to bile acid meta-
including whether they act directly upon the microbiota or the host, remains bolism and disaccharide fermentation were differentially expressed in the faeces
unclear. of recipient mice. Importantly, FMT led to a rapid and sustained improvement in
Aims & Methods: Our aim in the current study was to investigate if, and how, GI symptoms and overall quality of life in our CIPO patient. His microbiota
emulsifiers directly impact upon the microbiota in the absence of a host response dramatically changed after FMT and resembled that of the donor.
The M-SHIMEÕ (Mucosal Simulator of the Gastrointestinal Microbial Conclusion: The faecal microbiota composition and its metabolic activity are
Ecosystem) model was used to examine the effects of emulsifiers on the micro- altered in patients with CIPO. This dysbiotic microbiota has the ability to
biota in vitro. After a stabilization period of 7 days, this dynamic human gut induce clinical features reminiscent of this disorder in a gnotobiotic mouse
model was treated with emulsifiers (Carboxymethylcellulose (CMC) or model. Finally, faecal transplantation may be an effective treatment for patients
Polysorbate-80 (P80), 1%). Microbiota composition, meta-transcriptomic and with CIPO.
pro-inflammatory potential (Flagellin and LPS loads) were analyzed. Disclosure of Interest: All authors have declared no conflicts of interest.
Microbiota metagenome was predicted using PICRUSt (Phylogenetic Reference
Investigation of Communities by Reconstruction of Unobserved States).
Human microbiota from the SHIME system was transferred to Germfree reci- 1. Reed DE, Pigrau M, Lu J, et al. Bead study: a novel method to measure
pient mice, with subsequent intestinal inflammation analysis. gastrointestinal transit in mice. Neurogastroenterol Motil 2014; 26: 1663–8.
Result: Both P80 and CMC treatment increased the pro-inflammatory potential
of human microbiota, as revealed by a dramatic increase in bioactive flagellin
within one day for CMC and 5 days for P80. P80 induced drastic alteration of the
human gut microbiota composition, associated with an increased proportion of OP236 MICROBIOTA DIVERSITY AT TIME OF SURGERY PREDICTS
genes involved in bacterial motility. Both P80 and CMC treatment did not sig- ENDOSCOPIC RECURRENCE IN CROHN’S DISEASE: A STUDY
nificantly alter branched or short chain fatty acid compositions, but significantly FROM THE REMIND GROUP
increased the proportion of microbiota mRNAs encoding motility related pro- H. Sokol1, L. Brot2, C. Stefanescu3, C. Auzolle4, N. Barnich5, A. Buisson6,
teins. When transferred to germfree recipient mice, P80 and CMC-treated human M. Fumery7, M. Nachury8, X. Treton9, S. Nancey10, M. Allez11, P. Seksik12
microbiota was sufficient to drive low-grade intestinal inflammation and meta- 1
Avenir Team Gut Microbiota, INSERM U1157/UMR CNRS 7203UPMC, Paris/
bolic syndrome. France
Conclusion: Both emulsifiers directly acted upon the microbiota to increase its 2
ERL U1057Paris/France
pro-inflammatory potential, indicating that at least a portion of the effects of 3
Service De Gastroenterologie Et Assistance Nutritive, Beujon Hospital, Clichy,
emulsifiers in vivo results from direct action of these compounds on the micro- Clichy/France
biota. The mechanisms by which P80 and CMC act are distinct, with P80 altering 4
Gastroenterology, Hopital Saint-Louis, APHP, INSERM U1160Universite´ Denis
the composition of the microbiota, favoring species expressing high level of Diderot, Paris/France
flagellin, whereas CMC increase the pro-inflammatory potential of the micro- 5
M2iSH, Inserm U1071Clermont-Ferrand/France
biota in a composition independent manner, by inducing expression of motility 6
Dept. Of Gastroenterology, CHU Estaing Clermont-Ferrand, Clermont-ferrand/
genes. France
Disclosure of Interest: All authors have declared no conflicts of interest. 7
Amiens University Hospital, Amiens/France
8
Reference Hepato-gastroenterology, CHRU Lille, Lille/France
9
Hopital Beaujon, Clichy/France
1. Chassaing B, Koren O, Goodrich JK, Poole AC, Srinivasan S, Ley RE, et al. 10
Dept. De Gastroenterologie, CHU Lyon, Pierre Benite/France
Dietary emulsifiers impact the mouse gut microbiota promoting colitis and 11
Gastroenterology, Hopital Saint-Louis APHP, Universite´ Denis Diderot Paris
metabolic syndrome. Nature 2015; 519(7541): 92–6. 7
Paris/France
12
Gastroenterology Department, Saint-Antoine Hospital, Paris/France
Contact E-mail Address: [email protected]
Introduction: Operative resection in Crohn’s disease (CD) is not curative. After
ileocecal resection, endoscopic recurrence is frequently observed on the anasto-
mosis and/or on the neo-terminal ileum.
Aims & Methods: The aim of this study was to analyze the mucosa associated
microbiota at time of surgery and to look for predictors of post-operative endo-
scopic recurrence within the microbiota. This is a prospective study performed in
9 centers of the REMIND group, collecting clinical and biological data at time of
A94 United European Gastroenterology Journal 4(5S)

Table (OP237)

Specific aim Study groups Control groups

1) Role of microbiota in the etiopathogenesis of PSC Early disease (ERC score 5), n ¼ 37 Healthy controls (C), n ¼ 46
2) Role of microbiota in disease progression Advanced bile duct disease (ERC score  6), n ¼ 36 Early disease, n ¼ 37
3) Role of microbiota in biliary dysplasia and CCA (DC) Patients with biliary dysplasia/CCA, n ¼ 11 Early and advanced PSC, n ¼ 73

surgery and of endoscopy (performed at 6 months). Bacterial composition of the of the Clinic of Gastroenterology. The indication for ERCP examination was the
ileal mucosa associated microbiota was analyzed at time of surgery using 16S documentation of diagnosis of PSC due to: 1) constantly elevated or fluctuating
(MiSeq, Illumina) sequencing. The obtained sequences (rarefied to 5000 read/ serum alkaline phosphatase (ALP) levels in conjunction with IBD, or 2) magnetic
sample) were analyzed using the Qiime pipeline to assess composition, alpha and resonance cholangiography findings, or 3) liver biopsy suggestive of PSC, or
beta diversity. Bacterial taxa associated with clinical parameters were identified dysplasia surveillance. During patient’s ERCP and before injecting contrast
using Multivariate association with Linear Models (MaAsLin) taking into media a bile sample was aspirated from extrahepatic bile ducts using balloon
account disease phenotype, clinical parameters and treatments. catheter, whenever possible. Brush cytology was routinely performed during
Result: 146 patients were included: 73 (50%) were male, median age at surgery ERC. ERC findings were scored according to the modified Amsterdam score
was 32 years (IQR 26–42). Median disease duration was 6 years (IQR 2–12). 44 (mAm score) and the number of ERC examination were recorded in each patient
patients (30%) were active smoker at time of surgery. Thirty patients (21%) had group. Isolation, amplification and sequencing of the bacterial 16S rRNA gene
a previous resection, and 35 patients (24%) had perianal lesions. Indication for were performed. The resulting data was analyzed with negative binomial general-
surgery was stricturing disease (n ¼ 95), penetrating disease (n ¼ 53). At time of ized linear models, PERMANOVA, and non-parametric tests.
surgery, 67 patients (46%) had received anti-TNF therapy within the last 3 Result: 1) A very low abundance OTU (‘‘species’’) belonging to the family
months. After surgery, 31 patients received thiopurines, and 52 patients received Neisseriaceae was reduced in abundance in the early disease group. 2) Increase
anti-TNF therapy. The microbiota was mainly composed of bacteria from the in Streptococcus from early disease to long disease progression. Streptococcus
Firmicutes (Mean 53%, range 0.3–99%), Proteobacteria (Mean 36%, range 0.5– also correlates with increase in ERC severity score and potentially with the
99%), Bacteroidetes (Mean 3%, range 0–52%) and Actinobacteria (Mean 6%, number of ERCP examinations. More robust are the findings regarding overall
range 0–81%) phyla. As expected, antibiotics treatment within one month before community diversity, which decreases in long progression and dysplasia/CCA. 3)
surgery had a dramatic impact on microbiota composition (Anosim, p 5 0.0001) A low abundance Prevotella OTU disappears in patients with dysplasia or CCA.
and diversity (mean observed species: 302  17 vs 236  14, p ¼ 0.005). In multi- Streptococcus seems to again increase.
variate analysis (MaAsLin), antibiotics treatment was notably associated with an Conclusion: The data in our exploratory study suggests that the etiology of the
increase in Enterococcus sp. (q 5 0.0001) and with a decrease in Lachnospiraceae disease is not connected with changes in biliary microbiota. However,
family (q ¼ 0.004). Taking into account only the patients who did not received Streptococcus seems to be connected with disease progression and risk of dys-
antibiotics within a month before surgery, we then looked for predictive factors plasia and CCA. It may also be related to the number of ERC examinations and
of endoscopic recurrence. Patients with endoscopic recurrence, defined by a therefore a role, at least partially, for nosocomial infection cannot be ruled out at
Rutgeerts score 1 (n ¼ 27), had a lower bacterial diversity at time of surgery this stage. Overall microbial diversity decreases in long progression and further
compared to patients in endoscopic remission (n ¼ 65) (mean observed species: more in dysplasia/CCA.
276  14 vs 365  45, p ¼ 0.015). Disclosure of Interest: All authors have declared no conflicts of interest.
Conclusion: Ileal mucosa associated microbiota of CD patients at time of surgery References
is dominated by bacteria belonging to Firmicutes, Proteobacteria, Bacteroidetes
and Actinobacteria phyla. Antibiotics given during the last month prior to surgery 1. Hirschfield GM, et al. Lancet. 2013;382:1587–99.
induce major perturbations of the microbiota. Reduction in bacterial diversity at 2. Bergquist A, et al. J Hepatol. 2002; 36:321–327.
time of surgery is predictive of endoscopic recurrence. 3. Tabibian JH, et al. Scand J Gastroenterol. 2014; 49: 901–908.
Disclosure of Interest: H. Sokol: Consulting fee: danone, Roche, Enterome, 4. Tabibian JH, et al. Biomed Res Int. 2013;2013:389537.
Maat, MSD, Astellas 5. Eksteen B. Br Med Bull. 2014;110:89–98.
All other authors have declared no conflicts of interest.
Reference
1. This study has been supported by grants from MSD France, Association OP238 INCREASED FAECAL LEVELS OF GRANINS IN IRRITABLE
François Aupetit, the Helmsley Charitable Trust and INSERM. BOWEL SYNDROME ARE ASSOCIATED WITH LUMINAL
MICROBIOTA COMPOSITION AND SYMPTOM SEVERITY
J. Sundin1, S. M.P. Bennet2, J. Tap3, M. Derrien3, B. Le Nevé4, M. Stridsberg5,
H. Törnblom6, L. Öhman7, M. Simrén8
OP237 BILE MICROBIOTA IN PRIMARY SCLEROSING 1
Sahlgrenska Academy, Institute of Medicine, Gothenburg/Sweden
CHOLANGITIS: EFFECTS ON DISEASE STAGE AND RISK FOR 2
Sahlgrenska Academy, Sahlgrenska Academy At University Of Gothenburg,
BILIARY DYSPLASIA Gothenburg/Sweden
P. Pereira1, V. Aho2, J. Arola3, S. Boyd4, K. Jokelainen5, P. Auvinen6, 3
Life Science, Danone Research, Palaiseau/France
M.A. Färkkila5 4
Dept. Of Life Sciences, Danone Research Deprt. of Life Science, Palaiseau/
1
Institute Of Biotechnology, Dna Sequencing And Genomics Laboratory, Helsinki France
5
University Hospital, Helsinki/Finland Department of Clinical Chemistry, Uppsala/Sweden
2 6
Institute Of Biotechnology, Dna Sequencing And Genomics Laboratory, Helsinki Institute Of Medicine, Sahlgrenska Academy, University of Gothenburg,
University, Helsinki/Finland Gothenburg/Sweden
3 7
Huslab, Helsinki University Hospital, Helsinki/Finland Sahlgrenska Academy, University of Gothenburg Sahlgrenska Academy Dept. of
4
Department Of Pathology, Hyks, Helsinki/Finland Microbiology and Immunoly, Gothenburg/Sweden
5 8
Dept. Of Gastroenterology, Helsinki University Hospital, Helsinki/Finland Dept Of Internal Medicine, Sahlgrenska University Hospital, Gothenburg/Sweden
6
Institute Of Biotechnology, Dna Sequencing And Genomics Laboratory, Helsinki
University, Helsinkik/Finland Contact E-mail Address: [email protected]
Introduction: Chromogranins (Cg) and secretogranins (Sg) are acidic gut hor-
Contact E-mail Address: [email protected] mones, which are secreted from the neuroendocrine system and may regulate
Introduction: Primary sclerosing cholangitis (PSC) is a chronic inflammatory liver immune activation. We have previously shown increased levels of faecal Cg
disease leading to strictures in intra- and extrahepatic bile ducts and finally to and Sg in IBS patients (1). However, the consequences and cause of increased
cholestasis and secondary biliary cirrhosis (1). The chronic inflammation is asso- levels of luminal granins in IBS are still undefined.
ciated with increased proliferation of biliary epithelial cells and a markedly Aims & Methods: In this study we aimed to quantify faecal granin levels in IBS
increased risk of development of biliary dysplasia and cholangiocarcinoma (2). patients and evaluate potential relationships between granin levels, microbiota
The etiopathogenesis of PSC is unknown, but the frequent association with composition and immune activation. Levels of CgA, CgB, SgII, SgIII and cal-
inflammatory bowel disease, in 62–83% of PSC patients, and increased intestinal protectin were analysed with radioimmunoassay and ELISA, respectively, in
permeability in PSC has suggested a role for microbiota or microbial metabolites faecal samples from IBS patients (n ¼ 143) and healthy subjects (n ¼ 43).
or derivatives, e.g. pathogen-associated molecular patterns, PAMPs) such as mRNA expression of interleukin (IL)-8, IL-10, tumour necrosis factor (TNF)
lipopolysaccharide (LPS), lipoteichoic acid, and peptidoglycan in the etiopatho- and forkhead box P3 (FOXP3) in mucosal biopsies from the sigmoid colon was
genesis of the disease (3–5). It has been proposed that the association between determined with qRT-PCR. Faecal (n ¼ 111 subjects) and mucosal-associated
PSC and IBD can be due to increased enterohepatic circulation of PAMPs microbiota (n ¼ 50 subjects) were analysed by 16S rRNA targeted pyrosequen-
(‘‘leaking gut’’), or abnormal PAMPs (as a result of enteric microbial dysbiosis, cing. IBS symptom severity and psychological distress were evaluated with the
described in IBD). Moreover, 16S ribosomal ribonucleic acid (rRNA) has been Gastrointestinal Symptom Rating Scale-IBS (GSRS-IBS) and the Hospital
detected in bile and also in cholangiocytes in PSC patients. The microbiota in bile Anxiety and Depression Scale (HADs), respectively.
have also been shown to be modified by genetic factors such as FUT2 (2--L- Result: IBS patients demonstrated higher levels of faecal CgA (8.1 (3.3–17.4)
fucosyltransferase 2) polymorphism, a gene involved in protein glycosylation. pmol/L) compared to healthy subjects (4.7 (2.9–9.0), p 5 0.02 pmol/L). The
Aims & Methods: To study the possible role of biliary microbiota in ethiopatho- levels of SgII (0.8 (0.1–3.6) pmol/L) and SgIII (2.0 (0.8–4.8) pmol/L) in IBS
genesis, disease progression and risk of dysplasia and cholangiocarcinoma patients were also increased compared to healthy subjects ((0.1 (0.0–0.2),
(CCA). The clinical part of the study was conducted at Helsinki University, p 5 0.01) respectively (0.7 (0.4–2.4), p 5 0.001, pmol/L)). Faecal microbial diver-
Clinic of Gastroenterology. The patients were recruited from the PSC registry sity was negatively correlated with CgA (r ¼ 0.29, p 5 0.005), CgB (r ¼ 0.21,
United European Gastroenterology Journal 4(5S) A95

Table 1. (OP239): Dysbiosis status

Dysbiosis Patients Age [med.] Female IBD CD UC IBDU Non-IBD Healthy control Unknown

No 72 28 (19–68) 43 22 [18%] 7 [16%] 11 [18%] 4 [31%] 21 [17%] 27 [56%] 2 [100%]

Low 96 33 (19–66) 49 33 [28%] 14 [31%] 15 [24%] 4 [31%] 50 [40%] 13 [27%] 0
High 126 32 (18–69) 80 65 [54%] 24 [53%] 36 [58%] 5 [38%] 53 [43%] 8 [17%] 0
Total 294 NA 172 120 45 62 13 124 48 2

p 5 0.05) and SgIII (r ¼ 0.28, p 5 0.005). In addition, SgII showed a tendency compared to the healthy controls in a PLS analysis, the healthy controls (n ¼ 48)
to be negatively correlated with faecal microbial Shannon diversity (r ¼ 0.19, and E1 (n ¼ 22) patients clustered together, while the combined group of E2
p ¼ 0.05). No correlations were found between any of the granins (CgA, CgB, (n ¼ 17) and E3 (n ¼ 23) patients made a separate cluster. Among 10 bacteria
SgII and SgIII) and mucosal-associated microbiota Shannon diversity or muco- groups contributing to the clustering we looked into three of the groups in
sal immune activity (i.e. calprotectin or expression of IL-8, IL-10, TNF and details; Bifidobacterium and Eubacterium were significantly reduced (p 5 0.01),
FOXP3). A positive correlation between total GI symptom severity (GSRS- and Escherichia/Proteobacteria were significantly increased (p 5 0.01) in the E2/
IBS) and levels of CgB was detected (r ¼ 0.22, p 5 0.001). General psychological E3 group as compared to E1/ healthy controls group. Frequency of high dysbio-
distress measured with total HAD score was positively correlated to CgA sis among the healthy individuals was higher than observed in other studies (1).
(r ¼ 0.24) and CgB (r ¼ 0.34, both p 5 0.05). Conclusion: The present results support that alterations in microbial composition
Conclusion: This study confirms that IBS patients have increased faecal levels of is important in both IBD and symptomatic non-IBD patients. The result demon-
CgA, SgII and SgIII as compared to healthy subjects. Negative associations were strated: 1) Differences in microbiota profiles between IBD and symptomatic non-
found between levels of luminal granins and luminal microbiota diversity, but not IBD patients and healthy individuals; 2) Equal levels of dysbiosis frequency in
with either mucosal immune activity or mucosal-associated microbiota. GI symp- CD and UC, however the bacteria profiles differed; 3) In subgroups of UC,
tom severity and psychological distress were also associated with increased levels microbiota profiles were dependent upon the localization of the inflammation.
of chromogranins in the lumen. Disclosure of Interest: E. Ciemniejewska: Employee of Genetic Analysis
Disclosure of Interest: J. Tap: Employee at Danone M.H. Vatn: Member of Genetic Analysis’ Scientific Advisory Board
M. Derrien: Employee at Danone M. Sekelja: Former employee of Genetic Analysis AS
B. Le Nevé: Employee at Danone C. Casén: Employee at Genetic Analysis
H. Törnblom: Consultant/Advisory Board member for Almirall, Allergan, All other authors have declared no conflicts of interest.
Danone and Shire, Speaker for Tillotts, Takeda, Shire and Almirall Reference
L. Öhman: Unrestricted research grants from AstraZeneca; Consultant/
Advisory Board member for Genetic Analysis; Speaker for Genetic Analysis, 1. Casén et al. Aliment Pharmacol Ther 2015; 42: 71–83.
Takeda and Abbot
M. Simrén: Unrestricted research grants from Danone, and Ferring
Pharmaceuticals; Consultant/ Advisory Board member for AstraZeneca,
Danone, Nestlé, Chr Hansen, Almirall, Allergan, Albireo, Glycom and Shire; OP240 METABOLIC SYNDROME CORRELATES WITH MICROBIOTA
Speaker for Tillotts, Takeda, Shire and Almirall. ENCROACHMENT IN HUMAN INTESTINE
All other authors have declared no conflicts of interest. B. Chassaing1, S. Srinivasan2, A. Gewirtz1
1
Reference Institute For Biomedical Sciences, Georgia State University, Atlanta/United
States of America/GA
1. Öhman L, Stridsberg M, Isaksson S, Jerlstad P and Simrén M. Altered levels 2
Digestive Diseases Division, Department Of Medicine, Emory University School
of fecal chromogranins and secretogranins in IBS: relevance for pathophy-
of Medicine, Atlanta/United States of America/GA
siology and symptoms?. Am J Gastroenterol 2012; 107(3): 440–7.
Contact E-mail Address: [email protected]
Introduction: The intestinal tract is inhabited by a large and diverse community of
bacteria collectively referred as gut microbiota. Mucoid structures coating the
OP239 MICROBIOTA ALTERATIONS IN TREATMENT NAÏVE IBD AND epithelium, largely devoid of bacteria, are central to maintaining intestinal-
NON-IBD PATIENTS - THE EU IBD-CHARACTER PROJECT microbiota homeostasis. Our recently published work has led to the hypothesis
P. Ricanek1, S. Vatn1, R. Kalla2, Y. Ber3, E. Ciemniejewska4, M.J. Pierik5, that, in mice, bacterial encroachment of the epithelium, as a consequence of an
J. Halfvarson6, J.D. Söderholm7, J. Jahnsen8, F. Gomollon9, J. Satsangi10, M. innate immune deficiency or ingestion of substances that alter host-microbiota
H. Vatn11, M. Sekelja4, C. Casén12, The Ibd-Character Consortium12 interactions, promotes low-grade inflammation that can drive metabolic disease
1
Department Of Gastroenterology, Akershus University Hospital, Lørenskog/ (1–2).
Norway Aims & Methods: The aim of the current study was to study microbiota localiza-
2
Institute Of Genetics And Molecular Medicine, University of Edinburgh, tion in human subjects with metabolic syndrome. Subjects were enrolled at the
Edinburgh/United Kingdom Veteran’s Administration Hospital (Atlanta, GA, USA). A review of the patient
3
Servicio De Aparato Digestivo, Hospital Clı´nico Universitario Lozano, Zaragoza/ medical record was conducted to determine control and diabetic patients, as
Spain shown by their glycosylated hemoglobin and fasted serum glucose levels.
4
Clinical, Genetic Analysis AS, Oslo/Norway,5Gastroenterology-hepatology, During the colonoscopy procedure, two mucosal biopsies were taken in the left
Maastricht University Medical Center, Maastricht/Netherlands colon approximately 40 cm from the anus using a regular forceps. The biopsies
6
Dep. Of Internal Medicine, Örebro University Hospital, Örebro/Sweden were immediately placed in Carnoy fixative and mucus immunostaining was
7
University Hospital, Linköping University, Linköping/Sweden paired with fluorescent in situ hybridization in order to analyze bacteria localiza-
8
Department Of Gastroenterology, Oslo University Hospital, Oslo/Norway tion at the surface of the intestinal mucosa.
9
Servicio De Aparato Digestivo, Hospital Clı´nico Universitario Lozano Blesa, Result: We found that bacterial encroachment of the epithelium correlates with
Zaragoza/Spain central features of metabolic syndrome in humans. Specifically, confocal micro-
10
University Of Edinburgh, Gastrointestinal Unit, Edinburgh/United Kingdom scopic analysis of biopsies from middle-aged persons revealed an inverse correla-
11
Institute Of Clinical Medicine, Epigen, Campus Ahus, University of Oslo, Oslo/ tion between bacterial-epithelial distance and body mass index, fasting blood
Norway glucose, and hemoglobin A1C level. Ethnicity or antibiotic use did not signifi-
12
Clinical Dept., Genetic Analysis AS, Oslo/Norway cantly correlate with microbiota-epithelial distance.
Conclusion: These observations support the notion that microbiota promotion of
Contact E-mail Address: [email protected] low-grade inflammation may play a causative role in metabolic diseases in
Introduction: The microbiota is considered important for development of intest- human. Those findings are important advances that will significantly impact
inal diseases. In order to create a molecular snapshot of IBD in its early mani- our understanding of the epidemic of metabolic syndrome.
festation, one part of the IBD-Character project identified faecal microbiota Disclosure of Interest: All authors have declared no conflicts of interest.
profiles among the strictly treatment naı̈ve IBD and symptomatic non-IBD References
patients, and a healthy control group.
Aims & Methods: Patients where characterized by international criteria including 1. Chassaing B, Koren O, Goodrich JK, Poole AC, Srinivasan S, Ley RE, et al.
endoscopy and biopsies. Faecal samples collected during five days prior to diag- Dietary emulsifiers impact the mouse gut microbiota promoting colitis and
nosis where stored at –80 C before examination on GA-mapTM Dysbiosis Test metabolic syndrome. Nature 2015; 519(7541): 92–6.
(1), a 16S rRNA DNA test utilizing DNA probes to recognize gut bacteria 2. Chassaing B, Ley RE and Gewirtz AT. Intestinal epithelial cell toll-like
profiles. In total 54 probes have been selected (1) for recognition of dysbiosis. receptor 5 regulates the intestinal microbiota to prevent low-grade inflam-
Result: In total 294 adult patients and healthy individuals were investigated for mation and metabolic syndrome in mice. Gastroenterology 2014; 147(6):
microbiota profiling. Table 1 shows the distribution and frequency of dysbiosis in 1363–77 e17.
the diagnose groups, subgroups and healthy controls. Comparing the bacteria
profiles of IBD, non-IBD and control groups, the abundance of Proteobacteria
was increased in IBD and non-IBD as compared to the controls (p 5 0.02), while
the abundance of Bifidobacterium and Faecalibacterium prausnitzii was decreased
(p 5 0.02 and 50.07, respectively). Concerning the CD and UC subgroups, a
significantly reduced abundance of Firmicutes, Streptococcus and Clostridia was
found in UC patients (p 5 0.05 for all) as compared to CD. Looking at the
microbiota profiles of the Montreal classified subgroups of the UC patients, as
A96 United European Gastroenterology Journal 4(5S)

Table 1. (OP241): The taxa numbers of IBS-P, IBS-N and HC in genus levels [M (Q1, Q3)]

Taxa Numbers
Phylum Genus
IBS-P (n ¼ 31) IBS-N (n ¼ 39) HC (n ¼ 20) P

Actinobacteria Collinsella 95(34, 146)b 21(2, 155) 47(19, 133) 50.05

Bacteroidetes Prevotella_9 726(9, 14813)a 17(1, 9272) 4(1, 5677) NS
Alistipes 434(131, 1064)b 155(13, 467)a 579(70, 849) 50.05
Barnesiella 35(0, 217)b 3(0, 45) 23(0, 142) NS
Butyricimonas 22(4, 80)b 5(0, 15) 9(0, 49) 50.05
Parabacteroides 242(152, 683)b 108(45, 245)a 225(145,538) 50.05
Paraprevotella 6(0, 312)a 1(0, 23) 0(0, 28) 50.05
Odoribacter 35(1, 88)b 5(0, 47) 33(1, 73) NS
Firmicutes Faecalibacterium 3387(1778, 6294)b 2174(449, 4175) 2860(1290, 4699) NS
Pseudobutyrivibrio 3524(1284, 5860)b 1245(269, 3360) 1911(1163, 3133) 50.05
Subdoligranulum 1101(621, 2182)b 544(77, 1666) 1245(316, 1962) NS
Lachnospiraceae_NK4A136 234(82, 672)b 85(22, 468)a 406(169, 1446) 50.05
Eubacterium_coprostanoligenes 197(46, 571)b 90(3, 197) 139(10, 810) NS
Ruminococcus_1 145(35, 523)b 7(1, 111)a 291(4, 436) 50.05
Eubacterium_hallii 313(132, 636)b 118(44, 367) 141(61, 620) NS
ChristensenellaceaeR-7 104(4, 209)b 5(1, 81)a 61(6, 357) 50.05
Enterococcus 7(3, 13) 11(4, 30)a 3(0, 16) NS
Family_XIII 18(2, 28)b 3(0, 16)a 15(4, 31) 50.05
Incertae_Sedis 156(54, 426)b 53(10, 267) 77(15, 515) 50.05
Lachnospiraceae_NC2004 25(7, 60)a 16(2, 37) 13(2, 28) NS
Lachnospiraceae 1020(595, 1971)b 598(289, 1131) 863(409, 2232) 50.05
Romboutsia 86(15, 201)b 156(46, 478) 127(40, 284) NS
Ruminococcaceae 968(337, 1803)b 321(85, 905)a 804(266, 1183) 50.05
Proteobacteria Escherichia_Shigella 49(31, 471)b 338(65, 1458)a 27(9, 216) 50.05
Klebsiella 43(4, 130)b 106(11, 494) 40(1, 172) NS
Raoultella 7(3, 11)a 11(4, 28)a 2(0, 9) 50.05
Sutterella 7(1, 136) 2(0, 57)a 50(4, 163) NS

Indication: IBS-P, IBS with SIBO; IBS-N, IBS without SIBO; HC, health controls; NS, no significance; a, compared with HC, p 5 0.05; b, compared with IBS-N,
p 5 0.05

OP241 CLINICAL FEATURES AND FECAL MICROBIOTA PROFILE IN respectively]. (8) The microbiota abundance of IBS-P was different from IBS-
IRRITABLE BOWEL SYNDROME PATIENTS WITH SMALL N and HC (table 1). Besides, the fecal microbiota profile of IBS-P was more
INTESTINAL BACTERIAL OVERGROWTH similar to HC than IBS-N, according to Pcoa and Hcluster tree-bar.
Z. Liu1, H. Wei1, S. Zhu1, Y. Liu1, L. Zhang1, K. Wang1, J. Y. Kao2, Conclusion: (1) According to Rome II criteria, approximately 41.67% IBS-D
C. Owyang2, L. Duan3 patients present SIBO, which can be better screened by hydrogen and methane
1
Department Of Gastroenterology, Peking University Third Hospital, Beijing/ LBT. (2) SIBO can cause malnutrition and worsen nutritional status. (3)The
China intestinal permeability, systemic inflammation and visceral hypersensitivity of
2
Division Of Gastroenterology, University of Michigan, Ann Arbor/United States IBS-P are better than IBS-N. (4) Differences are observed in fecal SCFA between
of America IBS-P and IBS-N. (5) Both IBS-P and IBS-N are different from HC in micro-
3
Department Of Gastroenterology, Peking University Third Hospital Dept. of biota abundance and community diversity, in which IBS-P is also different from
Gastroenterology, Beijing/China IBS-N. As a consequence, IBS-P is different from IBS-N in many physiological
parameters and fecal microbiota profile, so IBS-P may be just SIBO which
Contact E-mail Address: [email protected] should be screened before diagnosis of IBS-D according to Rome II criteria.
Introduction: Irritable bowel syndrome (IBS) is a common functional gastroin- Disclosure of Interest: All authors have declared no conflicts of interest.
testinal disorder, but the relationship between diarrhea-predominant IBS (IBS-
D) and small intestinal bacterial overgrowth (SIBO) is unclear.
Aims & Methods: We aimed to investigate the clinical features and fecal micro-
biota profiles of IBS-D patients with SIBO by hydrogen and methane lactulose OP242 FECAL MICROBIOTA TRANSPLANTATION FOR RECURRENT
breath test (LBT), and compare them with IBS-D patients without SIBO and C. DIFFICILE INFECTION: ANALYSIS OF FACTORS ASSOCIATED
healthy controls. IBS-D patients who met Rome II criteria were divided into IBS- WITH THE NEED FOR MULTIPLE FECAL INFUSIONS
D with SIBO (IBS-P) and without SIBO (IBS-N) by hydrogen and methane LBT, G. Ianiro1, L. Masucci2, L. Valerio3, D. Nagel4, F. D’Aversa5, R. Poto1,
while healthy controls with negative LBT (HC) were recruited. All subjects F. Dibitetto1, F. Scaldaferri6, M. Gesualdo1, M. Sanguinetti2, A. Gasbarrini7,
underwent colonoscopy to exclude organic diseases, and barostat for visceral G. Cammarota1
hypersensitivity, intestinal permeability test [lactulose (L), mannitol (M) and L/ 1
Internal Medicine, Gastroenterology And Liver Unit, Agostino Gemelli Hospital
M in 6-hour urine], systematic inflammation severity (IL-10, IL-12 and IL-10/IL- Dept. of Gastroenterology, Rome/Italy
12 in supernate of peripheral blood mononuclear cells), fecal short chain fatty 2
Microbiology, Agostino Gemelli Hospital Dept. of Microbiology, Rome/Italy
acids(SCFA) evaluation, and fecal microbiota profiles analysis by Illumina 3
Public Health, Academic Medical Centre, University of Amsterdam, Amsterdam/
MiSeq high throughput sequencing. Netherlands
Result: 22 HC and 84 IBS-D patients were enrolled. 35 of patients were with 4
Microbiology, Agostino Gemelli Hospital, Rome/Italy
SIBO (41.67%) and 49 patients were IBS-N. (1) The body mass index of IBS-P 5
Internal Medicine and Gastroenterology, Agostino Gemelli Hospital Dept. of
was lower than IBS-N [(21.61  0.57) vs. (23.44  0.54) kg/m2, P 5 0.05]. (2) The Gastroenterology, Rome, Italy, Rome/Italy
IL-12 was higher in IBS-N than IBS-P and HC [2306.24(927.85, 3168.88) vs. 6
Internal Medicine And Gastroenterology, Agostino Gemelli Hospital Dept. of
1263.40(482.55, 1965.99)pg/mL, 2306.24(927.85, 3168.88) vs. 1087.04(884.53, Gastroenterology, Rome/Italy
1740.47) pg/mL, P 5 0.05, respectively]. (3) The L and M in IBS-P were higher 7
Internal Medicine, Gastroenterology And Liver Diseases, Gemelli Hospital Dept.
than that in HC (P 4 0.05), with similar L/M. While the L of IBS-N was higher of Internal Medicine Dept. of Gastroenterology, Rome/Italy
than that in HC [2.85(1.35, 6.40)vs.1.47(0.97, 2.62) mg/mL, P 5 0.05], with higher
M and L/M(P 4 0.05). (4) The initial defecation threshold of IBS-P was lower Contact E-mail Address: [email protected]
than HC [16.00(12.00, 20.00) vs. 20.00(18.00, 28.00) mmHg, P 5 0.05], while Introduction: Fecal microbiota transplantation (FMT) from healthy donors is
both thresholds for initial sensory and defecation in IBS-N were lower than considered a highly effective treatment against recurrent Clostridium difficile
HC [8.00(6.00, 12.00) vs. 12.00(8.00, 14.00) mmHg, 16.00(14.00, 18.00) vs. infection (rCDI). A single fecal infusion is usually sufficient to resolve symptoms
20.00(18.00, 28.00) mmHg, P 5 0.05]. (5) The fecal SCFA, include acetate, pro- and eradicate rCDI, but a subgroup of these patients need multiple infusions to
pionate, butyrate, isobutyrate and isovalerate in IBS-P were higher than that in cure the disease. In our previously published randomized controlled trial of FMT
HC, while valerate was lower. In IBS-N, the fecal propionate was higher than in versus vancomycin for rCDI,1 we observed that patients with pseudomembra-
HC [51.90(37.58, 70.82) vs. 35.26(30.48, 42.39) mmol/g, P 5 0.05], while the other nous colitis (PMC) needed repeat fecal infusions to be cured; further reports
SCFA were lower compared with HC. (6) There were significant differences in confirmed our findings.2 To date, however, neither PMC nor other factors
Shnnon index and Simpson index between IBS-P and IBS-N [3.57(3.20, 3.70) vs. have been clearly proven to be associated with the need for multiple FMT.
3.22(2.75, 3.45), 0.051(0.068, 0.093) vs. 0.094(0.065, 0.140), P 5 0.05,
United European Gastroenterology Journal 4(5S) A97
Aims & Methods: Therefore, our aim was to identify predictive factors for the is defined as the number of days from randomization to performing EBD for any
need for repeated fecal infusions in a series of patients treated with FMT for reason or death from any cause. Patients with a dysphagia symptom score of two
rCDI. We identified prospectively and included in the analysis all patients treated or more after esophagectomy with anastomotic stricture confirmed by endoscopy
with FMT by colonoscopy for rCDI in our Centre. Demographic, clinical, endo- were included. Patients and investigators were blinded to the type of agent
scopic, and follow-up data were collected. Repeat fecal infusions were adminis- injected. The syringe containing triamcinolone or placebo was prepared by nur-
tered if the patient recurred or failed to improve after first infusion. Gender, age, sing staff unconnected to the trial. Patients underwent EBD with a standard
inpatient status, number or CDI recurrences (43), poor/inadequate bowel pre- through-the-scope balloon dilator. The balloon was inflated with water, aiming
paration (according to Ottawa Scale), endoscopic evidence of colonic oedema, for a luminal diameter of maximum 15 mm for 3 min. After EBD, a second
presence of PMC, use of external donors, infusion of frozen material, and infused endoscopist who was not involved in the follow-up evaluation of the patients
grams of faeces were analysed as potential impact factors. Univariate associa- performed the injections into the mucosal laceration. A total of 50 mg of triam-
tions between possible predictors and the need for repeated fecal infusions were cinolone acetonide (50 mg/5 mL; Bristol-Myers Squibb) or an identical volume of
investigated, using t-test for continuous variables and Fisher’s chi-square for normal saline solution as a placebo was injected per single site using a 25-gauge
dychotomous variables. Multivariate associations between all candidate predic- needle. Neither the patient nor the treating physician knew which treatment was
tors and the need for repeated fecal infusions were investigated using logistic given. Esophagogastroduodenoscopy (EGD) was performed on demand when-
regression analysis. P-values of 50.05 were considered statistically significant. ever patients reported dysphagia. In patients without dysphagia, EGD was per-
Result: A total of 54 patients with rCDI (Males ¼ 24; mean age ¼ 71 years old, formed within 3 months after EBD to evaluate the stricture. EBD was performed
range ¼ 29–94) received FMT from healthy donors by colonoscopy. Fifteen when the stricture was confirmed. Stricture was defined as dysphagia to some
patients received multiple infusions, for a total of 81 procedures. Resolution of solids (dysphagia score 2) and an inability to pass an endoscope of at least 9.2-
rCDI occurred in 52 of 54 patients (96%); of them, none experienced further mm diameter.
recurrences after FMT. Univariate analysis showed that both poor/inadequate Result: Over a 4-year period, 68 patients met the inclusion criteria and were
bowel preparation (p ¼ 0.024) and PMC (p 5 0.001) were significantly associated screened. Three patients declined to participate. Sixty-five consecutive patients
with the need of repeated fecal infusions; also colonic oedema was more common were therefore recruited to the study and randomized: 33 to receive steroid and 32
among patients who needed repeated FMT, albeit nonsignificantly (p ¼ 0.083). to receive placebo. The median number of EBD sessions required to resolve
On multivariate analysis, both the presence of PMC (OR ¼ 2257; 95% stricture in the steroid group was 2 (range, 1–7), significantly smaller than the
CI ¼ 25.17–41000, p ¼ 0.014) and poor/inadequate bowel preparation median of 4 EBD sessions (range, 1–29) required by the control group
(OR ¼ 64.80; 95% CI ¼ 3.43–41000, p ¼ 0.021) were identified as significant (p 5 0.001). After 6 months of follow-up, 39% of patients who received steroid
predictors of the need of repeated infusions. Additionally, the need for repeated injections remained recurrence-free compared with 19% of those injected with
infusion was more common among patient who experienced a number or CDI saline (p 5 0.01). There were no adverse events during follow-up.
recurrences higher than 3 than among those who did not, although without Conclusion: Steroid injection showed promising results for the prevention of
reaching statistical significance (OR ¼ 26.80; 95% CI ¼ 1.69–41000; p ¼ 0.054). stricture recurrence in patients who underwent EBD for anastomotic stricture.
The large confidence interval observed for most predictors could be explained Disclosure of Interest: N. Hanaoka: The Japan Foundation for Research and
presumably by the relatively low number of cases in our sample. Finally, the Promotion of Endoscopy Grant
infusion of frozen material was significantly associated with lower need of multi- All other authors have declared no conflicts of interest.
ple FMT (OR ¼ 0.01; 95% CI ¼ 0.0–40.19, p ¼ 0.033).
Conclusion: Among patients treated with FMT for rCDI, both PMC and poor/
inadequate bowel preparation appear to be significant predictors of the need for
repeated fecal infusions. Additionally, frozen FMT appears to be significantly OP244 THE "TUNNEL þ CLIP" METHOD FACILITATES
associated with a decreased need of multiple FMT. As the small sample size OESOPHAGEAL ESD PROCEDURES: A PROSPECTIVE,
represents a limitation of our analysis, our findings, although promising, CONSECUTIVE BI-CENTRIC STUDY
should be confirmed by further, larger studies. J. Jacques1, R. Legros1, J. Rivory2, D. Sautereau3, T. Ponchon4, M. Pioche2
Disclosure of Interest: All authors have declared no conflicts of interest. 1
Hepato-gastro-enterology, CHU Limoges, Limoges/France
2
References Gastroenterology And Endoscopy Unit, Digestive Disease Department, H
Pavillon- Edouard Herriot Hospital, Lyon/France
1. Cammarota G, Masucci L, Ianiro G, et al. Randomised clinical trial: faecal 3
CHU Limoges Gastroente´rologie, Limoges/France
microbiota transplantation by colonoscopy vs. vancomycin for the treatment 4
Dept. Of Digestive Diseases, Herriot University Hospital Dept. de Hepato-gas-
of recurrent Clostridium difficile infection. Aliment Pharmacol Ther 2015; 41:
troenterologie, Lyon/France
835–43.
2. Fischer M, Sipe BW, Rogers NA, et al. Faecal microbiota transplantation Contact E-mail Address: [email protected]
plus selected use of vancomycin for severe-complicated Clostridium difficile Introduction: ESD is the treatment of choice for superficial neoplasms of the
infection: description of a protocol with high success rate. Aliment Pharmacol oesophagus due to its oncological efficiency and the morbidity associated with
Ther 2015; 42: 470–6. the surgical alternative. ESD requires a high level of skill and is technically
challenging and time consuming. Therefore, it is often reserved to experts.
TUESDAY, OCTOBER 18, 2016 14:00–15:30 Combining the tunnel technique and the clip-line counter-traction may enable
optimisation of oesophageal ESDs.
ENDOSCOPIC TREATMENT OF COMPLICATIONS AFTER UPPER GI SURGERY – ROOM Aims & Methods: From January 2014 to April 2016 we performed a prospective
E2_____________________ bi-centre case series of consecutive "tunnel þ clip" oesophageal ESDs. Four
young operators (fewer than 50 ESDs and fewer than 5 oesophageal ESDs)
OP243 ENDOSCOPIC BALLOON DILATION FOLLOWED BY STEROID performed consecutively the ESD using the tunnel þ clip method: generation of
INJECTION IN ANASTOMOTIC STRICTURES AFTER a classic tunnel beneath the lesion followed by constant counter-traction thanks
ESOPHAGECTOMY: A MULTICENTER RANDOMIZED, DOUBLE- to a clip with line dropped at the oral side of the tunnel.
BLIND CONTROLLED TRIAL Results: Thirty-three lesions (14 SCC and 19 ADK/HGD complicating Barrett’s
N. Hanaoka1, R. Ishihara2, N. Uedo3, K. Higashino4, Y. Takeuchi2, oesophagus) were resected consecutively. En bloc, R0 and curative resection rates
T. Akasaka3, M. Yano5, Y. Hayashi6, T. Takehara6, H. Iishi2 were 100% (33/33), 87.8% (29/33) and 75.8% (25/33), respectively. No perfora-
1
Gastrointestinal Oncology, Osaka Medical Center for Cancer and Cardiocvascular tion occurred. The mean speed of ESD was 22.3 mm2/min for a mean lesion size
Diseases Gastrointestinal Oncology, Osaka/Japan of 61,6 mm. The clip provided considerable assistance in performing the proce-
2
Osaka Medical Center for Cancer and Cardiovascular Diseases, Osaka/Japan dure. No pathological damage caused by the clipping was reported.
3
Department Of Gastrointestinal Oncology, Osaka Medical Center for Cancer and
Cardiovascular Diseases, Osaka/Japan n ¼ 33 Mean Min Max
4
Gastrointestinal Oncology, Osaka Medical Center for Cancer and Cardiovascular
Diseases, Osaka/Japan Age (years) 63,9,8 36 85
5
Surgery, Osaka Medical Center for Cancer and Cardiocvascular Diseases Male 22 (84.6%)
Gastrointestinal Oncology, Osaka/Japan
6 Procedure duration (min) 131 25 350
Gastroenterology And Hepatology, Osaka University Graduate School of
Medicine, Suita/Japan Large diameter (mm) 61.6 30 105
Small diameter (mm) 44 20 78
Contact E-mail Address: [email protected]
Introduction: Esophageal cancer is the fifth most common cause of cancer-related Surface (mm2) 2418 471 6300
death for men and the eighth for women worldwide. Although the effectiveness Speed (mm2/min) 22,3 7.0 79
of chemotherapy or chemoradiotherapy for the treatment of esophageal cancer Circumference (%) 60.0% 30.0% 100%
has been reported, esophagectomy remains the standard treatment to cure eso- Monobloc resection 33 (100%)
phageal cancer. Anastomotic stricture, a major complication after esophagect-
omy, substantially decreases patients’ quality of life, and requires treatment with R0 resection 29 (87.8%)
multiple sessions of endoscopic balloon dilation (EBD). Curative resection 25 (75.8%)
Aims & Methods: We conducted a multicenter randomized controlled trial to Periprocedural bleeding 14 (42.0%)
evaluate the usefulness of administration of local steroid injections to prevent Perforation 0 (0.0%)
the recurrence of anastomotic stricture. Patients were randomized to receive
either triamcinolone or placebo immediately after EBD. The primary endpoint Post-procedural bleeding 2 (6%)
was the number of dilations required to resolve the stricture. Secondary end- Stenosis 5 (15.1%)
points were restricture-free survival and adverse events. Restricture-free survival (continued)
A98 United European Gastroenterology Journal 4(5S)
Continued Introduction: The PIVI initiatives propose that a ‘‘leave in place’’ approach is
acceptable for a diminutive (5 mm), rectosigmoid hyperplastic polyp when
n ¼ 33 Mean Min Max endoscopist’s optical diagnosis provides over 90% negative predictive value
(NPV) for adenomas in high confidence predictions [1]; however, expertise is
Pathologic analysis required to achieve a high accuracy and some studies conducted in commu-
SCC 14 (42.4%) nity-based hospitals have been disappointing [2]. Recently, we have reported
ADK/DHG 19 (57.6%) the usefulness of computer-aided diagnosis (CAD) in supporting endoscopists’
decision making during colonoscopy [3,4]. The present study was aimed to vali-
Residual disease (3 months) 0 (0.0%)
date the efficacy of the latest CAD model for endocytoscopy (380-fold ultra-
magnifying endoscopy) in management of diminutive, rectosigmoid polyps.
Discussion: First study of the strategy "tunnel þ clip". Our en bloc and R0 resec- Aims & Methods: The present study was aimed to validate the efficacy of the
tion rates confirmed the usefulness of this technique, despite the relative inex- latest CAD model for endocytoscopy (380-fold ultra magnifying endoscopy) in
perience of the operators. Our resection results were similar to those reported in management of diminutive, rectosigmoid polyps. The CAD for endocytoscopy
large series by international experts, including those in Japan and our absence of comprises image acquisition, nuclear segmentation, feature extraction, and clas-
perforation highlighted the safety of this strategy. sification into three pathological groups (non-neoplastic, adenoma, and invasive
Conclusion: The tunnel þ clip method for oesophageal ESD is effective and safe, cancer). The classification algorithm was programmed based on 296 features of
in particular for physicians with little experience. This strategy standardizes the each image (e.g., area, circularity, diameter, and perimeter of nuclei, and over 250
ESD procedure for superficial oesophageal neoplasia and increases of the speed variables calculated by texture analysis of a whole image). We used a support
of dissection. Thus, it will help to widespread oesophageal ESD performed in vector machine to help classify these many features; 6051 endocytoscopic images
Western countries. were used for machine learning in the process of construction of the model. In
Disclosure of Interest: All authors have declared no conflicts of interest. order to validate this CAD model, the pilot study using a test set was undertaken
References between August and November 2015. The test set comprised endocytoscopic
images of 65 diminutive, rectosigmoid polyps from the database of Showa
1. Oyama T (2014) Gastrointest Endosc Clin N Am 24:201–212. doi: 10.1016/ University Northern Yokohama Hospital. Each image was automatically allo-
j.giec.2013.12.001. cated to the CAD, and the predicted pathology was immediately output by the
2. Oyama T (2012) Clin Endosc 45:375–378. doi: 10.5946/ce.2012.45.4.375. CAD in 0.2 seconds. The main outcome measure was NPV of the CAD for
3. Pioche M, et al. (2013) Endoscopy 45:1032–1034. doi: 10.1055/s-0033- adenomatous histology for diminutive, rectosigmoid colon polyps when they
1344855. had been diagnosed with high confidence.
4. Jacques J, et al. (2015) Endoscopy 47 Suppl 1 UCTN:E307–308. doi: 10.1055/ Result: Of the 65 diminutive rectosigmoid polyps (mean size, 3.6 þ 1.0 mm), the
s-0034-1392240. CAD diagnosed 55 (19 neoplastic and 36 non-neoplastic) with high confidence.
Details of the diagnostic performance by the CAD for these 55 polyps were
shown in the Table. The CAD correctly predicted neoplastic histology in 18 of
TUESDAY, OCTOBER 18, 2016 14:00–15:30
the 20 neoplastic polyps (positive predictive value of 90% [95% CI, 68–99]) and
WHAT TO DO WITH SMALL COLORECTAL POLYPS? – ROOM F1_____________________ non-neoplastic histology in 34 of the 35 non-neoplastic polyps (NPV of 97%
OP245 DEVELOPMENT AND VALIDATION OF A SIMPLE [95% CI, 85–100]). This performance of the CAD met the ‘‘leave in situ’’ criteria
CLASSIFICATION SYSTEM FOR IN VIVO DIAGNOSIS OF proposed by the PIVI initiative.
COLORECTAL POLYPS USING THE NEWLY INTRODUCED BLUE
LIGHT IMAGING (BLI) Table: Details of the diagnostic performance by the CAD
H. Neumann1, M. Vieth2, L. Fry3, G.E. Tontini1, K. Mönkemüller3
1 neoplastic in non-neoplastic
Department Of Medicine I, University Hospital Erlangen, Erlangen/Germany
2 pathology in pathology
Abt. Pathologie, Klinikum Bayreuth Abt. Pathology, Bayreuth/Germany
3
Basil Hirschowitz Endoscopic Center Of Excellence, University of Alabama at
Diagnosis of neoplastic by CAD 18 2
Birmingham, Birmingham/United States of America
Diagnosis of non-neoplastic by CAD 1 34
Contact E-mail Address: [email protected]
Introduction: BLI is a novel endoscopic imaging technique for enhancement of
subtle mucosal and vascular details. The potential of this novel technology for
in vivo diagnosis of colorectal polyps has yet to be established. Conclusion: The CAD applying endocytoscopy can be a powerful and quick
Aims & Methods: Primary study objective was to develop a simple classification support tool in management of diminutive, rectosigmoid polyps.
for in vivo differentiation of hyperplasic and adenomatous colorectal lesions by Disclosure of Interest: K. Mori: Cybernet System Corp.
using the novel BLI technology. Second study endpoint was to validate the All other authors have declared no conflicts of interest.
classification among experienced and non-experienced users. In the first phase, References
the capacity of experienced endoscopists to predict the histology of colorectal
polyps was assessed. In the second phase, a simplified classification was devel- 1. Rex DK, et al. The American Society for Gastrointestinal Endoscopy PIVI
oped allowing histologic prediction. Thirdly, the validity of the classification was (Preservation and Incorporation of Valuable Endoscopic Innovations) on
evaluated among inexperienced raters, including medical students and GI fel- real-time endoscopic assessment of the histology of diminutive colorectal
lows. At least, a pilot clinical evaluation was performed during real-time polyps. Gastrointest Endosc 2011.
colonoscopy. 2. Ladabaum U, et al. Real-time optical biopsy of colon polyps with narrow
Result: A simple classification system for differentiating hyperplasic and adeno- band imaging in community practice does not yet meet key thresholds for
matous colorectal lesions by using the novel introduced BLI technology was clinical decisions. Gastroenterology 2013.
developed and validated. Diagnosis was made in 80% to 88% of polyps with 3. Mori Y, et al. Novel computer-aided diagnostic system for colorectal lesions
high-confidence. Sensitivity and specificity ranged from 93% to 100% and 83% by using endocytoscopy (with videos). Gastrointest Endosc 2015.
to 92%, respectively. During real-time colonoscopy, diagnosis was made with 4. Misawa M, et al. Characterization of colorectal lesions using a computer-
high-confidence in 88% of polyps with sensitivity of 96%, specificity of 92%, and aided diagnostic system for narrow-band imaging endocytoscopy.
accuracy of 95%. Positive and negative predictive values were 96% and 92%, Gastroenterology 2016 [Epub ahead of print].
respectively.
Conclusion: This is the first study evaluating the novel BLI technology for in vivo TUESDAY, OCTOBER 18, 2016 14:00–15:30
prediction of colorectal polyps. The proposed classification allowed for adequate
in vivo diagnosis of hyperplastic and adenomatous lesions. Further prospective
BIOMARKERS IN IBD – ROOM K_____________________
multicenter trials should now confirm these preliminary results. OP247 IBDOC – FIRST SMARTPHONE BASED CALPROTECTIN HOME
Disclosure of Interest: All authors have declared no conflicts of interest. TEST – 18 MONTHS EXPERIENCE
C. Reinhard1, A. Ritz1, M. Überschlag1, A. Beyer2, H. Vogelsang2, J. Weber1
1
BÜHLMANN Laboratories AG, Schönenbuch/Switzerland
2
AKH Medical University, Vienna/Austria
OP246 MANAGEMENT OF DIMINUTIVE, RECTOSIGMOID POLYPS
BY USING COMPUTER-AIDED DIAGNOSTIC SYSTEM Contact E-mail Address: [email protected]
Y. Mori1, S. Kudo2, M. Misawa2, K. Wakamura3, T. Kudo3, K. Takeda2, Introduction: Inflammatory Bowel Disease (IBD) is a chronic inflammation of
T. Hayashi3, A. Katagiri3, H. Miyachi3, F. Ishida3, H. Inoue4, M. Oda5, the gut presenting with phases of active inflammation, remission and relapses.
K. Mori6 IBD treatment goals are mucosal healing and persistent remission. Calprotectin
1
Northen Yokohama Hospital, Showa University Northern Yokohama Hospital, measured in patients’ stool samples is a well-established biomarker to measure
Yokohama/Japan the inflammatory activity in the gut. Periodical assessment of calprotectin levels
2
Digestive Disease Center, Showa University Northern Yokohama Hospital, is important to measure effectiveness of the treatment as well as predicting
Yokohama/Japan relapses. Until now this meant that patients send in their stool sample for labora-
3
Digestive Disease Center, Showa University Northern Yokohama Hospital tory analysis, leading to long delays between sample collection, final test result
Digestive Disease Center, Yokohama/Japan,4Digestive Disease Center, Showa and potential adaptations of therapies.
University Koto-Toyosu Hospital, Tokyo/Japan Aims & Methods: We have developed a smartphone-based calprotectin home test,
5
Graduate School Of Information Science, Nagoya University, Nagoya/Japan called IBDocÕ, that allows real-time information about the inflammatory activ-
6
Information And Communications, Nagoya University, Nagoya/Japan ities in the gut for both, the patient and the health care provider. The IBDocÕ
consists of a stool collection and extraction device (CALEXÕ Valve) and an
Contact E-mail Address: [email protected] immunochromatographic calprotectin rapid test, which is measured using a
smartphone App (CalAppÕ) controlling the phone’s camera. Once the test is
United European Gastroenterology Journal 4(5S) A99
measured the result is instantly sent to a webserver (IBDocÕ Portal) allowing the questionnaire and a calprotectin home test shows a high sensitivity and thus
treating physician immediate access to the test result. IBDocÕ has achieved CE/ excellent diagnostic accuracy for use in telemedicine programmes to screen for
IVD mark for self-testing in March 2015 and has since then been in routine use patients who need further assessment of disease activity with biochemical mar-
by patients throughout Europe and overseas. We have gathered data concerning kers, imaging or endoscopy.
technical performance of the device in the hands of both professional and lay Disclosure of Interest: M.J. de Jong: Non financial support Immundiagnostik
users as well as usability aspects for patients. All other authors have declared no conflicts of interest.
Result: In a direct method comparison with an existing point-of-care test Reference
(Quantum BlueÕ) and a laboratory based ELISA method (BÜHLMANN
fCALÕ ELISA) IBDocÕ correlated very well with both methods with a mean 1. De Jong et al. JCC 2015.
bias below 10%. In regard to repeatability and precisions the smartphones as
measuring devices alone showed a coefficient of variability of below 10%, while
the entire method including pre-analytical steps showed a coefficient of variabil-
ity between 16% and 24%. IBDocÕ displays results as Normal/green (below OP249 ACCURACY OF NON-INVASIVE TESTS IN THE INITIAL
100 mg/g mean bias at cut-off, –7.0 to 5.4%), Moderate/amber (100–300 mg/g) DIAGNOSTIC WORK-UP OF PEDIATRIC INFLAMMATORY
and as High/red (above 300 mg/g, mean bias at cut-off, 1.1–6.5%). No false BOWEL DISEASES
positive or false negative results (Normal/green instead of High/red and vice F. Civitelli1, A. Dilillo1, M. Aloi2, S. Oliva2, F. Viola2, L. Stronati1, S. Cucchiara2
versa) were observed when lay-users performing the test were compared to pro- 1
Dept. Pediatrics, Gastroenterology And Liver Unit, Sapienza University of Rome,
fessional users. There was a 97% within-class agreement observed. Patients Rome/Italy
judged the entire IBDocÕ system as extremely user friendly with a mean of 93 2
Pediatric Gastroenterology And Liver Unit, Sapienza University of Rome, Rome/
points (out of 100) on a standardized System Usability Scale (SUS) score1,2,3. Italy
Conclusion: IBDocÕ is the first Calprotectin Home Test available for patients.
IBDocÕ is well accepted by patients and health care providers and correlates well Contact E-mail Address: [email protected]
to existing calprotectin point-of-care and laboratory based methods and has Introduction: Upper and lower endoscopy with histology together with imaging
proven to be a supportive tool in daily clinical routine. of the small bowel is the gold standard for the diagnosis of inflammatory bowel
Disclosure of Interest: C. Reinhard: Christian Reinhard is an employee of disease (IBD) in children. Due to high costs and invasive nature of these techni-
BÜHLMANN Laboratories AG ques, accurate selection of patients is mandatory.
A. Ritz: Alicja Ritz is an employee of BÜHLMANN Laboratories AG Aims & Methods: We aimed to assess the accuracy of non-invasive tests including
M. Überschlag: Marie-Eve Überschlag is an employee of BÜHLMANN fecal calprotectin (FC), blood inflammatory markers (BIM) and bowel ultra-
Laboratories AG sound (US) alone or in combination as first level investigations in children
J. Weber: Jakob Weber is an employee of BÜHLMANN Laboratories AG with suspected IBD. Consecutive patients referred to our Unit for a clinical
All other authors have declared no conflicts of interest. history compatible with IBD were enrolled during a 3-year period. All underwent
References FC (CalprestÕ, Eurospital), C-reactive protein [CRP], erythrocyte sedimentation
rate [ESR] and bowel US as first investigations. Endoscopy with biopsies was the
1. Beyer et al., Usability Study of a Smartphone-Based Calprotectin Home gold standard for diagnosis. At US pathological findings were: BWT 4 3 mm,
Test, UEGW 2015. BW vascularity, loss of stratification, enlarged mesenteric nodes. Multiple logis-
2. Brooke, J. (1996). ‘SUS: a ‘‘quick and dirty’’ usability scale’. In P. W. tic analysis with stepwise method considering IBD diagnosis as dependent vari-
Jordan, B. Thomas, B. A. Weerdmeester, & A. L. McClelland. Usability able was conducted. Sensitivity (SE), specificity (SP), positive and negative
Evaluation in Industry. predictive values (PPV and NPV) of laboratory and US parameters alone or in
3. Sauro, J., & Lewis, J. R (2012). Quantifying the user experience: Practical combination were analyzed according to the final diagnosis.
statistics for user research. Morgan Kaufmann, Waltham MA, USA. Result: 100 patients (58 males, median age 12) were enrolled. The final diagnosis
was IBD in 69 (57 CD, 12 CU) other than IBD in 31. The mean values of CRP,
ESR, FC and BWT were higher in IBD vs non-IBD patients (p 5 0.001).
Multiple logistic analysis showed that independent variables predictive of IBD
OP248 A COMBINATION OF THE MONITOR IBD AT HOME were: FC (OR 44.8; p 5 0.01), BWT (OR 20.4, p 5 0.001) and ESR (OR 9;
QUESTIONNAIRE AND A CALPROTECTIN HOME TEST AS p 5 0.05). The combination of 3 or 2 parameters was more frequent in IBD
EXCELLENT SCREENING TOOL FOR MUCOSAL INFLAMMATION patients (p 5 0.01). Table 2 shows SE, SP, PPV, NPV of these parameters
IN IBD PATIENTS alone or in combination.
M. J. De Jong1, D.M. Jonkers1, M. Romberg Camps2, A.G. l. Bodelier3, A. j.p.
Van De Wetering1, T. Van Etten1, S. h.p. Conjaerts1, T. Markus4, A.A. Masclee1, Parameters SE % SP % PPV % NPV %
M.J. Pierik1
1
Department Of Gastroenterology, Maastricht University Medical Centreþ, FC (ug/g) 94 89 94 89
Maastricht/Netherlands ESR (mm/h) 75 89 93 65
2
Department Of Gastroenterology, Zuyderland Medical Centre, Sittard-Geleen/
BWT (mm) 43 mm 94 83 88 57
Netherlands
3
Department Of Gastroenterology, Amphia Hospital, Breda/Netherlands 2 (at least 2 of 3) 96 84 97 92
4
CCUVN, Woerden/Netherlands 2 (FC þ BWT) 91 100 100 86
Contact E-mail Address: [email protected] 3 (FC þ BWT þ ESR) 71 100 100 64
Introduction: Telemedicine programmes are of interest for inflammatory bowel
diseases (IBD), but should include adequate monitoring of mucosal inflamma- Conclusion: the combination of FC, BIM and bowel US may help to select
tion to prevent long-term complications. Different clinical activity questionnaires children needing further invasive procedures and allow to avoid or delay endo-
are available, however, none are patient-reported, clear and easy to fill out and scopy in patients with negative initial diagnostic work-up.
validated against endoscopy. For this reason we previously developed the Disclosure of Interest: All authors have declared no conflicts of interest.
Monitor IBD At Home questionnaire (MIAH) (1). The score does not include
laboratory tests or physical examination. The objective of this study was to
investigate whether a combination of the MIAH questionnaire and a calprotectin
home test yields higher diagnostic accuracy. OP250 THE SEROLOGIC MARKERS ASCA AND PANCA SHOW
Aims & Methods: Between September 2015 and April 2016 all consecutive IBD BETTER PREDICTABILITY THAN CRP, ESR AND CALPROTECTIN
patients with a scheduled endoscopy in the Maastricht University Medical FOR ANTI- TNF TREATMENT AMONG PEDIATRIC IBD PATIENTS
Centreþ were eligible for inclusion. Patients with an ileostomy, colostomy, ileoa- C. Olbjørn1, M. S. Cvancarova2, E. Thiis-Evensen3, B. Nakstad4, M. H. Vatn5,
nal pouch anastomosis or ileorectal anastomosis were excluded. Patients were G. Perminow6
invited to fill out the 5-item MIAH-UC questionnaire for UC, regarding blood 1
Institute For Clinical Medicine, Campus Akershus University Hospital, University
loss, number of stools, urgency, abdominal pain and general well-being, or the 6- of Oslo, Lørenskog/Norway
item MIAH-CD questionnaire for CD, including questions on blood loss, mucus, 2
Gastroenterology, Oslo University Hospital, Ullevål, Oslo/Norway
number of stools, urgency, fatigue and general well-being. In addition, patients 3
Gastroenterology, Rikshospitalet, University of Oslo, Oslo/Norway
were asked to collect a stool sample prior to bowel cleansing. Fecal calprotectin 4
Dep Of Pediatrics And Adolescence And Institute Of Clinical Medicine, Akershus
was determined with a calprotectin home test. Mucosal inflammation was University Hospital and University of Oslo, Lørenskog/Norway
assessed with the simple endoscopic activity score (SES-CD) for Crohn’s disease 5
Institute Of Clinical Medicine, Epigen-institute, Campus Akershus University
(CD) and the Mayo endoscopic subscore (MES) for ulcerative colitis (UC). Hospital, University of Oslo, Lørenskog/Norway
Sensitivity, specificity, positive predictive value (PPV) and negative predicted 6
Pediatrics, Oslo University Hospital, Ullevål, Oslo/Norway
value (NPV) of the MIAH-UC and MIAH-CD in combination with the calpro-
tectin home test were calculated. Contact E-mail Address: [email protected]
Result: Thirty-two CD patients (50.0% male, mean age 51.4  15.2 years, 43.8% Introduction: Serologic nuclear and anti microbial antibodies have been recog-
active disease) and 28 UC patients (50.0% male, mean age 57.3  10.4 years, nized as predictive markers of disease course and complications in ulcerative
39.3% active disease) were included. The combination of the MIAH-CD and colitis (UC) and Crohn’s disease (CD). The significance of serological markers
the calprotectin home test showed a sensitivity of 100.0%, a specificity of 61.1%, from onset of the disease, their ability to predict disease outcome and their
a NPV of 100.0% and a PPV of 67.0%. The combination of the MIAH-UC and stability over time is not fully explored in IBD patients.
the calprotectin home test yielded a sensitivity of 91.7%, a specificity of 68.8%, a Aims & Methods: To study the prevalence of serological markers in treatment-
NPV of 91.7% and a PPV of 68.8%. naı̈ve pediatric patients with newly diagnosed inflammatory bowel disease and
Conclusion: The MIAH is the first patient-reported questionnaire developed to prospectively evaluate the antibody and titer-variations related to disease sub-
predict endoscopic inflammation in IBD patients. A combination of this groups, treatments and disease course. We also wanted to compare the value of
A100 United European Gastroenterology Journal 4(5S)
serological markers with the biochemical markers C-reactive protein (CRP), Result: Inter-variability is reported in Figure according to disease type, location
elevated sedimentation rate (ESR) and fecal calprotectin. Patients aged 5 18 and activity. The highest FC values were found in active UC patients while IBS
years, (n ¼ 58) diagnosed with IBD were included between 2005–2007 as a part and quiescent ileal CD patients had the lowest (p 5 0.05). Colonic location just
of a prospective population based study in South-Eastern Norway (IBSEN- II). as active disease seemed to affect FC values, as it has already been described.
Fecal samples were analyzed for calprotectin (Bühlmann, Basel, Switzerland) and Nevertheless, these results were not significant probably due to small sample size.
blood specimens were analyzed for antibodies (Prometheus labs, San Diego), Concerning intra-stool variability, the average CV between the punches was
CRP and ESR at diagnosis and after 1–2 years of treatment. Treatment was 32%, showing a wide intra-stool variability. The largest CV were observed for
decided at the courtesy of the treating pediatrician. Tumor necrosis factor low FC measurements (550mg/g). However, this resulted in clinical significance
(TNF) blocker treatment was regarded as aggressive treatment compared to for only 7 IBD patients (9,70%) or 3 IBD patients (4,20%) when using a FC cut-
treatment with immunomodulators. off of respectively 50 mg/g or 250 mg/g. A significant correlation was demon-
Result: Among the UC patients, 13 (72%) were perinuclear anti-neutrophil cyto- strated between FC measurements of 2 stool samples at 1–5 days intervals in
plasmic antibody (pANCA) positive, versus 13 (35%) of the CD patients. None 62 patients with correlation coefficient of 0.78 (p 5 0.0001). Statistical analysis
of the UC patients harbored anti–Saccharomyces cerevisiae (ASCA) antibodies, (T-test) could not show difference between the 2 stool samples (p 4 0,05).
whereas 20 (54%) of CD patients were ASCA IgA or IgG positive (p 5 0.0001), Conclusion: These results suggest that there are variations in FC values within the
18 (49%) were positive for ASCA IgA, 14 (38%) for ASCA IgG, and 12 (33%) same stool but with little clinical significance in IBD patients. Thus, a single stool
for both. There were no statistically significant differences between CD and UC punch appears to be reliable for FC measurement. This study confirms that
patients in the prevalence of antibodies against Pseudomonas fluorescens asso- disease type, location and activity influence the inter-individual FC variability,
ciated sequence (I2) (41% vs. 33%), the outer membrane porin of Escherichia coli while intra-stool and intra-individual FC variability, regardless of disease activ-
(OmpC) (8% vs. 6%) or flagellin expressed by Clostridial phylum (CBir) (22% ity, remains low.
vs. 0%, respectively). The 18 (49%) CD patients who received aggressive therapy Disclosure of Interest: All authors have declared no conflicts of interest.
with TNF blockers had higher presence of antibodies against ASCA IgA References
(p ¼ 0.05) and ASCA IgG (p ¼ 0.045) as well as higher titers of ASCA IgG
(p ¼ 0.046) compared to the 19 (51%) CD patients who received conventional 1. Kerkhoff C. Novel insights into structure and function of MRP8 (S100A8)
treatment. If ASCA antibodies were present at baseline the probability of receiv- and MRP14 (S100A9). Biochim Biophys Acta BBA-Mol Cell Res 1998; 1448:
ing infliximab treatment in CD patients was 70%, with OR 8.8 (2.0–37.7), 200–11.
p ¼ 0.004. The presence of pANCA antibodies was less frequent at diagnosis in 2. Lin J-F, Chen J-M, Zuo J-H, Yu A, Xiao Z-J, Deng F-H, et al. Meta-
TNF blocker treated CD patients compared to conventionally treated CD analysis: Fecal Calprotectin for Assessment of Inflammatory Bowel
patients. The OR of receiving aggressive therapy being pANCA negative was Disease Activity. Inflamm Bowel Dis 2014 Aug; 20(8): 1407–15.
5.2 (1.11–24.13), p ¼ 0.02. CD patients who were given infliximab had signifi- 3. Mao R, Xiao Y, Gao X, Chen B, He Y, Yang L, et al. Fecal calprotectin in
cantly higher levels of fecal calprotectin, CRP and ESR at diagnosis compared to predicting relapse of inflammatory bowel diseases: A meta-analysis of pro-
conventionally treated CD patients with median values of fecal calprotectin (mg/ spective studies: Inflamm Bowel Dis2012 Oct; 18(10): 1894–9.
kg) 1506 vs. 501 (p ¼ 0.01), CRP (mg/l) 28 vs. 7.5 (p ¼ 0.02) and ESR (mm/h) of 4. Røseth AG, Fagerhol MK, Aadland E and Schjønsby H. Assessment of the
32 vs. 18 (p ¼ 0.01) respectively. Being pANCA negative and/ or ASCA IgA or neutrophil dominating protein calprotectin in feces. A methodologic study.
ASCA IgG positive was associated with the need for TNF blocker therapy, even Scand J Gastroenterol 1992 Sep; 27(9): 793–8.
after adjustment for CRP, ESR and fecal calprotectin levels. After treatment
there was no difference in antibody prevalence for ASCA IgA, ASCA IgG, I2,
OmpC or CBir in the CD and UC patients, regardless of treatment modality.
Fewer UC patients, 9 (64%), tested positive for pANCA after treatment, com- OP252 ANALYTICAL PERFORMANCE OF A NEW IPHONE-BASED
pared to at baseline, 13 (72%), p ¼ 0.013. Only one of the 18 UC patients received PATIENT MONITORING SYSTEM COMPARABLE TO ELISA FOR
TNF blocker treatment. MEASURING FECAL CALPROTECTIN IN IBD PATIENTS
Conclusion: ASCA and pANCA status was associated with the need for early K.F. Wintgens1, A.A. Wulandari2, A. Dignass3, F. Hartmann4, J. Stein4
aggressive therapy with TNF blockers in our CD patients. We found that being 1
Dr., Immundiagnostik GmbH, Bensheim/Germany
pANCA negative and/ or ASCA IgA or ASCA IgG positive were more predictive 2
Gastroenterology And Clinical Nutrition, DGD Clinics Sachsenhausen, Frankfurt/
of needing aggressive treatment than CRP, ESP or fecal calprotectin levels. Germany
ASCA serology was stable, regardless of treatment modality, and might be a 3
Dept. Of Medicine I, Agaplesion Markus Hospital, Frankfurt/Germany
prognostic tool at any time in the disease course. 4
Crohn Colitis Centre Rhein-Main, Frankfurt/Germany
Disclosure of Interest: All authors have declared no conflicts of interest.
Contact E-mail Address: [email protected]
Introduction: Inflammatory bowel disease (IBD) is a chronic intestinal inflamma-
tory disorder presenting with phases of active inflammation, remission and
OP251 INTRA- AND INTER-VARIABILITY OF FECAL CALPROTECTIN relapse. Fecal calprotectin (fcalpro) measurement has become established for
IN INFLAMMATORY BOWEL DISEASE PATIENTS: A the monitoring of inflammation activity. Periodical assessment of fcalpro levels
PROSPECTIVE OBSERVATIONAL CASE-CONTROL STUDY has been demonstrated to be an important non-invasive indicator of treatment
J. Ku1, A. Cremer2, L. Amininejad2, C. Liefferinckx3, E. Quertinmont3, efficacy and predictor of relapse. However, until now, fcalpro determination
J. Deviere4, A. Van Gossum5, P. Stordeur1, D. Franchimont6 required patients to send stool samples in for laboratory analysis, resulting in
1
Institute For Medical Immunology, Erasme hospital, Brussels/Belgium a long delay between sample collection and final test results. We developed a
2
Department Of Gastroenterology, Hepatopancreatology And Digestive Oncology, simple home-based calprotectin test system called QuantOnCal to allow patients
Erasme Hospital, Brussels/Belgium to regularly monitor their own inflammatory status by testing fcalpro levels in the
3
Laboratory Of Experimental Gastroenterology, Universite´ Libre de Bruxelles, comfort of their own home.
Brussels/Belgium Aims & Methods: QuantOnCal consists of a stool extraction device (IDKÕ
4
Dept. Of Gastroenterology, Universite´ Libre de Bruxelles Erasme University Extract) and an immunochromatographic rapid test performed by an iPhone
Hospital, Bruxelles/Belgium App via the phone camera. Results are automatically sent to a webserver
5
Department Of Gastroenterology And Hepatology, Hôpital Erasme, Free (QuantOnCal website), where they are displayed for monitoring by the consult-
University of Brussels, Bruxelles/Belgium ing physician or IBD nurse. The objective of this study was to validate the
6
Free University of Brussels Erasme Hospital Dept. of Gastroenterology, QuantOnCal test system by comparing its quantitative performance with a stan-
Bruxelles/Belgium dard ELISA-based method. Stool samples from 157 IBD and non-IBD patients
containing various levels of calprotectin (95 IBD: CU/CD/active/remission, 42/
Contact E-mail Address: [email protected] 43/48/47; 33 IBS: 23 Chm: 6 Div) were either loaded onto immunochromato-
Introduction: Fecal Calprotectin (FC), a calcium binding protein in neutrophils, graphic test cassettes (TCs) or analysed with a commercial ELISA test
indirectly reflects intestinal inflammation and is today widely used in the manage- (Immundiagnostik, Bensheim, Germany). The QuantOnCal app was installed
ment of inflammatory bowel disease (IBD) patients. FC values appears to vary on 4 different iPhone models (iPhones 4, 4s, 5c, 6). Agreement between
according to disease type, activity and location. FC seems more sensitive in QuantOnCal testing versus ELISA was assessed by Analyse-it for Microsoft
assessing disease activity in ulcerative colitis (UC) than in Crohn’s disease Excel.
(CD). Several factors may affect FC values. However, few studies have looked Result: The QuantOnCal system produces a quantitative test result between 25–
at the intra- and inter-variability of FC in IBD patients. 2000 mg/g fcalpro/g of stool, covering the clinically relevant range of this bio-
Aims & Methods: We aimed to assess the robustness of using a single stool punch marker. The total agreement (TA) was 94.6% with 0% false positive and 0%
for the measurement of FC and prospectively evaluated the intra- and inter- false negative rates. The TA for fcalpro between the 4 different iPhone models
variability of FC in a cohort of IBD and irritable bowel syndrome (IBS) patients. was 91.3%.
72 IBD patients (49 CD and 23 UC) and a control group of 7 IBS patients were Conclusion: QuantOnCal is a new, complete and validated test system which
enrolled. Disease location and disease activity were determined using endoscopic allows the IBD patient to monitor and follow his inflammatory status by mea-
and clinical activity scores (Crohn’s disease activity index and Harvey–Bradshaw suring the IBD biomarker, faecal calprotectin, using his/her own smartphone.
score in CD and Mayo score in UC), as well as C-reactive protein levels. Stool The performance of the QuantOnCal test system was shown to be comparable to
samples were collected twice (within 1 to 5 days interval) in 62 patients and FC the professional, ELISA-based method.
was measured on both punches (100 mg stool per punch) and homogenates (5–8 g Abbreviations IBD, inflammatory bowel disease; Chm, Carbohydrate malab-
per stool) by fluorometric enzyme immunocapture assay (ELiA Calprotectin, sorption; CU, colitis ulcerosa; CD, Crohńs disease; Div, Diverticulitis; IBS, irri-
ThermoFischer). Intra-stool FC variability defined as the variability between 3 table bowel syndrome; TA, total agreement
punches in the same stool sample and intra-individual FC variability defined as Disclosure of Interest: K.F. Wintgens: Karl Florian Wintgens is an employee of
the variability between 2 stool samples of the same patient a few days apart were Immundiagnostik AG, Bensheim, Germany
both examined. Intra-stool variability was assessed by measuring the coefficient J. Stein: Jürgen Stein has received payment for lectures and consultancy from
of variation (CV) between the 3 punches of a stool sample. Inter-variability of FC Immundiagnostik AG, Bensheim, Germany
was also measured. All other authors have declared no conflicts of interest.
United European Gastroenterology Journal 4(5S) A101

TUESDAY, OCTOBER 18, 2016 14:00–15:30 Result: IBS symptoms consistently and significantly improved after 3 weeks of
CLINICAL TRIALS IN FUNCTIONAL GI DISORDERS – ROOM M_____________________ LFD, with a mean overall reduction of 163.8 points (p 5 0.0001). On average, 4
of 5 symptoms were significantly worsened in response to FOS compared with
OP253 RANDOMIZED, PLACEBO-CONTROLLED TRIAL OF placebo, with an overall difference of 65.1 points (p ¼ 0.014). Serum levels of IL-6
BIOFEEDBACK FOR THE TREATMENT OF ABDOMINAL and IL-8, but not TNF-, significantly decreased on the LFD (p ¼ 0.001 and
DISTENSION p 5 0.0001, respectively). The same did apply to luminal Faecalibacterium praus-
E. Barba1, A. Accarino2, J.R. Malagelada2, F. Azpiroz2 nitzii and Bifidobacterium (p ¼ 0.0084 and p ¼ 0.0094, respectively). Levels of
1
Digestive System Research Unit, University Hospital Vall D́hebron, Digestive total SCFAs and butyric acid were also significantly decreased on the LFD
System Research Unit, University Hospital Vall d´Hebron, Departament de (p ¼ 0.04 and p ¼ 0.01, respectively). Ten days of FOS supplementation normal-
Medicina. Universidad Autónoma de Barcelona, Barcelona/Spain ized the level of bacteria, but did not change the levels of cytokines nor SCFAs.
2
Digestive System Research Unit, University Hospital Vall D́hebron, Digestive Conclusion: FODMAP content was related to IBS symptoms, cytokine levels and
System Research Unit, University Hospital Vall d´Hebron, Departament de microbiota composition and function. Our results provide evidence to support
Medicina. Universidad Autónoma de Barcelona, Ciberehd, Barcelona, Barcelona/ the efficacy of a LFD in reducing functional GI symptoms. Further studies are
Spain warranted to explore the link between FODMAPs, gut microbiota and immune
activation.
Contact E-mail Address: [email protected] Disclosure of Interest: All authors have declared no conflicts of interest.
Introduction: Abdominal distension is the most bothersome complaint in patients
with functional gut disorders and has no effective treatment. In a previous study
we showed that abdominal distension is produced by diaphragmatic contraction
and descent with protrusion of the anterior abdominal wall, and we developed an OP255 PREDICTORS FOR THE OUTCOME OF THE FODMAP DIET IN
original biofeedback technique based on EMG-guided control of abdomino- PATIENTS WITH FUNCTIONAL GASTROINTESTINAL DISORDERS
thoracic muscular activity. C. H. Wilder-Smith1, S. S. Olesen2, A. Materna1, A. M. Drewes2
Aims & Methods: Our aim was to demonstrate the superiority of biofeedback 1
Gastroenterology Grp Practice, Brain-Gut Research Group Gastroenterology
versus placebo for the treatment of abdominal distension. We performed a ran- Group Practice, Bern/Switzerland
domized, placebo controlled in a referral center (Clinical Trials Gov Registration 2
Mech-sense, Department Of Gastroenterology & Hepatology, Aalborg University
Number 01205100). Forty-eight consecutive patients complaining of episodes of Hospital, Aalborg/Denmark
visible abdominal distension who fulfilled the Rome III criteria for functional
intestinal disorders (47 women, 1 men; 21–74 yr age range) were recruited and Contact E-mail Address: [email protected]
randomly allocated to biofeedback and placebo treatment. Abdomino-thoracic Introduction: The reduction of poorly fermentable carbohydrates collectively
muscle activity was recorded by EMG during basal conditions (no distension) termed FODMAPs (fermentable oligo-, di-, monosaccharides and polyols) is
and during an episode of distension to prove the abdomino-phrenic origin of increasingly being advocated in patients with functional gastrointestinal disor-
their distension. Each patient underwent three treatment sessions over a 10-day ders (FGID). At present, selection criteria or response predictors for dietary
period. In each session abdomino-thoracic muscle activity was recorded by elec- intervention are poorly defined.
tromyography. The patients in the biofeedback group were shown the signal and Aims & Methods: In this study the predictive associations between clinical char-
instructed to control muscle activity; the patients in the control group were given acteristics, breath test results and the global outcome measure advocated in
and oral placebo. The main outcome was subjective sensation of abdominal FGID were examined. Clinical characteristics and breath test results from 580
distension scored by a 0–6 graphic rating scale daily for 10 days before and successive patients presenting to our clinic with FGID (Rome III) and fructose or
after treatment lactose intolerance, and completing a standardized FODMAP dietary program
Results: Patients on biofeedback, but not on placebo, effectively learned to were analyzed. Intolerance was defined by a positive symptom index and malab-
reduce intercostal activity (by 45  3% vs 5  2% on placebo; p 5 0.001) and sorption by increases in H2 (420 ppm) or CH4 (410 ppm) values during breath
to increase anterior wall muscle activity (by 101  10% vs 4  2%). testing. The response to the dietary program was assessed using a standard
Biofeedback treatment resulted in a 56%  1% reduction of abdominal disten- adequate global symptom relief question. Predictive associations were assessed
sion (from 4.6  0.2 to 2.0  0.2 score after intervention) vs 13  8% on placebo; by uni- and multivariate analyses.
p 5 0.001 (from 4.7  0.1 to 4.1  0.4 score after intervention). Result: Adequate symptom relief was achieved in 81% of the 580 FGID patients,
Conclusion: Abdominal distension can be effectively corrected by biofeedback- with similar response rates in patients with fructose (82%) or lactose (79%)
guided control of abdomino-thoracic muscular activity. intolerances and across all FGID subtypes (IBS-diarrhea: 80%, IBS-constipa-
Disclosure of Interest: All authors have declared no conflicts of interest. tion: 71%, IBS-mixed: 89%, FD: 79%). A positive history of chronic diarrhea or
References pruritus predicted adequate symptom relief with the FODMAP diet (univariate
analysis OR (95% CI): 2.96 (1.83–4.79) and 2.50 (1.27–4.92), respectively, both
1. Barba E, Burri E, Accarino A, Cisternas D, Quiroga S, Monclus E, Navazo p 5 0.01), while nausea predicted inadequate relief (0.55 (0.34–0.89), p ¼ 0.01).
I, Malagelada JR, et al. Abdominothoracic mechanisms of functional Multivariate analysis confirmed the associations between adequate symptom
abdominal distension and correction by biofeedback. Gastroenterology relief and a history of diarrhea (positive predictor: 2.74 (1.52–4.94, p ¼ 0.001)
2015; 148: 732–9. doi:10.1053/j.gastro.2014.12.006. and nausea (negative predictor: 0.45 (0.25–0.81), p ¼ 0.07). There were no sig-
2. Burri E, Cisternas D, Villoria A, Accarino A, Soldevilla A, Malagelada JR nificant associations between the H2 or CH4 breath concentrations and the
and Azpiroz F. Accomodation of the abdomen to its content: integrated attainment of adequate relief. A positive dietary response in patients with fruc-
abdomino-thoracic response. Neurogastroenterol Motil 2012 Apr; 24(4): tose intolerance was associated with the development of diarrhea during breath
312–e162. testing (univariate analysis 1.7 (1.03–2.81, p ¼ 0.04). No other significant associa-
tions between symptoms experienced during fructose or lactose breath testing
and dietary outcome were demonstrated.
Conclusion: Adequate global symptom relief with a FODMAP diet is achieved in
OP254 LOW FODMAP DIET ALTERS SYMPTOMS, MICROBIOTA, a large majority of all FGID patients with fructose or lactose intolerance, and is
SHORT-CHAIN FATTY ACIDS AND CYTOKINE PROFILES IN predicted by a few clinical and breath-test associated symptoms and not by the
PATIENTS WITH IBS: A RANDOMIZED CONTROLLED TRIAL presence of malabsorption. Consequently, a reduction of FODMAPs appears to
T.N. Hustoft1, T. Hausken2, S. O. Ystad1, J. Valeur3, K. A. Brokstad4, modulate multiple physiological processes across the spectrum of FGIDs.
J.G. Hatlebakk2, G. A. Lied2 Furthermore, adequate relief likely reflects a complex constellation of psycholo-
1
University Of Bergen, Department of Clinical Medicine, Bergen/Norway gical and physical factors, rather than a reduction in individual symptoms,
2
Gastroenterology- Medicine, Haukeland University Hospital, Bergen/Norway explaining the few significant associations with clinical or provoked symptoms.
3
Unger-vetlesens Institute, Lovisenberg Diakonale Hospital, Oslo/Norway Disclosure of Interest: All authors have declared no conflicts of interest.
4
University Of Bergen, Department of Clinical Science, Bergen/Norway
Contact E-mail Address: [email protected]
Introduction: Irritable bowel syndrome (IBS) is the most common gastrointestinal OP256 A RANDOMIZED TRIPLE BLIND CONTROLLED TRIAL
(GI) disorder worldwide. In the lack of cures, different management strategies ASSESSING THE EFFECTS OF DOXEPIN AND NORTRIPTYLINE
have been purposed, including a diet low in FODMAPs (fermentable oligosac- ON DIARRHEA-PREDOMINANT IRRITABLE BOWEL SYNDROME
charides, disaccharides, monosaccharides and polyols). Although being increas- H. Habibinejad1, M. Ghadir2, A. Heidari3
ingly accepted and recommended as one of the most effective therapies, there is 1
Young Researchers Club, Tehran/Iran
insufficient high-quality evidence of its efficacy as well as uncertainties regarding 2
Gastroenterology, Qom University of Medical Sciences, Qom/Iran
long-term consequences on gut microbiota composition and function. 3
Social Medicine, Qom University of Medical Sciences, Qom/Iran
Aims & Methods: In the present study we aimed to investigate the effect of a low
versus high FODMAP diet on symptoms, gut microbiota, short-chain fatty acids Contact E-mail Address: [email protected]
(SCFAs) and pro-inflammatory cytokine profiles in a randomized, double- Introduction: Tricyclic antidepressants tend to be constipating and, therefore,
blinded, crossover trial of Norwegian patients with IBS. Twenty patients with may be of most benefit in diarrhea-predominant IBS (IBS-D). The aim of this
IBS (15 female/5 male, mean age 34.6 y) were instructed to follow a low study was to compare the effects of low doses of doxepin and nortriptyline on
FODMAP diet (LFD) throughout a study period of 9 weeks. After 3 weeks IBS-D.
they were randomized and double-blindly assigned to receive a daily supplement Aims & Methods: Seventy-five patients with IBS according to Rome III criteria
of either high (16 g fructo-oligosaccharides (FOS)) or low (16 g maltodextrin were treated for two months. All possible organic diseases responsible for bowel
(¼placebo)) FODMAP for the next 10 days, followed by a 3-week washout symptoms were excluded. The patients were randomly assigned to one of three
before crossing-over to the alternative supplementation for 10 new days. IBS groups treated with doxepin(10 mg), nortriptyline(10 mg) or placebo. Subjects
Severity Scoring System (IBS-SSS) was used to evaluate symptoms. Blood sam- were assessed clinically weekly. The symptoms and adverse effects of the drugs
ples were collected to analyse serum cytokines (IL-6, IL-8, TNF-), and faeces were recorded in the questionnaire. The primary outcome was the responder rate
samples for gut microbiota (s16r RNA) and SCFAs. for treatment at the end of treatment.
A102 United European Gastroenterology Journal 4(5S)
Result: Abdominal pain and bloating were the most common symptoms before adjuvant therapy with standard medication for managing IBS. Further large
initiation of treatment, occurring in 62 (82.7%) patients. The frequency of the prospective population study is needed.
symptoms was decreased significantly after treatment in doxepin and nortripty- Disclosure of Interest: All authors have declared no conflicts of interest.
line groups compared with pre-treatment. The responder rate was 80%, 52%,
and 36% for doxepin, nortriptyline, and placebo groups, respectively(p ¼ 0.007).
The responder rate for doxepin group was superior to nortriptyline and placebo
groups(p ¼ 0.037 and p ¼ 0.002, respectively) but there was no significant differ- OP258 1-MONTH TREATMENT WITH ELUXADOLINE FOR IBS-D
ence in responder rates of nortriptyline and placebo groups(p ¼ 0.254). There PREDICTS SUSTAINED RESPONSE: CONTINUATION ANALYSES
were no significant differences in improvement rates in individual symptoms OF RESPONSE IN TWO PHASE 3 STUDIES
between doxepin and nortriptyline groups(all p 4 0.05). W. D. Chey1, D. A. Andrae2, L. S. Dove3, C. R. Gutman2, P. S. Covington3
Conclusion: Treatment of diarrhea-predominant IBS with low dose of doxepin or 1
University of Michigan, Ann Arbor/United States of America/MI
nortriptyline could be effective. Improvement rates of the symptoms are similar 2
Allergan plc, Jersey City/United States of America/NJ
in doxepin and nortriptyline groups but doxepin has a better response rate than 3
Former employee of Furiex Pharmaceuticals, an Allergan affiliate, Jersey City/
nortriptyline. United States of America/NJ
Disclosure of Interest: All authors have declared no conflicts of interest.
References Contact E-mail Address: [email protected]
Introduction: Eluxadoline (ELX), a mixed m-opioid receptor (OR) and -OR
1. Kasper DL, Braunwald E, Fauci AS, Hauser SL, Longo DL, Jameson JL, agonist and -OR antagonist that is locally active in the gastrointestinal tract,
Loscalzo J. Harrison’s principles of internal medicine. 17th edition. USA: is approved for the treatment of irritable bowel syndrome with diarrhoea (IBS-D)
MC Graw Hill; 2008.p1889. in adults. In two Phase 3 studies, ELX significantly improved symptoms of IBS-
2. Feldman M, Friedman L, Brandt L. Sleisenger and fordran,s D based on a composite endpoint, defined by simultaneous improvement in stool
Gastrointestinal and liver disease. USA .2006.volume 2B.P.2533. consistency and reduction in abdominal pain scores, and the historical ‘adequate
3. Talley N, kelow J, Boyce P, Tennant C, Huskic S and Jones M. relief’ endpoint. Given the potential long-term use of eluxadoline treatment, it is
Antidepressant therapy (Imipramine and citaloparm) for Irritable bowel important to understand the time course of clinical benefits as experienced by
syndrome: A Double-Blind, randomized, placebo-controlled trial. Dig Dis patients and clinicians, including time to onset and the sustainability over time,
Sci 2008; 53(1): 108–115. to establish reasonable expectations about the effectiveness of treatment.
Aims & Methods: The efficacy of ELX over longer treatment intervals was eval-
uated in patients who were responders or non-responders for the composite end-
point or adequate relief endpoint over the first month of treatment in the Phase 3
OP257 TREATMENT OF IRRITABLE BOWEL SYNDROME WITH studies. Two double-blind, placebo-controlled, Phase 3 clinical trials (IBS-3001
FECAL MICROBIOTA TRANSPLANTATION: A CASE SERIES OF 10 and IBS-3002) randomised patients meeting Rome III criteria for IBS-D to twice-
PATIENTS daily treatment with ELX (75 or 100 mg) or placebo. Patients rated IBS symp-
J. Hong1, B. Bang2, Y. Shin2, H. Kim2, K. Kwon2 toms daily, including worst abdominal pain (WAP; 0–10 scale) and stool con-
1
Department Of Internal Medicine, Inha University School of Medicine, Incheon/ sistency (Bristol Stool Scale [BSS]). The primary efficacy endpoint was composite
Korea, Republic of response, based on simultaneous daily improvement of 30% in WAP score vs.
2
Dept. Of Gastroenterology, Inha University Hospital, Incheon/Korea, Republic of baseline and BSS score 55, with 50% of days demonstrating a response,
evaluated over 12 and 26 weeks. Composite endpoint response rates over
Contact E-mail Address: [email protected] Weeks 1–12 and 1–26 were calculated for patients who were responders and
Introduction: Irritable bowel syndrome (IBS) is commonly diagnosed gastroin- non-responders over Month 1 (Weeks 1–4) using a pooled analysis of the
testinal disease worldwide. The pathogenesis of IBS cannot be explained by a intent-to-treat (ITT) population. Comparable analyses for adequate relief were
simple mechanism, but alterations in the intestinal microbiome are increasingly a conducted, for which a responder was defined as reporting a ‘‘yes’’ response to
focus of interest. Traditional treatments of IBS, including psychological thera- the question ‘‘Over the past week have you had adequate relief of your IBS
pies, dietary change, probiotics, have had only limited success, underscoring the symptoms?’’ for 50% of weeks in the treatment interval.
need for additional therapeutic options. We hypothesized that fecal microbiota Result: The pooled ITT analysis set included 2423 patients with IBS-D. Over
transplantation (FMT) may be beneficial in managing IBS by restoring the Month 1, 12.5% (101/809), 22.8% (184/808), and 24.6% (198/806) of patients
intestinal homeostasis. The purpose of this study is to prospectively examine were composite responders in the placebo, ELX 75 mg, and ELX 100 mg groups,
the symptomatic response of FMT in patient with moderate IBS. respectively. Over Month 1, 49.3% (399/809), 59.9% (484/808), and 61.8% (498/
Aims & Methods: Patients with IBS who were not responsive to traditional 806) of patients were adequate relief responders in the placebo, ELX 75 mg, and
treatment were enrolled prospectively in this study. Diagnosis of IBS was ELX 100 mg groups, respectively. For both ELX doses, the majority of patients
based on Rome III Criteria and nonresponsive IBS was defined as failure to who were composite or adequate relief responders over Month 1 showed sus-
achieve symptomatic relief with traditional therapeutic modalities. The healthy tained response over Weeks 1–12 and 1–26 (Table). Of the patients who were not
donors from patient’s family were screened and tested for infectious diseases composite or adequate relief responders in Month 1, approximately 13–18%
before FMT. Patients were questioned with IBS severity score before and 1 subsequently achieved response over 6 months of treatment.
month and 3 month after FMT. IBS severity score consist of 5 questions. Conclusion: Approximately two-thirds of patients who achieved either the com-
Total score is 500. As the score is lower, their general condition is considered posite or adequate relief endpoint over the first month of ELX treatment demon-
to be better. Study outcomes included the length of symptom-free intervals, strated sustained response over 6 months.
abdominal pain, bloating, flatus, dyspepsia, frequency of bowel movements, Disclosure of Interest: W.D. Chey: Dr Chey: Research support: Ironwood,
and overall well-being before and after FMT. Nestle, Prometheus; consultancy: Allergan plc, Ironwood, Nestle, Prometheus,
Result: A total of 10 patients (mean age of 55 years; 60% male) were identified Valeant, Sucampo, Takeda; patents: My GI Health, My Nutrition Health; co-
and completed the study questionnaire. Mean time from initial diagnosis of IBS founder: My Total Health.
until FMT was 3.6 years. In our study, 80% of the patients experienced resolu- D.A. Andrae: Dr Andrae: employee of Allergan plc.
tion or improvement of symptoms after FMT. There were no long-term side L.S. Dove: Dr Dove: former employee of Furiex Pharmaceuticals, an Allergan
effects, and none of the participants developed any new diseases. Clinically sig- affiliate.
nificant improvements in IBS severity scores were observed one month after C.R. Gutman: Dr Gutman: employee of Allergan plc.
FMT (132  100) comparing to baseline (252  121.7) (p ¼ 0.027). However, P.S. Covington: Dr Covington: former employee of Furiex Pharmaceuticals, an
their symptoms tended to return to their pre-FMT state at 3 month after FMT Allergan affiliate.
(231  110).
Conclusion: This study showed that FMT may be helpful for one month.
However, their effect seemed to decrease over time. FMT may be used as an

Table (OP258): Composite response rates over longer treatment intervals in ELX-treated patients who were composite or adequate relief responders over Month 1

Placebo (n ¼ 809) ELX 75 mg BID (n ¼ 808) ELX 100 mg BID (n ¼ 806)

Patients, n (%) Responder Non-responder Responder Non-responder Responder Non-responder

Composite endpoint: Weeks 1–4 101 (12.5) 708 (87.5) 184 (22.8) 624 (77.2) 198 (24.6) 608 (75.4)
Composite endpoint: Weeks 1–12a 78 (77.2) 23 (22.8) 150 (81.5) 34 (18.5) 154 (77.8) 44 (22.2)
Composite endpoint: Weeks 1–26a 67 (66.3) 34 (33.7) 136 (73.9) 48 (26.1) 140 (70.7) 58 (29.3)
Adequate relief: Weeks 1–4 399 (49.3) 410 (50.7) 484 (59.9) 324 (40.1) 498 (61.8) 308 (38.2)
Adequate relief: Weeks 1–12b 329 (82.5) 70 (17.5) 405 (83.7) 79 (16.3) 419 (84.1) 79 (15.9)
Adequate relief: Weeks 1–26b 278 (69.7) 121 (30.3) 341 (70.5) 143 (29.5) 364 (73.1) 134 (26.9)

BID, twice daily; ELX, eluxadoline

a
Percentage calculated based on number of patients who were composite responders over Weeks 1–4
b
Percentage calculated based on number of patients who were adequate relief responders over Weeks 1–4
United European Gastroenterology Journal 4(5S) A103

TUESDAY, OCTOBER 18, 2016 14:00–15:30 References

HOT TOPICS IN PANCREATOLOGY – ROOM N2_____________________
1. Neesse A, Algül H, Tuveson DA and Gress TM. Stromal biology and ther-
OP259 HUMAN PLURIPOTENT STEM CELL-DERIVED EXOCRINE/ apy in pancreatic cancer: a changing paradigm. Gut 2015; 64: 1476–84.
DUCTAL ORGANOIDS GENERATE HUMAN PANCREAS UPON 2. Neesse A, Frese KK, Chan DS, Bapiro TE, Howat WJ, Richards FM,
ORTHOTOPIC TRANSPLANTATION AND ALLOW DISEASE Ellenrieder V, Jodrell DI and Tuveson DA. SPARC independent drug deliv-
MODELLING ery and antitumour effects of nab-paclitaxel in genetically engineered mice.
M. Hohwieler1, A. Illing1, M. Müller1, Q. Lin2, A. Lechel1, P.C. Hermann1, Gut 2014; 63: 974–83.
J. Rosendahl3, T. Seufferlein1, M. Wagner1, A. Kleger1 3. Neesse A, Frese KK, Bapiro TE, Nakagawa T, Sternlicht MD, Seeley TW,
1
Department Of Internal Medicine 1Ulm University Hospital, Ulm/Germany Pilarsky C, Jodrell DI, Spong SM and Tuveson DA. Connective tissue
2
Department Of Cell Biology, Institute for Biomedical Engineering, Aachen/ growth factor antagonism with FG-3019 enhances chemotherapy response
Germany without increasing drug delivery in murine ductal pancreas cancer. Proc Natl
3
Halle University Hospital, Halle/Germany Acad Sci U S A 2013; 110: 12325–30.
4. Neesse A, Hahnenkamp A, Griesmann H, Buchholz M, Hahn SA,
Contact E-mail Address: [email protected] Maghnouj A, Fendrich V, Ring J, Sipos B, Tuveson DA, Bremer C, Gress
Introduction: Exocrine/ductal pancreatic differentiation from human pluripotent TM and Michl P. Claudin-4 targeted optical imaging detects pancreatic
stem cells is a poorly understood process albeit various diseases arise from this cancer and its precursor lesions. Gut 2013; 62: 1034–43.
compartment. 5. Frese KK, Neesse A, Cook N, Bapiro T, Lolkema MP, Jodrell DI and
Aims & Methods: We designed a straightforward approach to direct human Tuveson DA. nab-paclitaxel potentiates gemcitabine activity by reducing
pluripotent stem cells (PSC) toward pancreatic organoids resembling exocrine cytidine deaminase levels in a mouse model of pancreatic cancer. Cancer
and ductal progeny. Discovery 2012; 2: 160–9.
Result: Extensive phenotyping of the organoids not only shows the appropriate 6. Olive KP, et al. Inhibition of Hedgehog signaling enhances delivery of che-
marker profile but also ultra-structural and functional hallmarks of human pan- motherapy in a mouse model of pancreatic cancer. Science 2009; 324:
creas in the dish. Upon orthotopic transplantation into immunodeficient mice, 1457–61.
these organoids form normal pancreatic ducts and acinar tissue resembling fetal
human pancreas without any evidence of tumour formation or transformation.
Finally, we implemented this unique phenotyping tool as a model for pancreatic
facets of cystic fibrosis (CF) but also other inherited pancreatic disorders. We OP261 CIRCULATING CELL-FREE DNA IS A RELIABLE TOOL TO
provide for the first time evidence that pancreatic commitment occurs generally DETECT HOT SPOT MUTATIONS IN INTRADUCTAL PAPILLARY
unhindered in CF. Importantly, CFTR-activation in mutated pancreatic orga- MUCINOUS NEOPLASMS
noids mirrors the CF-phenotype in a series of functional assays. We also con- A. Berger1, D. Schwerdel1, I. Costa2, O. Strobel3, T. Hackert3, T. Barth4,
ducted a scalable proof-of concept screen in CF-pancreatic organoids using a set A. Meining5, M. Büchler6, M. Zenke2, P.C. Hermann5, T. Seufferlein5, A. Kleger5
of CFTR correctors and activators. Finally, we did orthotopic transplantation of 1
Internal Medicine, Ulm University Hospital, Ulm/Germany
CF-organoids to generate diseased human pancreata in mice and established a 2
Centre Of Medical Technology (mtz), Helmholtz Institute for Biomedical
mRNA-mediated gene repair approach in CF-organoids. Similar assays were Engineering, Aachen/Germany
applied to another inherited pancreatic disorder. 3
Department Of General Surgery, University Hospital Heidelberg, Heidelberg/
Conclusion: Thus, our platform provides novel opportunities to model pancreatic Germany
disease and development but also to screen for disease rescuing agents. 4
Department Of Pathology, Ulm University Hospital, Ulm/Germany
Disclosure of Interest: All authors have declared no conflicts of interest. 5
Department Of Internal Medicine, Ulm University Hospital, Ulm/Germany
6
Abteilung Für Allgemeine, Viszerale Und Transplantationschirurgie, Universität
Heidelberg, Heidelberg/Germany
OP260 CANCER ASSOCIATED FIBROBLASTS (CAFS) SEQUESTER Contact E-mail Address: [email protected]
GEMCITABINE TO INCREASE INTRATUMORAL DRUG Introduction: Pancreatic ductal adenocarcinoma (PDAC) is the most common
DELIVERY IN MURINE PANCREAS CANCER cancer type of the pancreas. The three PDAC precursor lesions are: (i) pancreatic
A. Neesse1, E. Hessmann2, M. Patzak2, T. E. Bapiro3, D. I. Jodrell3, J.M. Löhr4, intraepithelial neoplasia (PanIN), (ii) mucinous cystic neoplasm (MCN), and (iii)
T.M. Gress5, V. Ellenrieder1 IPMN. In contrast, serous cystadenomas are strictly benign cystic neoplastic
1
Gastroenterology And Gastrointestinal Oncology, University Medical Centre lesions and rarely require surgery.
Goettingen, Goettingen/Germany Aims & Methods: Frequently, differential diagnosis of neoplastic cysts remains
2
University Medical Centre Goettingen, Goettingen/Germany cumbersome. Thus, non-invasive diagnostic stratification would be welcome.
3
Cancer Research UK, Cambridge/United Kingdom Such a test should allow both discrimination of (i) IPMN from strictly benign
4
Karolinska University Hospital, Stockholm/Sweden pancreatic cysts but also (ii) low- from high-grade IPMN.
5
Klinik Für Gastroenterologie, Endokrinologie, Stoffwechel Und Infektiologie, Result: Little is known about the molecular alterations of IPMN, but GNAS
Philipps Universität Marburg, Marburg/Germany mutations have been described to promote IPMN formation. A tumor-derived
fraction of cell-free DNA (cfDNA) circulating in the bloodstream represents the
Contact E-mail Address: [email protected] mutational makeup of tumors and could be a tool for non-invasive monitoring.
Introduction: The pronounced tumour stroma in pancreatic cancer has recently We demonstrate that cfDNA levels discriminate controls from a cohort of
been appreciated as physical barrier impeding delivery of therapeutic agents. Fukuoka-negative branch-duct IPMN but also from pancreatic cancer.
Herein, we aim to investigate the delivery of gemcitabine metabolites in primary Furthermore, GNAS mutations were detected in IPMN patients but were
pancreas tumours and matched liver metastases and dissect stromal and neoplas- absent in serous cystadenoma (SCA) and in controls. Moreover, we observed
tic compartments. relevant concordance between tissue and liquid biopsies-based GNAS mutations
Aims & Methods: The cellular and acellular tumour stroma was assessed in in an independent cohort of resected IPMN patients.
human and mouse primary tumours and matched liver metastases. Conclusion: These findings establish cfDNA and targeted genotyping as a diag-
Gemcitabine metabolites were analysed in LSL-KrasG12D/þ;LSL-Trp53R172H/þ; nostic tool for IPMN, which may aid differential diagnosis and risk stratification
Pdx-1-Cre (KPC) tumours and matched liver metastases, primary tumour cell of cystic pancreatic lesions.
lines, cancer associated fibroblasts (CAFs), and pancreatic stellate cells (PSCs) by Disclosure of Interest: All authors have declared no conflicts of interest.
liquid chromatography- mass spectrometry/mass spectrometry (LC-MS/MS).
Expression analysis of gemcitabine metabolism pathways was performed
in vitro and in vivo. Viability of CAFs was assessed in vivo following a preclinical
trial in the KPC model.
Result: Fibroblast density and collagen deposition were significantly reduced in
human and murine liver metastases as compared to matched primary tumours.
Gemcitabine (dFdC) and its activate metabolite dFdCTP were significantly
higher in stroma rich tumours compared to stroma poor liver metastases and
normal liver. Mean vessel density did not correlate with gemcitabine delivery at
pharmacodynamically relevant endpoints. In cell culture, significantly increased
concentrations of activated dFdCTP and greatly reduced levels of the inactive
gemcitabine metabolite dFdU were detected in PSCs and CAFs. Importantly,
key metabolite enzymes for gemcitabine inactivation such as deoxycytidylate
deaminase (Dctd), cytidine deaminase (Cda) and hydrolytic cytosolic 5’-nucleo-
tidases (Nt5c1A, Nt5c3) were differentially expressed in PSCs and CAFs.
Moreover, treatment of KPC mice revealed intrinsic resistance of CAFs to
gemcitabine.
Conclusion: Our findings suggest that CAFs sequester gemcitabine and thus may
contribute to the clinical failure of this drug in desmoplastic pancreatic cancer.
Therefore, metabolic engineering of CAFs may constitute a promising new
avenue to enhance the cytotoxic effects of gemcitabine in patients.
Disclosure of Interest: All authors have declared no conflicts of interest.
A104 United European Gastroenterology Journal 4(5S)

TUESDAY, OCTOBER 18, 2016 14:00–15:30 PAR1-AP (TFLLR; 1, 10 and 100 mM), PAR2-AP (SLIGRL; 100 mM) and
INTESTINAL FAILURE: FROM PATHWAYS TO TREATMENT – ROOM PAR4-AP (AYPGKF; 100 mM), their irrelevant peptides (PAR-IP; 100 mM) or
L7_____________________ proteases: trypsin (1 and 10 U) and thrombin (1 and 10 U) were studied in
cultured human DRG neurons, which were fixed thereafter, to study PAR
OP262 NOVEL GENE MUTATIONS IN NEUROGENIC CHRONIC expression.
INTESTINAL PSEUDO-OBSTRUCTION Result: In fixed human DRG, PAR1, PAR2 and PAR4 were expressed in 20, 40
E. Bonora1, C. Graziano1, F. Bianco1, A. Stanzani1, R. Rinaldi1, R. D’Angelo1, and 40% of human sensory neurons respectively. PAR expression was not mod-
E. Boschetti2, J. D. Smith3, G. Assadi4, M. Bamshad5, D. Nickerson6, ified after culture. PAR1-AP increased intracellular calcium concentration in a
G. Lindberg7, M. D’Amato8, V. Stanghellini1, M. Seri1, R. De Giorgio1 dose-dependent manner. This increase was inhibited by PAR1 antagonist
1
Dimec, University of Bologna, Bologna/Italy (SCH79797, 10 mM). In contrast, PAR2-AP, PAR4-AP and PAR-IP did not
2
Department Of Biomedical And Neuro-motor Science, University of Bologna, cause calcium mobilization. Thrombin (PAR1 and PAR4 agonist) but not trypsin
Bologna/Italy (PAR2 and PAR4 agonist) increased calcium flux in human sensory neurons.
3
University of Washington Center for Mendelian Genomics, Seattle/United States PAR1-AP-induced calcium mobilization was significantly reduced by pre-incuba-
of America/WA tion with PAR4-AP, but not with PAR2-AP or any of the PAR-IP.
4
Karolinska Institutet, Stockholm/Sweden Conclusion: Our study demonstrates that PAR1, PAR2 and PAR4 are expressed
5
Department Of Genome Sciences, University of Washington, Seattle/United in human sensory neurons. In contrast to PAR2 and PAR4, PAR1 activation
States of America induced calcium increase in human sensory neurons. PAR4 activation reduced
6
Department Of Genome Sciences, University of Washington Center for Mendelian PAR1 induced calcium mobilization. Thus, in Human PAR1 and PAR4 seem to
Genomics, Seattle/United States of America/WA play an important role in neuronal activation and may be relevant in IBS
7
Center For Medical Gastroenterology, Karolinska University Hospital, Huddinge, research.
Stockholm/Sweden Disclosure of Interest: All authors have declared no conflicts of interest.
8
Unit Of Clinical Epidemiology, Department Of Medicine Solna, Karolinska
Institutet, Stockholm/Sweden
Contact E-mail Address: [email protected] OP264 DIFFERENTIAL BASELINE CHARACTERISTICS IN SHORT
Introduction: Chronic intestinal pseudo-obstruction (CIPO) is a severe gut dys- BOWEL SYNDROME DUE TO VASCULAR CATASTROPHES ARE
motility mimicking an intestinal sub-occlusion without demonstrable mechanical ASSOCIATED WITH VARYING RESPONSE TO TEDUGLUTIDE
causes. Several genes have been identified in familial cases, suggesting a genetic TREATMENT: POST HOC ANALYSIS
heterogeneity. We identified a novel mutation in the RAD21 gene in a recessive P.B. Jeppesen1, U. Pape2, K. Iyer3, H. Lee4, C. Olivier5
form of familial CIPO1. RAD21 is a transcription factor essential for a number 1
Rigshospitalet, Copenhagen/Denmark
of functions including sister chromatid division during cell replication. 2
Hepatology And Gastroenterology, Charite´, University Medicine Berlin, Berlin/
Aims & Methods: This study aimed to identify other mutated genes in a selected Germany
subset of CIPO, i.e. those cases associated with peripheral small fiber neuropathy 3
Mount Sinai Medical Center, New York/United States of America/NY
(SFN), a condition affecting peripheral neurons including those of the autonomic 4
Shire plc, Lexington/United States of America/MA
system. Whole exome sequencing (WES) was performed on genomic DNA of 5
Shire plc, Zug/Switzerland
n ¼ 6 patients (3 trios and 3 sporadic cases) with clinical, radiological and mano-
metric well-defined CIPO. A neurological work-up established SFN in each of Contact E-mail Address: [email protected]
them. Libraries were enriched with the Nimblegen SeqCap EZ v3.0 and Introduction: Vascular catastrophes are an underlying condition for massive
sequenced via paired-end 50 bp reads on HiSeq2500 sequencer. Variants were intestinal resection and failure associated with short bowel syndrome (SBS–IF).
annotated with the SeattleSeq137 Annotation Server. Additional 77 patients were Aims & Methods: This post hoc analysis of data reported in patient e-case forms
collected for replication study. Target resequencing on selected genes was per- compared baseline characteristics of patients with SBS–IF due to vascular cata-
formed using the TruSeq amplicon panel designed with Design Studio software. strophes (SBS–Vasc) vs patients with nonvascular causes of SBS–IF (SBS–non-
Data analysis and variant calling was performed with the TruSeq Amplicon Vasc), including the clinical response to teduglutide (TED). STEPS
application in BaseSpace. (NCT00798967; EudraCT2008-006193-15) was a 24-week, placebo (PBO)–con-
Result: WES analysis was performed considering pathogenic variants present as trolled study of TED 0.05 mg/kg/day in patients with SBS–IF. Response was
autosomal recessive (compound heterozygotes), X-linked or de-novo in the defined as 20% reduction from baseline in weekly parenteral support (PS)
affected probands, since all the parents were healthy. We identified novel/rare volume at Week 20 that was maintained at Week 24. Vascular catastrophes
missense mutations in FAT1 and in CROCC genes, inherited in an autosomal were intestinal ischaemia or mesenteric vessel thrombi or emboli. Descriptive
recessive way (compound heterozygous) in two trios, and a de-novo variant in summary statistics are presented with standard deviations (SD) or 95% confi-
B3GAT2 in the affected individual of the other trio analyzed, in combination dence intervals (CI); this post hoc analysis was not powered for statistical
with two rare/novel variants in Lipoprotein Related Receptor 2 (LRP2), that significance.
binds APOB which we have previously related to CIPO1. Analysis of these Results: The patient characteristics for the SBS–Vasc (n ¼ 32) and SBS–non-Vasc
genes in 77 additional CIPO patients is currently ongoing. All the identified (n ¼ 53) groups are detailed in the Table. The reason for the majority of the
pathogenic variants were absent in our in-house database of 1,000 Italian intestinal resections was Crohn’s disease (SBS–non-Vasc) or mesenteric vessel
chromosomes. thrombi or emboli (SBS–Vasc), Table. At baseline, more SBS–Vasc patients
Conclusion: We identified three novel gene defects in three different CIPO were older (55 vs 48 years) and male (53% vs 41%) than SBS–non-Vasc patients.
patients with SFN. FAT1 is an unconventional cadherin, B3GAT2 is a glucur- SBS–Vasc patients had shorter bowel length (55 vs 92 cm), were more likely to
onyl transferase implicated in neuronal cellular migration and adhesion, while have colon-in-continuity (78% vs 43%), and were less likely to have stoma pre-
CROCC encodes for rootletin, a protein crucial for centrosome cohesion and sent (19% vs 61%) compared with SBS–non-Vasc patients. SBS–Vasc patients
separation during the cell cycle. Similarly to RAD21, also rootletin is related to had lower PS volume at baseline (11.2 vs 14.3 L/week) compared with SBS–non-
chromosome structural maintenance suggesting that recessive defects in these Vasc patients. After 24 weeks, 53% (CI, 27%–79%) of SBS–Vasc patients and
genes may severely impair autonomic, including enteric, neurons. WES imple- 70% (CI, 50%–86%) of SBS–non-Vasc patients were responders to TED. In the
mentation can contribute to decipher complex genetic mechanisms underlying PBO groups, 35% (CI, 14%–62%) of SBS–Vasc patients and 27% (CI, 11%–
neurogenic CIPO. 48%) of SBS–non-Vasc patients met the response criteria. In the TED groups,
Disclosure of Interest: All authors have declared no conflicts of interest. reduction in mean PS volume (change and percentage change) took longer in the
Reference SBS–Vasc group (Week 12: 1.9 [CI, 0.3–3.5], 12% [CI, 3%–20%]; Week 24, 3.6
[CI, 1.5–5.7], 25% [CI, 15%–35%]) compared with the SBS–non-Vasc group
1. Bonora et al. (2015) Gastroenterology. 148:771–782. (Week 12: 4.0 [CI, 2.0–5.9], 24% [CI, 16%–33%]; Week 24: 5.5 [CI, 3.4–7.6],
36% [CI, 29%–43%]). The overall TED safety profile was generally similar
between the 2 groups. Specifically, 415% of SBS–Vasc patients reported abdom-
inal pain, dyspnoea, fatigue, nausea, and peripheral oedema, whereas 15% of
OP263 PROTEASE SIGNALING IN HUMAN SENSORY NEURONS SBS–non-Vasc patients reported nausea, abdominal distension, abdominal pain,
C. Desormeaux1, T. Bautzova2, C. Rolland3, N. Vergnolle3, N. Cenac3 stoma complication, and peripheral oedema.
1
Haute Garonne, Digestive Health Research Institute, Toulouse/France Conclusion: To our knowledge, this post hoc analysis is the first to compare
2
Digestive Health Research Institute, Toulouse/France baseline characteristics and response to treatment in patients with SBS resulting
3
Haute Garonne, Digestive Health Research Institute, Toulouse/France from vascular catastrophes and nonvascular diseases. In this group of patients,
SBS-IF patients with vascular catastrophes were more likely to have colon-in-
Contact E-mail Address: [email protected] continuity, less likely to have stoma present, and had less baseline PS volume
Introduction: IBS is a functional bowel disorder characterized by abdominal pain, than in patients with nonvascular causes of SBS–IF. SBS-IF patients with vas-
associated with constipation and/or diarrhea. Among the mediators studied in cular catastrophes look longer to respond to teduglutide in the observed PS
IBS, increased colonic proteolytic activity appears as a common feature in all IBS volume reduction.
sub-groups. Through Protease-Activated Receptors (PARs) activation, proteases
can activate primary afferents and act on visceral pain pathways in rodents, but Table: Demographic and Baseline Characteristics
the relevance of PAR activation in human sensory neurons still has to be deter-
mined. Thus, the objective of our study was to decipher the PAR pharmacology SBS–Vasc SBS–Vasc SBS–non-Vasc SBS–non-Vasc
in human sensory neurons.
Parameter PBO (n ¼ 17) TED (n ¼ 15) PBO (n ¼ 26) TED (n ¼ 27)
Aims & Methods: Cryo-protected or fresh human thoracic dorsal root ganglia
(DRG) were obtained from the national disease resource interchange (NDRI). Age, y 56.6 (13.8) 52.3 (13.5) 45.2 (15.3) 50.8 (12.0)
Expression of PAR1, PAR2 and PAR4 was studied on slices of DRG (DRG T12, Sex, n%
n ¼ 3) by co-staining immunochemistry with a pan-neuronal marker (pgp9.5) and -Male 8 (47) 9 (60) 11 (42) 11 (41)
PAR antibodies. Calcium signaling responses to PAR agonist peptide (PAR-AP): (continued)
United European Gastroenterology Journal 4(5S) A105
Table Continued patients who underwent small bowel or multivisceral transplants at
Addenbrooke’s Hospital, Cambridge, UK. There were 54 patients in total
SBS–Vasc SBS–Vasc SBS–non-Vasc SBS–non-Vasc from January 2006 to April 2015. Patients with survival less than 6 months
post-transplant (n ¼ 9) and with incomplete data (n ¼ 1) were excluded. This
-Female 9 (53) 6 (40) 15 (58) 16 (59)
resulted in 44 eligible patients whose weights, BMI and grip strengths (in non-
Body weight, kg 66.6 (12.9) 63.9 (11.2) 58.5 (11.5) 62.1 (11.7) dominant hand) were analysed. Grip strengths were performed by one of two
BMI, kg/m2 23.3 (3.4) 22.6 (3.4) 21.5 (2.8) 22.4 (3.1) dedicated dietitians.
SBS history Result: Patient characteristics: Transplants included 12 isolated small bowel
-Vascular catastrophe cate- (SBT), 5 liver and small bowel (LSBT), 12 modified multivisceral (small bowel,
gories, n stomach, pancreas-MMVT) and 22 multivisceral (small bowel, stomach, pan-
–Intestinal ischaemia 4 5 creas, liver-MVT). 7 patients were re-transplanted. Recently, donor colon has
–Mesenteric vessel thrombi 13 9 – – been included in the graft to help with fluid balance. Mean age at transplant was
or emboli 43.9 years. Patients were followed up for a median of 30 months, to April 2016 or
–Unknown vascular cause 0 1 death (n ¼ 14). Primary outcomes: Out of the 30 long-term survivors, 73.3% (22)
-Nonvascular causes of of them are maintained on oral diet alone at the end of follow up. The other 5
SBS-IF, n patients require ONS, 2 require IV fluids and 1 patient continues on PN. Most
–Crohn’s disease 8 10 patients (95.5%; 21/22) who achieved nutritional autonomy were previously
dependent on nutritional support (2 ONS; 1 EN; 18 PN) except for one patient
–Injury 4 4
who was listed super-urgently. Of the patients who died, 3 out of 14 were requir-
–Volvulus – – 6 3
ing PN. The mean BMI pre-transplant was 21.7 (SD ¼ 3.5). Post-operatively, the
–Cancer 2 1 majority of patients (86.7%) lost weight (mean 14.3%; range 1–30%) with their
–Other 6 9 nadir weight occurring at a mean of 10.7 months. 11 lost 20% of their pre-
-Colon-in-continuity, n (%) 13 (76) 12 (80) 10 (38) 13 (48) transplant weight. However more than half (26/44) of the patients weights
-Stoma presence, n (%) 2 (12) 4 (27) 15 (58) 17 (63) improved over time. Compared to the time of assessment, their BMI improved
–Jejunostomy 1 (50) 2 (50) 4 (26) 9 (53) by 0.9 kg/m2 (SD ¼ 4.3) in the first year (median ¼ 11 months) and increased
–Ileostomy 0 1 (25) 9 (60) 5 (29) further by 1.4 kg/m2 (SD ¼ 4.3) at the end of the follow up. The most recent
mean BMI in 30 survivors were 23.3 kg/m2 (SD ¼ 5.2). Further analysis revealed
–Colostomy 0 1 (25) 1 (7) 3 (18)
20 patients have healthy weight (BMI 18.5–25), 4 underweight (BMI 5 18.5), 3
–Other 1 (50) 0 1 (7) 0
overweight (BMI 4 25) and 3 obese (BMI 4 30). Secondary outcomes: Post-
-Ileo-cecal value presence, n 9 (53) 4 (27) 5 (19) 6 (22) transplant, PN was given for a median of 22 days (range 2–241) and 39.5 days
(%)
(range 11–262) of EN. At the end of the follow up, those who have nutritional
–Yes 6 (67) 1 (25) 4 (80) 2 (33) autonomy required a considerably shorter duration of nutritional support post-
-Estimated remaining small 40.2 (29.9)* 70.9 (57.8) 87.6 (73.6)* 95.8 (67.8)* transplant compared to those who are nutrition dependent (mean of 65.3 vs 120.7
bowel length, cm days). This suggests that the duration on nutritional support post-transplant may
PS history predict nutritional autonomy. Of the patients who have colon (graft or continu-
-PS duration at baseline, y 6.1 (6.2) 5.4 (4.7) 5.8 (5.5) 7.2 (7.0) ity), 64% have nutritional autonomy. However those without functioning colon
-PS L/week at baseline 10.2 (5.4) 12.4 (5.5) 15.5 (7.3) 13.3 (8.3) are less likely to (47.4%) (P ¼ 0.36). Handgrip strength was measured in 31
-PS days per week at 5.4 (1.8) 5.6 (1.6) 6.3 (1.2) 5.6 (1.8) patients pre and post-transplant. At median of 9 months (range from 2–32),
baseline there was a slight reduction by 6% of expected value which correlates with
their weight loss. 18 patients had further handgrip strength test and they
Data are expressed as mean (SD) unless otherwise noted. improved with a mean of 7% at last follow up (median 16 months).
BMI ¼ body mass index; PBO ¼ placebo; PS ¼ parenteral support; SBS- Conclusion: The majority of patients achieved nutritional autonomy post-trans-
IF ¼ intestinal resection and failure associated with short bowel syndrome; plant and a colon-containing graft may be beneficial. It is common for patients to
TED ¼ teduglutide. lose a moderate amount of weight, up to 30% post-operatively. Therefore timely
*SBS–Vasc n ¼ 16 PBO; Nonvascular, n ¼ 24 PBO, n ¼ 24 TED. referral is crucial to allow optimisation of perioperative nutritional status.
Disclosure of Interest: All authors have declared no conflicts of interest.

Disclosure of Interest: P.B. Jeppesen: Has received grant/research support and

served as a consultant, advisory board member, and study investigator for NPS
Pharmaceuticals, Inc. OP266 SUBANALYSIS OF TEDUGLUTIDE EFFICACY AND SAFETY
U. Pape: Has received grant/research support and served as an advisory board DATA FROM PATIENTS WITH CROHN’S DISEASE AND
member or speaker’s bureau for NPS Pharmaceuticals, Inc., Shire plc, and ULCERATIVE COLITIS IN THE STEPS STUDY
Fresenius Kabi GmbH; served as a study investigator for NPS U. Pape1, P.B. Jeppesen2, H. Lee3, A. A. Grimm3, S. J. O’Keefe4
Pharmaceuticals, Inc. 1
Hepatology And Gastroenterology, Charite´, University Medicine Berlin, Berlin/
K. Iyer: Has received grant/research support and served as an advisory board Germany
member and consultant for NPS Pharmaceuticals, Inc and Shire plc. 2
Rigshospitalet, Copenhagen/Denmark
H. Lee: Employee and stockholder of Shire plc. 3
Shire plc, Lexington/United States of America/MA
C. Olivier: Employee and stockholder of Shire plc 4
UPMC, Pittsburgh/United States of America/PA
The clinical trial was funded by NPS Pharmaceuticals, Inc., Bedminster, NJ. NPS
Pharmaceuticals, Inc., is a wholly owned indirect subsidiary of Shire plc. This Contact E-mail Address: [email protected]
analysis research was funded by Shire plc Introduction: Inflammatory bowel disease (IBD; Crohn’s disease [CD] and ulcera-
tive colitis) is a major underlying condition for massive intestinal resection lead-
ing to intestinal failure associated with short bowel syndrome (SBS–IF).
Aims & Methods: This post hoc subgroup analysis compared response to tedu-
OP265 NUTRITIONAL OUTCOME IN SMALL BOWEL AND glutide (TED) in patients with SBS–IF due to IBD (SBS–IBD) vs those with
MULTIVISCERAL TRANSPLANT PATIENTS noninflammatory causes of SBS–IF (SBS–non-IBD). STEPS (NCT00798967,
S. P. Yeap1, R. Maddison2, S. J. Middleton1, A. J. Butler3, J. M. Woodward1, N. EudraCT2008-006193-15) was a 24-week, phase III, placebo-controlled study
K. Russell3, C. S. Rutter1, L. M. Sharkey4 of 0.05 mg/kg/day TED in patients with SBS–IF. Patients with CD were in
1
Gastroenterology, Addenbrooke’s Hospital, Cambridge/United Kingdom clinical remission for 12 weeks at baseline. Response was a 20% reduction
2
Nutrition, Addenbrooke’s Hospital, Cambridge/United Kingdom from baseline in weekly parenteral support (PS) volume at Week 20 that was
3
Transplant Surgery, Addenbrooke’s Hospital, Cambridge/United Kingdom maintained at Week 24. Descriptive summary statistics are presented with 95%
4
Small Bowel And Multivisceral Transplant, Addenbrooke’s Hospital, Cambridge/ confidence intervals (CIs); this post hoc analysis was not powered for statistical
United Kingdom significance.
Result: The Table details patient characteristics (SBS–IBD, n ¼ 19; SBS–non-
Contact E-mail Address: [email protected] IBD, n ¼ 67). Patients with SBS–IBD had lower colon-in-continuity, higher
Introduction: There has been an increase in the numbers of small bowel and stoma presence, and higher baseline PS volume than those with SBS–non-IBD.
multivisceral transplants performed in the UK over the past 10 years. Despite After 24 weeks, 73% (95% CI, 39%–94%) of patients with SBS–IBD and 59%
successful transplants, these patients require close monitoring long-term and (95% CI, 41%–76%) with SBS–non-IBD were responders to TED. In the TED
currently there is limited data on their nutritional outcome. patients, mean PS volume was reduced by 45% (95% CI, 31%–59%) in patients
Aims & Methods: Our primary end points are to examine 1) the percentage of with SBS–IBD and 29% (95% CI, 22%–35%) in those with SBS–non-IBD. Two
patients who achieved nutritional autonomy (without oral nutritional supple- of 9 (22%) patients with SBS–IBD and 6/30 (20%) patients with SBS–non-IBD
ment ONS, enteral nutrition EN, intravenous IV fluid or parenteral nutrition achieved a PS reduction of 2 days per week. Overall safety profile was similar in
PN) post-transplant and 2) the change in their weight and body mass index both groups (SBS–IBD, n ¼ 19; SBS–non-IBD, n ¼ 66). Among patients receiv-
(BMI) in the immediate and long term. Secondary end points include 1) the ing TED, treatment-emergent adverse events (TEAEs) were reported by 100% of
duration on nutritional support post- transplant; 2) change in anthropometry patients with SBS–IBD and 77% of those with SBS–non-IBD. Serious adverse
and 3) difference in nutritional outcome in patients who have colon-containing events among those receiving TED occurred in 27% of patients with SBS–IBD
graft or received continuity surgery. Data was collected prospectively on all and 39% of those with SBS–non-IBD. No TEAEs of CD were reported in either
A106 United European Gastroenterology Journal 4(5S)
subgroup. No patients with SBS–IBD and 1/47 (2%) with SBS–non-IBD with a globulin (ATG, n ¼ 4). 3 grafts required removal due to rejection and all 3
colon experienced 1 TEAE (TED) of colitis. patients have been re-transplanted. Within our cohort, there have been 5 cases
Conclusion: In this analysis, the subgroup of patients with inflammatory bowel of graft versus host disease (GVHD) and 6 cases of post-transplant lymphopro-
disease (SBS–IBD) had evidence of more severe disease based on a higher fre- liferative disorder (PTLD). Infections continued to be a problem. We have seen
quency of stoma presence, higher PS requirements, and lower colon-in-continu- increasing rate of vancomycin resistant enterococcus (VRE) and carbapenem
ity. Despite this, clinical responses to TED were equally strong. resistant pseudomonas. Cytomegalovirus is the most common viral infection.
Overall rates are 37.5% but this increases to 91% when seropositive donor is
Table: Demographic and Disease History Data given to a seronegative recipient. 1 year patient survival for SB recipients is 91%,
for MMV is 89% and for MVT/LSB is 69%. 3 year patient survival for SB
SBS– SBS– SBS–Non- SBS–Non- recipients is 81%, for MMV is 89% and for MVT/LSB is 52%.
IBDPlacebo IBDTED IBDPlacebo IBDTED Conclusion: Transplantation of intestinal-containing grafts is technically challen-
(n ¼ 8) (n ¼ 11) (n ¼ 35) (n ¼ 32) ging and recipients have a higher rate of complications compared to other solid
organ transplants. However, with advances in surgical techniques and increasing
Age, mean (SD), y 48 (7) 48 (7) 50 (17) 52 (14) experience of the management of medical complications, survival is improving.
Women, n (%) 5 (63) 5 (46) 19 (54) 17 (53) Intestinal or Multivisceral transplant should be considered for certain patients
Body mass index, mean 22.6 (3.6) 23.3 (4.1) 22.2 (3.1) 22.2 (2.8)* who have suffered an abdominal catastrophe, are unable to have a liver trans-
(SD), kg/m2 plant due to extensive portomesenteric thrombosis, or have complications arising
from intestinal failure. Timely referral to a transplant centre and careful follow-
Stoma present, n (%) 7 (88) 11 (100) 10 (29) 10 (32)* up is essential to continue improvement in outcomes.
Colon-in-continuity, n (%) 1 (13) 1 (9) 22 (63) 24 (77)* Disclosure of Interest: All authors have declared no conflicts of interest.
Estimated small bowel 128 (98) 129 (77)y 54 (43)z 73 (56)x
length, mean (SD), cm
TUESDAY, OCTOBER 18, 2016 14:00–15:30
Baseline PS, mean (SD), 21.6 (8.1) 15.9 (10.4) 11.5 (5.9) 11.2 (6.4)* PROGNOSTIC FACTORS IN LOWER GI CANCER – ROOM L8_____________________
L/wk
Baseline PS duration, mean 7.2 (7.4) 8.1 (8.0) 5.6 (5.3) 6.1 (5.7)* OP268 EXPRESSION OF DDR2 CORRELATES WITH HIGH
(SD), y FREQUENCY OF PERITONEAL DISSEMINATION AND POOR
PROGNOSIS IN COLORECTAL CANCER
*n ¼ 31, yn ¼ 9, zn ¼ 32, xn ¼ 30.
S. Sasaki1, M. Ueda2, T. Iguchi2, M. Kaneko1, H. Nakayama1, T. Watanabe1,
A. Sakamoto3, K. Mimori2
1
Dept. Of Surgery, Omori Red Cross Hospital, Tokyo/Japan
Disclosure of Interest: U. Pape: Has received grant/research support and served 2
Dept. Of Surgery, Kyushu University Beppu Hospital, Beppu/Japan
as an advisory board member or speaker’s bureau for NPS Pharmaceuticals, Inc., 3
Dept. Of Pathology And Laboratory Medicine, Omori Red Cross Hospital,
Shire plc, and Fresenius Kabi GmbH; served as a study investigator for NPS Tokyo/Japan
Pharmaceuticals, Inc.
P.B. Jeppesen: Has received grant/research support and served as a consultant, Contact E-mail Address: [email protected]
advisory board member, and study investigator for NPS Pharmaceuticals, Inc. Introduction: In the previous study, our colleagues identified that discoidin-
H. Lee: Employee and stockholder of Shire plc. domain receptor 2 (DDR2) is a promising driver gene of peritoneal dissemina-
A.A. Grimm: Employee of Shire plc. tions in gastric cancer by a comprehensive expression assay. We found DDR2
S.J. O’Keefe: Has received research funding support from NPS Pharmaceuticals, expression was associated with high frequency of peritoneal dissemination and
Inc. poor prognosis in gastric cancer, and also revealed that the DDR2 was upregu-
This clinical trial was funded by NPS Pharmaceuticals, Inc., Bedminster, NJ. lated by the loss of DNA methylation and that DDR2 knockdown reduced
NPS Pharmaceuticals, Inc., is a wholly owned indirect subsidiary of Shire plc. peritoneal dissemination in a xenograft. Furthermore, we found dasatinib, an
This analysis research was funded by Shire plc inhibitor of the DDR2 signaling pathway, suppressed peritoneal dissemination.
In colorectal cancer, peritoneal dissemination is second popular site for color-
ectal cancer metastasis, next to the liver. Its frequency is estimated to be 4–7% of
patients with colorectal cancer at primary surgery, and approximately 4–19% of
OP267 INDICATIONS AND OUTCOMES OF INTESTINAL AND patients during follow-up after curative surgery. Peritoneal dissemination is one
MULTIVISCERAL TRANSPLANT of most frequent non-curative clinical factors also in colorectal cancer.
L. M. Sharkey1, S. P. Yeap1, C. S. Rutter1, D. C.O. Massey1, J. M. Woodward1, Aims & Methods: In this study, we analyzed correlations of DDR2 expression
A. J. Butler2, N. K. Russell2, S. J. Middleton1 with clinicopathological factors in colorectal cancer, especially peritoneal disse-
1
Gastroenterology, Addenbrooke’s Hospital, Cambridge/United Kingdom mination. We selected 63 cases with colorectal cancer who had an operation in
2
Transplant Surgery, Addenbrooke’s Hospital, Cambridge/United Kingdom our hospital between 2009 and 2014. Among them, 13 cases had synchronous or
metachronous peritoneal dissemination. We performed immunohistochemical
Contact E-mail Address: [email protected] examinations for 63 primary colorectal cancers and 12 peritoneal dissemination
Introduction: Despite a reduction in numbers worldwide, we have seen an increase lesions in 11 cases with anti-DDR2 antibody. We evaluated histological localiza-
in adult Intestinal and Multivisceral transplants in the UK in the past 3 years. tion of DDR2 expressions, divided 63 cases into two groups by the degree of
Some recent transplants have been performed ‘superurgently’ for acute wide- DDR2 expressions, and compared various clinicopathological factors and overall
spread splanchnic ischaemia. Longstanding indications include complications survival between these two groups.
of parenteral nutrition in patients with type 3 Intestinal Failure (IF-associated Result: In primary lesions, DDR2 was expressed more preferentially in cancer
liver disease (IFALD), recurrent catheter-related infections and loss of vascular cells at invasive front of tumors. The group with high DDR2 expression had
access), cirrhosis with extensive portomesenteric venous thrombosis precluding significantly more proportion of T4, lymph node metastasis, and peritoneal dis-
an isolated liver transplant and the need for extensive evisceration due to benign semination than the group with low DDR2 expression (p ¼ 0.0025, 0.012, and
tumour. Re-transplantation is indicated for loss of previous graft due to rejec- 0.012, respectively), and the prognosis of the former was significantly poorer than
tion, ischaemia or primary non-function. the prognosis of the latter (p ¼ 0.0164). In peritoneal dissemination lesions, 11
Aims & Methods: We describe here the indications and outcomes for Intestinal out of 12 exhibited intense DDR2 expressions.
and Multivisceral transplant at Addenbrooke’s Hospital, Cambridge, UK Data Conclusion: High DDR2 expression correlates with peritoneal expression and
was collected prospectively on an internal database of all patients transplanted poor prognosis in colorectal cancer as well as in gastric cancer. DDR2 might
from January 2006 to April 2016. All patients considered for an intestine-con- be one of promising driver genes of peritoneal dissemination universally in gas-
taining graft require ratification at a national forum (NASIT). Grafts which trointestinal peritoneal dissemination.
include liver or kidney are also discussed at local listing committees. Induction Disclosure of Interest: All authors have declared no conflicts of interest.
immunosuppression is with Campath (Alemtuzumab) and maintenance initially Reference
with tacrolimus and steroids. If complications related to tacrolimus occur,
patients are switched to ciclosporin or sirolimus. An antimetabolite is added to 1. Kurashige J, et al. Integrated Molecular Profiling of Human Gastric Cancer
aid steroid withdrawal post discharge. Identifies DDR2 as a Potential Regulator of Peritoneal Dissemination. Sci
Result: In the study period, 66 transplants were performed in 61 patients (33 Rep 2016 Mar 3; 6: 22371doi: 10.1038/srep22371.
Multivisceral, MVT; 7 Liver/small bowel, LSB; 9 Modified multivisceral,
MMV; 17 small bowel, SB). Grafts can also contain colon and pancreas. 26
patients (39%) received a transplant for complications relating to intestinal fail-
ure (overt IFALD ¼ 11, impending IFALD ¼ 4, recurrent sepsis ¼ 1, loss of vas-
cular access ¼ 10). 14 patients (21%) received a multivisceral graft because an
isolated liver transplant was not possible due to extensive portomesenteric venous
thrombosis. An increasing indication is that of ‘acute abdominal catastrophe’ – 9
patients were transplanted for this including 5 with widespread splanchnic ischae-
mia. Less frequent indications included desmoid tumours (4), re-transplant (6),
short bowel and renal failure (2). The median length of hospital stay post trans-
plant is 77 days. 7 patients had a proven episode of acute cellular rejection (ACR)
within 90 days, 12 patients had an episode between 90 days and 1 year and 7 had
ACR after 1 year. The vast majority of episodes were treated with pulsed methyl-
prednisolone (23/26, 88%). Subsequent treatments given were Alemtuzumab
(n ¼ 9), Infliximab (n ¼ 1), second pulse of steroids (n ¼ 6),anti-thymocyte
United European Gastroenterology Journal 4(5S) A107
OP269 GENETIC SUSCEPTIBILITY AND FAMILY HISTORY OF pathways were elucidated by promoter luciferase assay and co-immunoprecipita-
COLORECTAL CANCER. RELEVANCE OF SINGLE NUCLEOTIDE tion. The clinical impact of PCID2 overexpression was assessed in three cohorts
POLYMORPHISMS IN THE DEVELOPMENT OF COLORECTAL of 114 CRC patients from Beijing (cohort I), 46 CRC patients from Hong Kong
PRENEOPLASTIC LESIONS (cohort II) and 376 CRC cases from TCGA dataset (cohort III).
C.J. Gargallo Puyuelo1, A. Lanas2, P. Carrera3, A. Ferrandez1, E. Quintero Result: Amplification of PCID2 was detected in 32.5% (37/114) of CRC patients
Carrion4, M. Carrillo Palau5, I. Alonso Abreu5, P. Roncales6, E. Piazuelo7, from cohort I and 62.0% (233/376) of CRC patients from cohort III by Copy
M.A. Garcia Gonzalez7 Number Assay. The copy number gain was positively correlated with its mRNA
1
Gastroenterology, University Hospital ‘‘Lozano Blesa’’, Zaragoza/Spain overexpression both in cohort I (r sq ¼ 0.327, p 5 0.0001) and in cohort III (r
2
Gastroenterology, Hospital Clinico Universitario Lozano Blesa, Zaragoza/Spain sq ¼ 0.619, p 5 0.0001). Biological functional investigation of PCID2 revealed
3
CIBEREHD, Zaragoza/Spain that ectopic expression of PCID2 in colon cancer cell lines (DLD1 and HT29)
4
Gastroenterology, Hospital Univ. de Canarias, Santa Cruz de Tenerife/Spain significantly increased cell proliferation (p 5 0.01 in DLD1 and p 5 0.001 in
5
Gastroenterology, Hospital Universitario de Canarias, Santa Cruz de Tenerife/ HT29), G1-S cell cycle transition (p 5 0.01 and p 5 0.05, respectively), invasion
Spain (p 5 0.01 and p 5 0.01, respectively) and migration (p 5 0.01 and p 5 0.05,
6
Gastroenterology, Hospital Universitario Lozano Blesa, Zaragoza/Spain respectively) abilities, and suppressed cell apoptosis (p 5 0.01 and p 5 0.05,
7
Instituto de Investigación Sanitaria de Aragón, Zaragoza/Spain respectively). In addition, PCID2 significantly promoted xenograft tumor
growth as well as lung metastasis in nude mice. On the other hand, knockdown
Contact E-mail Address: [email protected] PCID2 in colon cancer cell lines (HCT116 and SW480) showed opposite effects.
Introduction: First-degree relatives (FDR) of patients with colorectal cancer We further revealed that the oncogenic effect of PCID2 was mediated through
(CRC) have been shown to have a 2- to 3-fold increased risk of developing degrading its interaction partner promyelocytic leukemia (PML) by ubiquitina-
CRC compared with the overall population. It is likely that CRC susceptibility tion. PML played a tumor suppressive role in CRC. PCID2 induced Wnt signal-
in these individuals results from common variants in low-penetrance genes. ing pathway and inhibited p53/p21 pathway activity. PCID2 expression level was
However, very little is known about the relevance of genetic variants in the evaluated by quantitative PCR in cohort I and cohort II patients. Multivariate
development of colorectal preneoplastic lesions according to the family history analysis revealed that patients with PCID2 overexpression were significantly
of CRC correlated with CRC recurrence (p 5 0.05 for cohort I, p 5 0.05 for cohort II).
Aims & Methods: We aimed to evaluate the role of certain single nucleotide Recurrence curves showed that PCID2 overexpression was a prediction marker
polymorphisms (SNPs) associated with CRC risk in the development of color- for recurrence of patients with CRC (p ¼ 0.004 for cohort I, p ¼ 0.03 for cohort
ectal adenomas depending on the family history of CRC. We carried out a case- II).
control study comprising 750 FDR of patients with non-syndromic CRC (cases), Conclusion: PCID2 plays a pivotal oncogenic role in colorectal carcinogenesis by
and 750 sex- aged- and histological lesion- matched individuals with no family degrading its downstream effector PML. PCID2 overexpression is an indepen-
history of CRC (controls). Cases and controls were selected from the Spanish dent recurrence prediction marker for CRC patients.
CRC screening registries in Aragon and The Canary Islands. All subjects under- Disclosure of Interest: All authors have declared no conflicts of interest.
went at least one colonoscopy and diagnosis of adenoma was confirmed by
histological study. Genomic DNA from cases and controls was genotyped by
the MassArrayTM(Sequenom) platform for a panel of 99 SNPs previously asso-
ciated with CRC risk. Genetic analysis was performed using the SNPassoc pack- OP271 PREDICTION OF COMPLETE RESECTIONS AFTER
age implemented in R. To address the issue of adjustment for multiple testing, the CYTOREDUCTIVE SURGERY BASED ON THE EXTENT OF
false discovery rate method and Bonferroni’s correction were applied. COLORECTAL PERITONITEAL CARCINOMATOSIS
Result: Average age of participants was 54.5  9.4 years with a slight predomi- W. h. Van Eden1, M. Lahaye2, A. Delli Pizzi3, D.M. Lambregts4, N. Kok1,
nance of women (51.7%). In 57% of patients, no preneoplastic lesions were G.L. Beets1, R.G. h. Beets-Tan4, A. Aalbers5
found. By contrast, 288 patients (144 cases and 144 controls) showed non 1
Department Of Surgery, The Netherlands Cancer Institute, Amsterdam/
advanced adenomas (NAA), and 354 patients (177 cases and 177 controls) had Netherlands
advanced adenomas (AA). Concerning gene analysis, 2 SNPs (rs10505477 A 4 G 2
Radiology, The Netherlands Cancer Institute, Amsterdam/Netherlands
and rs6983267 G 4 T) located in the CASC8 gene were associated with the 3
The Netherlands Cancer Institute, Amsterdam/Netherlands
development of adenomas. Thus, the rs10505477G and the rs6983267T alleles 4
Department Of Radiology, The Netherlands Cancer Institute, Amsterdam/
were significantly associated with a reduced risk of adenomas in patients with no Netherlands
family history of CRC (controls) (log-additive models, OR: 0.67, 95% CI:0.54– 5
Surgery, The Netherlands Cancer Institute, Amsterdam/Netherlands
0.83 and OR: 0.66, 95% CI:0.54–0.84, respectively). However, such a protective
effect was not observed in FDR of patients with CRC (cases). In the stratified Contact E-mail Address: [email protected]
analysis by histological lesion, the rs10505477G and the rs6983267T variants Introduction: Cytoreductive surgery (CRS) and hyperthermic intraperitoneal che-
were significantly associated with a reduced risk of both, NAA and AA in con- motherapy (HIPEC) is the treatment of choice for colorectal peritoneal carcino-
trols, although this effect was stronger on the risk of developing NAA (recessive matosis (PC). Prior to surgery abdominal computed tomography (CT) was
models, OR:0.38, 95% CI:0.21–0.67 for rs10505477, and OR: 0.32, 95% CI: performed to gain insight into the extent of PC and the presence of distant
0.17–0. 61 for rs6983267), suggesting their possible implication in early stages metastases.
of CRC development. Finally, 2 SNPs (rs10795668G 4 A and rs11255841T 4 A) Aims & Methods: Our objective was to evaluate the relation between the com-
located in the lncRNA gene LINC00709 were significantly associated with a pleteness of cytoreduction and the Dutch seven region count evaluated with CT
reduced risk of NAA in both, FDR of patients with CRC (recessive models, and during surgery. Patients who underwent abdominal CT-imaging for PC prior
OR: 0.22, 95% CI: 0.06–0.72 for rs10795668, and OR: 0.08, 95% CI: 0.03– to CRS-HIPEC were eligible. The seven-point region count was assessed with CT
0.61 for rs11255841) and patients with no family history of CRC (dominant by an experienced radiologist and peroperative evaluation was performed by the
models, OR: 0.50, 95% CI: 0.34–0.75 for rs10795668, and OR:0.52, 95% CI: operating surgeon, based on the Dutch region count. The completeness of cytor-
0.35–0.78 for rs11255841), suggesting their possible implication in early stages of eduction was scored after CRS. Survival analyses were performed.
CRC development. Result: Two hundred thirty-four patients were included. Patients with incomplete
Conclusion: Family history of CRC and some specific variants associated with cytroductive surgery had more often PC in five to seven regions during surgery
CRC risk (rs10505477 and rs6983267 in CASC8 gene and rs10795668 and (p 5 0.001). This result was not found using de CT-related region count
rs11255841 in LINC00709 gene) are involved in the development of colorectal (p ¼ 0.06). Regarding disease free survival and overall survival significant differ-
adenomas or specific histological subtypes. ences were found with medians of 21.9 months (IQR 19.1–24.7) and 44.6 months
Disclosure of Interest: All authors have declared no conflicts of interest. (IQR 35.8–53.5) in patients with complete cytoreduction compared to 12.1
months (IQR 9.7–14.6) and 19.0 months (IQR 14.2–23.8) in patients with incom-
plete cytoreductive surgery (p 5 0.001 and [p 5 0.001).
Conclusion: Patients with four or less involved abdominal regions with PC per-
OP270 A NOVEL AMPLIFICATION GENE PCID2 PROMOTES operative were more likely to have a complete resection. CT assessment of the
TUMORIGENICITY OF COLORECTAL CANCER THROUGH region score could not accurately predict a complete resection. Patients with a
DIRECTLY DEGRADING A TUMOR SUPPRESSOR PML AND IS complete resection showed better survival than patients with an incomplete
ASSOCIATED WITH DISEASE RECURRENCE cytoreduction.
J. Zhang1, Y. Zhang1, H. Tsoi2, H. Wang2, J. Gao3, Y.Y. Go2, S.C. Ng1, Disclosure of Interest: All authors have declared no conflicts of interest.
J.J.Y. Sung1, J. Yu1
1
Medicine & Therapeutics, The Chinese University of Hong Kong, Hong Kong/
Hong Kong PRC
2
The Chinese University of Hong Kong, Hong Kong/Hong Kong PRC OP272 PREVALENCE OF LYMPH NODE METASTASIS AND LONG
3
Gastrointestinal Oncology, Peking University Cancer Hospital & Institute, TERM SURVIVAL OF T1 RECTAL CARCINOID TUMORS: AN
Beijing/China ANALYSIS OF SURVEILLANCE, EPIDEMIOLOGY, AND END
RESULTS (SEER) DATABASE
Contact E-mail Address: [email protected] S. Ngamruengphong, A. Kamal, G. Hajiyeva, Y. Chen, M. Bukhari, A. Ismail,
Introduction: PCI Domain Containing 2 (PCID2) located at 13q34 was identified D. Fluxa, Y. H. Chavez, V. Kumbhari, V. Singh, M.I. Canto, M. Khashab
to be amplified in colorectal cancer (CRC) by genome sequencing. We evaluated Dept. Of Gastroenterology, Johns Hopkins University, Baltimore/United States of
its amplification, overexpression, biological functions and clinical implication in America/MD
CRC.
Aims & Methods: The PCID2 gene amplification status in CRC tissues was Contact E-mail Address: [email protected]
evaluated by Copy Number Assay. The biological effects of PCID2 overexpres- Introduction: Rectal carcinoids are the most common neuroendocrine tumors of
sion and knockdown were determined by in vitro and in vivo tumorigenicity the gastrointestinal tract and their incidence is increasing due to colorectal cancer
assays. The PCID2 interaction partner was identified by immunoprecipitation screening. Several previous studies have suggested that local excision (endoscopic
followed by mass spectrometry. PCID2 downstream effectors and signaling or transanal excision) is effective for 10 mm lesions but data on long-term
A108 United European Gastroenterology Journal 4(5S)
outcomes are very limited. In addition, management of 11–19 mm tumors is not Conclusion: In the majority of patients with a complete response residual fibrosis
well defined because of variable estimates of risk of lymph node (LN)/ distant is present post-chemoradiotherapy which remains unchanged during long-term
metastasis. follow-up in almost all patients. A completely normalised wall is observed in
Aims & Methods: The aims of this study were: 1) to determine the prevalence of approximately 1 in 10–20 patients. The findings of this study may serve as a
metastasis of resected T1 rectal carcinoid tumors using a large national cancer reference and provide teaching for radiologists involved in the clinical follow-
database, 2) to identify risk factors for metastasis, 3) evaluate the long-term up of patients selected to undergo a watch-and-wait policy.
survival of patients with T1N0M0 rectal carcinoid tumors after local resection Disclosure of Interest: All authors have declared no conflicts of interest.
as compared to radical surgery. The SEER 18 database was used to identify Reference
patients aged 18–80 years with T1 histologically confirmed rectal carcinoids
52 cm in size diagnosed between 1998 and 2012. T1 was defined as tumor 1. Lambregts DM, Maas M, Bakers FC, Cappendijk VC, Lammering G, Beets
invading lamina propria or submucosa. Prevalence of LN (N1) /distant metas- GL and Beets-Tan RG. Long-term follow-up features on rectal MRI during
tases (M1) at initial diagnosis and risk factors for metastases were analyzed. a wait-and-see approach after a clinical complete response in patients with
Cancer-specific survival (CSS) and overall survival were calculated using rectal cancer treated with chemoradiotherapy. Dis Colon Rectum 2011;
Kaplan-Meier’s estimate and compared with log-rank test. 54(12): 1521–8.
Result: A total of 788 patients with T1 rectal carcinoids were identified [mean
age: 54.8 (SD 11.3); 49.5% men; 57% white]. Of these, 727 (92.3%) patients had TUESDAY, OCTOBER 18, 2016 14:00–15:30
tumors 510 mm in diameter and 61 (7.7%) had tumors 11–19 mm. Submucosal
involvement was noted in 54.9%. Overall, 12 patients (1.5%) had N1/M1 at the GENERAL HEPATOLOGY – ROOM 1.86_____________________
time of diagnosis with prevalence of 1.1% in lesions 10 mm and 6.6% in lesions OP274 ACCURACY OF A POINT SHEAR WAVE ELASTOGRAPHY
11–19 mm in size (p ¼ 0.01). Tumor size (OR 6.31; 95%CI 1.8 – 21.5; p ¼ 0.003) TECHNIQUE (ELASTPQ) IN THE NON-INVASIVE ASSESSMENT
and submucosal invasion (p ¼ 0.03) were associated with LN/ distant metastasis. OF LIVER FIBROSIS IN A LARGE COHORT OF LIVER PATIENTS
Median follow-up of the entire cohort was 23 months (range 0–172). Survival of M. Garcovich1, M. Pompili1, E. Di Stasio2, L. Riccardi1, M.E. Ainora1,
patients with T1 rectal carcinoids without N1/M1 was significantly better than A. Grieco1, G.L. Rapaccini3, M. Siciliano4, A. Gasbarrini1, M.A. Zocco1
those with N1/M1 with 5- yr CSS of 100% and 78%, respectively (p 5 0.001). Of 1
Internal Medicine, Gastroenterology And Liver Diseases Unit, Catholic University
559 patients with T1N0M0 rectal carcinoids 510 mm in size and follow 46 of Sacred Heart - Policlinico Gemelli, Rome/Italy
months, 527 (94.5%) underwent local excision and 32 (5.7%) had radical surgery. 2
Institute Of Biochemistry And Clinical Biochemistry, University of Sacred Heart -
5-yr CSS was 100% and 10-yr CSS was 98% (SE 0.01). For 46 patients with Policlinico Gemelli, Rome/Italy
T1N0M0 rectal carcinoids 11–19 mm in size [39 (84.8%) who underwent local 3
Gastroenterology, Complesso Integrato Columbus - CatholicUniversity, Rome,
excision and 7 (15.2%) underwent radical surgery], there were no carcinoid Italy, Roma/Italy
tumor-related deaths after a median follow up of 28 months (range 8–122). 4
Internal Medicine And Gastroenterology, Agostino Gemelli Hospital Dept. of
The overall survival of T1N0M0 rectal carcinoids treated by local excision Gastroenterology, Rome/Italy
versus radical surgery were comparable.
Conclusion: Larger T1 rectal carcinoid tumors (11–19 mm) are at increased risk of Contact E-mail Address: [email protected]
LN metastases compared those 10 mm. Survival is worse with regional or distal Introduction: ElastPQ is a novel point shear wave elastography (PSWE) techni-
metastatic disease. Hence, thorough evaluation for metastatic disease should be que that assesses liver fibrosis by measuring liver stiffness (in kPa) with few
considered for these lesions. Local therapy is adequate for T1 rectal carcinoids studies published so far. The aim of this study was to determine the accuracy
510 mm and 11–19 mm N0M0 with excellent long term outcomes. and the feasibility for the assessment of liver stiffness in a large cohort of patients
Disclosure of Interest: V. Singh: Vikesh Singh is a consultant for Abbvie, D- undergoing liver biopsy (LB) for various etiologies.
Pharm, and Santarus. Aims & Methods: Consecutive patients scheduled for LB were studied by using
M. Khashab: Mouen Khashab is a consultant for Boston Scientific the iU22 Philips ultrasound system with ElastPQ technique. The correlations
All other authors have declared no conflicts of interest. between laboratory findings, liver stiffness and the Metavir score were analyzed
using Spearman correlation and ROC curve analyses were performed to calculate
AUC for F  2, F  3 and F ¼ 4.
Result: We enrolled 289 patients (176/113 males/females) who underwent LB for
OP273 LONG-TERM FOLLOW-UP FEATURES ON RECTAL MRI viral or non-viral chronic hepatitis (HCV 49%; NASH 20%; AIH/PBC 18%;
DURING ‘WATCH-AND-WAIT’ IN CLINICAL COMPLETE other 13%). Liver stiffness measurements performed on the right lobe were reli-
RESPONDERS AFTER CHEMORADIOTHERAPY: AN UPDATE OF 68 able in all cases but eight patients (due to morbid obesity and narrow intercostal
PATIENTS spaces). After univariate and multiple regression analysis PSWE showed a strong
D.M. Lambregts1, M. Van Heeswijk2, B. Hupkens2, R. Beckers2, M. Maas1, M. correlation with the fibrosis stage; no significant correlation was found with the
Van Der Sande3, G.L. Beets4, R.G. h. Beets-Tan1 degree of necroinflammation or steatosis. Mean kPa values in the whole cohort
1
Department Of Radiology, The Netherlands Cancer Institute, Amsterdam/ were 3.7 (range 2.3–4.9) for F0, 4.9 (range 2.6–9.6) for F1, 7.6 (2.8–20.7) for F2,
Netherlands 10.2 (6.1–19.9) for F3 and 20.4 (10.9–38.4) for F4 in the right lobe. AUROCs
2
Radiology And Surgery, Maastricht University Medical Centre, Maastricht/ were 0.92 (0.02), 0.93 (0.02) and 0.96 (0.01), when comparing F0-F1 vs F2-
Netherlands F4, F0-F2 vs F3-F4 and F0–3 vs F4, respectively. The optimal cut-off values for
3
Department Of Radiology And Surgery, The Netherlands Cancer Institute, different levels of fibrosis were 6.0, 7,7 and 10.9 kPa for F  2, F  3 and F4,
Amsterdam/Netherlands respectively. When analyzing PSWE values according to different etiologies,
4
Surgery, The Netherlands Cancer Institute, Amsterdam/Netherlands AUROCs were 0.89 (0.04), 0.93 (0.29) and 0.96 (0.03) for F  2; 0.88
(0.04), 0.85 (0.03) and 0.95 (0.03) for F  3; 0.90 (0.01), 0.95 (0.01)
Contact E-mail Address: [email protected] and 0.96 (0.01) for F4 in HCV, NASH and AIH/PBC patients, respectively.
Introduction: Non-operative treatment with stringent follow-up (‘watch-and- Conclusion: To date this is the largest case series evaluating the accuracy of
wait’) is emerging as an alternative to surgical resection in rectal cancer patients ElastPQ technique. This novel PSWE system appears to be a very useful tool
who show a clinical complete response after chemoradiotherapy. An important for non-invasive evaluation of liver fibrosis not only in patients with viral chronic
question is how (how frequently and with what modalities) to monitor patients hepatitis, but also for patients with different liver diseases. In order to validate
once surgery is omitted. In addition to clinical examination and endoscopy, such a non-invasive technique these findings need to be confirmed in larger
imaging – mainly MRI – plays an important role. Given the novelty of the studies comparing different elastography devices.
‘watch-and-wait’ approach, limited data exists yet on what we can expect to Disclosure of Interest: All authors have declared no conflicts of interest.
see on MRI during long-term follow-up after chemoradiotherapy. A pilot
study described various patterns of a complete response during watch-and-wait
in a small group of 19 patients.1
Aims & Methods: Aim of this study was to follow-up on this previous research in OP275 COMPARATIVE STUDY BETWEEN TWO 2D-SHEAR WAVES
a larger patient cohort. Objectives are to describe the morphology of the rectal ELASTOGRAPHY TECHNIQUES FOR THE ASSESSMENT OF
wall in patients with a complete response after chemoradiotherapy and study the LIVER STIFFNESS: 2D-SWE.SSI VS. 2D-SWE.GE
evolution in rectal wall morphology during long-term clinical follow-up in these F. Bende, I. Sporea, R.L.D. Sirli, A. Popescu, M. Danila, R. G. Mare,
patients. R. Lupusoru
68 patients with a sustained complete response (i.e. no evidence of recurrence on Department Of Gastroenterology And Hepatology, University of Medicine and
sequential imaging and endoscopy biopsy examinations) were analysed during Pharmacy "Victor Babes" Timisoara, Timisoara/Romania
long term follow-up within the scope of a watch-and-wait protocol. Patients
underwent MRI (as well as corresponding clinical examination and endoscopy) Contact E-mail Address: [email protected]
3-monthly in the first year and 6 monthly during the second to fifth year. Two Introduction: Chronic liver diseases are quite frequent encounterd in daily prac-
readers in consensus analysed the rectal wall morphology on the initial post- tice and are due to chronic viral infections (B or C viruses) and other conditions
chemoradiotherapy MRI scan and studied the evolution in morphology on the such as chronic alcohol abuse (ASH) and NAFLD. In this conditions, the eva-
various sequential follow-up MRIs. MRIs were performed at 1.5 T. Routine T2- luation of chronic liver disease’s severity is mandatory, for prognosis, for man-
weighted sequences in sagittal, trasverse and coronal plane were analysed. agement and for decision regarding therapy.
Result: Median follow-up time was 30 months (range 6–98). A total of 512 MRIs Aims & Methods: The aim of this study was to compare the feasability of two 2D-
was analysed (median 7, range 3–15/patient). In 7% of patients the rectal wall Shear Waves Elastography (2D-SWE) methods for the assessment of Liver
completely normalised post-CRT. The other 93% showed a fibrotic remnant Stiffness (LS) and also to compare the methods with a validated one-
(60% minimal fibrosis limited to the bowel wall; 21% thick/mass-like fibrosis Transient Elastography(TE). Our study included 130 consecutive patients with
and 12% irregular/spicular fibrosis). In 94% the rectal wall morphology chronic hepatopathies (HCV–90%, HBV–6%, other–4%), in which Liver
remained unchanged during long-term follow-up, in 2% initial fibrosis later Stiffness (LS) was evaluated in the same session by means of two 2D-SWE
developed into a normalised wall, in 3% the fibrosis slightly thickened (without tehniques: 2D-SWE.GE(LOGIQ E9, GE Healthcare) and 2D-SWE.SSI
evidence of recurrence). (AixplorerÕ ultrasound system, SuperSonic Imagine) and also by an
United European Gastroenterology Journal 4(5S) A109
elastographic refference method: Transient Elastography (TE)- FibroScan, AUROCs for SWE, MRE, M2BPGi, FIB-4, and PLT for detecting severe fibro-
EchoSens (M and XL probes). Reliable LS measurements were defined as fol- sis (F3) were 0.93 (95% CI, 0.89–0.98; cut-off, 1.81 m/s), 0.92 (CI, 0.86–0.97;
lows: for 2D-SWE.GE: the median value of 10 measurements acquired in a cut-off, 4.21 kPa), 0.89 (CI, 0.83–0.95; cut-off, 2.99 COI), 0.84 (CI, 0.77–0.91;
homogenous area and an interquartile range (IQR) 530% (1), for 2D- cut-off, 4.11) and 0.85 (CI, 0.79–0.92; cut-off, 12.6  104/mL), respectively. There
SWE.SSI: the median value of 3 measurements acquired in an homogenous was a strong correlation between SWE and MRE (r ¼ 0.77, p 5 0.001).
area (2) and for TE- the median value of 10 measurements with a success rate Conclusion: The AUROC for SWE for diagnosing severe fibrosis in patients with
of 60% and an interquartile range 530% (3). Spearman’s rank correlation chronic hepatitis C was similar to that for MRE and higher than those for other
coefficient (r) was used to assess the correlation of LS measurements by means fibrosis biomarkers (M2BPGi, FIB-4, and PLT). Compared to MRE, SWE
of 2D-SWE.GE, 2D-SWE.SSI and TE. demonstrated greater utility in its feasibility, with fewer contraindications,
Result: Valid measurements were obtained in 94.6% (123/130) for 2D-SWE.GE, greater ease of performance, and lower cost.
90.7% (118/130) for 2D-SWE.SSI, 89.2% (116/130) for TE (p 4 0.05). Reliable Disclosure of Interest: All authors have declared no conflicts of interest.
liver stiffness results were obtained in 107 subjects by means of 2D-SWE.SSI, 2D-
SWE.GE and TE. The values ranged from 4.17 to 20.48 kPa for 2D-SWE.GE
and from 3.4 to 82.4 kPa for 2D-SWE.SSI. The mean LS values by 2D-SWE.SSI
were significantly higher than for 2D-SWE.GE: 19  12.3 kPa vs. 12.1  3.7 kPa OP277 ASSOCIATIONS OF TOLL LIKE RECEPTORS (TLR-2) & (TLR-4)
(p 5 0.0001). There was a significant correlation between 2D-SWE.GE and 2D- ALLELES WITH THE HEPATITIS C VIRUS INFECTION OUTCOME
SWE.SSI LS values (r ¼ 0.712, p 5 0.0001). The correlation between 2D- IN EGYPTIAN POPULATION: A MULTICENTRE FAMILY BASED
SWE.GE and TE was r ¼ 0.746, p 5 0.0001, and between 2D-SWE.SSI and TE STUDY
was r ¼ 0.604, p 5 0.0001 with no significant differences between them M. El-Bendary1, M. Neamatallah2, G. Esmat3, E. Kamel4, H. Elalfy1,
(p ¼ 0.0565). Taking TE as the refference method, both 2D-SWE.SSI and 2D- T. Besheer1, L. Kandeel5, A. Gomaa6, N. Mousa1, M. Abd El-Maksoud1,
SWE.GE had a good value to differentiate between other stages of liver fibrosis R. Talaat7, W. Abdel- Mageed7, A. Aladl8, E. Medhat9, T.R.W.F.B.S. &
and liver cirrhosis. For 2D-SWE.SSI the best liver stiffness cut-off value to T.D.F.10
differentiate between liver cirrhosis and other stages of fibosis was 413.7 kPa 1
Tropical Medicine & Hepatology, Mansoura Faculty of Medicine, Mansoura/
with 88.57 Se, 75.68 Sp, 87.3 positive predictive value (PPV) and 77.8 negative Egypt
predictive value (NPV) (AUROC ¼ 0.831, p 5 0.0001). For a liver stiffness cut- 2
Medical Biochemistry, Mansoura Faculty of Medicine, Mansoura/Egypt
off value 410.7 kPa, 2D-SWE.GE had 91.43 Se, 78.38 Sp, 88.9 PPV, 82.9 NPV 3
Department Of Endemic Medicine And Hepatology, Faculty Of Medicine, Cairo
(AUROC ¼ 0.904, p 5 0.0001) for differentiating liver cirrhosis. The AUROCs University, Cairo/Egypt
of 2D-SWE.SSI and 2D-SWE.GE for predicting the presence of liver cirrhosis 4
Community & Preventive Medicine, Mansoura Faculty of Medicine, Mansoura/
were similar (p ¼ 0.09). Egypt
Conclusion: Both 2D-SWE techniques have a very good feasibility for the non- 5
Shrbeen General Hospital, Shrbeen/Egypt
invasive liver fibrosis assessment and both have a strong correlation with TE. 6
Zoology Department, Alazhar University, Cairo/Egypt
Liver stiffness values obtained by 2D-SWE.GE are significantly lower than those 7
Molecular Biology Department, Genetic Engineering And Biotechnology Research
obtained by 2D-SWE.SSI. Both methods have good performance for predicting Institute, Menofya University, Menofya/Egypt
liver cirrhosis. 8
Internal Medicine, Assuit Alazhar University, Mansoura/Egypt
Disclosure of Interest: I. Sporea: Ioan Sporea participated in an Advisory Board 9
Department Of Endemic Medicine And Hepatology, Cairo University, Cairo/
for Siemens and received speaker fees from Philips, Siemens and General Electric Egypt
R.L.D. Sirli: Roxana Sirli received speaker fees from Philips 10
Alazhar university, Cairo/Egypt
A. Popescu: Alina Popescu received speaker fees from Philips
All other authors have declared no conflicts of interest. Contact E-mail Address: [email protected]
References Introduction: The human Toll like receptors (TLRs) family consists of ten recep-
tors that are critically important for innate immunity. TLRs recognize and
1. GEHealthcare LOGIQ E9 Shear Wave Elastography Whitepaper recom- respond to diverse microbial molecules and enable the innate immune system
mendations, March 2015). available at http://www3.gehealthcare.com. to discriminate among groups of pathogens and to induce an appropriate cascade
2. Sporea I, Grădinaru-Taşcău O, Bota S, et al. How many measurements are of effector responses. HCV has different effects upon TLR pathway stimulation
needed for liver stiffness assessment by 2D-Shear Wave Elastography (2D- in various cellular compartments and in this way is able to both stimulate proin-
SWE) and which value should be used: the mean or median?. Med Ultrason flammatorycytokine production leading to liver damage and evade immune
2013; 15: 268–272. responses to establish viral persistence.
3. Castera L, Foucher J, Bernard PH, et al. Pitfalls of liver stiffness measure- Aims & Methods: The aim of this work is to investigate the association of TLR
ment: a 5-year prospective study of 13,369 examinations. Hepatology 2010; SNPs with the outcome of the HCV infection. Four SNPS of TLR2 and TLR4
51: 828–835. were genotyped by real time PCR using TaqManallelic discrimination kit (Applied
Biosystems) according to the manufacturer’s protocol. A total 392 families (1176
individuals) were recruited in this study from upper & lower Egypt (east & west
delta), we compared the risk of allele carriage of selected markers in different
OP276 UTILITY OF REAL-TIME SHEAR WAVE ELASTOGRAPHY FOR groups. These groups included spontaneous virus clearance (SVC) (108 subject),
ASSESSING LIVER FIBROSIS IN PATIENTS WITH CHRONIC chronic HCV patients (549), and negative control (519) individuals. The rs
HEPATITIS C 121917864 (C/T) and rs5743708 (G/A) were genotyped for TLR2 while
H. Numao1, K. Shimaya1, A. Kakuta2, K. Shibutani2, H. Kurotaki3, S. Igarashi1, rs4986791 (C/T) and rs62522600 (G/A) were genotyped for TLR4.
K. Hasui1, N. Hanabata1, K. Kanazawa1, M. Munakata1 Result: As regard TLR2, The T allele of rs 121917864 (C/T) is significantly higher
1
Gastroenterology, Aomori Prefectural Central Hospital, Aomori/Japan in HCV group compared to that control group and spontaneous(SVC) group
2
Radiology, Aomori Prefectural Central Hospital, Aomori/Japan ({OR 2.960 (95% CI 1.95 to 3.45 P ¼ 0.0005) and 2.635 (95%CI 2.14 to 4.15
3
Pathology, Aomori Prefectural Central Hospital, Aomori/Japan P ¼ 0.0001)} respectively. While A allele of rs5743708 (G/A) is highly significant
associated with HCV group compared to that control group and spontaneous
Contact E-mail Address: [email protected] (SVC) group {OR ¼ 2.2071 (95% CI 1.2056 to 4.0404 P ¼ 0.007) and 2.1321
Introduction: Real-time shear wave elastography (SWE) is a newly developed (95% CI 1.5528 to 2.9274. P ¼ 0.0001)} respectively. On the other hand the
method of evaluating liver stiffness, which previously had limited comparability TLR4 genotyping revealed that the carriages of C allele of rs4986791 was sig-
with other non-invasive fibrosis biomarkers. nificantly higher in negative and spontaneous (SVC) group compared to that of
Aims & Methods: This study aimed to compare the utility of SWE, magnetic chronic HCV group (OR:0.4843 95% CI :0.388–0.646 and 0.4449 and 95% CI:
resonance elastography (MRE), M2BPGi, Fibrosis-4 index (FIB-4), and platelet 0.2917–0.6787) simultaneously indicating that the C allele act as protective allele
count (PLT) for diagnosing liver fibrosis. One hundred thirty-seven patients with against HCV infection and development of chronic HCV. Linkage
biopsy-proven chronic hepatitis C (73 men and 64 women; mean age, 64.6  10.6 Disequilibrium of rs4986791 and rs62522600 SNPs indicating that the carriage
years; mean body mass index, 23.6  5.08 kg/m2) were enrolled. Fibrosis was of TA haplotype was significantly higher in chronic HCV compared to that of
staged from liver biopsies according to the MATAVIR score. We compared negative group (OR ¼ 3.8 95% CI: 2.95–4.95). No one of spontaneous group was
the diagnostic performances of SWE (GE Healthcare, USA), MRE (GE carriage for TA haplotype, this revealing the role of TA haplotype as a risk
Healthcare, USA), M2BPGi, FIB-4, and PLT. SWE, MRE, and liver biopsy indicator for HCV infection.
were performed on the same day, when we also collected blood samples for Conclusion: Current study demonstrated that spontaneous clearance of HCV was
M2BPGi, FIB-4, and PLT. Data analysis included Mann-Whitney U test, non- associated with The allele C ofrs4986791 of TLR-4 and chronicity of HCV
parametric correlation analysis (Spearman), and the area under the receiver infection is associated with the risk haplotype (TA) of TLR-4& T allele of
operating characteristic curve (AUROC). rs121917864 & A allele of rs5743708 of TLR-2.
Result: All patients completed all examinations except MRE, which could not be Disclosure of Interest: All authors have declared no conflicts of interest.
performed in 51 patients, primarily due to the presence of metal parts in the This Research Was Funded By Science, Technology Development Foundation
body. Fibrosis severity was F0/F1/F2/F3/F4 in 7/50/33/24/23 patients, respec- (Stdf), Project No.1784 (Tc/2/health/2009/hep-1.3
tively. The median SWE (m/s), MRE (kPa), M2BPGi (COI), FIB-4, and PLT
(104/mL) in patients with F0/F1/F2/F3/F4 were 1.37/1.53/1.71/1.95/1.96, 1.97/
2.78/3.43/5.46/6.15, 1.00/1.25/2.20/6.30/6.40, 1.64/2.25/2.94/4.58/6.56, and 20.0/
17.1/14.4/10.6/9.4, respectively. Significant differences were observed between
F1/F2 and F2/F3 in SWE, F0/F1, F1/F2, and F2/F3 in MRE, F1/F2 and F2/
F3 in M2BPGi, F1/F2 and F2/F3 in FIB-4, and F2/F3 in PLT. The AUROCs for
SWE, MRE, M2BPGi, FIB-4, and PLT for detecting considerable fibrosis (F2)
were 0.86 (95% CI, 0.78–0.92; cut-off, 1.75 m/s), 0.88 (CI, 0.80–0.95; cut-off,
3.40 kPa), 0.87 (CI, 0.81–0.93; cut-off, 2.2 COI), 0.81 (CI, 0.74–0.88; cut-off,
2.83) and 0.78 (CI, 0.70–0.86; cut-off, 14.5  104/mL), respectively. Similarly,
A110 United European Gastroenterology Journal 4(5S)
new-onset diabetes mellitus after kidney transplantation.5 From previous studies
References
we can reasonably infer that adiponectin would be an important protein in the
1. B. Ferwerda, M. B. B. McCall, K. Verheijen et al., ‘‘Functional consequences development of NODAT. However, there have been no report to describe the
of Toll-like receptor 4 polymorphisms,’’ Molecular Medicine, vol. 14, no. association between ADIPOQ gene polymorphism and new-onset diabetes mel-
5–6, pp. 346–352, 2008. litus after liver transplantation.
2. U. Dô´uesberg, A. von Dem Bussche, C. J. Kirschning, K. Miyake, T. Aims & Methods: In the current study, we aim to investigate whether single
Sauerbruch, and U. Spengler, ‘‘Cell activation by synthetic lipopeptides of nucleotide polymorphisms of ADIPOQ were correlated with the NODAT and
the hepatitis C virus (HCV)–core protein is mediated by toll like receptors also to compare the overall survival and graft survival between NODAT group
(TLRs) 2 and 4,’’ Immunology Letters, vol. 84, no. 2, pp. 89–95, 2002. and non-NODAT. The study included 256 patients who underwent liver trans-
3. S. Chang, A. Dolganiuc, and G. Szabo, ‘‘Toll-like receptors 1 and 6 are plantation in our center from January 2009 to December 2011. They were divided
involved in TLR2-mediated macrophage activation by hepatitis C virus into two groups: NODAT group and Non-NODAT group. We screened inde-
core and NS3 proteins,’’ Journal of Leukocyte Biology, vol. 82, no. 3, pp. pendent risk factors of NODAT with univariate and multivariate analyses. We
479–487, 2007. further built three NODAT prediction models containing the risk factors and got
optimized model with AUROC curve method. In addition, the association
between metabolic syndrome and NODAT was also examined. Overall survival
and graft survival were determined by the Kaplan-Meier method and tested by
OP278 USEFULNESS OF MULTIPOLAR BIPOLAR RADIOFREQUENCY the log-rank statistics.
SYSTEM AND VALUE OF 3D SIM-NAVIGATOR Result: The incidence rate of NODAT within 6 months post liver transplantation
A. Sakamoto1, T. Kimura1, G. Tanke1, M. Taki1, M. Fukuhara2, Y. Ohara1, was 29% (75/181). There were 214 men and 42 women in the study and the
S. Henmi1, T. Yamashina1, Y. Sawai1, S. Saito1, N. Nishijima1, A. Nasu1, average age was 48.0  9.9 y. Age (54.0  4.1 vs 45.4  6.9, P 5 0.001), BMI
H. Komekado1, A. Sekikawa1, M. Asada1, T. Tsumura1, R. Kita1, T. Maruo1, (23.1  3.0 vs 22.3  3.0, P 5 0.014), blood tacrolimus level at 1 month post
Y. Osaki1 liver transplantation (10.23  3.30 vs 8.76  1.74, P 5 0.001), ADIPOQ
1
Gastroenterology And Hepatology, Osaka Red Cross Hospital, Osaka/Japan rs1501299 (P 5 0.007) and rs822396 (P 5 0.013) were significantly correlated
2
Gastroenterology, Osaka red cross hospital, Osaka/Japan with NODAT with univariate analyses. Dominant model and recessive model
confirmed these risk factors further. Three NODAT prediction models were built
Contact E-mail Address: [email protected] containing these risk factors and we finally found the optimized model
Introduction: Fusion imaging technology is reportedly useful for radiofrequency (AUROC ¼ 0.743). Metabolic syndrome was also associated with NODAT
ablation (RFA), and various types of ultrasound equipment with integral fusion (21% vs 8%, P 5 0.003). The overall survival rate (P 5 0.015) and graft survival
imaging systems have been developed. Several RFA devices have also become rate (P 5 0.011) of NODAT were significantly lower than that of Non-NODAT.
available in Japan. CelonPOWER (Olympus Surgical Technology), a multipolar Conclusion: This study is the first to provide evidence of the association between
and bipolar RFA device, was approved for use in Japan in 2012. A single pro- recipient rs1501299 genotype polymorphism and new-onset diabetes mellitus
cedure using several applicators simultaneously can ablate an extensive area and after liver transplantation on large samples. Our findings demonstrate that reci-
reduce treatment time. A sufficiently wide area of ablation requires the optimal pient rs1501299 is associated with higher risk of NODAT and would be a poten-
placement of multiple applicators. The accurate positioning of two applicators tial genetic factor to improve the predictive ability of NODAT. we also confirm
can be quite easily visualized by ultrasonography, whereas precise three-dimen- age, BMI, blood tacrolimus level at 1-month after LT are independent risk
sional (3D) positioning of three applicators cannot. The 3D Sim-Navigator factors of NODAT. These findings may be beneficial in helping to estimate the
(HITACHI) is a new navigation system that can be used during real-time virtual risk of NODAT development in liver transplantation and thereby in controlling
sonography (RVS) by simulating the 3D positions of multiple applicators, which modifiable risk factors.
can facilitate their ideal 3D positioning. We evaluated local hepatocellular carci- Disclosure of Interest: All authors have declared no conflicts of interest.
noma (HCC) recurrence rates after treatment using a multipolar RF system and References
determined the applicability of the 3D Sim-Navigator to the system.
Aims & Methods: We compared the local recurrence rates of 209 HCC treated 1. Xu X, Ling Q, He Z L, Gao F and Zheng S S. Post-transplant diabetes
using multipolar or monopolar RF systems between January 2013 and October mellitus in liver transplantation: Hangzhou experience. Hepatob Pancreat
2015 using propensity-score matching analysis. We evaluated 77 nodules from 63 Dis 2008; 7: 465–470.
patients treated using a bipolar RFA system with multiple applicators and com- 2. Samuelson A L, Lee M, Kamal A, Keeffe E B and Ahmed A. Diabetes
pared complete necrosis rates (CNR) generated with or without the 3D Sim- Mellitus Increases the Risk of Mortality Following Liver Transplantation
Navigator. Independent of MELD Score. Digest Dis Sci 55: 2089–2094. doi:10.1007/
Results: Propensity-score matching analysis showed that the mean tumor dia- s10620-010-1267-5 (2010).
meter was 24.7  5.9 mm, and the cumulative annual local recurrence rates were 3. Pageaux G P, Faure S, Bouyabrine H, Bismuth M and Assenat E. Long-
0% and 14.9% for the multipolar and monopolar RF systems, respectively Term Outcomes of Liver Transplantation: Diabetes Mellitus. Liver
(p ¼ 0.228). Thirty-two and 45 nodules with mean diameters of 28.1  11.5 and Transplant 15: S79–S82. doi:10.1002/lt.21913 (2009).
22.2  5.7 mm (p ¼ 0.011) were treated with and without the 3D Sim-Navigator, 4. Cook J R and Semple R K. Hypoadiponectinemia-Cause or Consequence of
respectively, with CNR of 68.8% and 66.6%, respectively, indicating that the two Human "Insulin Resistance"?. J Clin Endocr Metab 95: 1544–1554.
groups did not significantly differ (p ¼ 0.847). doi:10.1210/jc.2009-2286 (2010).
Conclusion: Case matching analysis of local recurrence rates of HCC after RFA
showed that that the multipolar RF system is more effective than the monopolar
TUESDAY, OCTOBER 18, 2016 15:45–17:15
RF system against tumors with a diameter 425 mm. Although tumor diameter
was significantly larger in the group with, than without the 3D Sim-Navigator, MANAGEMENT OF REFRACTORY CROHN’S DISEASE – ROOM A_____________________
CNR did not significantly differ between the two groups, because multiple appli- OP280 DISAPPEARANCE OF ANTI-DRUG ANTIBODIES TO
cators could be placed in ideal 3D positions using the 3D Sim-Navigator. INFLIXIMAB AND ADALIMUMAB AFTER ADDITION OF AN
Therefore, HCC with a tumor diameter 425 mm should be ablated using a IMMUNOMODULATOR IN PATIENTS WITH INFLAMMATORY
multipolar RF system with ideal 3D positioning facilitated by the 3D Sim- BOWEL DISEASE
Navigator. A. S. Strik1, G.R. Van Den Brink2, C.Y. Ponsioen3, R. Mathot4,
Disclosure of Interest: All authors have declared no conflicts of interest. M. Lowenberg5, G. D’Haens6
1
Reference Gastroenterology, Academic Medical Centre, Amsterdam/Netherlands
2
Dept. Of Gastroenterology, Academisch Medisch Centrum, Amsterdam/
1. PLoS One. 2016 Feb 4;11(2):e0148298.
Netherlands
3
Gastroenterology & Hepatology, AMC Amsterdam Gastroenterology and
Hepatology, Amsterdam/Netherlands
4
Pharmacy, Academic Medical Centre, Amsterdam/Netherlands
OP279 ASSOCIATION BETWEEN ADIPOQ GENE POLYMORPHISMS 5
Academic Medical Center Amsterdam, Academisch Medisch Centrum,
AND THE RISK OF NEW-ONSET DIABETES MELLITUS AFTER Amstelveen/Netherlands
LIVER TRANSPLANTATION 6
Academic Medical Center, AMC Amsterdam Inflammatory Bowel Disease
C. Cen1, S. Yu1, J. Yu1, Q. Ling1, L. Zhou2, S. Zheng1 Centre, Hofstade/Belgium
1
Department Of General Surgery, the First Affiliated Hospital of Zhejiang
University School of Medicine, Hangzhou/China Contact E-mail Address: [email protected]
2
Key Lab Of Combined Multi-organ Transplantation, Key Lab Of Organ Introduction: Since therapeutic options for patients with inflammatory bowel
Transplantation, Ministry Of Public Health, the First Affiliated Hospital of disease (IBD) who lose response to anti-TNF therapy are limited, optimal use
Zhejiang University School of Medicine the First Affiliated Hospital of Zhejiang of these agents is crucial. Loss of response can be caused by anti-drug antibody
University School of Medicine, Hangzhou/China (ADA) formation and subsequent neutralization of the effect of the drug.
Addition of an immunomodulator (IM) to anti-TNF therapy has been proposed
Contact E-mail Address: [email protected] as an approach to reduce antibody formation, increase serum concentrations and
Introduction: New-onset diabetes mellitus (NODAT) is a common metabolic to regain clinical response.
complication after liver transplantation (LT). The prevalence of NODAT stays Aims & Methods: We investigated whether addition of an IM to anti-TNF mono-
high and has been reported as 17–36%.1 NODAT contributes to an increased therapy can lead to a decrease of ADA levels and regained clinical response.
risk of infections, cardiovascular disease, chronic rejection and renal failure, Therefore, we retrospectively collected measurements of infliximab (IFX) and
which subsequently lead to a reduced life quality and high mortality.2,3 Recent adalimumab (ADL) serum concentrations together with ADA levels from 602
findings suggest a tight link between ADIPOQ gene polymorphism and glucose patients at our IBD centre (September 2005-September 2015). ADA levels were
metabolism and diabetes mellitus. Several studies have found that serum adipo- determined with a drug sensitive assay by Sanquin Biologicals Laboratory. As a
nectin levels are lower in diabetic patients than healthy people.4 In addition, next step, we identified all ADA positive patients with secondary loss of response
reduced pretransplantation serum adiponectin levels are also correlated with to IFX or ADL who received an IM in an attempt to eliminate ADA and to
United European Gastroenterology Journal 4(5S) A111
regain clinical response. Detailed documentation of disease activity was complications when female gender and delay between diagnosis and surgery
registered. were associated with late POC. These results reinforce the need for specialized
Result: In 98/376 patients ADA directed against IFX and in 61/226 patients and dedicated management of these at-risk elderly patients.
ADA against ADL were detectable. From all 159 ADA positive patients, 17 Disclosure of Interest: All authors have declared no conflicts of interest.
patients had received an IM, either a thiopurine or MTX, because of secondary References
loss of clinical response. Seven patients received MTX, ten a thiopurine (4
azathioprine, 4 mercaptopurine and 2 6-TG). In 7 out of 8 patients treated 1. Charpentier et al. Gut 2014.
with IFX, addition of an IM resulted in an increase of serum drug levels accom- 2. Dindo et al. Ann. Surg. 2004.
panied with a decrease of ADA till they were undetectable. The median time for
ADA to IFX to become undetectable was 11 months (IQR 6–28). For patients
TUESDAY, OCTOBER 18, 2016 15:45–17:15
treated with ADL, an increase of the serum drug concentrations, together with a
decrease of ADA levels, was reached in 6 out of 7 patients after addition of an
FROM GUIDELINES TO CLINICAL PRACTICE: H. PYLORI – ROOM D_____________________
IM. The median time for the ADA levels to be undetectable was also 11 months OP282 PAN-EUROPEAN REGISTRY ON H. PYLORI MANAGEMENT
(IQR 2–37). All patients receiving MTX responded clinically which resulted in (HP-EUREG): INTERIM ANALYSIS OF THE SINGLE-CAPSULE
continuation of the ongoing anti-TNF treatment. BISMUTH QUADRUPLE TREATMENT (PYLERAÕ)
Conclusion: Addition of an IM to IFX or ADL monotherapy in IBD patients A.G. Mcnicholl1, F. Megraud2, B. Tepeš3, M. Venerito4, K. Przytulski5,
with secondary loss of response due to ADA formation, led to a decrease of ADA J. Delchier6, A. Courillon-Mallet7, B. Richard-Molard8, D. Vaira9, A. Perez
levels and an increase in serum drug concentrations in the majority of the Aisa10, L. Fernández Salazar11, L. Bujanda Fernández De Piérola12, J. Ortuño13,
patients. Patients who regained response due to this strategy could continue M. G. Donday1, O.P. Nyssen14, C. O’Morain15, J. P. Gisbert16
the current anti-TNF treatment and switching to another agent was not 1
Digestive Services, Centro de Investigación Biome´dica en Red de Enfermedades
necessary. Hepáticas y Digestivas (CIBERehd), Madrid/Spain
Disclosure of Interest: G.R. van den Brink: G. van den Brink has received con- 2
Inserm U853Hopital Pellegrin, Laboratoire de Bacteriologie, Bordeaux Cedex/
sulting and lecture fees from Abbott laboratories, Merck Sharp & Dohme and France
Ferring Pharmaceuticals. He has received research grants from Abbott labora- 3
Gastroenterology, Abakus Medico d.o.o., Rogaska Slatina/Slovenia
tories, Crucell and Ferring Pharmaceuticals. 4
Department Of Gastroenterology, Hepatology And Infectious Diseases, Otto-von-
M. Lowenberg: M. Löwenberg has served as speaker for AbbVie, Covidien, Dr. Guericke University Magdeburg, Magdeburg/Germany
Falk, Ferring Pharmaceuticals, Merck Sharp & Dohme, Receptos, Takeda, 5
Digestive Services, Medical C. Postgraduate Education, Warszawa/Poland
Tillots and Tramedico. He has received research grants from AbbVie, Merck 6
Hôpital H. Mondor Service de Gastroente´rologie, Cre´teil/France
Sharp & Dohme, Achmea healthcare and ZonMW. 7
Endoscopie, C.H.I., Villeneuve St Georges/France,8Digestive Services, Hopital
G. D’Haens: G. D’Haens reports having received consulting fees from AbbVie, Pellegrin, Bordeaux/France
Boehringer, Ferring, Jansen Biologics, Merck Sharp and Dohme, Takeda, Pfizer, 9
Sant’Orsola Hospital, Bologna/Italy
Tillotts Pharma and reports receiving research grants from Abbott Laboratories, 10
Agencia Sanitaria Costa del Sol, Marbella/Spain
Jansen Biologics, MSD, DrFalk Pharma 11
Hospital Clı´nico de Valladolid, Valladolid/Spain
All other authors have declared no conflicts of interest. 12
Hospital de Donostia, san sebastian/Spain
13
Hospital Universitario de La Fe, Valencia/Spain
14
Digestive Services, Hospital Universitario de La Princesa, Madrid/Spain
15
Faculty Of Health Sciences, Trinity College Dublin, Dublin/Ireland
OP281 POST-OPERATIVE COMPLICATIONS IN ELDERLY-ONSET 16
Digestive Services, Hospital Universitario de La Princesa, Instituto de
INFLAMMATORY BOWEL DISEASE: A POPULATION-BASED Investigación Sanitaria Princesa (IP) and Centro, Madrid/Spain
STUDY
S. Sacleux1, H. Sarter2, C. Charpentier1, M. Fumery3, N. Guillon-Dellac4, Contact E-mail Address: [email protected]
J. Laberenne5, B. Pariente6, L. Peyrin-Biroulet7, C. Gower Rousseau2, Introduction: The most novel treatment used in H. pylori management in Europe
G. Savoye1 is the single-capsule bismuth quadruple treatment (PyleraÕ), but there is still very
1
Gastroenterology Unit & Epimad Registre, Rouen University and Hospital, little evidence of its efficacy and safety on routine clinical practice. PyleraÕ is still
Rouen/France non-commercially available in most countries in Europe and, in most of those
2
Public Health, Epidemiology And Economic Health, Registre Epimad, Inserm available, it has just recently reached pharmacies.
Liric Umr 995Lille University and Hospital, Lille/France Aims & Methods: We aimed to evaluate the use and outcomes of PyleraÕ in the
3
Gastroenterology Unit & Epimad Registre, Amiens University and Hospital, European Registry on H. pylori Management (Hp-EuReg). Methods: A systema-
Amiens/France,4Public Health, Epidemiology And Economic Health, Registre tic prospective registry of the clinical practice of European gastroenterologists
Epimad, Inserm Liric Umr 995Lille University & Hospital, Lille/France regarding H. pylori infection and treatment (31 countries and 280 recruiting
5
Gastroenterology Unit & Epimad Registre, Seclin General Hospital, Seclin/France investigators). A local coordinator was selected from each country. Each coor-
6
Gastroenterology Unit & Epimad Registre, Inserm Liric Umr 99 Lille University & dinator selected a representative group of recruiting investigators from its coun-
Hospital, Lille/France try. An electronic clinical research file (e-CRF) was created on AEG-REDCap to
7
Department Of Gastroenterology, Nancy University Hospital, Vandoeuvre les systematically register all adult patients infected with H. pylori. Variables
Nancy/France included: Patient’s demographics, previous eradication attempts, prescribed era-
dication treatments, adverse events, and outcomes (cure rates, compliance, follow
Contact E-mail Address: [email protected] up, etc.). Patients with both eradication confirmatory test and with less than one-
Introduction: Inflammatory Bowel Diseases (IBD) diagnosed after the age of 60 year follow-up have been considered ongoing and were excluded from the
are increasing and seems to have a milder course compared to younger patients. analysis.
However, the intestinal surgery rates are similar to those in the young adult Result: Up to now, 15,660 patients have been included, and 12,921 have finished
population. Data on post-operative complications (POC) in elderly-onset IBD follow up (59% females, 88% Caucasian). Mean age was 55 years. PyleraÕ was
are scarce. We reported the incidence and factors associated with POC in general used in 175 patients (1.2% of all treatments registered: 44% in first-line, 27% in
population. second, 22% in third, and 8% in following rescues). Omeprazole was used in
Aims & Methods: Among 841 elderly-onset population-based EPIMAD Cohort 69% of cases and esomeprazole in 24%. Overall efficacy was 76%
(1), 139 patients underwent surgery. Among those, 100 had Crohn’s Diseases (95%C.I. ¼ 66–86%) by ITT and 78% (69–87%) by PP. In first line, efficacy
(CD) and 39 Ulcerative Colitis (UC). Medical charts for early (within 30 days was 93% (84–100%) both by ITT and PP. Second line efficacy was 68% (51–
of surgery) and late (430 days of surgery) POC (POC) have been reviewed 85%) by ITT and 74% (58–90%) by PP. Compliance with treatment was 98%.
according to Dindo’s classification (2). Associated factors have been tested by Adverse events were reported in 14% of cases and did not cause treatment
Cox regression models. discontinuation in any patient.
Result: After a median follow-up of 7.3 years [Q1 ¼ 3-Q3 ¼ 12], 50 patients (36%) Conclusion: Experience with single-capsule bismuth quadruple therapy (PyleraÕ)
had at least one POC. No significant difference was observed for POC frequency is still limited. Wide confidence intervals do not allow drawing conclusions for
between UC and CD. Thirty-two early POC were found in 23 patients (16.5%); rescue regimens; however, our preliminary data suggests that given its safety
52% were severe (defined by a Dindo’s grade 42) and 47% infectious. Among the profile, compliance rates and efficacy, it may be an acceptable option as first-
37 late complications observed in 33 patients (23.7%), 42 were severe (grade 4 2) line treatment in Europe.
and 56% were mechanical (bridle, eventration, anastomotic stricture). The cumu- Disclosure of Interest: A.G. McNicholl: Speaker for Allergan
lative probability of POC was 7.4% at 6 months (95% CI: 3.9–13.7), 10.9% at 1 A. Perez Aisa: Speaker for Allergan
year (6.5–18.1), 22.8% at 5 years (16.0–32.0) and 30.5% at 10 years (21.8–41.4). In J.P. Gisbert: Has acted as speaker and advisor for Almirall, Allergan,
multivariate analysis, emergency surgery (HR ¼ 4.46 [1.75–11.36]) and acute AstraZeneca, Casen Recordati, Nycomed.
severe ulcerative colitis (HR ¼ 7.84 [2.15 – 28.52]) were significantly associated All other authors have declared no conflicts of interest.
with early POC while recent steroid exposure and co morbidities (Charlson’s
index) were not independently associated with an increased risk. Female gender
(HR ¼ 2.10 [1.01 – 4.37]) and time between diagnosis and surgery 43 months
(HR ¼ 2.09 [1.01 – 4.31]) were significantly associated with late POC.
Conclusion: In elderly onset IBD patient who underwent surgery, POC were
frequent. The early POC were more severe than the late POC. Emergency surgery
and acute severe ulcerative colitis were significantly associated with early
A112 United European Gastroenterology Journal 4(5S)
OP283 PAN-EUROPEAN REGISTRY ON H. PYLORI MANAGEMENT small bowel diseases. Secondary objectives: procedural success, - time, depth of
(HP-EUREG): INTERIM ANALYSIS OF FIRST-LINE TREATMENT maximal insertion, therapeutic yield, adverse events. Patients with occult gastro-
WITH BISMUTH, AMOXICILLIN AND CLARITHROMYCIN intestinal bleeding (OGB) or indeterminate iron-deficiency anemia (IDA) or
A.G. Mcnicholl1, D. S. Bordin2, O. Shvets3, Y. Niv4, G. Fadeenko5, positive findings of small bowel imaging examinations were included in a two-
L. Vologzhanina6, L. Bujanda Fernández De Piérola7, I. Modolell8, A. Perez center prospective clinical trial. In total 132 cases will be enrolled to determine
Aisa9, C. De La Coba10, S. Burkov11, O. Zaytsev12, M. G. Donday13, the diagnostic yield. A rate of 28% would be considered as clinically efficacious
O.P. Nyssen1, C. O’Morain14, J. P. Gisbert15 under consideration of a two sided non-inferiority margin of 20% in comparison
1
Digestive Services, Hospital Universitario de La Princesa, Madrid/Spain to conventional enteroscopy. A novel reusable endoscope (Olympus Corp.) with
2
Department Of Pancreatic, Biliary And Upper Gi Diseases, Moscow Clinical an integral motor was used for rotating a disposable short spiral overtube
Scientific Center, Moscow/Russian Federation mounted on the insertion tube portion. Rotation of the spiral allows to
3
Internal Medicine No.1National Medical University, Kyiv/Ukraine ‘‘pleat’’ or ‘‘unpleat’’ the bowel either on or off the insertion tube as the spiral
4
Dept. Of Gastroenterology, Rabin Medical Center, Tel Aviv University thread rotates in a clockwise or counter-clockwise direction. All procedures were
Gastroenterology, Petach Tikva/Israel performed under general anesthesia.
5
Institute of Therapy of Ukrainian Academy of Sciences, Kiev/Ukraine Result: Thirty patients (12 f, 18 m; mean age [range]: 62 [20–92] years) with
6
Gastrocentr, Perm, Moscow/Russian Federation positive findings of video capsule endoscopy or other small bowel imaging mod-
7
Hospital de Donostia, san sebastian/Spain ality (angiectasias n ¼ 18, jejunal/ileal polyps n ¼ 3, thickening of wall/stricture
8
Gastroenterology, Consorci Sanitari Terrassa, Terrassa/Spain n ¼ 3, other n ¼ 1) have so far been included in the trial. 27 of 30 patients had
9
Agencia Sanitaria Costa del Sol, Marbella/Spain IDA. NMSE could be performed in 29 of the 30 patients with advancement of
10
Hospital Cabueñes, Oviedo/Spain the endoscope beyond the ligament of Treitz. In one case further insertion was
11
RSLS, Moscow/Russian Federation not be performed because of a bradycardia which caused discontinuation of the
12
First Clinical Medical Centre, Kovrov/Russian Federation procedure. Mean insertion time to the jejunum was 6.4 [2–19] min. and to the
13
Digestive Services, Centro de Investigación Biome´dica en Red de Enfermedades deepest point of insertion distal from ligament of Treitz 22.6 [7–52] min. The
Hepáticas y Digestivas (CIBERehd), Madrid/Spain mean insertion depth from ligament of Treitz was 393 [0–600] cm.
14
Faculty Of Health Sciences, Trinity College Dublin, Dublin/Ireland Panenteroscopy to cecum could be achieved in one patient from the oral route.
15
Digestive Services, Hospital Universitario de La Princesa, Instituto de The diagnostic yield of NMSE was 83.4% corresponding to no findings in 5
Investigación Sanitaria Princesa (IP) and Centro, Madrid/Spain cases, at least one angiectasia in 18 cases, one or more benign polyps in 6 and
other findings in 12 patients. Thirty-two interventions were performed in 22
Contact E-mail Address: [email protected] patients (biopsies n ¼ 8, APC n ¼ 17, tattooing n ¼ 3, clipping n ¼ 3, EMR
Introduction: Addition of bismuth to triple therapy has been proposed as a strat- n ¼ 1). Mean withdrawel time without interventions was 14.7 [5–45] min. Mild
egy to improve its efficacy. mucosal trauma in the esophagus or duodenum was registered in 6 cases. There
Aims & Methods: To evaluate the use and outcomes of a quadruple therapy were no serious adverse events.
containing a proton pump inhibitor, bismuth, clarithromycin and amoxicillin Conclusion: First clinical data of an ongoing large prospective trial demonstrate
(BCA) in the European Registry on H. pylori Management (Hp-EuReg). that NMSE can be effectively and safely performed for diagnostic and therapeu-
Methods: A systematic prospective registry of the clinical practice of European tic enteroscopy. The procedure offers advantages over traditional methods in
gastroenterologists regarding H. pylori infection and treatment (31 countries and terms of procedural duration and ease of use.
280 recruiting investigators). A local coordinator was selected from each country. Disclosure of Interest: All authors have declared no conflicts of interest.
Each coordinator selected a representative group of recruiting investigators from
its country. An electronic clinical research file (e-CRF) was created on AEG-
REDCap to systematically register all adult patients infected with H. pylori.
Variables included: Patient’s demographics, previous eradication attempts, pre- OP285 CROSS-SECTIONAL EVALUATION OF TRANSMURAL
scribed eradication treatments, adverse events, and outcomes (cure rates, com- HEALING IN PATIENTS WITH CROHN’S DISEASE ON
pliance, follow up, etc.). Patients with both eradication confirmatory test and MAINTENANCE TREATMENT WITH BIOLOGICS
with less than one year follow up have been considered ongoing and were A. Testa1, A. Rispo1, P. P. Mainenti2, N. Imperatore1, G. D. De Palma3,
excluded from the analysis. M. Rea1, G. Luglio4, F. Maione3, O. M. Nardone1, N. Caporaso1,
Result: Up to now, 16,025 patients have been included, and 12,921 have finished F. Castiglione1
follow up (59% females, 87% Caucasian). Mean age was 55 years. BCA was used 1
Gastroenterology, Department of Clinical Medicine and Surgery, School of
in 248 patients (1.7% of all treatments registered): 92% in first-line. Overall Medicine "Federico II" of Naples, Naples, Italy, Naples/Italy
efficacy was 94% (95%C.I. ¼ 91–97%) by ITT and 95% (92–98%) by PP. 2
Radiology, Department of Clinical Medicine and Surgery, School of Medicine
First line efficacy was 95% (91–99%) both by ITT and PP. Esomeprazole coad- "Federico II" of Naples, Naples, Italy, Naples/Italy
juvation (36%) achieved higher eradication rates than other PPIs (98% vs. 94%). 3
Surgical Endoscopy, Department of Clinical Medicine and Surgery, School of
Treatment was prescribed in 10 or 14 days regimens (50% in each). 14-day regi- Medicine "Federico II" of Naples, Naples, Italy, Naples/Italy
men achieved higher eradication rates than 10 day both by ITT (97% vs. 92%; 4
Colorectal Surgery, Department of Clinical Medicine and Surgery, School of
N.S.) and PP (97% vs. 93%; N.S.) Compliance with treatment was 95%. Adverse Medicine "Federico II" of Naples, Naples, Italy, Naples/Italy
events were reported in 28% of cases and caused treatment discontinuation in 1
patient. Contact E-mail Address: [email protected]
Conclusion: A 14-day regimen combining bismuth salts with standard triple ther- Introduction: Transmural healing (TH) of Crohn’s disease (CD is a new under-
apy (PPI þ amoxicillin þ clarithromycin) as first-line treatment for H. pylori era- explored and interesting outcome of the concept of deep remission.
dication offers near 95% eradication rates. Aims & Methods: The aim of this study was to assess the rate of TH evaluated by
Disclosure of Interest: A.G. McNicholl: Speaker for Allergan bowel sonography (BS) and magnetic resonance enterography (MRE) in CD
A. Perez Aisa: Speaker for Allergan patients treated with biologics, directly comparing the two cross-sectional pro-
J.P. Gisbert: Scientific and teaching speaker and advisor for: Almirall, Allergan, cedures. We performed a 2-year observational longitudinal prospective study
AstraZeneca, Casen Recordati, Nycomed. evaluating steroid-free clinical remission (CR), mucosal healing (MH), and TH
All other authors have declared no conflicts of interest. in all patients with CD who would complete a 2-year period of maintenance
treatment with biologics. All patients underwent endoscopy, BS and MRE
before starting biologics and 2 years later. Furthermore, the Crohn’s Disease
TUESDAY, OCTOBER 18, 2016 15:45–17:15 Activity Index (CDAI) score was calculated before treatment and 2 years later.
VISUALISING SMALL BOWEL DISEASES – ROOM E1_____________________ Result: The study included 40 CD patients biologics (38% infliximab and 62%
adalimumab). TH was evident in 10 patients (25%) at BS and in 9 patients (23%)
OP284 NOVEL MOTORIZED SPIRAL ENDOSCOPY: FIRST RESULTS at MRE (k ¼ 0.84; P 5 0.01). No significant differences were noted about TH in
OF A EUROPEAN PROSPECTIVE TRIAL relation to the type of biologic used (P ¼ NS). MH was obtained in 14 subjects
T. Beyna1, M. Arvanitakis2, M. Schneider3, A. Van Gossum4, J. Deviere5, (35%). A good agreement was observed between MH and TH at BS (k ¼ 0.63;
H. Neuhaus6 P 5 0.001) and TH at MRE (k ¼ 0.64; P 5 0.001). CR was achieved in 24
1
Department Of Internal Medicine, Evangelisches Krankenhaus Düsseldorf, patients (60%). A poor agreement was found between CR and TH, both at BS
Düsseldorf/Germany and MRE (k ¼ 0.27 and 0.29, respectively; P 5 0.01).
2
Gastroenterology, Erasme Hospital, Universite´ Libre de Bruxelles, Bruxelles/ Conclusion: TH can be reached in about 25% of CD patients treated with bio-
Belgium logic with high agreement between BS and MRE on defining this outcome. After
3
Dpt. Of Internal Medicine, Evangelisches Krankenhaus, Düsseldorf/Germany considering the advantages of BS (high diagnostic accuracy, low costs, high
4
Department Of Gastroenterology And Hepatology, Hôpital Erasme, Free patient compliance, high availability) and the limitations or MRE (high costs,
University of Brussels, Bruxelles/Belgium low availability), we suggest the use of BS as first cross-sectional procedure in
5
Dept. Of Gastroenterology, Universite´ Libre de Bruxelles Erasme University defining TH in patients with CD.
Hospital, Bruxelles/Belgium Disclosure of Interest: All authors have declared no conflicts of interest.
6
Head, Dpt. Of Internal Medicine, Evangelisches Krankenhaus Düsseldorf,
Düsseldorf/Germany
Contact E-mail Address: [email protected]
Introduction: Currently available methods for small bowel endoscopy are com-
plex to use and time consuming. Novel Motorized Spiral Endoscopy (NMSE)
represents a new technology which offers all advantages of spiral enteroscopy
with a faster and less invasive approach.
Aims & Methods: To prospectively study the efficacy and safety of peroral
NMSE. Primary objective: diagnostic yield of NMSE in patients with suspected
United European Gastroenterology Journal 4(5S) A113

Table 1 (OP288): Association between number of pathophysiological alterations and Patient Reported Outcomes (data shown as mean  SD)

No abnormality (n ¼ 76) 1 abnormality (n ¼ 128) 2 abnormalities (n ¼ 121) 3 abnormalities (n ¼ 82) ANOVA

IBS symptom severity (z score) 0.55  0.94 0.22  1.06 0.11  0.96 0.37  0.86 F ¼ 14.0; p 5 0.0001
Somatic symptom severity (z score) 0.47  0.80 0.30  0.93 0.17  9.91 0.68  0.98 F ¼ 26.7; p 5 0.0001
IBSQOL Emotional 60  19 55  24 44  19 37  17 F ¼ 20.3; 5 0.0001
IBSQOL Mental Health 82  16 76  22 65  20 51  20 F ¼ 35.4; p 5 0.0001
IBSQOL Sleep 82  16 76  23 69  24 58  24 F ¼ 15.3; p 5 0.0001
IBSQOL Energy 69  24 58  27 48  24 35  23 F ¼ 25.0: p 5 0.0001
IBSQOL Physical Functioning 75  20 74  21 68  20 57  26 F ¼ 11.8; p 5 0.0001
IBSQOL Food 67  20 64  21 59  18 55  20 F ¼ 6.3; p 5 0.0001
IBSQOL Social Role 71  20 65  23 56  20 51  24 F ¼ 13.5; p 5 0.0001
IBSQOL Physical Role 64  28 56  31 47  29 40  28 F ¼ 10.3; p 5 0.0001
IBSQOL Sexual 71  23 70  25 63  25 50  25 F ¼ 8.2; p 5 0.0001

Scale) were randomized and instructed by dieticians: Group A excluded all wheat
TUESDAY, OCTOBER 18, 2016 15:45–17:15 starch and ‘‘traces of gluten’’ from their diet, Group B excluded FODMAPs as
COELIAC DISEASE FOR THE CLINICIAN – ROOM F1_____________________ well as gluten. Symptoms on IBS-SSS were recorded at baseline, 3 and 6 weeks,
as well as quality of life (SF-36). Four days prospective dietary intake records at
OP286 THE ENZYME ACTIVITY OF SMALL INTESTINAL MUCOSA IN baseline and 6 weeks, compliance and satisfaction after 6 weeks, and 1 month
ADULT PATIENTS WITH CELIAC DISEASE later. Dietist Net Free was used for FODMAP calculations. Statistics: paired T-
E. Sabelnikova1, O. Ahmadullina2, N. Belostotsky3, A. Parfenov1 tests and Wilcoxon’s.
1
Intestinal Pathology, Moscow Clinical Research Center, Moscow/Russian Result: 20 patients were included in each group; A (18F/2M, age 39  15) and B
Federation (15F/5M, age 43  12). 42.5% had constipation, 27.5% diarrhoea and 30% both.
2
IBD, Moscow Clinical Research Center, Moscow/Russian Federation The mean total IBS-SSS score was significantly reduced: Group A from 260 to
3
Pathophysiology, Moscow Clinical Research Center, Moscow/Russian Federation 204 (p ¼ 0.0022), group B from 263 to 145 (p 5 0.0001), p ¼ 0.0247, group B vs.
A. In group A 10% reached remission, in Group B 25% (p ¼ 0.408). All subscales
Contact E-mail Address: [email protected] improved significantly in group B, but only abdominal pain severity in group A.
Introduction: Some patients with celiac disease (CD), who have followed gluten- SF-36 physical health score improved in group B (p ¼ 0.0081), but not in group
free diet (GFD) and have a normal histological structure of small intestine A. Patients in group B were significantly more satisfied with pain relief
mucosa, may still have symptoms of bloating, rumbling and diarrhea. These (p ¼ 0.0132), but it was also more challenging to follow their diet (p ¼ 0.0008).
symptoms may be associated with changes of the activity of the small intestine Conclusion: Patients with coeliac disease and IBS-symptoms had significant
enzymes. Objective: To determine the activity of enzymes (glucoamylase, mal- improvement in abdominal symptoms and physical health from a low
tase, sucrase and lactase) in CD patients. FODMAP diet for 6 weeks. A gluten-free diet with reduced FODMAP content
Aims & Methods: Thirteen patients with newly diagnosed CD: 9 women and 4 was more effective than a more strict gluten-free diet, and should be offered to
men, (mean age 38.68  15,75 years) and 30 patients with previously diagnosed coeliac patients with refractory IBS-symptoms on a gluten-free diet.
CD: 22 women and 8 men (mean age 41.96  18,46 years) were observed. The Disclosure of Interest: All authors have declared no conflicts of interest.
diagnosis of CD was based on clinical presentation, serology, including anti-
gliadin antibodies (AGA) IgA and anti-tissue transglutaminase (anti-tTG) IgA
antibodies and duodenal biopsy. Histological changes of intestinal biopsy were TUESDAY, OCTOBER 18, 2016 15:45–17:15
classified according to the revised Marsh criteria 1999. In 1 group Marsh IIIb PATHOPHYSIOLOGY OF IBS – ROOM N2_____________________
lesions were seen in 23%, Marsh IIIc – in 77%. In 2 group - Marsh IIIa and
Marsh IIIb lesions were seen in 30% respectively, Marsh II - in 13.3%, the OP288 ADDITIVE EFFECT OF PATHOPHYSIOLOGICAL FACTORS ON
normal structure of small intestine were observed in 26.6%. The enzyme activity PATIENT REPORTED OUTCOMES IN IBS
was measured in small intestine mucosa by Dahlquist modified method. M. Simrén1, H. Törnblom1, O. Palsson2, M. Van Tilburg2, L. Van Oudenhove3,
Result: In patients with newly diagnosed CD, the activity of all enzymes was W. E. Whitehead4, J. Tack5
decreased in 92.3% in the group of patients followed GFD - in 36.5% (p 5 0.05). 1
Dept Of Internal Medicine, Sahlgrenska University Hospital, Gothenburg/Sweden
It was found that the total atrophy (Marsh IIIc) was associated with a reduced 2
UNC Center For Functional Gi And Motility Disorders, University of North
activity of all enzymes in all patients; whereas all patients with Marsh IIIb atrophy Carolina at Chapel Hill, Chapel Hill/United States of America/NC
had a decreased activity of lactase, 90% had a decreased activity of glucoamylase 3
Translational Research Center For Gastrointestinal Disorders (targid),
and maltase, and in 81.8% of cases we observed a decreased activity of sucrase. The Katholieke Universiteit Leuven, Leuven/Belgium
recovery of the intestine mucosa showed improvement of activity of all enzymes. 4
Dept. Of Medicine, University of North Carolina at Chapel Hill, Chapel Hill/
However, even in normal small intestine mucosa the reduction of glucoamylase United States of America/NC
activity was observed in 37.5% reduction of maltase activity - in 62.5%, the activity 5
University Hospital Gasthuisberg, University of Leuven, Leuven/Belgium
of sucrase was reduced in 50% and activity of lactase was decreased in 37.5%. The
reduced activity of all enzymes was found in 37.5% of patients with normal structure Contact E-mail Address: [email protected]
of small intestine mucosa. A weak correlation between the degree of atrophy and the Introduction: Both central and peripheral pathophysiological factors are thought
activity of sucrase and maltase (rs ¼ 0.513, p ¼ 0.005 and rs ¼ 0.406, p ¼ 0.029, to contribute to the symptoms of IBS. Psychological symptoms reflect CNS
respectively) was established. Activity of other enzymes had no significant correla- dysfunction, while abnormal GI sensorimotor function reflects mainly peripheral
tion with the degree of atrophy. dysfunction; both have been associated with symptoms in IBS. These factors may
Conclusion: In 37.5% of adult patients with CD who follow GFD and have have additive effects on patient reported outcome (PRO) measures in IBS.
a normal structure of mucosa, a decreased activity of intestinal enzymes may Aims & Methods: Our aim was to study whether these pathophysiological altera-
occur, which may be one of the reasons for the persistence of intestinal tions have additive effect on PROs in patients with IBS. To achieve this, we
symptoms. included 407 patients fulfilling the Rome II or Rome III IBS criteria (74%
Disclosure of Interest: All authors have declared no conflicts of interest. females; mean age 36  12 years). The following pathophysiological factors
were measured in all subjects: colonic transit time (radiopaque markers); com-
pliance, allodynia (low pain thresholds) and hyperalgesia (increased pain inten-
sity) (rectal barostat); and anxiety and depression (HAD scale). Abnormal
OP287 FODMAP RESTRICTION OF A GLUTEN-FREE DIET IN findings on the physiology assessments were defined based on the 5th and 95th
PATIENTS WITH COELIAC DISEASE: A RANDOMIZED, percentiles in healthy controls, and on the HAD scale by a score 47. The
CONTROLLED CLINICAL STUDY patients also completed questionnaires to assess IBS symptom severity (IBS-
K. Nuland1, I. Strindmo2, G. Kahrs3, J.G. Hatlebakk4 SSS or GSRS-IBS), and bowel habit (stool diary). To be included in the analysis,
1
Department Of Clinical Medicine, University of Bergen, Bergen/Norway a pathophysiological factor had to be associated with severity of one IBS-
2
Department Of Clinical Medicine, Uiiversity of Bergen, Bergen/Norway related symptom. As PRO measures we used z-scores of IBS symptom severity
3
Department Of Medicine, Haukeland University Hospital, Bergen/Norway (IBS-SSS or GSRS-IBS total score) and somatic symptom severity (SCL-90
4
Haukeland University Hospital Dept. of Medicine, Bergen/Norway somatization subscale or PHQ-15), and quality of life (IBSQOL).
Result: Allodynia was seen in 40% of patients, hyperalgesia in 17%, accelerated
Contact E-mail Address: [email protected] colonic transit in 18%, delayed transit in 7%, anxiety in 52% and depression in
Introduction: 20–30% of coeliac patients on a gluten free diet still have irritable 24% - these factors were associated with severity of at least one IBS symptom.
bowel syndrome (IBS) symptoms. A low FODMAP (fermentable oligo-, di-, Rectal compliance (increased in 10% and reduced in 14%) was not associated
monosaccharides and polyols) diet is effective to reduce symptoms in IBS with more severe IBS symptoms. At least 3 pathophysiological abnormalities
patients. relevant for symptoms were present in 20% of patients, 2 in 30%, 1 in 31%,
Aims & Methods: We wanted to investigate the benefit from restricting the and 18% of patients had none. The number of pathophysiological abnormalities
FODMAP content of the diet in patients with coeliac disease, who are still was not associated with age (p ¼ 0.15), gender (p ¼ 0.12) or IBS subgroup
symptomatic on a gluten-free diet. 40 patients with coeliac disease and IBS (p ¼ 0.21). With increasing number of pathophysiological abnormalities, there
symptoms confirmed by the Rome III-criteria and IBS-SSS (Symptom Severity was a gradual increase in the severity of IBS symptoms (p 5 0.0001) and somatic
A114 United European Gastroenterology Journal 4(5S)
symptoms (p 5 0.0001), and a gradual reduction of QOL (p 5 0.0001) (table 1). OP290 BACTERIAL PASSAGE IS INCREASED IN THE COLON OF
When assessing central (anxiety and depression) and ‘‘peripheral’’/GI pathophy- WOMEN WITH IRRITABLE BOWEL SYNDROME
siological factors (allodynia, hyperalgesia, accelerated and delayed transit) sepa- INDEPENDENTLY OF STOOL CONSISTENCY SUBGROUP
rately, cumulative effects on symptom severity and QOL were also observed. O. Bednarska1, S. Walter2, M. Ström1, Å. Keita1
Conclusion: Visceral hypersensitivity, i.e. allodynia and hyperalgesia, abnormal 1
Department Of Clinical And Experimental Medicine, Linköping University,
colonic transit and psychological factors are all pathophysiological factors that Linköping/Sweden
are associated with GI symptom severity in IBS. These factors have an additive 2
Department Of Gastroenterology, Linköping University Hospital, Linköping/
effect on GI and non-GI symptoms, as well as on quality of life in IBS, and are Sweden
therefore relevant treatment targets.
Disclosure of Interest: M. Simrén: Unrestricted research grants from Danone, and Contact E-mail Address: [email protected]
Ferring Pharmaceuticals; Consultant/ Advisory Board member for AstraZeneca, Introduction: Irritable bowel syndrome (IBS) is a chronic functional intestinal
Danone, Nestlé, Chr Hansen, Almirall, Allergan, Albireo, Glycom and Shire; disorder with a strong female predominance. The pathophysiology is incomple-
Speaker for Tillotts, Takeda, Shire and Almirall tely understood, but an increasing body of evidence demonstrates a role of the
H. Törnblom: Consultant/Advisory Board member for Almirall, Danone and brain-gut-microbiota axis1. Alterations in microbiota have been associated with
Shire onset as well as changes in symptoms of IBS. Prior data suggest that intestinal
O. Palsson: Salary support from research grants from Salix Pharmaceuticals, barrier function is disturbed in IBS, but to our knowledge the passage of living
Takeda Pharmaceuticals and Ironwood pharmaceuticals, as well as honoraria bacteria through the colonic mucosa has never been investigated.
for participation in educational programs supported by these companies. Aims & Methods: Aims: To study the paracellular permeability and the passage
M. van Tilburg: Research support from Takeda for investigator initiated study of living bacteria, both commensal and pathogenic, through the colonic mucosa
W.E. Whitehead: Unrestricted research grants from Takeda Pharmaceuticals; of women with IBS and female healthy controls (HCs). The second aim was to
Unrestricted educational grants from Takeda and Ferring Pharmaceuticals; investigate whether IBS stool consistency subgroups differ in terms of intestinal
Consultant/ Advisory Board member for Ono and Ferring Pharmaceuticals barrier function. Methods: Colonic biopsies from 32 women with IBS (mean age
and Biomerica USA. 32.6y; 17 with mixed stool pattern IBS-M, 7 with diarrhea IBS-D and 8 with
J. Tack: Almirall, AstraZeneca, Danone, Menarini, Novartis, Nycomed, Ocera, constipation predominance IBS-C, according to Rome III criteria) and 15 HCs
Ono pharma, Shire, SK Life Sciences, Theravance, Tranzyme, Xenoport, Zeria (mean age 29.7y) were mounted in Ussing chambers2. Mucosal passage of living
Pharmaceuticals, Abbott, AlfaWasserman, Janssen. Escherichia coli (E.coli) HS and Salmonella typhimurium was investigated. The
All other authors have declared no conflicts of interest. paracellular passage was measured by using 51Cr-EDTA.
Result:

Table: Mucosal passage of bacteria (bacteria/chamberx103) and51CrEDTA (cm/

OP289 INCREASED INHIBITORY NEUROTRANSMISSION WITHIN sx106) are shown in median (25%–75% percentile)
ANTERIOR CINGULATE CORTEX IS RELATED TO COMORBID
ANXIETY IN IRRITABLE BOWEL SYNDROME IBS HC p
A. Icenhour1, O. Bednarska2, S. Tapper3, A. Tisell4, P. Lundberg1, S. T. Witt1,
E.coli 627 (563–688) 333 (291–387) 0.0001
S. Elsenbruch5, S. Walter1
1
Cmiv, Linköping University, Linköping/Sweden Salmonella 880 (689–1104) 315 (194–437) 0.0001
2
Institute Of Clinical And Experimental Medicine, Division Of Gastroenterology, 51Cr-EDTA 1.1 (0.7–1.5) 0.9 (0.5–1.1) 50.05
Linköping University, Linköping/Sweden
3
Department Of Radiology, Linköping University, Linköping/Sweden
4
Department Of Radiation Physics, Linköping University, Linköping/
Sweden,5Institute Of Medical Psychology & Behavioral Immunobiology, University The colonic mucosa of IBS patients had a significantly greater passage both for
Hospital Essen, University of Duisburg-Essen, Essen/Germany living Salmonella typhimurium and E. coli HS compared with HCs (p 5 0.0001
and p 5 0.0001 respectively). The 51Cr-EDTA passage was also significantly
Contact E-mail Address: [email protected] increased in IBS (p 5 0.05). IBS-M, IBS-D and IBS-C did not differ significantly
Introduction: Inspired by the concept of Irritable Bowel Syndrome (IBS) as a in terms of mucosal barrier function measures, neither for bacterial nor for
disorder of brain-gut-communication, alterations in central mechanisms are paracellular passage.
increasingly acknowledged in IBS pathophysiology. Given high comorbidity Conclusion: The present study demonstrated that passage through the colonic
with affective disorders, emotional factors likely play a role in disturbed central mucosa of both pathogenic and commensal living bacteria is altered in female
processes in IBS. Dysfunctions particularly in brain regions involved in emotion IBS patients. These findings elucidate new aspects of peripheral abnormalities
processing, including the rostral anterior cingulate cortex (rACC) as a unique and support the importance of microbiota as a major factor in the pathophysiol-
hub of both, affect regulation and anti-nociception, may constitute a central link ogy of IBS.
between abdominal pain and psychiatric comorbidities. While a growing number Disclosure of Interest: All authors have declared no conflicts of interest.
of neuroimaging studies support a crucial role of rACC in altered pain processing References
and emotional disturbances in IBS, the biochemical basis of these alterations
remains unknown. 1. Mayer et al (2015) Towards a systems view of IBS. Nat Rev Gastroenterol
Aims & Methods: We compared IBS patients and healthy controls (HC) regard- Hepatol.
ing concentrations of glutamate (Glu) and -Aminobutyric acid (GABAþ) in 2. Keita, A.V. and Soderholm, J.D. (2012) Barrier dysfunction and bacterial
rACC using quantitative magnetic resonance spectroscopy (qMRS). We further uptake in the follicle-associated epithelium of ileal Crohn’s disease. Ann N Y
addressed associations with anxiety and depression as the most common psychia- Acad Sci.
tric comorbidities in IBS. In a combined MRI and MRS study, GABAþ and Glu
concentrations in 38 female IBS and 19 age-matched female HC were measured
using a Philips Ingenia 3T scanner and a MEGA-PRESS sequence with a
3x3x3cm3 voxel placed in the rACC, localized based on individual T1-weighted OP291 LUBIPROSTONE IMPROVES THE INTESTINAL
images. Symptoms of anxiety and depression were assessed with the Hospital PERMEABILITY, A NEW APPROACH FOR ‘‘LEAKY GUT’’; A
Anxiety and Depression Scale (HADS) and correlated with metabolite concen- PROSPECTIVE RANDOMIZED PILOT CLINICAL STUDY IN
trations. Patients were subdivided into a group with (IBSþ) and without (IBS-) HEALTHY VOLUNTEERS
comorbid anxiety based on published HADS cut-offs. T. Kato, I. Tsuchiya, A. Nakajima
Result: Compared to HC, IBS as a group exhibited significantly increased Department Of Gastroenterology And Hepatology, Yokohama City University,
GABAþ concentrations within rACC (p 5 0.05), while no differences were Yokohama/Japan
observed in concentrations of Glu. Both anxiety (r ¼ 0.407; p 5 0.01) and depres-
sion (r ¼ 0.276; p 5 0.05) correlated with GABAþ concentrations. Inclusion of Contact E-mail Address: [email protected]
HADS scores as covariates diminished group differences in GABAþ concentra- Introduction: Several diseases and disorders are associated with ‘‘leaky gut’’ (or
tions in ANCOVA with anxiety, but not with depression. Analyses on IBS sub- increased intestinal permeability), such as inflammatory bowel diseases, celiac
groups revealed a group effect (p 5 0.05) with higher GABAþ levels in IBSþ disease, food allergy, irritable bowel syndrome, and obesity-metabolic disorders.
compared to HC (p 5 0.01) and compared to IBS- (p ¼ 0.056), whereas differ- Therefore, this topic is an area of growing interest, and a well-established therapy
ences between IBS- and HC did not yield significance. for preventing or reverting increased intestinal permeability would be valuable.
Conclusion: Our findings provide first evidence of dysregulated rACC neuro- Since there are no effective medications for ’’leaky gut’’ to date, it would be
transmission in IBS. This imbalance appears to be driven by increased important to establish a new therapy which aiming at improvement of intestinal
GABAþ concentrations in rACC as a crucial structure for anti-nociception permeability. Previous studies have reported that non-steroidal anti-inflamma-
and affect regulation. Abnormal GABAþ levels were most pronounced in tory drugs (NSAIDs) induce small intestinal damage and increased permeability
patients with comorbid anxiety, supporting a key role of psychiatric comorbid- [1]. Other basic studies have reported that lubiprostone, a chloride channel acti-
ities in altered brain processes in IBS. Altered inhibitory GABAergic neurotrans- vator used for chronic constipation, repairs intestinal mucosal barrier function
mission may be fundamental for dysregulations of affective and nociceptive and also prevents NSAID-induced small intestinal damage in rodent models [2].
processing, contributing to functional as well as long-lasting neuroplastic changes Aims & Methods: Our aim was to verify the effect of lubiprostone on intestinal
in IBS. permeability in healthy volunteers administrated with diclofenac. We conducted
Disclosure of Interest: All authors have declared no conflicts of interest. a prospective, randomized parallel-group trial. Healthy male volunteers, with
documented abstinence from certain drugs (NSAIDs, proton-pump inhibitors,
antibiotics, and probiotics) for at least 3 months prior to the study were enrolled.
The subjects were randomly assigned to either the lubiprostone or control
groups. All participants performed sugar permeability tests on baseline, after
14 days of treatment (day14), and after 28 days of treatment (day28). The
United European Gastroenterology Journal 4(5S) A115
subjects ingested 400 ml of water containing 10 g lactulose and 5 g mannitol, after 34  12 years); colonic barostat (phasic distensions, 30 s duration, 30 s rest;
an overnight fast. Total urine for the following 4 hours was collected and rapidly 2 mmHg increments); 3. US IBS cohort (n ¼ 159; 126 f; age 37  14 years);
frozen for analysis. Both groups started with oral intake of 75 mg diclofenac daily rectal barostat (phasic distensions, 30 s duration, 30 s rest; 2 mmHg increments);
for 7 days. Thereafter, the lubiprostone group was treated by oral intake of 24 mg 4. Swedish IBS cohort (n ¼ 353; 267 f; age 38  13 years); rectal barostat (phasic
lubiprostone daily for 28 days, while the control group did not receive any distensions, 30 s duration, 30 s rest; 5 mmHg increments); 5. Swedish IBS cohort
medicine after diclofenac. Permeability was expressed as lactulose/mannitol (n ¼ 147; 102 f; age 34  11 years); rectal barostat (ramp inflation, 4 mmHg steps,
ratio (LMR), calculated from urinary excretion of the initial administrated 1 min/step). Subjects were divided into sensitivity tertiles based on pain/discom-
dose of each sugar. fort thresholds. GI symptom severity (z scores of IBS-SSS, GSRS-IBS or dys-
Result: Fourteen subjects for each group with a median age of 23.5 (range, 21–32) pepsia symptom severity (DSS)) was compared between sensitivity tertiles in each
completed the study. The background characteristics including baseline LMR cohort and corrected for somatization (RPSQ, PHQ-12 or SCL-90), and anxiety
between the two groups showed no significant difference. Treatment after 28 and depression (HAD or BSI).
days of lubiprostone showed significant improvement of LMR (p ¼ 0.0497), Result: The results are summarized in table 1. In all five cohorts GI symptom
while 14 days treatment did not reach statistical significance compared to control severity increased gradually with increasing GI sensitivity, with significant differ-
group (p ¼ 0.403). ences in GI symptom severity between the sensitivity tertiles, and small, but
significant correlations between pain/discomfort thresholds and GI symptom
LMR results (analyzed by analysis of covariance: ANCOVA) severity, across all five patient groups (r ¼ 0.20 – 0.29). The differences
between sensitivity tertiles remained significant in all cohorts after correction
LMR control group (n ¼ 14) lubiprostone group (n ¼ 14) p value for anxiety and depression, and also after correction for somatization (without
GI symptoms) in all of the cohorts (p 5 0.05).
baseline 0.019 (0.016–0.022) 0.021 (0.017–0.025) Conclusion: A gradual increase in GI symptom severity with increasing GI sensi-
day14 0.035 (0.023–0.047) 0.024 (0.019–0.029) 0.403 tivity was demonstrated in IBS and functional dyspepsia, which was consistent
day28 0.028 (0.023–0.033) 0.017 (0.015–0.019) 0.0497 across several large patient groups from different countries, different methods to
assess sensitivity, and assessments in different parts of the GI tract. This associa-
Conclusion: In our study, 28 days treatment with lubiprostone demonstrated an tion, although modest, was independent of tendency to report symptoms or
improvement of increased intestinal permeability after 1-week administration of anxiety/depression comorbidity. These findings confirm that visceral hypersensi-
diclofenac in healthy volunteers. This is the first study to demonstrate a signifi- tivity is a contributor to symptom generation in FGIDs.
cant effect of a medication for treatment of increased intestinal permeability, and Disclosure of Interest: M. Simrén: Unrestricted research grants from Danone, and
suggests a new approach towards several diseases associated to ‘‘leaky gut’’. Ferring Pharmaceuticals; Consultant/ Advisory Board member for AstraZeneca,
Disclosure of Interest: T. Kato: This research was supported by a grant from Danone, Nestlé, Chr Hansen, Almirall, Allergan, Albireo, Glycom and Shire;
Mylan EPD G.K.(MylanEPD). Speaker for Tillotts, Takeda, Shire and Almirall.
A. Nakajima: This research was supported by a grant from Mylan EPD H. Törnblom: Consultant/Advisory Board member for Almirall, Danone and
G.K.(MylanEPD). Shire.
All other authors have declared no conflicts of interest. O. Palsson: Salary support from research grants from Salix Pharmaceuticals,
References Takeda Pharmaceuticals and Ironwood pharmaceuticals, as well as honoraria
for participation in educational programs supported by these companies
1. Bjarnason I, Williams P, Smethurst P, et al. Effect of non-steroidal anti- M. van Tilburg: Research support from Takeda for investigator initiated study.
inflammatory drugs and prostaglandins on the permeability of the human J. Tack: Almirall, AstraZeneca, Danone, Menarini, Novartis, Nycomed, Ocera,
small intestine. Gut 1986; 27: 1292–7. Ono pharma, Shire, SK Life Sciences, Theravance, Tranzyme, Xenoport, Zeria,
2. Hayashi S, Kurata N, Yamaguchi A, et al. Lubiprostone prevents nonster- Abbott, Almirall, AlfaWasserman, Janssen,
oidal anti-inflammatory drug-induced small intestinal damage by suppres- W.E. Whitehead: Unrestricted research grants from Takeda Pharmaceuticals;
sing the expression of inflammatory mediators via EP4 receptors. J Unrestricted educational grants from Takeda and Ferring Pharmaceuticals;
Pharmacol Exp Ther 2014; 349: 470–9. Consultant/ Advisory Board member for Ono and Ferring Pharmaceuticals
and Biomerica USA.
All other authors have declared no conflicts of interest.

OP292 VISCERAL HYPERSENSITIVITY IS ASSOCIATED WITH GI

SYMPTOM SEVERITY IN FUNCTIONAL GI DISORDERS:
CONSISTENT FINDINGS FROM FIVE DIFFERENT PATIENT OP293 CHRONIC ORAL ADMINISTRATION OF THE GUANYLATE
COHORTS CYCLASE-C AGONIST LINACLOTIDE ATTENUATES COLITIS
M. Simrén1, H. Törnblom1, O. Palsson2, M. Van Tilburg2, L. Van Oudenhove3, INDUCED LONG-TERM BLADDER AFFERENT HYPERACTIVITY
J. Tack4, W. E. Whitehead5 L. Grundy1, S. Garcia-Caraballo1, J. Maddern1, G. Rychkov1, G. Hannig2, C.
1
Dept Of Internal Medicine, Sahlgrenska University Hospital, Gothenburg/Sweden B. Kurtz2, A. Silos-Santiago2, S. M. Brierley1
2 1
Unc Center For Functional Gi And Motility Disorders, University of North Visceral Pain Group, Centre For Nutrition And Gastrointestinal Diseases,
Carolina at Chapel Hill, Chapel Hill/United States of America/NC Discipline Of Medicine, University of Adelaide, Adelaide/Australia
3 2
Translational Research Center For Gastrointestinal Disorders (targid), Ironwood Pharmaceuticals, Inc., Cambridge/United States of America
Katholieke Universiteit Leuven, Leuven/Belgium
4
University Hospital Gasthuisberg, University of Leuven, Leuven/Belgium Contact E-mail Address: [email protected]
5
Dept. Of Medicine, University of North Carolina at Chapel Hill, Chapel Hill/ Introduction: There is significant comorbidity between the symptoms of IBS and
United States of America/NC the urological symptoms of urgency and frequency experienced in overactive
bladder and interstitial cystitis/painful bladder syndromes. Viscero-visceral
Contact E-mail Address: [email protected] cross-talk has also been described in pre-clinical studies, whereby acute colitis
Introduction: Divergent results have been reported regarding the association in rodents is associated with altered bladder cystometry and bladder afferent
between visceral hypersensitivity and GI symptoms in patients with functional sensitisation [1,2]. However, it remains to be determined if bladder overactivity
GI disorders (FGIDs). Moreover, it has been proposed that the association persists following the resolution of colitis, in a model of chronic colonic hyper-
between hypersensitivity and GI symptoms is secondary to psychological factors sensitivity (CCH) [3], or if reducing colonic nociception is able to alter bladder
and tendency to report symptoms. overactivity. Linaclotide, an FDA approved guanylate cyclase-C (GC-C) agonist,
Aims & Methods: Our aim was to evaluate the association between visceral reduces abdominal pain in IBS patients with constipation [3], reverses colonic
hypersensitivity and GI symptom severity in large cohorts of FGID patients. mechanical hyper-sensitivity in CCH mice, and reduces noxious signalling to the
To do this, we included 5 cohorts of patients with FGIDs, who had undergone spinal cord in mice in vivo. We hypothesized that oral linaclotide administration
GI balloon distensions and completed questionnaires to assess GI symptom may also reduce bladder hypersensitivity.
severity, somatization, anxiety and depression: 1. Belgian functional dyspepsia Aims & Methods: We investigated healthy C57BL/6 J mice and mice with CCH,
cohort (n ¼ 242; 180 females (f); age 39  13 years (mean  SD); gastric barostat 28 days after intra-colonic TNBS administration. CCH mice were randomly
(ramp inflation, 2 mmHg steps, 2 min/step). 2. US IBS cohort (n ¼ 243; 203 f; age assigned to either chronic linaclotide (3 mg/kg/day) or placebo (water)

Table 1 (OP292): Association between visceral hypersensitivity and GI symptom severity in five FGID cohorts

Belgian FD cohort US IBS cohort US IBS cohort Swedish IBS cohort 1 Swedish IBS cohort 2
(n ¼ 242) (colon; n ¼ 243) (rectum; n ¼ 159) (n ¼ 353) (n ¼ 147)
z score GI sx severity (mean  SD) DSS IBS-SSS IBS-SSS IBS-SSS/GSRS-IBS IBS-SSS

Low sensitivity tertile 0.48  0.99 0.29  0.99 0.34  0.90 0.40  0.98 0.46  0.89
Mid sensitivity tertile 0.07  0.88 0.04  1.00 0.00  1.04 0.11  0.99 0.31  0.83
High sensitivity tertile 0.32  0.99 0.25  0.95 0.28  0.97 0.25  0.95 0.06  1.14
ANOVA F ¼ 13.2; p 5 0.0001 F ¼ 5.9; p ¼ 0.003 F ¼ 5.1; p ¼ 0.007 F ¼ 14.0; p 5 0.0001 F ¼ 8.5; p 5 0.0001
ANCOVA (adjusted for somatization) F ¼ 9.2; p 5 0.001 F ¼ 4.9; p ¼ 0.008 F ¼ 3.1; p ¼ 0.046 F ¼ 6.3; p ¼ 0.002 F ¼ 3.9; p ¼ 0.02
ANCOVA (adjusted for anx & depr) F ¼ 13.3; p 5 0.0001 F ¼ 5.0; p ¼ 0.006 F ¼ 4.1; p ¼ 0.018 F ¼ 10.8; p 5 0.0001 F ¼ 8.3; p 5 0.0001
Correlation sensitivity - GI sx r ¼ 0.27; p 5 0.0001 r ¼ 0.20; p 5 0.0001 r ¼ 0.27; p ¼ 0.001 r ¼ 0.29; p 5 0.0001 r ¼ 0.20; p 5 0.02
A116 United European Gastroenterology Journal 4(5S)
administration, consisting of a once daily oral gavage for 2 weeks prior to experi- Conclusion: Our study issued from a population-based registry, provides further
mentation. In all four groups, whole cell patch clamp recordings from retro- evidence to recommend screening for inherited disorders using targeted NGS in
gradely traced thoracolumbar and lumbosacral bladder dorsal root ganglion children with an EO-IBD with the potential to enhance optimal selection of
(DRG) neurons determined neuronal excitability, whilst ex-vivo electrophysiolo- treatment options and adequate counseling of families. This study also indicates
gical recordings determined bladder afferent and contractile sensitivity to ramp that targeted NGS used in this study may be an adequate and efficient tool for
distension as well as muscarinic, purinergic and TRPV1 channel agonists. the reappraisal of the diagnosis in these patients.
Micturition pattern analysis was performed by analysing in-vivo natural voiding Disclosure of Interest: All authors have declared no conflicts of interest.
behaviour.
Result: Bladder traced DRG neurons from mice with CCH displayed hyperexcit-
ability with a significant decrease in rheobase (P 5 0.01) as well as enhanced
bladder afferent responses to distension (P 5 0.001), and exogenous agonists OP295 HYPOXIA INHIBITS INTESTINAL INFLAMMATION THROUGH
(P 5 0.01), with no changes in muscle compliance or contraction responses. As THE INHIBITION OF NLRP3 INFLAMMASOME AND THE
a reflection of altered physiological signalling, CCH mice also displayed signifi- ACTIVATION OF AUTOPHAGY
cant changes in voiding frequency (P 5 0.01). CCH mice treated with linaclotide P.A. Ruiz-Castro1, J. Cosin-Roger1, S. Simmen1, K. Atrott1, H. Melhem1,
displayed attenuated bladder DRG neuron excitability compared with placebo I. Frey-Wagner1, C. De Vallière1, P. Spielmann2, R. H. Wenger2, J. Zeitz1, S.
treated mice (P  0.001), and attenuated bladder afferent hypersensitivity to dis- R. Vavricka1, G. Rogler1
tension (P 5 0.001). Linaclotide treatment in the CCH mice also resulted in a 1
Gastroenterology And Hepatology, University Hospital Zurich, Zurich/
restoration of natural voiding behaviour (P  0.05). Switzerland
Conclusion: Mice with CCH also display increased bladder afferent excitability 2
Institute Of Physiology, University of Zurich, Zurich/Switzerland
accompanied by abnormal bladder voiding behaviour, an example of viscero-
visceral cross-talk. Chronic oral administration of linaclotide, a gut-restricted Contact E-mail Address: [email protected]
GC-C agonist that inhibits colonic nociceptors, reverses these colitis-induced Introduction: The impact of environmental hypoxia on the development of
changes in bladder function and sensitivity. Agents that improve abdominal inflammatory bowel disease (IBD) is controversial, with studies supporting
pain may be able to improve urological symptoms through common sensory both a proinflammatory and a protective effect. Hypoxia is known to activate
innervation pathways. the autophagy and inflammasome pathways, which are ancient innate immune
Disclosure of Interest: L. Grundy: Grant support from Ironwood mechanisms linked by mutual regulation. In recent years, polymorphisms in gene
pharmaceuticals. loci containing autophagy- and inflammasome proteins have been associated
G. Hannig: Employee, stock holder, and stock options from Ironwood pharma- with an increased risk of IBD. Evidential data suggest that the imbalance in
ceuticals Inc. the mutual regulation of autophagy and NLRP3 inflammasome activation
C.B. Kurtz: Employee, stock holder, and stock options from Ironwood pharma- under hypoxia plays a role in the development of IBD.
ceuticals Inc. Aims & Methods: To study the effects of hypoxia in IBD, healthy volunteers
A. Silos-Santiago: Employee, stock holder, and stock options from Ironwood (n ¼ 10), patients with Crohn’s disease (CD, n ¼ 11) and patients with ulcerative
pharmaceuticals Inc and Decibel Therapeutics. colitis (UC, n ¼ 9) were subjected to hypoxic conditions resembling an altitude of
S.M. Brierley: Research support: Ironwood Pharmaceuticals Inc., Takeda 4,000 m above sea level for 3 h using a hypobaric chamber. Distal colon biopsies
Pharmaceuticals Inc., Key Pharmaceuticals Inc. were collected the day before hypoxia, immediately after hypoxia, and one week
All other authors have declared no conflicts of interest. after collection of the first biopsy. To further study the effects of hypoxia in
References colitis and the role of the NLRP3 inflammasome, wild-type (WT), interleukin
(IL)-10-/-, Nlrp3-/- and IL-10-/- Nlrp3-/- double knockout mice were subjected to
1. Lamb et al, AJPGI 2006. hypoxia (8% O2) for 18 h prior to colon biopsy collection. Mice under normoxic
2. Ustinova et al, Neurourol Urodynam 2010. conditions were used as controls. For the in vitro studies, the human monocytic
3. Castro et al, Gastroenterology 2013. cell line THP1 and the intestinal epithelial cell line HT-29 were subjected to
hypoxia (0.2% O2) in the presence and absence of lipopolysaccharide.
TUESDAY, OCTOBER 18, 2016 15:45–17:15 Result: Colon biopsies of patients with CD, but not UC showed increased levels
of tumor necrosis factor (TNF) and NLRP3 mRNA expression prior to
(EPI)GENETICS IN IBD – ROOM L7_____________________ hypoxia. Interestingly, hypoxia inhibited the expression of both genes immedi-
OP294 DIAGNOSING RARE INHERITED DISORDERS USING ately and one week after hypoxia concomitantly with the induction of the autop-
TARGETED NEXT GENERATION SEQUENCING IN PATIENTS hagy-associated gene p62. IL-10-/-, but not IL-10-/- Nlrp3-/- mice presented an
WITH EARLY-ONSET INFLAMMATORY BOWEL DISEASE: A increased expression of TNF, IL-6, and inflammasome-associated IL-1b as well
POPULATION-BASED STUDY as increased levels of phospho-p65/RelA concomitantly with an accumulation of
F. Broly1, M. Fumery2, F. Vasseur3, G. Savoye4, D. Ley5, H. Sarter6, J. Dupas2, the autophagy proteins p62 and LC3, suggesting an autophagy blockage orche-
D. Turck5, C. Gower Rousseau6 strated by NLRP3. Interestingly, hypoxic conditions significantly inhibited the
1
Toxicology And Genopathies Unit, Centre De Biologie-pathologies Genetique, Ea expression of TNF, IL-6 and IL-1b, and restored autophagy in IL-10-/- mice.
4481Lille University & Hospital, Lille/France THP1 and HT-29 cells subjected to hypoxia showed a decrease in NF-B activa-
2
Gastroenterology Unit & Epimad Registre, Amiens University and Hospital, tion concomitantly with an increase in autophagy, evidenced by a reduction in
Amiens/France p62 and LC3, and the phosphorylation of mTOR, a major regulator of autop-
3
Biostatistics And Genetics, Ea 2694Lille University & Hospital, Lille/France hagy. siRNA-mediated silencing of NLRP3 further activated autophagy under
4
Gastroenterology Unit & Epimad Registre, Rouen University and Hospital, hypoxia.
Rouen/France Conclusion: Our results suggest a protective effect of hypoxia in CD patients and
5
Gastroenterology Pediatric Unit And Inserm Liric Umr 995Lille University & the IL-10-/- mouse model of colitis. IL-10-/-, but not IL-10-/- NLRP3-/- mice under
Hospital, Lille/France presented inhibition of autophagy indicating that NLRP3 is involved in the
6
Public Health, Epidemiology And Economic Health, Registre Epimad, Inserm blockage of autophagy. Interestingly, hypoxia restored autophagy in IL-10-/-
Liric Umr 995Lille University and Hospital, Lille/France mice, as well as in THP1 and HT-29 cells concomitantly with a reduction of
inflammatory gene expression and signaling. Hypoxia-induced autophagy was
Contact E-mail Address: [email protected] enhanced in the absence of NLRP3 further supporting a role for NLRP3 in the
Introduction: Several recent referral center studies showed that a significant pro- regulation of autophagy. Our results confirm a reciprocal regulation between
portion (3–10%) of children with an early-onset (EO, defined by an age at hypoxia, inflammation, and autophagy, and suggest that hypoxia ameliorates
diagnosis less than 12 years) inflammatory bowel disease (IBD) present with inflammation through the induction of autophagy via the regulation of NLRP3.
an underlying monogenic disorder. Currently, more than sixty disorders of this Disclosure of Interest: All authors have declared no conflicts of interest.
type have been identified and their pathophysiological mechanisms are very References
heterogeneous. Most of them affecting the intestinal epithelial barrier, are asso-
ciated with defects in phagocytosis or immune deficiency, or are hyper- and auto- 1. Rioux JD, et al. Genome-wide association study identifies new susceptibility
inflammatory diseases. However, they all share the ability to present in the form loci for Crohn disease and implicates autophagy in disease pathogenesis. Nat
of an array of intestinal inflammation with EO. Genet 2007; 39(5): 596–604.
Aims & Methods: Using a next-generation sequencing (NGS) of the 63 genes 2. Pursiheimo JP, et al. Hypoxia-activated autophagy accelerates degradation
whose abnormalities are responsible for these disorders, and a targeted CGH of SQSTM1/p62. Oncogene 2009; 28(3): 334–44.
array analysis of their chromosomal loci, 91 patients with an initial diagnosis of 3. Villani AC, et al. Common variants in the NLRP3 region contribute to
EO-IBD between 1988 and 2004 (54% of the whole EO-IBD cohort) issued from Crohn’s disease susceptibility. Nat Genet 2009; 41(1): 71–6.
EPIMAD population-based registry were screened; 71 had a Crohn’s disease and 4. Nakahira K, et al. Autophagy proteins regulate innate immune responses by
20 an ulcerative colitis. inhibiting the release of mitochondrial DNA mediated by the NALP3
Result: Analysis isolated 24 patients (26.4%) with very rare or not yet reported inflammasome. Nat Immunol 2011; 12(3): 222–30.
potential pathogenic variants in 17 genes. Seven of them (7/91; 7.6%) had a 5. Müller-Edenborn K, et al. Hypoxia attenuates the proinflammatory response
genotype compatible with one of the tested disorders: Burton agammaglobuline- in colon cancer cells by regulating IB. Oncotarget 2015; 6(24): 20288–301.
mia, familial diarrhea, familial C 2 defect, hyper-IgM syndrome or Omenn syn-
drome. The remaining 17 patients (17/91; 18.7%) were heterozygous carriers of
genes variants involved in autosomal recessive trait. The genotype identified in
these patients was thus probably not likely to be the underlying cause of one of
these disorders. However, one cannot exclude that it may contribute to IBD as
suggested by the unusually high prevalence of these genotypes.
United European Gastroenterology Journal 4(5S) A117

Table 1. (OP297)

Feature CCD n ¼ 19 UC n ¼ 32 P value

Age at testing (mean  SD, y) 32.0  14.9 36.0  10.6 0.3

Age at diagnosis (mean  SD,y) 25.7  15.5 25.3  10.2 0.9
Disease Duration at testing (mean  SD,y) 6.2  4.8 10.5  8.4 0.047
Gender (%,n), male 42 (8) 50 (16) 0.44
Clinically active (%,n) 58 (11) 66 (21) 0.77
Endoscopically active (%,n) 89 (17) 71 (25) 0.45
Histologically active (%,n) 79 (15) 63 (20) 0.35
Treatment (%,n) Biologic Azathioprine ASA Steroid Antibiotic 15.8 (3) 15.8 (3) 15.8 (3) 0 0 7.2 (3) 0 69 (22) 2.3 (1) 0 0.67 0.047 0.0004 1 1
CRP (mean  SD, mg/mL) 16.1  21.1 8.7  16.3 0.2
WCC (mean  SD,X 109/ L) 6.5  2.0 6.3  1.3 0.7

OP296 EPIGENETIC ALTERATIONS IN INFLAMMATORY BOWEL J. Satsangi: JS has served as a speaker, a consultant and an advisory board
DISEASE - THE INFLUENCE OF GERMLINE VARIATION member for MSD, Ferring Abbvie and Shire, consultant with Takeda, speaking
(MEQTLS) ON GENOME-WIDE METHYLATION ALTERATIONS fees from MSD and has received research funding from Abbvie
A. T. Adams1, R. Kalla1, E. R. Nimmo1, Ibd Character Consortium1, M. All other authors have declared no conflicts of interest.
H. Vatn2, J. Jahnsen3, P. Ricanek4, J. Halfvarson5, J.D. Söderholm6, References
M.J. Pierik7, F. Gomollon8, I.G. Gut9, M. D’Amato10, J. Satsangi1
1 1. Adams AT, et al. Two-stage Genome-wide Methylation Profiling in
Institute Of Genetics And Molecular Medicine, University of Edinburgh,
Childhood-onset Crohn’s Disease Implicates Epigenetic Alterations at the
Edinburgh/United Kingdom
2 VMP1/MIR21 and HLA Loci. Inflamm Bowel Dis 2014; 20(10): 1784–1793.
Institute Of Clinical Medicine, Epigen, Campus Ahus, University of Oslo, Oslo/
2. Ventham NT, et al. Comprehensive Epigenome-Wide DNA Methylation
Norway
3 Profiling in Inflammatory Bowel Disease. Gastroenterology 2016; 150(4):
Dept. Of Gastroenterology, Akershus University Hospital, Lørenskog/Norway
4 S156–7.
Department Of Gastroenterology, Akershus University Hospital, Lørenskog/
Norway
5
Dep. Of Internal Medicine, Örebro University Hospital, Örebro/Sweden
6
University Hospital, Linköping University, Linköping/Sweden
7
Dept Of Gastroenterology And Hepatology, Maastrich University Medical Center OP297 AN AUTOPHAGY-RELATED PERIPHERAL BLOOD MICRORNA
Dept. of Gastroenterology, Maastricht/Netherlands SIGNATURE DIFFERENTIATES COLONIC CROHN’S DISEASE
8
Servicio De Aparato Digestivo, Hospital Clı´nico Universitario Lozano Blesa, FROM ULCERATIVE COLITIS
Zaragoza/Spain A. Mohammadi, O. Kelly, B. Kabakchiev, K. Borowski, M. I. Smith, D. Kevans,
9
Cnag Centre For Genomic Regulation, Barcelona Institute of Science and M.S. Silverberg
Technology, Barcelona/Spain Mount Sinai Hospital, Toronto/Canada
10
Unit Of Molecular Genetics Of Digestive Diseases, BioCruces Health Research
Institute, Bilbao/Spain Contact E-mail Address: [email protected]
Introduction: Phenotypic expression of colonic inflammation in inflammatory
Contact E-mail Address: [email protected] bowel disease (IBD) in patients with colonic Crohn’s disease (CCD) and ulcera-
Introduction: Exploring DNA methylation in Inflammatory Bowel Disease (IBD) tive colitis (UC) can sometimes have a similar appearance and be difficult to
may provide an insight into complex gene-environment interactions, identify differentiate. MicroRNAs (miRNAs) may offer a method of distinction as dif-
novel targets involved in pathogenesis, and allow development of powerful ferential expression of peripheral blood miRNAs has been shown in small studies
new biomarkers. Our study aims to characterize disease-associated methylation of IBD patients and healthy controls.
changes in newly diagnosed IBD and to define the contribution of genetic varia- Aims & Methods: This study aimed to assess peripheral blood mononuclear cell
tion, by discovery of associated quantitative trait loci (meQTL). (PBMC)-derived miRNA signatures in a well-phenotyped cohort of colonic IBD
Aims & Methods: Genome-wide methylation was measured in 641 DNA samples and to identify differentially expressed miRNAs in patients with CCD and UC.
from peripheral blood (298 controls, 150 Crohn’s disease (CD), 167 ulcerative An IBD cohort with UC and CCD was prospectively accrued. Ileocolonoscopy
colitis (UC), 26 IBD unclassified (IBDU)) using the Illumina 450k platform with was performed and patients with CCD (Montreal Classification L2/L3) or left-
covariates of age, sex, and differential cell counts, deconvoluted by the sided UC (Montreal Classification E2/E3) were enrolled. Colonoscopies were
Houseman method; genotyping was performed using Illumina reviewed by IBD endoscopists and scored for presence/absence, severity and
HumanOmniExpressExome-8 BeadChips. Samples were obtained from new site of inflammation. Pathology reports were reviewed for presence/absence
onset IBD cases in six European centres as part of the European Comission and severity of inflammation. On the day of endoscopy, C-reactive protein
funded IBD-Character project. (CRP) was measured and blood was collected in PAXgene tubes (Qiagen).
Result: 195 probes exhibited Bonferroni significant IBD-associated methylation Total RNA was extracted from blood using the PAXgene Blood miRNA kit
differences, including VMP1/MIR21 (p ¼ 3.7  10-20), RPS6KA2 (1.1  1019), (Qiagen) and miRNA counts from 798 probes were measured using the
SBNO2 (2.7  1019), and TNFSF10 (1.1  1015); data which provide important Human v3 miRNA nCounter Platform (NanoString Technologies). Raw
replication and confirmation of methylation differences previously reported in counts were normalized, log2 transformed and batch corrected. Non-parametric
paediatric CD and adult IBD. Novel findings include PHOSPHO1 (1.3  1015), Kruskal-Wallis tests assessed differential miRNA expression across phenotypes.
MUC4 (5.5  1015), and CDH24 (1.7  1014). 1709 differentially methylated Raw p-values were corrected for multiple testing by the Benjamini-Hochberg
regions of consecutive FDR significant probes were defined in genes including false discovery rate method. Target prediction and gene ontology biological
VMP1/MIR21, ITGB2, TNF, and at multiple sites throughout the HLA region. process (GO BP) enrichment analyses were performed with miRWalk 2.0.
Results were highly similar in CD and UC, with only one probe showing a Receiver operating characteristic (ROC) curves were generated following logistic
significant methylation difference between diagnoses (NAV2, 6.82  108). regression through 5-fold cross validation repeated 10 times. Area under the
Paired genetic and methylation data showed 2327 FDR significant MeQTLs curve (AUC) values for the ROCs were derived in order to evaluate the discri-
indicating a genetic influence on key methylation loci such as RPS6KA2 minating capacity of the differentially expressed miRNAs in CCD versus UC.
(8.6  1034), and ITGB2 (3.3  1038), and a replication of two SNPs previously Result: 51 subjects, 32 UC (50% male, 36 yrs mean age), 19 CCD (42% male, 32
described as correlated to VMP1/MIR21 methylation (rs8078424, yrs mean age) were included in the analysis (see Table 1). There were no signifi-
p ¼ 4.4  1025, rs10853015, p ¼ 7.4  1021). There was an enrichment of cant differences in mean CRP or among clinical, endoscopic or histologic disease
highly significant IBD-associated methylation changes in proximity to IBD activity between the CCD and UC groups suggesting that the degree of inflam-
GWAS loci. Previously published two-probe methylation biomarkers derived mation was similar in both groups. Comparing CCD and UC, 5 miRNAs were
from a new onset paediatric CD cohort accurately distinguished IBD from con- differentially expressed: miR-129-5p, miR-603, miR-619-3p, miR-874-3p, miR-
trols in this new onset adult cohort (AUC  0.82). 933 (FDRp ¼ 0.0214 all probes), all of which were upregulated in CCD vs UC. In
Conclusion: These data allow methylome profiling in a large multinational cohort the ROC analysis, the AUC for CCD vs UC for the combined expression of the 5
of new onset IBD, identifying novel disease-associated methylation changes and miRNAs was 0.89 (95% CI: 0.88–0.90). 2 out of 5 miRNAs putatively target the
important unequivocal replication of recent discoveries, together with insight Autophagy Related 16-Like 1 (ATG16L1) gene, and 4 out of 5 miRNAs had
into the genetic contribution to epigenetic alterations in complex disease, and significant GO BPs on putative target genes in the regulation of autophagy path-
the utility of peripheral blood DNA metylation as a biomarker. way (FDRp 5 0.05).
Disclosure of Interest: R. Kalla: Received research funding from the EU FP7 Conclusion: A PBMC-derived miRNA panel of markers identified here differ-
(2858546) and served as a speaker for Ferring entiates CCD from UC with similar degrees of inflammation. All of these differ-
J. Jahnsen: Served as a speaker, a consultant and a advisory board member for entially expressed miRNAs are upregulated in CCD compared to UC, and
MSD, Tillot, Ferring, AbbVie, Celltrion, Orion Pharma, Takeda, Napp Pharm,
Meda, AstroPharma, Hikma and Pfizer.
F. Gomollon: Advisor: Grifols, Abbvie, MSD. Travel Grants: Abbvie,MSD.
Research funding (Department) MSD
A118 United European Gastroenterology Journal 4(5S)
several appear to be associated with the autophagy pathway. These findings may We recently showed that AIEC-infected human macrophages released exosomes
aid individualization of patient care through identification of novel diagnostic that trigger a pro-inflammatory response and an increased bacterial intracellular
and therapeutic targets. replication in recipient cells.
Disclosure of Interest: All authors have declared no conflicts of interest. Aims & Methods: Here, we investigated whether exosomal miRNAs are involved
in such processes. Exosomes were purified using ExoQuick Exosome
Precipitation kit. miRNA expression levels were analyzed by qRT-PCR.
In vivo infection with AIEC bacteria was performed using ileal loop assays
OP298 ASSESSMENT OF INFLAMMATORY BURDEN IDENTIFIES and exosomes were purified. Purified exosomes were then intravenously injected
CROHN’S DISEASE AND ULCERATIVE COLITIS PATIENT in naı̈ve mice (10 mg/mouse).
GROUPS WITH DIFFERENT DISEASE-DRIVING PATHWAYS AND Result: We analyzed the levels of the CD-associated circulating miRNAs
THERAPEUTIC RESPONSE TO ANTI-TNF TREATMENT reported in literature in exosomes released from AIEC LF82-infected (Exo-
S. Pavlidis1, M. J. Loza2, P. Branigan2, C. Monast2, A. Rowe3, F. Baribaud2 AIEC) THP-1 macrophages. A significant upregulation of several miRNAs in
1
Immunology, Janssen Research & Development Ltd, High Wycombe/United Exo-AIEC compared with exosomes released from uninfected (Exo-UI) cells or
Kingdom cells infected with a non-pathogenic commensal E. coli HS strain was observed
2
Immunology, Janssen Research and Development, LLC, Spring House/United (Exo-HS). To analyze their transfer to recipient cells, naı̈ve THP-1 macrophages
States of America/PA were stimulated with the exosomes, and the levels of miRNAs in recipient cells
3
Immunology, Janssen Research and Development, Ltd., High Wycombe/United were analyzed. The levels of several exosomal miRNAs were increased in THP-1
Kingdom cells stimulated with Exo-AIEC compared with cells stimulated by Exo-UI or
Exo-HS, suggesting an efficient transfer. In silico analysis showed that the upre-
Contact E-mail Address: [email protected] gulated and transferred miRNAs are involved in inflammatory responses and
Introduction: Crohn’s disease (CD) and ulcerative colitis (UC) are considered to autophagy, which is necessary to control AIEC intracellular replication, among
be driven by both common and distinct underlying mechanisms of pathobiology. other biological processes. Transfection of antisenses of these miRNAs in THP-1
In both diseases there is heterogeneity underscored by the variable clinical cells inhibited the Exo-AIEC-triggered increases in pro-inflammatory response
responses obtained to therapeutic interventions. We aimed to identify disease- and AIEC intracellular replication in recipient cells, suggesting that these exoso-
driving pathways as well as classify individuals into subpopulations that differ in mal miRNAs are functional and are involved in the effects of Exo-AIEC in
their disease pathobiology and response to a specific treatment. recipient cells. To confirm the in vitro data, we developed an in vivo model to
Aims & Methods: Hierarchical clustering on enrichment scores (ES) from gene set analyze the impact of Exo-AIEC on gut colonization by AIEC and AIEC-
variation analysis (GSVA) was used probing a normal healthy volunteer (NHV), induced inflammation. In this model, exosomes were isolated from ileal loops
CD and UC data set of colonic biopsies (GSE16879) with a library of gene set of genetically susceptible mice infected with AIEC. Purified exosomes were then
signatures representative of various immunological and inflammatory processes intravenously injected in naı̈ve genetically susceptible mice (10 mg/mouse), and
as well as specific activated cell types. Patient stratification at baseline (BL) or AIEC colonization in the gut and AIEC-induced intestinal inflammation were
after anti-TNF treatment (PT) in either clinical responders (R) or non-responders analyzed.
(NR) was queried. Conclusion: Our study shows that infection with CD-associated AIEC induces
Result: Gene set signatures whose ES differed significantly (ES change  0.2, secretion of exosomes carrying several CD-associated circulating miRNAs by
p  0.05) between comparisons were identified from general linear model ana- human THP-1 macrophages. These exosomal miRNAs, when being transferred
lyses. Comparisons were made at BL in all participants irrespective of clinical into recipient naı̈ve THP-1 macrophages, may be involved in the regulation of
response, in clinical R and in clinical NR respectively compared to NHV. 59% of inflammatory and autophagic responses, contributing to host innate defense to
the tested signatures were commonly enriched in both CD and UC at BL under- AIEC infection.
lining the commonality of both diseases. These signatures included e.g. activated Disclosure of Interest: All authors have declared no conflicts of interest.
T cells, monocytes, macrophages or neutrophil signatures as well as poly:IC and
bleomycin signatures, representing acute inflammation and a complex mix of
potential disease-driving biology. Comparing R and NR separately at BL to TUESDAY, OCTOBER 18, 2016 15:45–17:15
NHV, 43% and 70% of signatures were enriched, respectively, indicative of a NOVEL TECHNIQUES IN LOWER GI MALIGNANCIES – ROOM L8_____________________
higher inflammatory burden in NR. Indeed, specific macrophage, innate lym-
phoid and dexamethasone signatures were uniquely enriched in NR. Hierarchical OP300 THE IMPLANTABLE MEDICATED MICRORESERVOIRS IN
clustering of the ES that significantly differed in the comparisons clearly sepa- THE TREATMENT OF COLORECTAL CANCER. THE GOOD
rated diseased BL from NHV samples. It also clustered R PT samples with the EFFECTS OF A SIMPLE PROCEDURE. EARLY RESULTS
NHV while the NR PT samples clustered with the BL diseased samples, with a Y. S. Bereznitsky, V. P. Sulyma, O. N. Popova
better separation observed in CD when compared to UC. Also, clear UC and CD Surgery N 1State Establishment "Dnipropetrovsk Medical Academy",
patient clusters could be observed with increasing ES at BL correlated with NR Dnipropetrovsk/Ukraine
to anti-TNF treatment recapitulating the observation of a higher inflammatory
burden in NR. Contact E-mail Address: [email protected]
Conclusion: Our analysis has identified common disease-driving pathways for CD Introduction: Colorectal cancer (CRC) is the third most common in the world of
and UC supporting the notion of a disease continuum rather than two distinct men, and the second - in women. In Europe remains steady increase in incidence
diseases. However, within that disease continuum, distinct patient groups could and mortality according to Globocan 2012 and source EuropaColon. The main
be defined by their overall inflammatory burden correlating with their response problem after surgery is local recurrences that often develop even after resection
to an anti-TNF therapy. This methodological approach could facilitate better R0. Five-year survival is less than 60% in developed countries [2,3]. Due to this
targeted design of clinical studies to test therapeutics under development, con- more and more often there are ideas about intraoperative prevention of local
centrating on subsets of patients sharing similar underlying molecular pathology recurrence. There are a number of studies on intraoperative radiation therapy,
and therefore increasing the likelihood of clinical response. which gives good results for the prevention of CRC recurrence and increase the
Disclosure of Interest: S. Pavlidis: Employee of Janssen Research & Development five-year survival [4,5]. In fact, we have proposed a method of supporting intrao-
Ltd, High Wycombe, UK perative chemotherapy with prolonged effect, because most of the local recur-
M.J. Loza: Employee of Janssen Research & Development LLC, Spring House, rence accounts for the second half of the first year after surgery. [2]
United States Aims & Methods: We aimed to investigate the possibility of using implanting
P. Branigan: Employee of Janssen Research & Development LLC, Spring House, microreservoirs to improve the results of surgical treatment CRC. To study the
United States safety and efficacy of this modification surgery. Materials and methods: We have
C. Monast: Employee of Janssen Research & Development LLC, Spring House, investigated the number of CRC recurrence for patients without distant metas-
United States tases, lymph node involvement and no germination of the tumor to other organs
A. Rowe: Employee of Janssen Research & Development Ltd, High Wycombe, after surgery in a volume R0 for a year after surgery. The study involved 87
UK. patients (54 women and 33 men, mean age 62.4 years þ/ 8.4 years) who were
F. Baribaud: Employee of Janssen Research & Development LLC, Spring House, operated in the Dnipropetrovsk regional proctology centre from February 2014
United States. to February 2015. The control group (42 patients, 17 men and 25 women) per-
formed surgery in standart volume according to giudeline. In the test group (45
patients, 16 males and 29 females) before the anastomosis were formed medicated
microreservoirs with 5-fluorouracil (5FU) supported on polyvinylpyrrolidone
OP299 CROHN’S DISEASE-ASSOCIATED CIRCULATING MICRORNAS (PVP). In fact, it was a mixture of 30% PVP solution 5 ml and 5 ml 5FU
ARE SECRETED IN EXOSOMES FROM AIEC-INFECTED HUMAN (250 mg). This mixture was introduced into the muscle layer from the side of
MACROPHAGES AND INVOLVED IN REGULATION OF HOST mucosa the 1 ml syringe with needle 0,40  10 mm 27G  1/2 at a distance of 1–
INNATE IMMUNE RESPONSES IN RECIPIENT CELLS 1.5 cm from the edge of the intestine. In one procedure was introduced approxi-
J. Carrière1, A. Larabi1, C. Lucas1, N. Barnich1, H.T.T. Nguyen2 mately 10 ml of the drug. The volume of the reservoir was 0.5 ml. Next, the
1
UMR 1071 Inserm/University of Auvergne, Clermont-Ferrand/France operation was completed in a standard way. As the drug delivery system has
2
M2ish, Umr 1071 Inserm/university Of Auvergne Inra Usc 2018University of been selected PVP in the concentration of 30% as its safety is confirmed by the
Clermont Auvergne, Clermont-Ferrand/France FDA. [8] PVP as a delivery system allows for the gradual release of the drug, due
to 5FU linked ionic bonds with PVP [9], and drug release depends on the rate of
Contact E-mail Address: [email protected] destruction of the carrier polymer. An important advantage is the fact that the
Introduction: A high prevalence of invasive Escherichia coli strains, named AIEC PVP is practically not destroyed at a pH of less than 7 [7], which allows to delay
(adherent-invasive E. coli), has been reported in the intestinal mucosa of Crohn’s the release of 5FU, since pH in the stage of inflammation in the tissues is reduced
disease (CD) patients. A deregulated microRNA (miRNA) expression profile has and consequently the release of the bulk of 5FU will begin after completion of the
been reported in CD patients’ peripheral blood. Exosomes are small endosomal- inflammation. The 5FU was selected as a drug for the treatment because it does
derived vesicles involved in cell-to-cell communication. Exosomes have been not require pre-transformation to acting form and is quite effective on condition
shown to carry miRNAs that can be efficiently transferred to recipient cells. achieving sufficient concentration in the tissues.
United European Gastroenterology Journal 4(5S) A119
Result: In the control group, local recurrence was detected in 12 cases (28.6%). LST-G type in 236 and LST-NG in 46 patients. Histopathology revealed carci-
The following postoperative complications were found: early adhesive intestinal noma in 124, tubulovillous adenoma in 102, tubular adenoma in 28, villous
obstruction in 2 (4.8%) cases of postoperative pneumonia in 1 (2.4%) case. adenoma in 17, serrated adenoma in 11 lesions. The rate of carcinoma was
Within 8 months after surgery 1 patient died of acute coronary syndrome. In more frequent in LST-NG types than in LST-G type (55,5% vs 37.7%).
the studied group of local recurrence was detected in 8 cases (17.8%). The fol- Complete resection was not achieved in 9.6% of the patients with positive vertical
lowing postoperative complications were found: early adhesive intestinal obstruc- border. Perforation occurred in 9 patients which were treated successfully with
tion in 1 (2.2%) case, even one patient has been adhesive intestinal obstruction in endoscopic clip without the need for surgery except for one patient with delayed
3 months after the operation, which resulted in the death of the patient on 2 day perforation. Surgical treatment was performed in all patients with deep submu-
after the re-operation due to acute of cardiovascular failure. cosal (sm2) invasion, however neoplasia was observed in none of these patients.
Conclusion: 1. Intraoperative implantation of medicated microreservoirs is a safe Conclusion: Colorectal ESD is a safe and effective method to provide en-bloc and
and effective procedure for the prevention of early recurrent CRC. 2. curative resection of LSTs.
Notwithstanding the low total dose, good effect can be achieved due to the Disclosure of Interest: All authors have declared no conflicts of interest.
high concentration of the drug in the tissues. 3. This procedure avoids many
resorptive effects of the chemotherapeutic drug, associated with systemic admin-
istration and high doses required to achieve therapeutic concentrations in tissues.
4. Obviously, it is necessary to continue the monitoring of these patients. 5. It is OP302 EVALUATION OF RECTAL CANCER ANGIOGENESIS USING
possible to consider a combination of other drugs and carrier polymers. IMMUNOHISTOCHEMICAL AND COMPUTER-ASSISTED
Disclosure of Interest: All authors have declared no conflicts of interest. ENDOSONOGRAPHIC METHODS
L. Tankova1, R. Nakov1, G. Stoilov2, A. Gegova3, V. Nakov1, V. Gerova1,
D. Kovatchki4
1
Gastroenterology, Clinic of Gastroenterology, ‘‘Tsaritsa Ioanna – ISUL’’
OP301 ENDOSCOPIC SUBMUCOSAL DISSECTION IN LATERALLY University hospital, Medical University – Sofia, Sofia/Bulgaria
SPREADING TUMORS: EXPERIENCE OF 282 CASES FROM A 2
Institute Of Mechanics, Bulgarian Academy of Sciences, Sofia/Bulgaria
TERTIARY REFERENCE CENTER IN TURKEY 3
Pathology, Faculty of Medicine, University of Sofia ‘‘St. Kliment Ohridski’’,
F. Aslan1, M. Kucuk1, Z. Akpinar1, N. Ekinci2, D. A. Yurtlu3, E. Alper1, Sofia/Bulgaria
B. Unsal1 4
Golden Cross Private Clinic, Vienna/Austria
1
Gastroenterology, Izmir Ataturk Training And Research Hospital, Izmir/Turkey
2
Pathology, Izmir Ataturk Training and Research Hospital, Izmir/Turkey Contact E-mail Address: [email protected]
3
Anestesiology And Reanimation, Izmir Ataturk Training and Research Hospital, Introduction: The conventional way for evaluation of rectal cancer angiogenesis
Izmir/Turkey requires a biopsy or a tissue specimen applying specific immunohistochemical or
molecular biological tests. The evaluation of microvessel density is a gold stan-
Contact E-mail Address: [email protected] dard in the assessment of tumour angiogenesis. Doppler ultrasound is an attrac-
Introduction: Endoscopic submucosal dissection (ESD) is a minimally invasive tive modality for imaging angiogenesis in vivo which can be repeated without
technique, providing en-bloc resection of premalignant and malignant lesions in exposing the patient to any risk.
early stage gastrointestinal (GI) cancers. Lateral Spreading Tumors (LSTs), Aims & Methods: The aim of the current study is to evaluate the preoperative
which are endoscopically seen as granular (LST-G) or non granular (LST-NG) rectal cancer angiogenic status with Endorectal Power Doppler Ultrasound by
types, are technically difficult to remove as en-bloc with ESD method because of using Doppler Vascularity Index calculated by imaging analysis software and to
anatomical features of the colon. In the present study, we present our results of compare results with microvessel density in surgical specimens A total of 110
colorectal ESD procedures in LSTs. patients (59 males; 51 females, mean age 61.5 years) with rectal cancer were
Aims & Methods: Between April 2012- April 2016, a total of 655 colorectal enrolled in this study. The patients were operated and staged as follows: in
lesions were referred to our unite for the purpose of removal with advanced stage I – 20pts (18%), stage II – 29 (26%); stage III – 47 pts (43%); stage IV –
endoscopic techniques (EMR or ESD). Colorectal ESD was performed to 290 14 pts (13%). Microvessel density was evaluated by using immunohistochemical
lesions. Data was recorded prospectively before and after the procedure. 8 ESD staining of surgical specimens with anti-CD-31 antibody. The PDVI of each
cases were excluded because the lack of control endoscopy. The results of 282 tumor was determined using endorectal power Doppler ultrasound with compu-
ESD procedures performed in colon and rectum with diagnosed LST were ana- ter-assisted quantification of colour pixels. The PDVI was defined as the ratio of
lyzed retrospectively. the number of the colored pixels within a tumor section to the number of total
Result: pixels in that specific tumor section, and was calculated by using a software.
Result: The mean microvessel density (MVD) was 163  69 microvessels/
Table: Demographic data and colorectal endoscopic submucosal dissection mm2(50–328). Median MVD used as the cutoff point divided two groups of
results [Case (n) ¼ 273 Lesion (N) ¼ 282] tumours with high (160 vessels/mm2) and low angiogenic activity (4160 ves-
sels/mm2). Mean PDVI was 8.9  6.0% (range: from 0 to 27,3). Median PDVI
N ¼ 282 (8%) was used as the cutoff divided two groups of tumours with high (8%) and
low PDVI (48%). The MVD and PDVI showed a good positive linear correla-
Lesion size, mm, mean (SD) (median; 40.44 (26.2) tion (r ¼ 0.438, p ¼ 0.002).
range) Conclusion: Endorectal Power Doppler ultrasonography is a useful noninvasive
(33; 14–176) method of evaluating the extent of angiogenesis. Tumor angiogenesis assessed by
Tissue size, mm, mean (SD) (median; 49.81 (28.9) power Doppler vascular index correlated with histological microvessel density
range) determination The presented endoultrasound Power Doppler examination is a
reliable and reproducible mean for in vivo preoperative quantitative assessment
(42; 20–198) of the tumour vascularisation.
Duration of procedure, min, mean (SD) 79.5 (71.1) Disclosure of Interest: All authors have declared no conflicts of interest.
(median; range)
(61.5; 6–540)
Dissection speed, mm2/min, mean (SD) 24.46 (15.41)
(median; range) OP303 COMPARISON OF CLINICAL OUTCOMES AMONG
DIFFERENT ENDOSCOPIC MODALITIES FOR RECTAL
(21; 1.74–79.55) NEUROENDOCRINE TUMOR
En-Bloc resection rate, N (%) 257 (91.1)
S.H. Park1, Y. Cho2, H.H. Choi1, D.Y. Cheung1, J.S. Kim1, B. Lee1, M. Choi1
Complete Resection, N (%) 255 (90.4) 1
Internal Medicine, cathoilic university of medicine, seoul/Korea, Republic of
2
Paris Classification, N (%) 1s 1s þ 2a 2a 4 (1.4) 142 (50.4) 101 (35.8) 35 Internal Medicine, catholic university of medicine, seoul/Korea, Republic of
2a þ 2c (12.4)
Contact E-mail Address: [email protected]
Adverse Events, N Delayed bleeding 29 Introduction: Rectal neuroendocrine tumor (NET) less than 10 mm in diameter
Perforation can be removed by various endoscopic techniques, such as endoscopic mucosal
Localization, N Rectum Sigmoid colon 133 42 16 6 15 25 25 14 6 resection (EMR), modified EMR, and endoscopic submucosal dissection (ESD).
Descending colon Splenic flexura This study aimed to compare efficacy and safety of endocrine submucosal resec-
Transverse colon Hepatic flexura tion with a ligation device (ESMR-L) or circumferential submucosal incision
Ascending colon Cecum Ileocecal prior to EMR (CSI-EMR) versus ESD
valve Aims & Methods: Fitty-six patients, who underwent endoscopic resection of a
Pathology, N (%) Carcinoma 124 (44) 99 (35.2) 4 (1.4) 21 (7.4) rectal NET less than 10 mm in diameter, were enrolled consecutively from March
Intramucosal Sm1 invasion Sm2 28 (9.9) 102 (36.2) 17 (6.0) 2013 to June 2015. The patients were classified into three groups according to the
invasion Tubular Adenoma 11(3.9) type of endoscopic procedure: ESMR-L group (n ¼ 17), CSI-ESD group (n ¼ 18),
Tubulovillous Adenoma Villous and ESD group (n ¼ 21). We compared treatment outcomes and complications
Adenoma Serrated Adenoma associated with these methods.
LST LST-G LST-NG 236 46 Result: There was no different in tumor diameter between different endoscopic
procedures (ESMR-L, 4.5  1.6 mm; CSI-EMR, 5.6  2.0 mm; ESD,
5.0  2.2 mm, p ¼ 0.236). En bloc rsection was achieved in all patients. There
was no lateral margin involvement in all patients. Basal margin involvement
The 282 colorectal ESD procedures were performed in 273 patients, the demo- occurred in one patients in the ESD group and two in the CSI-EMR group.
graphic data and results of which are shown in the table. The overall en-bloc and The rates of pathological complete resection were 100% (17 of 17) in the
complete resection rates were 91.1% and 90.4%, respectively. The lesions were ESMR-L group, 88.9% (16 of 18) in the CSI-EMR group, and 95.2% (20 of
A120 United European Gastroenterology Journal 4(5S)
21) in the ESD group, respectively (p ¼ 0.354). Perforation or delayed bleeding endoscopic or trans-anal therapy. The GelPoint Path trans-anal access port
did not occur. Procedure time of ESMR-L was significantly shorter than those of comprises a soft plastic extension, (with a diameter of 3.6 cm) allowing simulta-
the other groups and procedure time increased in order of ESMR-L, CSI-EMR, neous passage/triangulation of an endoscope and two laparoscopic retractors
and ESD group (4.3  2.0 min, 11.2  12.5 min, 18.6  3.9 min, respectively, and permitting dynamic tissue manipulation to facilitate endoscopic submucosal
p ¼ 0.000) dissection/ESD. Supplementary techniques were also used to complete the resec-
Conclusion: All endoscopic resection method, including ESMR-L, CSI-EMR, tion such as piecemeal endoscopic mucosal resection or ablation/P-EMR or
and ESD were effective and safe for the treatment of rectal NET. compared EMA and trans-anal excision/TAE. The aim of this study was to evaluate the
with CSI-EMR or ESD, ESMR-L procedure has the advantages of easier and feasibility, technical success and safety profile of this new hybrid, endo-surgical
shorter procedure time. ESMR-L may be considered the treatment of choice for Trans-Anal Submucosal Endoscopic Resection- (TASER) approach for CRPs.
rectal NET less than 10 mm in diameter Result: Thirty-two TASER procedures were employed in 31 patients (mean age
Disclosure of Interest: All authors have declared no conflicts of interest. 65years/17 males–14 females) with 31 CRPs (mean size 8 cm/range 5 cm–18 cm).
Complete endoscopic excision in a single session was achieved in 28/31 patients
(93%); in one patient a second TASER session was required for completion
polypectomy, in another deep submucosal invasion was suspected during
OP304 ANAL CYTOLOGY, HISTOPATHOLOGY, AND ANOSCOPIC TASER-ESD/P-EMR/EMA – patient had an elective laparoscopic anterior
VISUAL IMPRESSION IN AN ANAL DYSPLASIA SCREENING resection (T1,sm3,N0,M0 confirmed) and in a third patient intraperitoneal per-
PROGRAM: IS ANAL CYTOLOGY ENOUGH? foration necessitated a de-functioning ileostomy before complete polypectomy
M. Silva1, A. Peixoto1, J.A. Sarmento1, A. Albuquerque1, R. Coelho1, could be undertaken. Mean procedure time was 185 min, range 65–480 min.
R. Serrão2, C. Pinero3, H. Barroca4, G. Macedo1 Thirty two TASER sessions were employed using ESD in 12/32, ESD þ P-
1
Departments Of Gastroenterology, Centro Hospitalar São João, Faculty of EMR in 6/32, ESD þ P-EMR þ EMA in 4/32, ESD þ TAE in 3/32, ESD/P-
Medicine of the University of Porto. Porto, Portugal, Oporto/Portugal EMR/TAE in 3/32 and ESD þ P-EMR þ EMA þ TAE in 4/32. Intra-procedural
2
Departments Of Infeciology, Centro Hospitalar São João, Faculty of Medicine of bleeding was controlled with haemostatic endoscopic devices (coagrasper/clips);
the University of Porto. Porto, Portugal, Oporto/Portugal surgical clipping and suturing on 2 occasions. Prophylactic endoscopic clipping
3
Department Of Infeciology, Centro Hospitalar São João, Faculty of Medicine of was also applied in 8 cases and suturing on 4 occasions. In 6/10 TASER -TAE
the University of Porto. Porto, Portugal, Oporto/Portugal cases there was a need for a full-thickness rectal dissection due to severe sub-
4
Departments Of Pathology, Centro Hospitalar São João, Faculty of Medicine of mucosal fibrosis: 4/6 cases were closed with surgical sutures plus endoscopic clips
the University of Porto. Porto, Portugal, Oporto/Portugal and in the remaining 2/6 cases only endoscopic clips were deployed. Two epi-
sodes of delayed bleeding were reported among the TASER-ESD/P-EMR and
Contact E-mail Address: [email protected] TASER-ESD sub-cohorts with no transfusion or re-intervention requirement.
Introduction: The human papilloma virus (HPV) is the leading cause of anal All patients were discharged the day after the TASER PROCEDURE apart
squamous cell carcinoma. The cytological screening can reduce morbidity and from one patient who developed bacteremia post TASER-ESD requiring intra-
mortality associated with this cancer, although current recommendations are venous antibiotics and a 4-night hospital stay and the patient who required a
based on expert opinion. defunctioning ileostomy, discharged on day 4 post operation. First follow-up
Aims & Methods: The authors intend to estimate agreement between anal cyto- performed at 4–6 months interval in 25/31 patients showed: 21/25 with no recur-
logic examination, histopathology, and anoscopic visual impression. This is a rence (84%) and 4/25 (16%) with a minimal (515 mm) polyp recurrence, amen-
prospective study of patients receiving anal dysplasia screening between 2010 able to endoscopic therapy. No rectal stricturing was identified and only one
and 2015, in a proctology consultation of a tertiary referral center. Descriptive episode of transient faecal incontinence were reported.
statistics was performed using IBM SPSS Statistics 22 with p 5 0.05 deemed to Conclusion: TASER appears to be a safe and efficient endo-surgical approach
be statistically significant. Agreement between measures was estimated by providing an optimal platform for the minimally-invasive management of high-
weighted kappa-statistics. risk, complex rectal polyps.
Result: During the period of the study, 141 patients (91% men, mean age 37  14 Disclosure of Interest: Z.P. Tsiamoulos: Consultancy Agreement Creo Medical
years, 87% with HIV infection) underwent 175 anal cytology tests: 33% negative Ltd Paid Lectures Norgine Pharmaceutical Ltd
for intraepithelial lesion or malignancy (NILM), 22% atypical squamous cells of B.P. Saunders: Consultancy Agreement Creo Medical Ltd Paid Lecturers
uncertain significance (ASCUS), 33% low-grade squamous intraepithelial lesion Olympus Keymed
(LSIL), 10% high-grade squamous intraepithelial lesion (HSIL) and 1% carci- All other authors have declared no conflicts of interest.
noma in situ (CIS). Concerning anoscopic visual impression, 40% patients had Reference
no lesions (53% NILM, 22% ASCUS, 25% LSIL). In the remaining patients,
excision/biopsy of the identified lesions was performed detecting 40 (23%) high- 1. Tsiamoulos ZP. et al Gut doi:10.1136/gutjnl-2015-309643.
grade dysplasia (HGD), 33 (19%) low-grade dysplasia (LGD) and 4 (2%) CIS.
Weighted kappa-agreement between abnormal cytological results and anoscopic TUESDAY, OCTOBER 18, 2016 15:45–17:15
visual impression was moderate (k ¼ 0.48). Weighted kappa-agreement between
the presence and degree of dysplasia in anal cytologic tests and concurrent his-
THE INTESTINAL EPITHELIUM - STEM CELLS, INFLAMATION AND CANCER – ROOM
topathology was low (k ¼ 0.23 and k ¼ 0.20, respectively). Of the 57 NILM cyto- 1.86_____________________
logic tests, 26% had suspicious lesions in anoscopic visual impression and of
these, 9 (60%) had dysplasia on histopathological exam (4 HGD and 5 LGD). OP306 THE PROREGENERATIVE ROLE OF INTERLEUKIN-22
By other hand, concerning the patients with HGD/CIS on histologic exam, 28 SIGNALS IN THE INTESTINAL EPITHELIUM DEPENDS ON
(64%) patients had lower dysplasia grade on cytological exam (6 ASCUS, 18 AUTOPHAGY AND ER STRESS
LSIL and 4 NILM). F. Tran1, K. Aden1, M. Tschurtschenthaler2, R. Sheibani-Tezerji1, J. Kuiper1,
Conclusion: The low correlation between anal cytology, histopathology and ano- A. Luzius1, M. Jentzsch1, S. Schreiber3, R.S. Blumberg4, A. Kaser5,
scopic visual impression associated with the high number of histological exams P. Rosenstiel1
with HGD/CIS with lower dysplastic degree on cytological exam (including 1
Institute of Clinical Molecular Biology, University Hospital Schleswig-Holstein,
NILM anal cytologies) suggest that anal cytology screening should not be used Kiel/Germany
as the unique method of anal dysplasia screening. The authors suggest that 2
Division of Gastroenterology and Hepatology, Department of Medicine,
anoscopic screening should be offered to all patients. Addenbrooke’s Hospital, University of Cambridge, Cambridge/United Kingdom
Disclosure of Interest: All authors have declared no conflicts of interest. 3
Uksh, Universität Kiel UKSH Medizinische Abt. I, Kiel/Germany
4
Reference Brigham and Womens Hospital, Boston/United States of America
5
Dept. Of Medicine, University of Cambridge Gastroenterology and Hepatology,
1. Mathews WC, Sitapati A, Caperna JC, Barber RE, Tugend A and Go U.
Cambridge/United Kingdom
Measurement characteristics of anal cytology, histopathology, and high-
resolution anoscopic visual impression in an anal dysplasia screening pro- Contact E-mail Address: [email protected]
gram. Acquir Immune Defic Syndr 2004; 37: 1610–5. Introduction: Endoplasmic reticulum (ER) function and autophagy are necessary
to maintain cellular homeostasis. Genetic variants of inflammatory bowel disease
(IBD) risk genes ATG16L1 or XBP1 are associated with epithelial endoplasmic
reticulum (ER) stress which promotes cell death. While XBP1 plays a beneficial
OP305 NEW PLATFORM FOR TRANS-ANAL SUBMUCOSAL role in resolving ER stress, ATG16L1 represents an essential component of the
ENDOSCOPIC RESECTION- (TASER): UPDATED CLINICAL autophagic machinery, a conserved mechanism for protein degradation. Both
RESULTS FROM TERTIARY CENTRE processes are strongly connected since impaired autophagy subsequently results
Z.P. Tsiamoulos1, R. Rameshshanker2, J. Warusavitarne3, B.P. Saunders2 in deregulation of ER function. Interleukin-22 (IL-22) is known to be a protec-
1
St Mark’s Hospital And Academic Institute, St. Marks Hospital Wolfson Unit for tive cytokine in mucosal regeneration by promoting epithelial proliferation via
Endoscopy, London/United Kingdom STAT3 activation. Therefore, conjugates of IL-22 are in trials as potential drugs
2
Wolfson Unit For Endoscopy, St. Mark’s Hospital/Academic Institute, London/ in IBD treatment.
United Kingdom Aims & Methods: Here, we investigate the impact of the IBD risk genes ATG16L1
3
Department Of Colorectal Surgery, St. Marks Hospital, London/United Kingdom and XBP1 on regenerative function of IL-22 in intestinal epithelium in mice and
human. Human colon carcinoma HT-29 and Caco2 cells were treated with
Contact E-mail Address: [email protected] recombinant IL-22 and ER stress inductors like Tunicamycin or autophagy
Introduction: Current trans-anal surgical (TEMS/TEO) and advanced endoscopic inducers like Rapamycin before they were subjected to wound healing assays,
resection procedures (P-EMR/ESD) have the potential to resect complex rectal gene expression analysis and immunoblot analysis. Intestinal organoids derived
polyps (CRPs). However both approaches have limitations in terms of practi- from Xbp1
IEC (intestinal epithelial cell-specific deletion) and Atg16l1
IEC
cality and safety. mice were treated with recombinant IL-22 and gene expression analysis using
Aims & Methods: Consecutive patients (Jan13/Dec15), referred for the excision of qRT-PCR, RNA sequencing and transcriptome analysis were performed.
CRPs, were being considered for proctectomy and/or had failed conventional Secreted cytokines in supernatants from cells and organoids were detected with
United European Gastroenterology Journal 4(5S) A121
ELISA. Atg16l1
IEC and Atg16l1
IEC/Xbp1
IEC mice were treated with BMP4 mRNA level (p ¼ 0.02). HOXA9 overexpression led to increased cell
recombinant IL-22 for 6 or 12 days before sacrificing. numbers when assessed with an automatic cell counter (p ¼ 0.004).
Result: IL-22 induces transient self-limiting ER stress in the intestinal epithelium. Additionally, when assessed with a MTT assay (p 5 0.001), HOXA9 overexpres-
While IL-22 improves wound healing in the absence of ER stress, IL-22 leads to sion led to increased total cell pool. The growth factor IGF1 increased signifi-
impaired wound closure and increased cell death under ER stress conditions. cantly (p ¼ 0.02) as a result of HOXA9 overexpression. Genes important for
This effect is dependent on STAT3 and autophagy as pharmacological STAT3 epithelial to mesenchymal transition were not found to have significantly
inhibition or autophagy induction with Rapamycin completely restores IL-22 changed.
dependent ER stress induction. On the contrary, impairment of the autophagic Conclusion: HOXA9 expression is increased in colonic adenomas. Overexpression
flux by Bafilomycin A provokes inflammatory features as well, which are aggra- of HOXA9 leads to a decrease in FGF2 and an increase in BMP4, which empha-
vated by IL-22. Regulation of transient ER stress is dependent on Xbp1 and sizes that HOXA9 alters anterior to posterior specification. HOXA9 overexpres-
Atg16l1 as IL-22 treatment of intestinal organoids derived from Atg16l1
IEC sion leads to growth of the cell pool. A mechanism through which HOXA9 exerts
und Xbp1
IEC mice induces a dramatic increase of inducible ER stress and pro- this effect is the upregulation of IGF1. In conclusion, HOXA9 appears to have
inflammatory gene expression. In addition, mRNA transcriptome analysis pro-oncogenic activity in the premalignant stage of colorectal cancer.
reveals differential expression of several IBD related risk genes in Xbp1
IEC Disclosure of Interest: All authors have declared no conflicts of interest.
and Atg16l1
IEC organoids in response to IL-22 stimulation. Atg16l1
IEC
mice display defective autophagy in the intestinal epithelium and spontaneous
cell death in intestinal crypts which exacerbates after IL-22 treatment. Finally,
IL-22 aggravates preexisting spontaneous transmural intestinal inflammation in OP308 TOLL-INTERACTING PROTEIN DEFICIENCY PROTECTS MICE
Atg16l1
IEC/Xbp1
IEC mice. On the flipside, same treatment of wild type FROM COLITIS-ASSOCIATED CANCER BY MODULATING ANTI-
control mice does not affect cell death and inflammation, underlining a genotype TUMORAL IMMUNITY
dependency of beneficial and adverse effects of IL-22 application. C. Begka1, S. Ragusa2, T. Petrova2, D. Velin1, M. H. Maillard1
Conclusion: These data suggest an unexpected role of the IBD risk genes 1
Gastroenterology And Hepatology, CHUV, Lausanne/Switzerland
ATG16L1 and XBP1 in coordinating regenerative IL-22 function in intestinal 2
Department Of Fundamental Oncology, CHUV, Lausanne/Switzerland
epithelium and may contribute to the development of genotype-based persona-
lized medicine. However, further studies are necessary to decipher the molecular Contact E-mail Address: [email protected]
link between IL-22 signaling and the ER stress/autophagy axis. Introduction: Genetic deletion of the Toll-interacting protein (Tollip) -an IL-1R
Disclosure of Interest: All authors have declared no conflicts of interest. and TLR2/4 regulator- leads to increased acute and chronic colitis in mice (1).
References We sought to investigate whether increased susceptibility to inflammation had an
impact on inflammation-driven colorectal carcinogenesis.
1. Adolph TE et al. Paneth cells as a site of origin for intestinal inflammation. Aims & Methods: Colitis-associated cancer (CAC) was induced in 18–20-week old
Nature. 2013. littermates C57BL/6 mice by azoxymethane (AOM) i.p. injection and 3 cycles of
2. Niederreiter L et al. ER stress transcription factor Xbp1 suppresses intestinal 2.5% oral dextran sodium sulfate (DSS) treatment. Tumor development was
tumorigenesis and directs intestinal stem cells. The Journal of Experimental assessed endoscopically, microscopically and histologically. Apoptotic and pro-
Medicine. 2013. liferative index in the colon were determined by Tunel assay and Ki67 immuno-
3. Pickert G et al. STAT3 links IL-22 signaling in intestinal epithelial cells to histochemistry and quantified using the Image J software. Cytokine and gene
mucosal wound healing. The Journal of Experimental Medicine. 2009. expressions were measured by RT-qPCR. SMAD2 phosphorylation was assessed
4. Sato et al. Single Lgr5 stem cells build crypt-villus structures in vitro without by Western blot.
a mesenchymal niche. Nature. 2009. Result: Tollip KO mice had significantly lower endoscopic tumor scores than WT
littermates upon AOM-DSS exposure (8.4  7.8 vs 13.4  6.4, p 4 0.05).
Likewise, tumor numbers (4.9  3.5 vs 7.1  3.0, p 4 0.05) and size were reduced.
Immunohistological studies demonstrated reduced apoptotic index (79.3  75.0
OP307 HOXA9 IS OVEREXPRESSED IN COLONIC ADENOMAS AND vs 246.8  152.9, p 4 0.05) and lower proliferation (21.0  8.5 vs 27.9  7.3, ns) in
CAUSES AN INCREASE IN CELL GROWTH Tollip KO tumors when compared to wt controls. RNA analyses showed that
P. H.A. Wisse1, V. T. Janmaat2, A.P. Verhaar2, M.J. Bruno3, M.C. w. Spaander4, Tollip ablation favors an anti-tumorigenic environment with reduced Bcl-xl
M. Peppelenbosch5 (85.8  50.9 vs 36.2  39.5) and c-myc expression (6.2  4.9 vs 2.1  2.6).
1
Department Of Gastroenterology & Hepatology, Erasmus Medical Center, Importantly, Tollip deficiency led to reduced Foxp3 abudance (3.7  2.6 vs
Rotterdam/Netherlands 2.1  1.7) in unchallenged colonic as well as in tumoral tissues. In addition,
2
Gastroenterology & Hepatology, Erasmus Medisch Centrum, Rotterdam/ Tollip deficient tumors harbored reduced TGFbeta expression as well as reduced
Netherlands SMAD2 phosphorylation suggesting that TGFbeta signaling is dysfunctional in
3
Department Of Gastroenterology & Hepatology, University Medical Center the absence of Tollip.
Rotterdam, Rotterdam/Netherlands Conclusion: Our data show that Tollip partially favors colonic oncogenesis
4
Gastroenterology & Hepatology, Erasmus Medical Center Gastroenterology and despite being protective against colitis. Putative mechanisms include reduced
Hepatology, Rotterdam/Netherlands tumor-associated regulatory T cells and aberrant TGFb-induced signals in
5
Gastroenterology & Hepatology, Universitair Medisch Centrum, Rotterdam/ Tollip deficient mice.
Netherlands Disclosure of Interest: All authors have declared no conflicts of interest.
Reference
Contact E-mail Address: [email protected]
Introduction: Colonic adenomas are premalignant epithelial tumors with gland- 1. Maillard MH, et al. Toll-interacting protein modulates colitis susceptibility
ular origin. Identifying the molecular aberrations in this tissue may help to in mice. Inflamm Bowel Dis 2014; 20: 660–670.
understand its malignant potential and could lead to better understanding of
colorectal cancer development. The mammalian HOX clusters encode regulators
of embryonic anterior to posterior specification and are important for the for-
mation of tissues, structures, and organs. Besides having a function in embryol- OP309 CONSTRUCTION OF IN VITRO MODEL OF ULCERATIVE
ogy, HOX genes have pro-oncogenic activity in various malignant diseases. For COLITIS USING MOUSE PRIMARY COLONIC ORGANOID
example, HOXA13 overexpression predicts poor outcome for patients with S. Hibiya1, K. Tsuchiya1, S. Watanabe1, T. Shirasaki1, R. Nishimura1,
cancer of the esophagus, stomach, and liver. In a portion of acute myeloid S. Oshima1, R. Okamoto2, T. Nakamura3, M. Watanabe1
leukemias (AML), a translocation encoding the NUP98-HOXA9 oncogene 1
Gastroenterology And Hepatology, Tokyo Medical and Dental University, Tokyo/
gives overexpression of HOXA9. HOXA9 overexpression is the molecular Japan
factor most strongly correlated with poor prognosis in AML and is also corre- 2
Center For Stem Cell And Regenerative Medicine, Tokyo Medical and Dental
lated with poor prognosis in ovarian epithelial cancer. HOX gene aberrations are University, Tokyo/Japan
reported in colorectal cancer, however, it is unclear whether HOX gene aberra- 3
Advanced Therapeutics For Gastrointestinal Diseases, Tokyo Medical and Dental
tions are present at a premalignant stage and could, thus, contribute to cancer University, Tokyo/Japan
formation.
Aims & Methods: This study firstly aimed to assess the expression of HOXA9 in Contact E-mail Address: [email protected]
colonic adenoma tissue and location matched control tissue. Secondly, it aimed Introduction: The patients with ulcerative colitis (UC) are at increased risk of
to evaluate potential effects of increased HOXA9 expression, both in terms of its developing colitis-associated cancer, because long-term inflammation leads to the
influence in anterior to posterior specification and its oncogenic properties. We development of carcinogenesis. However, the transformation of colonic epithelial
collected biopsies from colonic polyps and location matched normal colonic cells during long-term inflammation has not been elucidated. Recently, 3-dimen-
tissue in patients undergoing colonoscopy. A pathologist classified the colonic tional (3D) primary organoid culture of colonic epithelial cells in mice has been
polyp after its resection and we only included tubular adenomas. We used RT- established in our group (TMDU method)1.
qPCR to quantify the expression of HOXA9 in relation to UBC, TPT1 and Aims & Methods: We therefore aimed to assess the effect of long-term inflamma-
GAPDH using the efficiency^

Ct method. In addition, we transduced Caco2 tion on the epithelial cells by in vitro model, which might mimic natural history
cells with a lentiviral vector containing HOXA9 and a lentiviral vector without of UC. Colonic crypts were isolated from 8 week old female mouse and were
an insert, enabling inducible expression. Subsequently, we analyzed expression of cultured by TMDU method. To mimic chronic inflammation, the inflammatory
genes important in anterior to posterior specification. We determined cell reagents, the mixture of cytokines and the ligands of toll like receptors, were
number and total cell pool with an automatic cell counter and a MTT assay. added into the medium every other day for 40 weeks. Thereafter, glycogen
Finally, we assessed the expression of genes implicated in oncological transfor- synthase kinase 3 (GSK3) inhibitor, CHIR99021 was added into the medium
mation and epithelial to mesenchymal transition. for 8 weeks with stimulation of inflammatory reagents. To evaluate transforma-
Result: HOXA9 expression in tubular adenomas of the colon is increased com- tion into tumor, the organoids were cultured without R-spondin1 and Wnt3a.
pared to location matched control tissue (p ¼ 0.04). HOXA9 overexpression in The assessment of cell signaling pathways in organoids during long-term inflam-
Caco2 cells led to a decrease in FGF2 mRNA level (p 5 0.001) and an increase in mation was performed by 3D immunohistochemistry of whole organoid and
A122 United European Gastroenterology Journal 4(5S)
western blot analysis. The gene expression of transformed organoids was assessed OP311 COMMENSAL FUNGI AND THEIR CELL-WALL GLYCANS
by microarray analysis and quantitative RT-PCR. INDUCE AUTOPHAGY IN INTESTINAL EPITHELIAL CELLS
Result: The treatment with the inflammatory reagents in mouse colonic orga- S. Cohen-Kedar1, H. Elad1, Y. Ron2, I. Dotan1
noids showed the time-dependent induction of NF-B target genes. Particularly, 1
IBD Center, Department Of Gastroenterology And Liver Diseases, Aviv Sourasky
the expression of DUOXA2 gene was gradually increased by the continuous Medical Center, Tel Aviv/Israel
stimulation with the inflammatory reagents for 40 weeks. 3D immunostaining 2
IBD Center, Department Of Gastroenterology And Liver Diseases, Tel Aviv
analysis showed NF-B p65 was accumulated in nuclei by longer time of the Sourasky Medical Center, Tel Aviv/Israel
stimulation, indicating that long-term stimulation might lead to a stronger acti-
vation of NF-B signaling. Interestingly, accumulated NF-B signaling by long- Contact E-mail Address: [email protected]
term stimulation remained active after the removal of all inflammatory reagents, Introduction: Intestinal epithelial cells (IECs) are the first to encounter luminal
whereas NF-B signaling induced by short-term stimulation was completely shut antigens and play an active role in intestinal immune responses. We recently
down by the removal of all inflammatory reagents, suggesting that NF-B might reported that the b-glucan receptor Dectin-1 and its major signaling mediator
be irreversibly activated by long-term stimulation. Moreover, the organoids spleen tyrosin kinase (Syk) are expressed by normal ileal and colonic IECs.
required neither R-spondin1 nor Wnt3a after the treatment with GSK3 inhibitor Furthermore, b-glucans, major fungal cell wall glycans, induced chemokine
for 8 weeks, indicating that the organoids might be transformed like colitis- secretion by IEC lines in a Dectin-1 and Syk dependent manner. Autophagy is
associated cancer. Microarray analysis and Gene Set Enrichment Analysis of a homeostatic process in the gut and defects in autophagy were associated with
transformed organoids showed irreversible Akt signal activation and reduced Crohn’s disease (CD) susceptibility. Vague data exist regarding the role of fungi
expression of Tgfb2, indicating that this transformation might involve the inflam- and their glycans in inducing autophagy.
matory-rerated carcinogenesis. Aims & Methods: To investigate whether fungi and fungal glycans induce autop-
Conclusion: Long-term inflammation and nuclear accumulation of b-catenin hagy in IECs. Human IEC lines (HT-29 and SW480) were activated by C. albi-
leads to irreversible cell transformation, which is wnt independent survival capa- cans and S. cerevisiae and the b-glucan-rich cell-wall component zymosan.
city of colonic organoids. This in vitro model might mimic the natural history of Autophagy was detected by Western blot (WB) and immunofluorescence (IF)
epithelial cell transformation during inflammation-related carcinogenesis in UC. of microtubule-associated protein 1A/1B-light chain 3 (LC3) or directly visua-
Disclosure of Interest: All authors have declared no conflicts of interest. lized in cells stably expressing GFP-LC3. Syk phosphorylation was assessed by
Reference WB and IF. Mucosal samples were obtained from patients undergoing colono-
scopy and active autophagy was assessed by the punctal stain of endogenous LC3
1. Yui S, et al. Functional engraftment of colon epithelium expanded in vitro in paraffin embedded sections or in frozen sections by IF.
from a single adult Lgr5þ stem cell. Nat Med 2012; 18: 618–623. doi:10.1038/ Result: C. albicans (live, heat-killed [HK] - or UV-inactivated, S. cerevisiae (HK)
nm.2695. and zymosan particles induced autophagy of IEC lines. This was indicated by 1)
Increase in the active (cleaved) form of LC3 (LC3 II) e.g. up to 3.5 fold increase
in LC3 II/actin ratio in response to HKCA vs. no treatment in HT-29 cells; 2)
Appearance of LC3 puncta, indicating autophagosome binding, of endogenous
OP310 THE RIBONUCLEASE RNASEH2B CONTROLS INTESTINAL LC3 as well as GFP-LC3. Comparable levels of autophagy were obtained upon
STEM CELL INTEGRITY amino- acid starvation of IECs -e.g. up to 3.7 fold increase in LC3 II/GAPDH
K. Aden1, K. Bartsch2, F. Tran3, S. Rose John4, S. Schreiber5, P. Rosenstiel3, ratio in starved SW480 cells vs. no treatment. Fungal–induced autophagy was
B. Rabe2 accompanied by Syk phosphorylation and prevented upon Syk inhibition. In ileal
1
Kiel University, IKMB þ First Medical Department, Kiel/Germany and colonic mucosal samples, active autophagy in IECs was observed as LC3
2
Insitute Of Biochemistry, Kiel University, Kiel/Germany puncta. Autophagy was further induced ex-vivo by UV-inactivated C. albicans,
3
Institute of Clinical Molecular Biology, University Hospital Schleswig-Holstein, zymosan or rapamycin (mTOR inhibitor, autophagy inducer).
Kiel/Germany Conclusion: Commensal fungi and their cell-wall glycans induce autophagy in
4
Institute Of Biochemistry, Kiel University, Kiel/Germany IECs. Syk-dependent autophagy suggests the involvement of antifungal receptors
5
Uksh, Universität Kiel UKSH Medizinische Abt. I, Kiel/Germany such as Dectin-1. Fungal-induced autophagy may play a role in mucosal sensing
of luminal microorganisms, and contribute to fungal tolerance. Thus, imbalanced
Contact E-mail Address: [email protected] response to commensal fungi (recognition, autophagy or downstream processes),
Introduction: The stability of genomic DNA is under a tightly controlled surveil- may impair homeostasis and contribute to the pathogenesis of CD.
lance. Especially in highly proliferating cells, as e.g. intestinal stem cells, RNA/ Disclosure of Interest: All authors have declared no conflicts of interest.
DNA hybrids display a menace to DNA integritiy. The ribonuclease RNAseH2b
removes RNA/DNA hybrids and thereby ensures cellular proliferation.
Hypomorphic mutations of the RNAseH2b gene are associated with Aicardi- TUESDAY, OCTOBER 18, 2016 15:45–17:15
Goutières syndrome that results in a spontaneous inflammatory phenotype. We ABSTRACTS ON FIRE: ACUTE PANCREATITIS: FROM MECHANISMS TO DISEASE –
tested the role of RNAseH2b in maintaining proliferation and regeneration in the HOTSPOT_____________________
intestinal epithelium.
Aims & Methods: We generated RNAseH2bfl/fl and RNAseH2b
IEC to study the OP312 HEPARANASE IN ACUTE PANCREATITIS: NEW INSIGHTS
role of RNAseH2b in the intestinal epithelium. WB, RT-PCR and IHC were INTO PATHOGENESIS AND THERAPY
performed to study the basal phenotype of unchallenged WT and KO mice. I. Khamaysi1, P. Singh2, N. Ilan2, I. Vlodavsky2, A. Noseda3, H. Awad4,
Acute DSS colitis was induced to investigate the impact of RNAseH2b on intest- Y. Chowers1, Z. Abassi5
inal regeneration. AOM-DSS colitis was induced to study the role of RNAseH2b 1
Gastroenterology, Ramabm Medical Center, haifa/Israel
on intestinal carcinogenesis. Organoids of RNAseH2bfl/fl and RNAseH2b
IEC 2
Cancer And Vascular Biology, Technion, ITT, Haifa/Israel
were subjected to RNA sequencing. 3
Sigma-Tau Research Switzerland SA, Mendrisio – CH/Switzerland
Result: No macromorphological difference was seen between RNAseH2bfl/fl and 4
Department Of Physiology, Technion, ITT, Haifa/Israel
RNAseH2b
IEC, with respect to age dependent body weight gain. Histological 5
Department Of Physiology, Technion, ITT, haifa/Israel
characterization reveals spontaneous DNA double strand breaks (DSB) in
epithelial crypts of RNAseH2b
IEC, which leads to a restriction of epithelial Contact E-mail Address: [email protected]
stemness, as measured by expression of stem cell markers (Olfm4, Lgr5) and Introduction: Despite advances in understanding the pathogenesis of acute pan-
reduced KI67 staining of intestinal stem cells. When mice were challenged to creatitis (AP), the mechanisms underlying this disease have not been fully deter-
acute DSS colitis, RNAseH2b
IEC mice reveal a strong phenotype with dramatic mined. In the majority of cases, AP is a self-limited process, yet 20% of patients
weight loss, increased histological disease activity and impaired intestinal regen- develop a severe form of AP with pancreatic necrosis, multi-organ involvement,
eration. Interestingly, when mice were challenged to AOM-DSS colitis, mice and high mortality. Heparanase (HPSE), an endoglycosidase which cleaves
again showed increased intestinal inflammation but developed significantly less heparan sulfate, degrades and remodels the extracellular matrix. HPSE is pre-
tumors. Decreased tumor development was due to DNA induced cellular senes- ferentially expressed in human tumors, including pancreatic adenocarcinoma.
cence, as shown by acid ß- galactosidase staining in intestinal crypts in While the role of HPSE in cancer has been extensively studied, the involvement
RNAseH2b
IEC but not RNAseH2bfl/flmice. of this enzyme in inflammation and in AP in particular remains obscure.
Conclusion: We show for the first time, that the RNAseH2b plays an essential Therefore, this current study examines if HPSE is involved in the pathogenesis
role in maintaining intestinal regeneration by protecting genomic DNA of high of Cerulein-induced AP in mice.
proliferating cells from DNA/RNA hybrids induced DNA damage. Knockout of Aims & Methods: HPSE over-expressing transgenic mice (hpa-TG) and wild-type
RNAseH2b leads to loss of epithelial stemness and induction of cellular (WT) BALB/c mice were intraperitoneally injected with either Cerulein (50 mg/
senescence. kg, 5 times, at 1 hour apart) or vehicle, with or without low and high doses of
Disclosure of Interest: All authors have declared no conflicts of interest. Roneparstat (SST0001, HPSE inhibitor) pretreatment. The animals were sacri-
Reference ficed 24 hours following the development of pancreatitis. The pancreatic response
and the severity of AP were evaluated by pancreatic HPSE activity (determined
1. Reijns, Martin AM, et al. Enzymatic Removal of Ribonucleotides from by Na235SO4-labeled ECM), pancreatic edema index (determined by organ to
DNA Is Essential for Mammalian Genome Integrity and Development. animal weight ratio), tissue inflammatory response (determined by histopatholo-
Cell 2012; 149: 1008–1022. doi:http://dx.doi.org/10.1016/j.cell.2012.04.011. gical analysis), autophagy response (determined by electron microscopy and
immunohistochemistry staining) and serum pancreatic enzymes (amylase and
lipase) levels.
Result: Cerulein-induced AP in wild type mice was associated with significant
rises in the serum levels of amylase and lipase. These increases were characterized
by an enhancement of HPSE activity, a higher pancreatic edema index, tissue
inflammation and autophagy response. All types of responses to administration
of Cerulein were profoundly exaggerated in hpa-TG mice. In contrast, when
Cerulein was injected to hpa-KO mice, the severity of pancreatic injury was
United European Gastroenterology Journal 4(5S) A123
attenuated as compared with their wild type controls. Importantly, pretreatment pretreatment of the AP rats with GHRL. Above mechanism could be implicated
with Roneparstat significantly reduced, in a dose-related manner, the HSPE in the protective action of this polypeptide in AP.
activity, the tissue inflammatory response, autophagy and serum amylase and Disclosure of Interest: All authors have declared no conflicts of interest.
lipase levels. References
Conclusion: HSPE appears to play an important role in the pathogenesis of AP.
The HSPE inhibitor (Roneparstat) significantly reduced the severity of the AP in 1. Kojima M and Kangawa K. Ghrelin: structure and function. Physiol Rew
an animal model. This new concept may provide a basis for prophylaxis and 2005; 85: 495–522.
treatment of AP. 2. Dembiński A, Warzecha Z, Ceranowicz P, Tomaszewska R, Stachura J,
Disclosure of Interest: All authors have declared no conflicts of interest. Konturek SJ and Konturek PC. Ghrelin attenuates the development of
acute pancreatitis in rat. J Physiol Pharmacol 2003; 54(4): 561–573.
3. Bonior J, Jaworek J, Leja–Szpak A, Kot M, Macko M, Tomaszewska R,
Stachura J, Konturek SJ and Pawlik WW. Protective effect of ghrelin in
OP313 CIGARETTE SMOKE EXTRACT INHIBITS FLUID AND HCO3- experimental acute pancreatitis. Clin. Exp. Med. Lett 2005; 46(3): 39–46.
SECRETION AND CFTR ACTIVITY IN GUINEA PIG PANCREATIC
DUCTAL CELLS
P. Pallagi1, V. Venglovecz2, K. Tóth1, A. Schnúr1, E. Tóth1, J. Maléth1,
D. Csupor3, Z. Rakonczay4, K. Cseko5, Z. Helyes5, P. Hegyi6
00 OP315 IDENTIFICATION AND CHARACTERISATION OF A NOVEL
1
First Department Of Medicine, University of Szeged, Szeged/Hungary EARLY ONSET DIABETES GENE USING HUMAN PLURIPOTENT
2
Department Of Pharmacology And Pharmacotherapy, University of Szeged, STEM CELLS
Szeged/Hungary A. Illing1, I. Costa2, A. Lechel1, Q. Lin3, T. Seufferlein1, A. Kleger1
3 1
Department Of Pharmacognosy, University of Szeged, Szeged/Hungary Department Of Internal Medicine 1Ulm University Hospital, Ulm/Germany
4 2
Department Of Pathophysiology, University of Szeged, Szeged/Hungary Centre Of Medical Technology (mtz), Helmholtz Institute for Biomedical
5
Department Of Pharmacology And Pharmacotherapy, University of Pe´cs, Pe´cs/ Engineering, Aachen/Germany
3
Hungary Department Of Cell Biology, Institute for Biomedical Engineering, Aachen/
6
1st Department of Internal Medicine, Institute for Translational Medicine, Germany
University of Pe´cs, Pe´cs/Hungary
Contact E-mail Address: [email protected]
Contact E-mail Address: [email protected] Introduction: Diabetes represents one of the major burdens in the 21st century
Introduction: Smoking represents an independent risk factor for the development with approx. 350 million people affected worldwide. Monogenic diabetes such as
of chronic pancreatitis (CP). It is well documented that secretion of pancreatic juvenile onset insulin-dependent diabetes (JOD) or maturity onset diabetes of the
ductal alkaline fluid (which is regulated mostly by anion exchangers and CFTR) young (MODY) accounts for approximately 1–2% of diabetes cases and results
is diminished in CP. from mutations that primarily reduce b-cell function. The identification of the
Aims & Methods: In this study, we would like to understand whether smoking has genetic basis of these diabetes forms has translated into novel avenues of perso-
any effects on pancreatic ductal fluid and HCO3- secretion. Guinea pigs were nalized medicine in the diabetes field, but only few of these genes have been
exposed to cigarette smoke four times a day for 30 min for 6 weeks. The expres- identified to date.
sion of CFTR was analysed by immunohistochemistry. Intra/interlobular pan- Aims & Methods: Based on published data, we hypothesize that a proportion of
creatic ducts were isolated from guinea pig pancreas. Cigarette smoke extract the genetic contribution to common diabetes (T1D and T2D) may be caused by
(CSE) was prepared by smoking of 15 cigarettes into 10 ml distilled water by a rare monogenic variants/mutations missed by the current GWAS strategies tar-
smoking machine. Three different concentraion (20, 40 and 80 mg/ml) were geting common variants. The current project reports on such a novel gene rele-
diluted using the stock solution. Intracellular pH was evaluated by microfluoro- vant as regulator of human pancreatic islet formation but also as a novel early
metry. Basal and forskolin-stimulated fluid secretion was measured by video onset diabetes gene.
microscopy. CFTR currents were detected by whole cell configuration of patch Result: Using stage-specific genome-wide profiling complemented with Chip-Seq
clamp technique. data in differentiating human embryonic stem cells, we show that our gene binds
Result: Cigarette smoking significantly diminished the expression of CFTR and and activates Nkx2.2, Nkx6.1 and Pdx1, all belonging to the core suite of isle-
the fluid and HCO3- secretion in guinea pig pancreas. 40 mg/ml CSE decreased togenesis transcription factors. Interestingly, this gene co-occupies the enhancer
HCO3- secretion via inhibition of Cl-/HCO3- exchanger activity. CSE dose- and promoter regions of the latter genes together with Foxa2, Pdx1 and Gata6.
dependently decreased forskolin-stimulated fluid secretion in guinea pig pancrea- Finally, we engineered human embryonic stem cells with previously identified
tic ducts and forskolin-stimulated Cl- current of CFTR Cl- channel (20 mg/ml by mutations in JOD patients. Directed differentiation studies of these cells shows
44.5%, 40 mg/ml by 69.3% and 80 mg/ml by 81.3%). an altered binding pattern of Nkx2.2, Nkx6.1 and Pdx1 finally leading to reduced
Conclusion: Cigarette smoking and CSE inhibits pancreatic ductal fluid and amounts of monohormonal b-cells. This reduced target gene binding results from
HCO3- secretion and the activity of CFTR which may play role in the smoke- a limited zinc affinity, due to the mutation, that would be necessary as co-factor
induced pancreatic damage. This study was supported by OTKA, MTA and for gene binding.
TÁMOP. Conclusion: This platform not only allows personalised drug-testing but also
Disclosure of Interest: All authors have declared no conflicts of interest. sheds light on the mechanism how our JOD gene regulates pancreatic develop-
ment and leads to diabetes in case of certain mutations in humans.
Disclosure of Interest: All authors have declared no conflicts of interest.

OP314 GHRELIN INHIBITS TNF-ALPHA PRODUCTION IN ACUTE

PANCREATITIS
J. Bonior1, P. Ceranowicz2, M. Kot1, A. Dembiński2, Z. Warzecha2, OP316 LACK OF CFTR RESULTS IN THE IMPAIRED FUNCTION OF
P. Pierzchalski1, J. Jaworek1 THE PLASMA MEMBRANE CA2þ PUMP THAT CAUSES
1
Department Of Medical Physiology, Jagiellonian University Medical College INTRACELLULAR CA2þ OVERLOAD AND MITOCHONDRIAL
Faculty of Health Sciences, Krakow/Poland DAMAGE IN THE PANCREATIC DUCTAL EPITHELIAL CELLS OF
2
Department Of Physiology, Jagiellonian University Medical College, Krakow/ CFTR KNOCK OUT MICE
Poland T. Madacsy1, J. Fanczal1, P. Pallagi1, V. Venglovecz2, Z. Rakonczay3, P. Hegyi4,
J. Maléth1
Contact E-mail Address: [email protected] 1
First Department Of Medicine, University of Szeged, Szeged/Hungary
Introduction: Ghrelin (GHRL), a 28-amino acid polypeptide, that was originally 2
Department Of Pharmacology And Pharmacotherapy, University of Szeged,
isolated from the stomach, was shown to protect the pancreas from caerulein- Szeged/Hungary
induced pancreatitis (AP) [1–3]. 3
First Department Of Medicine, University of Szeged 1st Dept. of Medicine,
Aims & Methods: To determine the effects of GHRL on tumor necrosis factor- Szeged/Hungary
alpha (TNF-) concentration in the rats with AP and on the signals for growth 4
University of Pe´cs, Pe´cs/Hungary
hormone secretagogues receptor type 1a (GHS-R1a) and TNF- in the pancrea-
tic acini. AP was induced by caerulein infusion (25 mg/kg s.c.). GHRL (12.5; 25; Contact E-mail Address: [email protected]
50 mg/kg i.p.) was given to the control rats and prior to the start of inflammation Introduction: The cystic fibrosis transmembrane conductance regulator (CFTR)
in vivo. Plasma TNF- concentration was measured by ELISA. Pancreatic acini has a significant role in pancreatic ductal epithelial secretion and it’s genetic
were isolated from control, GHRL rats and then hyperstimulated by caerulein defects damage the pancreas. The exact mechanism of this pancreatic damage
(10-8 M) in vitro. The gene expressions were determined by RT-PCR and the is only partially known. The toxic cellular Ca2þ overload is a hallmark of acute
protein contents by Western-blot pancreatitis and in CFTR-deficient airway epithelial cells the intracellular
Result: Administration of GHRL to the control rats failed to affect TNF- Ca2þhomeostasis was disturbed. However the Ca2þ homeostasis of CFTR-defi-
concentration in plasma. AP significantly increased its, but application of cient pancreatic ductalepithelial cells (PDEC) has never been investigated
GHRL prior to the inflammation significantly dose-dependently reduced this Aims & Methods: Our aim was to characterize the Ca2þ homeostasis of CFTR-
pro-inflammatory cytokine. Protein expressions and mRNA signals for GHS- deficient PDEC. Pancreatic ducts and acinar cells were isolated from wild type
R1a and TNF- have been detected in the pancreatic acini under basal conditions (WT) and CFTR knockout (KO) mice. Intracellular Ca2þ concentration ([Ca2þ]i)
and GHRL resulted in a statistically increase of GHS-R1a without changing and changes of the mitochondrial membrane potential was measured.
signals of TNF-. Caerulein significantly changed the test signals: downregulated Result: Maximal [Ca2þ]i release upon carbachol stimulation showed no difference
receptor and upregulated cytokine. These adverse effects were reversed by in WT and CFTR KO PDEC. Notably, the plateau phase of the Ca2þ signal was
GHRL. significantly higher in CFTR-deficient PDEC, but completely normal in pancrea-
Conclusion: Caerulein upregulated molecular signals for TNF- and downregu- tic acinar cells. Interestingly, the functional inhibition of CFTR with 10mM
lated that for GHS-R1a in the pancreatic acini. This effect could be prevented by CFTR(inh)-172 had no effect on the Ca2þ signals. Next we investigated the
Ca2þefflux in PDEC and found that the Ca2þ extrusion was significantly lower
A124 United European Gastroenterology Journal 4(5S)
in CFTR KO PDEC compared to WT due to the impaired function of the but if PEI secondary to CP is associated with the risk of CVD and cardiovascular
plasma membrane Ca2þ pump (PMCA). In addition, the sustained elevation of (CV) events is unknown.
[Ca2þ]i caused a drop in mitochondrial membrane potential in CFTR KO Aims & Methods: Aim of the present study was to assess the risk of CV events in
PDEC. patients with CP and the impact of PEI and other factors in these patients. A
Conclusion: Dysfunction of PMCA leads to disturbed Ca2þ homeostasis in retrospective analysis of a prospectively collected database of patients with CP,
CFTR-deficient PDEC and the consequent cellular Ca2þ overload impairs mito- who were under follow-up in our Pancreas Unit was carried out. Diagnosis of CP
chondrial function. These changes might contribute to the pancreatic damage was based on endoscopic ultrasound (EUS), magnetic resonance cholangio-pan-
seen in cystic fibrosis. creatoscopy (MRCP) and pancreatic MRI. PEI was defined as the need of pan-
Disclosure of Interest: All authors have declared no conflicts of interest. creatic enzyme replacement therapy due to the presence of maldigestion-related
symptoms and/or abnormal nutritional markers together with an abnormal 13C-
MTG breath test result. Major CV events (stroke, heart attack) and peripheral
arterial disease (claudication, thrombosis) during follow-up were analysed.
OP317 ENDOSCOPIC DILATION OF PANCREATIC DUCT Patients with a past history of CV events previous to the diagnosis of CP were
STRICTURES IN CHRONIC PANCREATITIS WITH MULTIPLE excluded. Data about sex, age at diagnosis of CP, aetiology, alcohol consump-
PLASTIC STENTS: RESULTS IN 48 PATIENTS tion, smoking, PEI and other comorbidities (including diabetes mellitus) were
A. Tringali1, V. Bove1, G. Valerii1, R. Landi1, P. Familiari1, I. Boskoski1, evaluated. Statistical analysis was done by logistic regression adjusted for con-
V. Perri1, G. Costamagna2 founding factors.
1
Digestive Endoscopy Unit, Catholic University - Gemelli University Hospital, Result: 455 patients were finally included (77,8% men), with a median age of 46
Roma/Italy years (range 15–88 years). Mean follow-up was 7.8 years. CP was secondary to
2
IHU, USIAS Strasbourg University, Strasbourg, France, Strasbourg/France alcohol and/or smoking in 301 patients (66.1%). 149 patients (32.7%) had PEI
and 131 (28.8%) had diabetes mellitus. A total of 46 CV events were recorded in
Contact E-mail Address: [email protected] 43 patients (9.5%). 22 patients (4.8%) suffered from a mayor CV event and the
Introduction: Main pancreatic duct (MPD) strictures located in the head of the remaining 24 patients (5.3%) presented a peripheral arterial disease. CV events
pancreas often occur in the course of chronic pancreatitis (CP). Common man- occurred more frequently in patients with PEI (n ¼ 28, 18.8%) than in patients
agement of these strictures is endoscopic placement of a single plastic stent. without PEI (n ¼ 15, 4.9%) (p 5 0.001). In the logistic regression analysis, PEI
Refractory strictures require repeated stent replacement or surgical pancreatico- (OR 3.76; 95%CI 1.65–8.58), diabetes mellitus (OR 2.55; 95%CI 1.11–5.83) and
jejunostomy. Insertion of multiple plastic stents (MPS) obtained, in a series of 19 smoking (OR 3.90; 95%IC 1.19–12.7) were significantly and independently asso-
patients, symptomatic MPD stricture resolution in 84% of the cases, after 3-year ciated with CV events.
follow-up (1) The aim of this study was to evaluate the results of the MPS Conclusion: Patients with CP are at high risk of CV events. PEI, diabetes mellitus
strategy in a larger series of CP patients. and smoking are independent risk factors associated with the risk of CV events in
Aims & Methods: Forty-eight patients (34 men; mean age 44 years, range 5–86) patients with CP.
with severe CP and a symptomatic dominant MPD stricture located in the head Disclosure of Interest: J.E. Domı́nguez-Muñoz: Has actued as speaker and advi-
of the pancreas, were evaluated. All the patients experienced pain resolution sor international of Mylan and Abbot
following MPD drainage with a single plastic stents. The MPD stricture was All other authors have declared no conflicts of interest.
refractory to single plastic stent placement in all cases and patients underwent
insertion of MPS according to the following protocol: balloon dilation of the
stricture if necessary, insertion of the maximum number of plastic stents allowed
by the stricture tightness and pancreatic duct diameter, stents removal after 6 OP319 USE OF THE URINARY TRYPSINOGEN-2 DIPSTICK TEST IN
months. EARLY DIAGNOSIS OF PANCREATITIS AFTER ENDOSCOPIC
Result: The median number of stents placed through the major or minor papilla RETROGRADE CHOLANGIOPANCREATOGRAPHY
was 3 (range 2–5), 8.5 to 11.5 Fr in diameter and 3 to 7 cm in length. MPS were A. Alhakam
removed after a mean time of 6.7 months (range 2–18). Eight patients (16.6%) Gastroenterology, Kasr Alainy Hospital, Cairo/Yemen
had persistence of the MPD stricture after MPS removal and underwent replace-
ment of an increased number of stents; 3/8 patients had a dilation of the stricture Contact E-mail Address: [email protected]
after further multistent placement (overall success 89.5%). Following a mean Introduction: One of the most serious complications of (ERCP) is acute pancrea-
followup of 9.5 years (range 0.3–15.5) after MPS removal, 77.1% of patients titis. The reported incidence varies from 1.3% to 24.4% [1]. Measurement of
were asymptomatic. Symptomatic MPD stricture recurrence was reported in 11 serum amylase and lipase levels after the procedure may have a possible role
patients (22.9%), after a mean time of 26.4 months (range 5–108) from MPS for early recognition of post-ERCP pancreatitis [3]. Asymptomatic elevation in
removal. No major complications were recorded. serum amylase and lipase activities after ERCP is common, occurring in approxi-
Conclusion: Endoscopic dilation of CP-related dominant MPD strictures seems mately 25% to 75% of all patients. A rapid test strip has been developed for the
possible with the MPS technique. According to this experience on 48 patients, detection of trypsinogen-2 in urine (The urinary trypsinogen-2 dipstick
MPS is highly effective even at long-term follow-up in the majority of patients. test—UT2DSTactim pancreatitis) which is based on the immunochromatogra-
Disclosure of Interest: A. Tringali: Boston Scientific Corporation No current phy principle and shows a good sensitivity and specificity in diagnosing acute
consulting agreements in place One day animal lab in 2012 and 2013. Speaking pancreatitis [6]. The aim of this study was to evaluate the diagnostic value of
and teaching in 2014 urinary trypsinogen-2 dipstick test for early diagnosis of post-ERCP pancreatitis.
I. Boskoski: Cook Inc. Consultant Aims & Methods: After an informed consent by the patients the selected patients
G. Costamagna: Olympus Japan Grant/Research Support Cook, Inc Advisory were subjected to: Full clinical assessment (history taking and clinical examina-
Committees or Review Panels. Grant/Research Support Boston Scientific tion), laboratory investigations including (complete blood count (CBC), Bilirubin
Corporation Advisory Committees or Review Panels. Taewoong Medical Inc (total and direct), (ALT), (AST), alkaline phosphatase (ALP), Prothrombin time
Advisory Committees or Review Panels. and concentration (PT & PC), urea, creatinine, serum amylase, serum lipase,
All other authors have declared no conflicts of interest. urinary trypsinogen-2 dipstick test (UT2DST).
Reference Result: Post ERCP UT2DST was negative in 30 patients of the non pancreatitis
group (96.8%) and positive in one of them (3.2%) The test was positive in all
1. Costamagna G, Bulajic M, Tringali A, et al. Multiple stenting of refractory patients with Pancreatitis (100%). The sensitivity of the post ERCP UT2DST
pancreatic duct strictures in severe chronic pancreatitis: long-term results. was 100% the Specificity was 97% with PPV 86%, NPV 100% and the P value
Endoscopy 2006; 38: 254–9. was 50.01. Comparison between serum lipase and amylase levels post ERCP in
relation to UT2DST test shows that positive UT2DST test was significantly
associated with higher amylase and lipase serum levels after ERCP (post amylase
and post lipase) (P 5 0.01).
OP318 CARDIOVASCULAR RISK IN PATIENTS WITH CHRONIC Conclusion: The urinary trypsinogen-2 dipstick test can be used as an easy and
PANCREATITIS AND PANCREATIC EXOCRINE INSUFFICIENCY rapid test for early diagnosis of post-ERCP pancreatitis with high sensitivity and
N. Vallejo-Senra1, D. De La Iglesia-Garcı́a2, A. López-López3, J. Iglesias- specificity and can help clinicians to provide intensive care and possible medical
Garcı́a1, L. Nieto4, J.E. Domı́nguez-Muñoz5 treatment as early as possible.
1
Gastroenterology, University Hospital of Santiago. Health Research Institute of Disclosure of Interest: All authors have declared no conflicts of interest.
Santiago de Compostela (IDIS), Santiago de Compostela, Spain, Santiago de
Compostela/Spain References
2
Gastroenterology, University Hospital of Santiago. Health Research Institute of
1. Kobayashi K, Sasaki T, Serikawa M, Inoue M, Itsuki H and Chayama K.
Santiago de Compostela (IDIS), Santiago de Compostela/Spain
3 Assessment of trypsinogen-2 levels as an early diagnostic marker for post
Cardiology, University Hospital of Santiago de Compostela, Santiago de
endoscopic retrograde cholangio-pancreatography pancreatitis. Pancreas
Compostela/Spain
4 2011; 40: 1206–1210. http://dx.doi.org/10.1097/MPA.0b013e318223d362.
Health Research Institute of Santiago de Compostela (IDIS), Santiago de
2. Sankaralingam S, Wesen C, Barawi M, Galera R and Lloyd L. Use of the
Compostela/Spain
5 urinary trypsinogen-2 dip stick test in early diagnosis of pancreatitis after
Gastroenterology, University Hospital of Santiago de Compostela, Santiago de
Compostela/Spain endoscopic retrograde cholangiopancreatography. Surgical Endoscopy 2007;
21: 1312–1315. http://dx.doi.org/10.1007/s00464-006-9099-2.
Contact E-mail Address: [email protected] 3. Chen CC, Wang SS, Lu RH, Lu CC, Chang FY and Lee SD. The early
Introduction: Mortality in patients with chronic pancreatitis (CP) is increased. changes of serum proinflammatory and anti-inflammatory cytokines after
Some previous studies suggest that chronic pancreatitis (CP) is an independent endoscopic retrograde cholangiopancreatography. Pancreas 2003; 26:
risk factor of cardiovascular disease (CVD). It is well known that malnutrition 375–380. http://dx.doi.org/10.1097/00006676-200305000-00011.
secondary to different diseases and conditions increases the risk of CVD too. 4. Ito K, Fujita N, Noda Y, Kobayashi G, Horaguchi J, Takasawa O and
Pancreatic exocrine insufficiency (PEI) causes malnutrition in patients with CP, Obana T. Relationship between post-ERCP pancreatitis and the change of
United European Gastroenterology Journal 4(5S) A125
serum amylase level after the procedure. World Journal of Gastroenterology WEDNESDAY, OCTOBER 19, 2016 08:30–10:00
2007; 13: 3855–3860. PERCUTANEOUS GASTROSTOMY AND JEJUNOSTOMY – ROOM F2_____________________
5. Chang K, Lu W, Zhang K, Jia S, Li F, Wang F, Deng S and Chen M. Rapid
urinary trypsinogen-2 test in the early diagnosis of acute pancreatitis: A OP321 GASTROINTESTINAL SAFETY OF LEVODOPA-CARBIDOPA
meta-analysis. Clinical Biochemistry 2012; 45: 1051–1056. http://dx.doi.org/ INTESTINAL GEL IN ADVANCED PARKINSON’S DISEASE
10.1016/j.clinbiochem.2012.04.028. PATIENTS: FINAL RESULTS FROM THE GLORIA LONG-TERM
6. Kemppainen EA, Hedström JI, Puolakkainen PA, Sainio VS, Haapiainen REGISTRY
RK, Perhoniemi V, Osman S, Kivilaakso EO and Stenman UH. Rapid D Domagk1, S Dam-Larsen2, A Antonini3, L Bergmann4, A Yegin4, W Poewe5
measurement of urinary trypsinogen-2 as a screening test for acute pancrea- 1
Josephs-Hospital Warendorf Academic Teaching Hospital, University of
titis. New England Journal of Medicine 1997; 336: 1788–1793. http:// Muenster, Warendorf/Germany
dx.doi.org/10.1056/NEJM199706193362504. 2
Zealand University Hospital, Koege/Denmark
7. Murray B, Carter R, Imrie C, Evans S and O’Suilleabhain C. Diclofenac 3
Institute of Neurology, IRCCS, Venice/Italy
4
reduces the incidence of acute pancreatitis after endoscopic retrograde cho- AbbVie Inc., North Chicago/United States of America/IL
5
langiopancreatography. Gastroenterology 2003; 124: 1786–1791. http:// Medical University of Innsbruck, Innsbruck/Austria
dx.doi.org/10.1016/S0016-5085(03)00384-6.
Contact E-mail Address: [email protected]
Introduction: Levodopa-carbidopa intestinal gel (LCIG, designated in the US as
carbidopa-levodopa enteral suspension [CLES]) is a long-term treatment option
OP320 WHAT KIND OF INTRAVENOUS HYDRATION SHOULD BE for advanced Parkinson’s disease (PD) patients and administered via percuta-
USED FOR THE PREVENTION OF POST-ERCP PANCREATITIS: A neous gastrojejunostomy (PEG-J) from an external pump.
PROSPECTIVE RANDOMIZED MULTICENTER CLINICAL TRIAL Aims & Methods: The gastrointestinal (GI)-related safety of the LCIG treatment
system (drug/device) has been assessed in advanced PD patients with final safety
C Park1, W.H Paik2, E.T Park3, C.S Shim4, T.Y Lee4, C Kang5, M.H Noh6, data from the GLORIA1 registry. This observational registry of 375 advanced
S.Y Yi7, J.K Lee8, J.J Hyun9, J.K Lee10 PD patients treated with LCIG was conducted at 75 centers in 18 countries.
1
Internal Medicine, Chonnam National University Medical School, Kwangju/ Patients were initially titrated to an optimal dose of LCIG via nasojejunal
Korea, Republic of (NJ) tube for up to 2 weeks, followed by infusion via PEG-J for 24 months.
2
Inje University Ilsan Paik Hospital, Goyang/Korea, Republic of Final safety data from patients with advanced PD who had 1 infusion of LCIG
3
Internal Medicine, Univerisity of Kosin College of Medicine, Busan/Korea, (n ¼ 356) were included in this analysis. Adverse drug reactions (ADR), which
Republic of are adverse events with a reasonable possibility of causal relationship to the
4
Internal Medicine, Konkuk University School of Medicine, Seoul/Korea, Republic treatment according to investigators’ judgment, were recorded throughout the
of registry. The authors categorized ADRs post hoc as either PEG-J procedure-
5
Internal Medicine, Kangwon National University School of Medicine, Kangwon/ related, device-related, or ‘‘other’’ type of GI event.
Korea, Republic of Result: Of the 375 enrolled patients, 332 (89%) were treated with LCIG via PEG-
6
Internal Medicine, Dong-A University College of Medicine, Busan/Korea, J, and 258 (69%) completed the 24 month follow-up. The median [range] dura-
Republic of tion of exposure via NJ was 6.0 [1, 53] days (n ¼ 307) and via PEG-J was 722 [1,
7
Internal Medicine, School of Medicine, Ewha Womans University, Seoul/Korea, 957] days (n ¼ 351). During titration via NJ, there were 3 patients (0.8%) who
Republic of had 1 GI related ADR. Within the 24 months of treatment post-PEG-J place-
8
Samsung Medical Center, Seoul/Korea, Republic of ment (n ¼ 356)  1 GI related ADR was reported in 139 patients (39%), of which
9
Medicine, Korea University Ansan Hospital, Seoul/Korea, Republic of procedure-related ADRs were reported in 35 patients (9.8%), device-related in 93
10
Internal Medicine, Dongguk University Ilsan Hospital, Ilsan/Korea, Republic of (26%), other GI events in 63 (18%); the ADRs in all GI categories reported for
Contact E-mail Address: [email protected] 4% patients were weight decreased (6.7%), device related infection (5.9%),
Introduction: A pilot study suggests that aggressive intravenous hydration with device dislocation (4.8%), device issue (4.8%); and the serious ADRs reported
lactated Ringer’s solution may reduce the development of post-endoscopic retro- for 2% patients were device dislocation (2.2%) and device issue (2.0%). During
grade cholangiopancreatography (ERCP) pancreatitis. The present larger multi- the 28-day follow up period, there were 4 patients (1.1%) who had 1 GI related
center study aimed to determine what kind of intravenous hydration could ADR. ADRs led to the discontinuation of 10 patients (2.8%) overall, 2 of whom
reduce the incidence of post-ERCP pancreatitis. discontinued due to a procedure-related ADR, 5 due to a device-related ADR,
Aims & Methods: In a prospective randomized multicenter clinical trial, patients and 3 due to another type of GI ADR. Of the 29 deaths reported, 23 were deemed
who underwent first-time ERCP were randomly assigned to 3 groups (1:1:1) that unrelated to treatment, 5 possibly related (to drug/device) and 1 probably related
received aggressive hydration with lactated Ringer’s solution (3 mL/kg/h during (to tubing). Of the possibly/probably related deaths, 2 had GI related events; 1
the procedure, a 20 mL/kg bolus after the procedure, and 3 mL/kg/h for 8 hours had a small bowel obstruction and died approximately 3 weeks later of unknown
after the procedure), standard hydration with the same solution (1.5 mL/kg/h causes, and 1 had a small bowel perforation and peritonitis.
during and for 8 hours after the procedure), or aggressive hydration with phy- Conclusion: Most GI-related ADRs were related to the device in this registry. The
siologic saline (3 mL/kg/h during the procedure, a 20 mL/kg bolus after the pro- incidence of GI-related ADRs and discontinuations due to GI-related ADRs
cedure, and 3 mL/kg/h for 8 hours after the procedure). The primary end point, were relatively low, which is supportive of the overall tolerability of LCIG and
post-ERCP pancreatitis, was defined as hyperamylasemia (level of amylase 4 3 consistent with previous studies.2
times the upper limit of normal) and increased epigastric pain (3 points on Disclosure of Interest: D. Domagk: Dirk Domagk has received research support
visual analogue scale) persisting for 24 hours after the procedure. by Merck, honoraria for lectures from Olympus Europe and Dr. Falk
Result: A total of 406 patients were enrolled, and 395 of them completed the Foundation, and has served as consultant for Hitachi Medical Systems and
protocols. The three groups had no significant difference in demographic char- AbbVie Inc.
acteristics or other risk factors before ERCP (P 4 0.05). The intention-to-treat A. Antonini: Angelo Antonini has received research support from Mundipharma
post-ERCP pancreatitis rates were 3.0% (4/132) in the aggressive hydration with and compensation from UCB, Boston Scientific, Boheringer-Ingelheim, AbbVie
lactated Ringer’s solution group and 11.6% (15/129) in the standard hydration Inc., and Zambon for serving as a consultant and lecturer.
group (P ¼ 0.008), whereas the per protocol (PP) post-ERCP pancreatitis rates L. Bergmann: Lars Bergmann is an employee of AbbVie Inc. and hold stock or
were 1.6% (2/128) in the aggressive hydration with lactated Ringer’s solution stock options.
group and 11.6% (15/129) in the standard hydration group (P ¼ 0.001). No sig- A. Yegin: Ashley Yegin is an employee of AbbVie Inc. and holds stock or stock
nificant differences in the intention-to-treat and PP post-ERCP pancreatitis were options.
found between the aggressive hydration with physiologic saline group (6.7%, 9/ W. Poewe: Dr. Poewe: royalities from Thieme, Wiley Blackwell, Oxford
134; 7.0%. 9/128) and standard hydration group (11.6%, 15/129, P ¼ 0.167, University Press; compensation from AbbVie, Astra Zeneca, Teva, Novartis,
P ¼ 0.205). GSK, Boehringer-Ingelheim, UCB, Orion Pharma, Zambon, Merz
Conclusion: Aggressive hydration with lactated Ringer’s solution is more effective Pharmceuticals for consulting and lecturing.
than standard hydration for prevention of post-ERCP pancreatitis. All other authors have declared no conflicts of interest.
Disclosure of Interest: All authors have declared no conflicts of interest. References
1. Antonini A., et al., Parkinsonism Relat Disord. 2015; 21(3):231–5.
References 2. Lang A., et al., Mov Disord. 2016; 31(4):538–46.

1. Buxbaum J, Yan A, Yeh K, et al. Aggressive hydration with lactated ringer’s

solution reduces pancreatitis after endoscopic retrograde cholangiopancrea-
tography. Clinical Gastroenterology and Hepatology: the official clinical prac- OP322 ENDOSCOPICALLY ASSISTED PERCUTANEOUS
tice journal of the American Gastroenterological Association 2014; 12: 303–7 TRANSESOPHAGEAL GASTROTUBING (PTEG) AND THE
e1. PROGRESS
2. Muddana V, Whitcomb DC, Khalid A, et al. Elevated serum creatinine as a
M Murakami1, K Nishino2, S Murakami2, K Mori2, B Murakami2, M Azuma1,
marker of pancreatic necrosis in acute pancreatitis. The American Journal of
S Tanabe1, M Kida1, W Koizumi1
Gastroenterology 2009; 104: 164–70. 1
Dept Of Gastroenterology, Kitasato University School of Medicine, Sagamihara/
3. Anderson MA, Fisher L, Jain R, et al. Complications of ERCP.
Japan
Gastrointestinal Endosc 2012; 75: 467–473. 2
Dept. Of Internal Medicine, Murakami Memorial Hospital Dept. of Internal
4. Andriulli A, Leandro G, Federici T, et al. Prophylactric administration of Medicine, Saijo/Japan
somatostatin or gabexate does not prevent pancreatitis after ERCP: an
uptated meta-analysis. Gastrointest Endosc 2007; 65: 624–632. Contact E-mail Address: [email protected]
Introduction: Endoscopically assisted percutaneous transesophageal gastrotubing
(PTEG) was developed as an alternative route to access the gastrointestinal tract
A126 United European Gastroenterology Journal 4(5S)
for the patients that Percutaneous Endoscopic Gastrostomy was contraindicated. Conclusion: A two-food elimination diet (animal milk, gluten-containing cereals)
PTEG by endoscopic assistance may enhance the safety of the procedure and the achieves EoE remission in up to 40% of patients unresponsive to PPI therapy.
new item that may enhance the reliability was developed. This diet allows prompt identification of two thirds of responders to empiric
Aims & Methods: The aim of this study is to evaluate the clinical usefulness of elimination diets, with few food triggers (one food trigger in 85% of responders)
PTEG supported by endoscopy. A rupture-free balloon (RFB) catheter is and consequently, good candidates for dietary maintenance therapy. A step-up
inserted into the upper esophagus. Percutaneous balloon puncture with a specia- empiric diet strategy (2–4–6) might be a cost-effective dietary strategy for pedia-
lized needle is then performed from the left side of patient’s neck under ultra- tric and adult EoE.
sonographic control. A guide wire is inserted through the needle into the RFB, Disclosure of Interest: All authors have declared no conflicts of interest.
followed by a dilator and sheath. A placement tube is then inserted through the
sheath, and the sheath is removed. We started to perform PTEG under endo-
scopy in a total of 119 patients (74 men and 45 women, mean age 71.5 years) in
whom PEG was not feasible. Double Balloons equipped Overtube type RFB OP324 INCREASED MUCOSAL EXPRESSION OF TOLL-LIKE
were used instead of primary RFB in seven cases that the puncture needle is RECEPTORS IN ADULT PATIENTS WITH EOSINOPHILIC
punctured into the overtube trough the balloon. PTEG was performed for nutri- ESOPHAGITIS
tion in 65 patients and for decompression in 54. Á Arias Arias1, M Vicario2, P Martı́nez Fernández3, A. M González-Castro2,
Result: Satisfactory results were achieved in all 119 patients. Median follow-up M Fortea2, J González-Cervera4, J. L Yagüe-Compadre5, T Mota-Huertas5,
was 64.0 days in patients who received decompression because of the obstruction A. J. Lucendo6
due to malignancies and 270.0 days in those who received nutrition. Four of 65 1
Research Unit, Hospital La Mancha Centro, Alcazar de San Juan/Spain
patients for nutrition were able to be free from tube feeding due to PTEG tube 2
Vall d´Hebron Institut Recerca Gastroenterology, Barcelona/Spain
feeding support. There was one patient had tracheal penetration, which was 3
Institute Of Medical And Molecular Genetics, Hospital Univerisitario La Paz,
managed conservatively. Other complications were minor oozing bleeding in Madrid/Spain
seven patients that did not require blood transfusion, subcutaneous emphysema 4
Allergy, Hospital General de Tomelloso, Tomelloso/Spain
in two patients, which were managed conservatively. The complication rate was 5
Pathology, Hospital General La Mancha Centro, Alcázar de San Juan/Spain
13.4%. A stable procedure could performed in all seven cases using the new 6
Gastroenterology, Hospital General de Tomelloso, Tomelloso/Spain
overtube, and also there was no complications. No patient required surgical
treatment or died after PTEG. Contact E-mail Address: [email protected]
Conclusion: PTEG is feasible, safe, and useful. PTEG could be an optimal pro- Introduction: An adaptive Th2-type immune response to food antigens is involved
cedure for long-term nutrition and/or decompression even for the patients who in eosinophilic esophagitis (EoE). Evidences of a potential role for the innate
failed PEG insertion. The use of endoscopy enhances the safety of the procedure immunity in EoE has also arisen in parallel to the recognition of changes in
and allows better confirmation of each step involved. New overtube type RFB esophageal microbiome in adult and pediatric EoE patients compared to non-
will be useful but need more experiences. EoE controls. The likely role that microbial pattern recognition receptors (PRRs)
Disclosure of Interest: All authors have declared no conflicts of interest. might play in EoE arises as a potential source of research in understanding the
relationship of diet, the esophageal microbiome, and the immune system activa-
tion in EoE, that has not been assessed yet.
WEDNESDAY, OCTOBER 19, 2016 08:30–10:00 Aims & Methods: To gather data about the potential implication of Toll like
EOSINOHILIC OESOPHAGITIS AND GORD – ROOM M_____________________ receptors (TLRs), the most investigated group of transmembrane PRR in EoE,
we characterized TLR mRNA expression and protein staining in esophageal
OP323 STEP-UP EMPIRIC ELIMINATION DIET FOR PEDIATRIC AND mucosal biopsy samples from adults before and after dietary treatment, and
ADULT EOSINOPHILIC ESOPHAGITIS: THE 2–4-6 STUDY compared with control patients. Esophageal mucosal samples were fixed in for-
J Molina Infante1, I Modolell2, J Alcedo3, R Garcia-Romero4, Arias Arias5, malin, embedded in paraffin, and routinely processed for hematoxylin and eosin
A Prieto-Garcia6, P.L Gonzalez-Cordero1, V Vila-Miravet7, C Santander8, staining. Specific antigen retrieval and permeabilization processes were per-
E Savarino9, C Guarner-Argente10, J. L Martin-Lorente11, M. L Masiques- formed before samples were incubated with the primary antibodies anti-TLR1,
Mas12, R Garcia-Puig13, M. C Murzi Pulgar10, O Nogales Rincon14, TLR2, TLR3, TLR4, TLR6, or TLR9. Incubation with the secondary antibodies
A.J Lucendo15 Alexa Fluor 594 goat anti-rabbit IgG or Alexa Fluor 488 goat anti-mouse IgG
1
Gastroenterology, Hospital San Pedro de Alcantara, Caceres/Spain Nuclei were counterstained with DAPI. Gene expression for the different TLR
2
Gastroenterology, Consorci Sanitari Terrassa, Barcelona/Spain assessed was evaluated in all samples after RNA was isolated with MirVanaTM
3
Gastroenterology, Hospital Universitario Miguel Servet, Zaragoza/Spain Kit. Simultaneous real-time PCRs were performed with TaqMan Low-Density
4
Pediatric Gastroenterology, Hospital Universitario Miguel Servet, Zaragoza/ Arrays. Thermal cycling conditions were 2 min at 50 C, 10 min at 95 C, followed
Spain by 40 cycles of denaturation at 95 C for 15 s, and annealing and extension at
5
Research Unit, Hospital La Mancha Centro, Alcazar de San Juan/Spain 60 C for 1 min in an ABI PRISM 7900 HT Sequence Detection System. Relative
6
Allergy, Hospital Universitario Gregorio Marañon, Madrid/Spain changes in mRNA expression were calculated with the cycle threshold (Ct)
7
Pediatric Gastroenterology, Hospital Sant Joan de Deu, Barcelona/Spain method.
8
Gastroenterology, Hospital Universitario de la Princesa, Madrid/Spain Result: A total of 10 EoE patients (8 men) and 10 gender-matched control sub-
9
Department Of Surgery, Oncology And Gastroenterology, University of Padua, jects were included in the analysis. The groups had a mean age of 33.1 (10.1) and
Padua/Italy 53 (19.9) years, respectively. In the EoE group, peak intraepithelial eosinophil
10
Gastroenterology, Hospital de la Santa Creu i San Pau, Barcelona/Spain density was 56.8 (29.9) cells/hpf, which decreased to 3 (4.2) cells/hpf after SFED-
11
Gastroenterology, Hospital Universitario de Burgos, Burgos/Spain based treatment (p 5 0.001). No intraepithelial eosinophils were detected in any
12
Pediatric Gastroenterology, Hospital de Granollers, Barcelona/Spain of the esophageal samples from controls. No differences in eosinophil counts
13
Pediatric Gastroenterology, Hospital Universitario Mutua Terrassa, Barcelona/ were detected for atopic and non-atopic EoE patients, being 55 (30.4) vs. 61
Spain (34.8) cells/hpf, respectively. Active EoE characterized by significant upregula-
14
Gastroenterology, Hospital General Universitario Gregorio Marañon, Madrid/ tion of TLR1 (2.7-fold increase), TLR2 (3.7-fold increase) TLR4 (4.6-fold
Spain increase) and TLR9 (3.4-fold-increase) in comparison with the controls
15
Gastroenterology, Hospital General de Tomelloso, Tomelloso/Spain (p 5 0.05 for all comparisons). Dietary treatment significantly decreased all the
four TLRs to control group values (p 5 0.05) Immunofluorescence staining
Contact E-mail Address: [email protected] demonstrated epithelial-predominant staining in TLR2 and TLR4, and scattered
Introduction: A six-food elimination diet (SFED) for eosinophilic esophagitis cell staining for TLR1 and TLR9. TLR expression patters showed differences in
(EoE) requires almost a year on a high level of dietary restriction and multiple lamina propria and epithelial layers.
endoscopies. A four-food elimination diet (FFED), eliminating the four most Conclusion: EoE is associated with changes in expression levels of several TLRs,
common culprit foods in EoE (animal milk, gluten-containing cereals, egg, that reverse after effective dietary therapy. Our results points towards an inter-
legumes) has been a first step to simplify empiric elimination strategies. play of diet, microbiome and innate immune responses in the pathophysiology of
Aims & Methods: To assess the effectiveness of a step-up empiric elimination diet EoE.
strategy for EoE. Prospective multicenter study conducted in 12 Spanish hospi- Disclosure of Interest: All authors have declared no conflicts of interest.
tals in both children and adults. All patients included fulfilled clinic and histo-
logic criteria for EoE and lack of response to PPI therapy was documented before
inclusion. Initial two-food elimination diet (animal milks and gluten-containing
cereals) was evaluated in all patients, stepping up to a FFED and eventually to a
SFED in non-responders. Response to dietary therapy was defined by symptom
improvement and 515 eos/HPF. In responders to empiric diet, each food group
was individually reintroduced for 6 weeks with further histologic reevaluation.
Food triggers were defined as those leading to esophageal inflammation 415
eos/HPF after individual reintroduction.
Result: Presently, 93 patients (25 pediatric) have been included. A two-food
elimination diet achieved EoE remission in 38 patients (40%) unresponsive to
PPI therapy. Remission rates increased to 52% and 65% with a FFED and
SFED, respectively. Individual food reintroduction has been completed in 26/
38 of responders to a two-food elimination diet, of whom 85% had a single food
trigger. The most common food triggers were animal milk (60%), gluten-contain-
ing cereals (25%) and both (15%). Compared to starting with a SFED, this step-
up strategy (2–4–6) allows reducing endoscopic procedures and the diagnostic
process time by 35%.
United European Gastroenterology Journal 4(5S) A127
OP325 A RANDOMISED, DOUBLE-BLIND, PLACEBO-CONTROLLED OP326 IMPAIRMENT OF CHEMICAL CLEARANCE AND MUCOSAL
TRIAL OF A NOVEL RECOMBINANT, HUMANISED, ANTI- INTEGRITY DISTINGUISH HYPERSENSITIVE ESOPHAGUS FROM
INTERLEUKIN-13 MONOCLONAL ANTIBODY (RPC4046) IN FUNCTIONAL HEARTBURN
PATIENTS WITH ACTIVE EOSINOPHILIC OESOPHAGITIS: M Frazzoni1, N De Bortoli2, L Marzio3, M Furnari4, I Martinucci5, S Tolone6,
RESULTS OF THE HEROES STUDY A Farioli3, S Marchi7, L Fuccio8, V Savarino9, E Savarino10
I Hirano1, M Collins2, Y Assouline-Dayan3, L Evans4, S Gupta5, A Schoepfer6, 1
Digestive Pathophysiology Unit, Baggiovara Hospital, Modena/Italy
A Straumann7, M Grimm8, H Smith9, C Tompkins9, A Woo9, R Peach9, 2
Dept. Of Gastroenterology, University of Pisa, Pisa/Italy
P Frohna9, S Gujrathi9, R Aranda10, E Dellon11 3
Gastroenterology Unit, Departmen Of Medical And Surgical Sciences, University
1
Feinberg School of Medicine, Chicago/United States of America of Bologna, Bologna/Italy
2 4
College Of Medicine, University of Cincinnati, Cincinnati/United States of Di.m.i., Gastroenterology Unit, DiMI, Gastroenterology Unit, University of
America/OH Genoa., Genoa/Italy
3 5
Carver College of Medicine, Iowa City/United States of America/IA Gastroenterology Unit, University of Pisa, Pisa/Italy
4 6
Grand Teton Research Group, Idaho Falls/United States of America Surgery, Second University of Naples, Naples/Italy
5 7
Indiana University School of Medicine, Indianapolis/United States of America/IN Dipartimento Di Medicina Interna - Università Degli Studi Di Pisa, Clinica
6
Centre Hospitalier Universitaire Vaudois, Lausanne/Switzerland Medica I/II Complesso S. Chiara, Pisa/Italy
7 8
University Hospital Basel, Basel/Switzerland Deprtment Of Medical And Surgical Sciences, S.Orsola-Malpighi University
8
Clinical Development, Receptos Inc., San Diego/United States of America/CA Hospital, Bologna/Italy
9 9
Clinical Development, Receptos Inc., San Diego/United States of America/CA Dept Internal Medecine, Universita di Genova, Genova/Italy
10 10
Clinical Development, Receptos Services, LLC, a fully owned subsidiary of Department Of Surgery, Oncology And Gastroenterology, University of Padua,
Celgene, San Diego/United States of America/CA Padua/Italy
11
School Of Medicine, University of North Carolina, Chapel Hill/United States of
America/NC Contact E-mail Address: [email protected]
Introduction: Hypersensitive esophagus (HE) is defined by endoscopy-negative
Contact E-mail Address: [email protected] heartburn with normal esophageal acid exposure time (EAET) but positive symp-
Introduction: Interleukin-13 (IL-13) has been implicated in the pathogenesis of tom association probability (SAP) and symptom index (SI) at reflux monitoring,
eosinophilic oesophagitis (EOE). RPC4046 prevents the binding of IL-13 to both and/or heartburn suppression with proton pump inhibitor (PPI) therapy.
the IL-13R1 and IL-13R2 receptors. This study evaluated the efficacy and Functional heartburn (FH) is distinguished by PPI-refractoriness and negative
safety of 2 dose levels of RPC4046 compared to placebo (PBO). SAP/SI. However, diagnostic accuracy of SAP and SI has been recently ques-
Aims & Methods: Subjects were randomized 1:1:1 to receive either RPC4046 tioned leading to consider with caution the diagnosis of FH/HE based on symp-
180 mg [LD] (n ¼ 31), RPC4046 360 mg [HD] (n ¼ 34), or PBO (n ¼ 34). An IV tom-reflux association analysis only.
dose on Day 1 was followed by weekly subcutaneous doses. Oesophageal biop- Aims & Methods: We aimed to investigate whether impairment of chemical clear-
sies, read by a central blinded pathologist, were obtained at baseline (BL) and ance, expressed by post-reflux swallow-induced peristaltic wave (PSPW) index,
Wk16 to assess change in mean eosinophil count, the primary endpoint. and of mucosal integrity, expressed by mean nocturnal baseline impedance
Secondary endpoints included symptom improvement measured by a Daily (MNBI), distinguish HE from FH independently from SAP and SI.
Symptom Diary (DSD), improvement in endoscopic features as measured by Impedance-pH tracings from 303 patients with PPI-dependent (i.e. heartburn
the EOE Endoscopic Reference Score (EREF), and Subject’s Global repeatedly abolished by 4-week PPI-therapy and repeatedly recurring after PPI
Assessment of Disease Severity. Safety was also assessed. withdrawal) or PPI-refractory (i.e. 550% of symptom relief after 8-week high-
Result: 90 subjects completed the 16Wk double-blind period. Demographic/dis- dosage PPI therapy) heartburn were blindly reviewed, 125 with non-erosive
ease characteristics were generally comparable between treatment arms. At BL, reflux disease (NERD) defined by abnormal EAET, 108 with HE (normal
mean oesophageal eosinophil counts (cells/hpf) were 92.4 (PBO), 116.6 (LD), and EAET, but positive symptom-reflux correlation) and 70 with FH (normal
122.6 (HD). At Wk16, the mean count was significantly reduced from BL for EAET and negative symptom-reflux correlation). Impedance-pH tracings were
both RPC4046 dose levels compared to PBO (mean change: PBO –4.4, LD –94.8, manually analyzed to detect: EAET (abnormal if 3.2% over 24 hours), char-
and HD –99.9 [both p 5 0.0001 vs PBO]). There was a greater improvement in acteristics of reflux episodes (acid/weakly acidic) and symptom-reflux association
dysphagia symptoms as measured by the DSD with HD compared to PBO, but using both SAP (positive if 95%) and SI (positive if 50%). MNBI values were
this did not achieve statistical significance (PBO –6.4, LD –5.3 [p ¼ 0.996 vs calculated at 3 cm above the LES, during the overnight rest, for at least 30
PBO], and HD –13.3 [p ¼ 0.073 vs PBO]). There were significant improvements minutes after excluding swallows and reflux induced changes. The PSPW index
in endoscopic features as determined by the reduction in the total mean EREF was calculated by dividing the number of refluxes followed within 30 seconds by
score with both RPC4046 dose levels (mean change: PBO –0.9, LD –4.2, and HD swallow-induced peristaltic waves with the number of total refluxes.
–4.8 [both p 5 0.0004 vs PBO]). There was a significant improvement in Subject’s Result: In PPI-dependent patients with HE, PSPW index and MNBI were the
Global Assessment of Disease Severity at the HD (PBO 1.5, LD 2.0, HD 2.8 most sensitive impedance parameters; at multivariate analysis, they were inde-
[HD p ¼ 0.0107 vs PBO]). The rates of overall adverse events (AEs) were 64.7% pendent predictors of HE. At receiver operating characteristic analysis, PSPW
(PBO), 64.5% (LD), and 85.3% (HD). The most frequent AEs were headache index with MNBI efficiently separated HE from FH: the area under the curve
(PBO 14.7%, LD 16.1%, HD 20.6%), upper respiratory infection (PBO 8.8%, was 0.957. Only 50/108 (46%) patients with HE had concordant SAP/SI positiv-
LD 16.1%, HD 14.7%), and arthralgia (PBO 0%, LD 12.9%, HD 5.9%). ity, 48 (96%) of them with abnormal PSPW index and/or MNBI. Abnormal
Conclusion: RPC4046 demonstrated significant reductions in oesophageal eosi- values for PSPW index and/or MNBI were found in 34/39 (87%) of SAP/SI
nophilic inflammation and improvements in endoscopic features at both dose negative and in 15/17 (88%) of SAP/SI discordant cases.
levels. Subjects receiving the HD had greater symptom improvement than those Conclusion: HE is characterized by impairment of chemical clearance and of
on LD. These phase 2 data support the further study of RPC4046 as a novel mucosal integrity. When EAET is normal and SAP/SI afford inconclusive results,
treatment for EOE. (clinicaltrials.gov ID: NCT02098473) PSPW index and MNBI should be analyzed to objectively distinguish HE from
Disclosure of Interest: I. Hirano: I am a consultant for Receptos, Regeneron, FH
Shire pharma Disclosure of Interest: All authors have declared no conflicts of interest.
M. Collins: I have received research funds (through contracts) from Receptos
(now Celgene), Meritage (now Shire), Shire, and Regeneron, and I am a con-
sultant for Banner Life Sciences and Adare.
S. Gupta: Sandeep K. Gupta received consulting fees and/or speaker fees from OP327 THE ADDED VALUE OF POST-REFLUX SWALLOW-INDUCED
Abbott Laboratories, Nestlé S. A., QOL, Receptos, Inc., and Meritage Pharma, PERISTALTIC WAVE INDEX AND NOCTURNAL BASELINE
Inc. IMPEDANCE IN REFRACTORY GERD STUDIED WITH ON-
A. Schoepfer: I received consultant fees from: Receptos, Regeneron and grant THERAPY IMPEDANCE-PH MONITORING
support from: Receptos, Regeneron, Falk. M. Frazzoni1, N. De Bortoli2, L. Frazzoni3, M. Furnari4, I. Martinucci5,
A. Straumann: Dr. Staumann is a consultant to Dr Falk Pharma GmbH and has S. Tolone6, S. Marchi7, V. Savarino8, E. Savarino9
received consulting fees and/or speaker fees and/or research grants from 1
Digestive Pathophysiology Unit, Baggiovara Hospital, Modena/Italy
Actelion, AG; AstraZeneca, AG;, Aptalis Pharma; GSK, AG; Nestlé S. A.; 2
Dept. Of Gastroenterology, University of Pisa, Pisa/Italy
Novartis, AG; Pfizer, AG, and Regeneron. 3
Gastroenterology Unit, Department Of Medical And Surgical Sciences, University
M. Grimm: I am an employee of Celgene. of Bologna, Bologna/Italy
H. Smith: I am an employee of Celgene. 4
Di.m.i., Gastroenterology Unit, DiMI, Gastroenterology Unit, University of
C. Tompkins: I am an employee of Celgene. Genoa., Genoa/Italy
A. Woo: I am an employee of Celgene. 5
Gastroenterology Unit, University of Pisa, Pisa/Italy
R. Peach: I am a former employee of Celgene. 6
Surgery, Second University of Naples, Naples/Italy
P. Frohna: I am an employee of Celgene. 7
Dipartimento Di Medicina Interna - Università Degli Studi Di Pisa, Clinica
S. Gujrathi: I am a former employee of Celgene. Medica I/II Complesso S. Chiara, Pisa/Italy
R. Aranda: I am an employee of Celgene. 8
Dept Internal Medecine, Universita di Genova, Genova/Italy
E. Dellon: I have received research funding from Receptos/Celgene; and am a 9
Department Of Surgery, Oncology And Gastroenterology, University of Padua,
Consultant for Receptos/Celgene. Padua/Italy
All other authors have declared no conflicts of interest.
Contact E-mail Address: [email protected]
Introduction: On-therapy impedance-pH monitoring in proton pump inhibitor
(PPI)-refractory gastroesophageal reflux disease (GERD) yielded conflicting
results. Recently, novel impedance parameters assessing esophageal chemical
clearance and mucosal integrity, namely the post-reflux swallow-induced peri-
staltic wave (PSPW) index and the mean nocturnal baseline impedance (MNBI),
have been shown to increase the diagnostic yield of impedance-pH monitoring in
A128 United European Gastroenterology Journal 4(5S)
investigating PPI-refractory patients studied off-therapy, further improving the myocardial infarction related sudden death at 11 month post-op, not related to
management of these patients. device or procedure was reported. One event of lead erosion into the esophagus
Aims & Methods: We aimed to investigate whether the impairment of chemical was detected during routine endoscopy. The device was removed during laparo-
clearance, expressed by PSPW index, and of mucosal integrity, expressed by scopic fundoplication procedure. Two events of gastroparesis, possibly related to
MNBI, are helpful in segregating NERD from FH studied with impedance-pH the device requiring hospitalization were reported in one patient.
monitoring on-PPI therapy. Further, we assessed the value of these novel para- Conclusion: Electrical stimulation of the LES is safe and effective in clinical
meters as predictors of PPI-refractory GERD confirmed by 3-year positive sur- practice in treating GERD patients with disruptive GERD symptoms despite
gical outcome. On-therapy impedance-pH tracings from consecutive patients PPI. LES stimulation results in significant improvement in GERD outcomes
referred for PPI-refractory heartburn with/without regurgitation (i.e. 550% of and reduced healthcare resource utilization. LES-ES should be considered a
symptom relief or mucosal healing after 8-week high-dosage PPI therapy) were viable treatment option for treating GERD patients with disruptive GERD
blindly reviewed. All tracings were manually analyzed to detect: acid exposure symptoms despite maximal medical management.
time (AET; abnormal if 3.2% over 24 hours), characteristics of reflux episodes Disclosure of Interest: All authors have declared no conflicts of interest.
(acid/weakly acidic) and symptom-reflux association using both symptom asso-
ciation probability (SAP; positive if 95%) and symptom index (SI; positive if
50%). MNBI values were calculated at 3 cm above the LES, during the over- WEDNESDAY, OCTOBER 19, 2016 08:30–10:00
night rest, for at least 30 minutes after excluding swallows and reflux induced DIAGNOSIS AND TREATMENT OF PANCREATIC CANCER AND ITS PRECURSORS –
changes. The PSPW index was calculated by dividing the number of refluxes ROOM N1_____________________
followed within 30 seconds by swallow-induced peristaltic waves with the
number of total refluxes. Patients were subdivided into refractory reflux esopha- OP329 SURVEILLANCE OF HIGH-RISK INDIVIDUALS DETECTS
gitis (RRE), healed reflux esophagitis (HRE), non-erosive reflux disease (NERD; RESECTABLE PANCREATIC MALIGNANCIES AND HIGH-GRADE
defined by abnormal acid exposure time or normal AET but positive symptom- PRECURSORS: RESULTS OF A 16-YEAR EARLY DETECTION
reflux correlation) and functional heartburn (FH; defined by normal AET and PROGRAM FOR FAMILIAL PANCREATIC NEOPLASIA
negative symptom-reflux correlation) according to endoscopy and conventional J.A. Almario1, M.I. Canto2, R.H. Hruban3, A.M. Lennon1, C. Wolfgang4,
impedance-pH variables. M. Weiss4, K. Hirose4, E.J. Shin1, E. K. Fishman5, I. R. Kamel5, C. Yeo6,
Result: Median PSPW index and MNBI were significantly lower in 39 RRE R. Schulick7, M. Goggins3
(16%; 1145 Ohms) than in 41 HRE (25%; 1741 Ohms) and in 68 NERD 1
Department Of Gastroenterology, Johns Hopkins Medical Institution, Baltimore/
(29%; 2374 Ohms) patients, and in all three GERD subgroups compared to 41 United States of America/MD
FH cases (67%; 3488 Ohms) (P ¼ 0.0001). Comparing NERD to FH, PSPW 2
Gastroenterology, Johns Hopkins Medical Institution, Baltimore/United States of
index showed an area under curve greater than MNBI at receiver-operating- America/MD
characteristic analysis (0.886 vs. 0.677, P ¼ 0.005). PSPW index was abnormal 3
Department Of Pathology, Johns Hopkins Medical Institution, Baltimore/United
preoperatively in 53/53 patients with positive surgical outcome and resulted States of America/MD
independent predictor of PPI-refractory GERD at multivariate analysis, (odds 4
Department Of Surgery, Johns Hopkins Medical Institution, Baltimore/United
ratio 0.6983, P ¼ 0.012). States of America/MD
Conclusion: At on-therapy impedance-pH monitoring, impaired chemical clear- 5
Department Of Radiology And Radiological Science, Johns Hopkins Medical
ance and mucosal integrity characterize PPI-refractory typical GERD. PSPW Institution, Baltimore/United States of America/MD
index and MNBI efficiently distinguish PPI-refractory NERD from FH and 6
Department Of Surgery, Thomas Jefferson University Hospital, Philadelphia/
PSPW index appears useful for selecting surgical candidates. United States of America/PA
Disclosure of Interest: All authors have declared no conflicts of interest. 7
Department Of Surgery, University of Colorado School of Medicine, Aurora/
United States of America/CO
Contact E-mail Address: [email protected]
OP328 PRELIMINARY RESULTS OF A PROSPECTIVE MULTI-CENTER Introduction: Endoscopic ultrasonography (EUS) and/or magnetic resonance
REGISTRY OF LOWER ESOPHAGEAL SPHINCTER STIMULATION imaging (MRI) screening of asymptomatic individuals (HRI) at high risk for
FOR GERD: THE LESS-GERD REGISTRY PDA to detect for early pancreatic neoplasia can lead to the detection of small
J. Labenz1, H. Schulz2, A. Leodolter3, J. Pedersen4, A. Nieponice5, R. Weise6, pancreatic cysts in almost 40%1. However, there is limited understanding risk for
N. Bouvy7 neoplastic progression and the natural history of low risk detected lesions after
1
Abt. Für Innere Medizin, Diakonie Klinikum Abt. für Innere Medizin, Siegen/ baseline screening. The long-term clinical outcomes of radiologic surveillance
Germany aiming to detect early PDA and high-grade precursor lesions (IPMN HGD or
2
Evangelisches Krankenhaus Castrop-Rauxel, Castrop-Rauxel/Germany PanIN3 ¼ HPCLs) are also not well understood.
3
Evangelisches Krankenhaus Herne, Herne/Germany Aims & Methods: To determine the incidence of surveillance-detected pancreatic
4
Aarhus University Hospital, Aarhus/Denmark lesions following baseline screening and calculate the incidence rates of invasive
5
Fundación Favaloro, Buenos Aires/Argentina malignancy and high-grade neoplasia in HRI undergoing long-term surveillance.
6
St.-Marien-Hospital, Friesoythe/Germany We prospectively enrolled HRI in the Cancer of the Pancreas Screening (CAPS)
7
Clinical Research, Maastricht University Medical Center, Maastricht/ studies from 1998 to 2014 (n ¼ 578) at a tertiary referral academic medical center
Netherlands with a comprehensive multidisciplinary pancreas screening program. HRI con-
sisted of familial PDA relatives or PDA-associated gene mutation carriers
Contact E-mail Address: [email protected] (BRCA 1/2, PALB2, p16, PRSS1, STK11) who had a 46 months of follow-up
Introduction: Safety and effectiveness of electrical stimulation of the lower eso- imaging after baseline EUS and MRI. HRI with baseline solid masses or pre-
phageal sphincter (LES-ES) using the EndoStimÕ LES Stimulation System (The valent PDA were excluded from the surveillance cohort analyses. Radiological
Hague, The Netherlands) was demonstrated in clinical trials. Limited data avail- features of progression (new solid mass, and worrisome features defined by
able on outcomes in clinical practice. Sendai International Consensus Guidelines (ICG) for pancreatic mucinous
Aims & Methods: An ongoing, prospective international multicenter web-based cysts) were compared to pathologic diagnoses or repeat abdominal imaging
registry is collecting data in patients with disruptive GERD symptoms treated according to clinical surveillance protocol.
with LES-ES in clinical practice at baseline and at routine follow-ups for 5-year. Result: 343 HRI were screened and underwent follow-up imaging with EUS and/
Demographics, adverse events, GERD symptoms recorded in daily diaries, or MRI every 6–12 months (depending on baseline findings). 293 (85%) familial
GERD health related quality of life scores (GERD-HRQL), structured GI symp- PC relatives and 50 (15%) mutation carriers were studied, mean age 56.4 (range
tom questionnaires for extra-esophageal symptoms, use of proton pump inhibi- 22–81), 47% male. Mean follow-up time was 5.1 years (range 0.5–15.1). 132/341
tors (PPIs) and physiological data (esophageal pH / manometry) are collected HRI (38%) had no pancreatic lesions at baseline and follow-up, 155 (45%) had a
when available. low risk cyst at baseline, and 12 (3.5%) had a solid mass or nodule at baseline. 74
Result: Data was available in 50 patients enrolled in eleven sites with 6 months HRI (22%) developed new low risk cysts on follow-up. 54/343 HRI (16%)
post-op follow upand from 28 patients with 12 months follow-up. Ninety% (43/ developed radiological progression, with detection of a new solid mass
48) patients showed an improvement in their GERD-HRQL score on LES-ES at 6 (n ¼ 24,7%%), cyst growth 42 mm in 6 months (n ¼ 11, 3.2%), or 41 ICG
months and 93% (25/27) showed an improvement at 12 months compared to worrisome features (mural nodule n ¼ 7, 2%), dilated main pancreatic duct
baseline. The median (IQR) composite GERD-HRQL score improved from 22 (MPD) 45 mm(n ¼ 15,4.4%), abrupt change in MPD caliber (n ¼ 1), cyst size
(17–27) preoperatively to 8.0 (4.0–13.3) at 6-month (p 5 0.001) and from 20.0 43 cm (n ¼ 2). Of these 54 HRI with progression, 38 had surgery and 21 of these
(17–23.5) to 5.0 (2.0–7.0) at 12-months (p 5 0.001). At baseline, 44% of patients (58%) had PDA, malignant pancreatic neuroendocrine tumor (PanNET), or
(22/50) complained on daily bothersome heartburn symptoms affecting sleep HPCLs. The median time to radiological progression from baseline screening
which decreased to 8% (4/50) at 6 months (p 5 0.001) and 0% (0/28) at 12 was 3.2 years (IQ range 1.2–6 years), with some HRI progressing at 10.9 years.
months (p 5 0.001). At baseline, 52% and 15% of subjects reported moderate In contrast, none of HRI without detected lesions at baseline or follow-up devel-
or severe regurgitation, respectively which decreased to 22% and 7% at 6 months oped PDA (p ¼ .002). During surveillance, 13/343 (3.8%) incident PDA and 8/
(n ¼ 27) and 14% and 0% at 12 months (n ¼ 14). Data on prior hospitalization 343 (2.3%) incident malignant neuroendocrine tumors were detected (all with
due to GERD was available from 40 patients who with hospitalization data radiologic progression). An additional 8/343 (2.3%) HRI had HPCLs. The inci-
available for their 6 m visit (1 m). Annualized hospitalization rates due to dence of PDA was 1/50 (2%) in mutation carriers and 12/293 (4%) in familial PC
GERD at baseline pre EndoStim was 1.1 days/year (n ¼ 40) and 45% (18/40) relatives. Of the 50 patients with pathological diagnoses (45 surgical resection, 5
reported at least one hospitalization due to GERD which at last follow up biopsy), 27 of 29 (93%) with radiological features of progression had a malig-
decreased to 0.3 days/year with 83% of patients who were required hospitalization nancy (PDA ¼ 13 or PanNET tumor ¼ 6), or at least one HPCL (n ¼ 8). 10 of 13
pre-op reporting no hospitalization post-op. All patients were on long-term PPI at (77%) of incident PDA were resectable (3 unresectable PDAs were late for sur-
baseline. Seventy-one% (45/63) patients at 6 month and 75% (27/36) patients at veillance or lost to follow-up). 16/45 (36%) HRI who had surgery had lower-
12 months were completely off PPI. Data on 24 h esophageal pH at 6 m showed a grade neoplasms (BD-IPMN LGD/IGD, PanIN2, combined IPMN, SCA,
non-statistically significant improvement. Safety data was adjudicated by an inde- benign neuroendocrine microadenomas). In surgically-treated HRI, the preva-
pendent DSMB. Four serious adverse events in three patients were reported. One lence of IPMN HGD in cysts with mural nodules was 5/7 (71%).
United European Gastroenterology Journal 4(5S) A129
Conclusion: In our 16-year cohort with long-term surveillance, the incidence of or black particles’’ for PseudoCyst (PC). In case of doubt between IPMN and
PDA was modestly elevated but majority of detected cancers were asymptomatic MCN, Undetermined Mucinous Lesion (UML) was proposed. The absence of
and resectable. Surveillance also detects early stage PanNETs and HPCLs. The criteria led to inconclusive nCLE diagnosis considered as false-negative. Nine
majority of detected proven malignancies had radiologic progression but more patients were withdrawn for screen failure (n ¼ 6) or procedure failure (n ¼ 3).
research is needed to improve the selection of patients for surveillance and Among the 208 analyzable patients, final diagnosis was proven in 90 cases by
surgery. cytopathological analysis of cystic fluid obtained by FNA (n ¼ 59) or by surgical
Disclosure of Interest: All authors have declared no conflicts of interest. histopathology (n ¼ 31). Statistical analysis of nCLE performance was done for
Reference cysts sufficiently represented.
Result: Among the 217 nCLE procedures, 98.6% were successfully performed.
1. Canto M, et al. Frequent Detection of Pancreatic Lesions in Asymptomatic The pancreatitis rate was 2.3% and no other significant complication occurred.
High-Risk Individuals. Gastroenterology 2012; 142: 796–804. nCLE was inconclusive in 27 cases. The 90 proven final diagnosis were 32 SCA,
46 Mucinous Lesions (ML) (23 IPMN, 14 MCN and 9 UML), 6 NEN, 2 PC, 1
cystic solid pseudopapillary neoplasm, 1 cystic lymphoma, 1 cystic lymphan-
gioma and 1 congenital pancreatic cyst. These last 6 cysts were underrepresented
OP330 CLINICAL IMPACT OF ENDOSCOPIC ULTRASONOGRAPHY and therefore withdrawn from statistical analysis. In the remaining 84 patients,
IMAGING OF CHRONIC PANCREATITIS IN THE PANCREATIC nCLE was inconclusive in 5 cases. The performances of nCLE were as follows:
PARENCHYMA IN PATIENTS WITH INTRADUCTAL PAPILLARY
MUCINOUS NEOPLASMS SCA ML IPMN MCN NEN
M. Takenaka1, A. Masuda2, M. Kitano3, H. Shiomi4, S. Oomoto3, K. Minaga3,
T. Miyata3, K. Kamata3, K. Yamao3, H. Imai3, Y. Arisaka5, Y. Okabe5, n 32 46 23 14 6
M. Kudo3 Se (%) 88 87 87 57 100
1
Department Of Gastroentelorogy, Kinki University, Osaka-sayama/Japan
2 Sp (%) 98 97 96 97 100
Gastroenterology, Kobe university, Kobe/Japan
3
Gastroenterology & Hepatology, Kinki University, Osaka-sayama/Japan
4
Gastroenterology, KobeUniversity Graduate School ofMedicine, Kobe, Japan, Conclusion: This large prospective study validates the very high sensitivity and
Kobe/Japan specificity of nCLE for the diagnosis of solitary non communicating PCL which
5
Gastroenterology, Kobe University, Kobe/Japan represents the main diagnostic issue. Being able to precisely discriminate between
benign (SCA) or premalignant lesions (ML, NEN), the nCLE procedure would
Contact E-mail Address: [email protected] significantly improves patient management by avoiding either repeated follow-up
Introduction: The recent guideline for intraductal papillary mucinous neoplasms procedures or unnecessary resections due to diagnosis uncertainties. nCLE pro-
(IPMNs) focuses on morphological features of the lesion as signs of malignant cedures should now be included in the guidelines.
transformation, but ignores the background pancreatic parenchyma, including Disclosure of Interest: B. Napoléon: Dr. Napoleon reports non financial support
features of chronic pancreatitis, a risk factor for pancreatic malignancies. from Mauna Kea Technologies, Grants from Mauna Kea Technologies; personal
Endoscopic ultrasonography frequently reveals evidence of chronic pancreatitis fees from Mauna Kea Technologies, during the conduct of the study; personal
(EUS-CP findings) in the background pancreatic parenchyma of patients with fees from Mauna Kea Technologies, outside the submitted work.
IPMNs. Therefore, we investigated whether background EUS-CP findings were L. Palazzo: Dr. Palazzo reports non financial support from Mauna Kea
associated with malignant IPMN. Technologies during the conduct of the study.
Aims & Methods: Clinical data for 69 consecutive patients with IPMNs who B. Pujol: Dr. Pujol reports non financial support from Mauna Kea Technologies,
underwent preoperative EUS and surgical resection between April 2010 and Grants from Mauna Kea Technologies; personal fees from Mauna Kea
October 2014 were collected prospectively. The association of EUS-CP findings Technologies, during the conduct of the study; personal fees from Mauna Kea
(total number of EUS-CP findings; 0 vs. 1) with invasive IPMN was examined. Technologies, outside the submitted work.
The association of EUS-CP findings with pathological changes of the back- F. Caillol: Dr. Napoleon reports non financial support from Mauna Kea
ground pancreatic parenchyma (atrophy/inflammation/fibrosis) was also Technologies, Grants from Mauna Kea Technologies.
examined. M. Palazzo: Dr. Palazzo reports non financial support from Mauna Kea
Result: Among patients with EUS-CP findings, invasive intraductal papillary Technologies during the conduct of the study.
mucinous carcinoma (IPMC) was significantly more frequent than among A. Aubert: Dr. Aubert reports non financial support from Mauna Kea
patients without EUS-CP findings (42.5% (17/40) vs. 3.4% (1/29), p ¼ 0.0002). Technologies during the conduct of the study.
In addition, patients with EUS-CP findings had higher grades of pancreatic F. Maire: Dr. Maire reports non financial support from Mauna Kea
atrophy and inflammation than patients without EUS-CP findings (atrophy: Technologies during the conduct of the study.
72.5% (29/40) vs. 34.5% (10/29), p ¼ 0.003, inflammation: 45.0% (18/40) vs. L. Buscail: Dr. Palazzo reports non financial support from Mauna Kea
20.7% (6/29), p ¼ 0.04). Technologies during the conduct of the study.
Conclusion: In IPMN patients, detection of EUS-CP findings in the background A.I. Lemaistre: Dr. Lemaistre reports personal fees from Mauna Kea
pancreatic parenchyma was associated with a higher prevalence of invasive Technologies, during the conduct of the study; personal fees from Mauna Kea
IPMC. Accordingly, EUS examination should not only assess the morphological Technologies, outside the submitted work.
features of the lesion itself, but also EUS-CP findings in the background M. Giovannini: Dr. Giovannini reports non financial support from Mauna Kea
parenchyma. Technologies, Grants from Mauna Kea Technologies, during the conduct of the
Disclosure of Interest: All authors have declared no conflicts of interest. study.
References
1. Konda VJ et al., Endoscopy 2013.
OP331 NEEDLE-BASED CONFOCAL LASER ENDOMICROSCOPY 2. Nakai Y et al., Gastrointestinal Endoscopy 2015.
(NCLE) FOR THE DIAGNOSIS OF SOLITARY PANCREATIC 3. Napoléon B et al., Endoscopy 2015.
CYSTS: A PROSPECTIVE MULTICENTER STUDY 4. Napoleon B et al., Surgical Endoscopy 2015.
B. Napoléon1, L. Palazzo2, B. Pujol1, F. Caillol3, M. Palazzo4, A. Aubert5,
F. Maire6, L. Buscail7, A.I. Lemaistre8, M. Giovannini3
1
69 Hôpital Prive´ Jean Mermoz, Lyon/France
2
Department Of Endoscopy, Trocadero Clinic, Paris/France OP332 RISK OF PROGRESSION AMONG LOW RISK IPMNS IN A
3
Endoscopy, Institut Paoli Calmette, marseille/France LARGE MULTICENTER SURVEILLANCE COHORT STUDY
4
92, Hôpital Beaujon, Clichy/France V. Gausman1, M. Moris2, M. Kayal3, J. M. Poneros4, A. Sethi3, F.G. Gress4, B.
5
92, Hopital Beaujon, Clichy/France A. Schrope5, L. Luk6, E. Hecht6, M. B. Wallace7, T.A. Gonda4
6 1
92, Hôpital beaujon, Clichy/France Internal Medicine, NYU - Langone Medical Center, New York/United States of
7
31, Hôpital Rangueil, Toulouse/France America/NY
8 2
69, Centre Le´on Be´rard, Lyon/France Department Of Gastroenterology And Hepatology, Mayo Clinic, Jacksonville/
United States of America/FL
Contact E-mail Address: [email protected] 3
Division Of Digestive And Liver Diseases, Department Of Medicine, Columbia
Introduction: Diagnosis of solitary pancreatic cyst is clinically challenging due to University, New York/United States of America/NY
the malignant potential of several cyst subtypes. nCLE is emerging as a powerful 4
Division Of Digestive And Liver Diseases, Columbia University, New York/United
technique which enables the observation of the inner wall of pancreatic cysts, States of America/NY
in vivo and in real-time, during an endoscopic ultrasound-guided fine needle 5
Department Of Surgery, Columbia University, New York/United States of
aspiration (EUS-FNA). Three clinical trials evaluated the feasibility, the safety America/NY
and highlighted specific criteria for the characterization of pancreatic cystic 6
Department Of Radiology, Columbia University, New York/United States of
lesions. This study aims to prospectively evaluate the diagnostic performance America/NY
of nCLE procedure on a larger cohort of patients. 7
Department Of Gastroenterology And Hepatology, Mayo Clinic, Jacksonville/
Aims & Methods: 217 patients carrying a single large (42 cm) pancreatic cystic United States of America/FL
lesion (PCL) without evidence of communication with the main pancreatic duct
and scheduled for EUS-FNA procedure were included in five centers. nCLE Contact E-mail Address: [email protected]
diagnosis was based on published criteria: ‘‘superficial vascular network’’ for Introduction: Intraductal papillary mucinous neoplasms (IPMNs) are pancreatic
Serous CystAdenoma (SCA), ‘‘papillae’’ for Intraductal Papillary Mucinous cysts that carry a risk of malignant transformation to pancreatic ductal adeno-
Neoplasms (IPMN), ‘‘epithelial border’’ for Mucinous Cystic Neoplasms carcinoma (PDAC). Guidelines have been evolving to best identify which criteria
(MCN), ‘‘dark spots of cell aggregates surrounded by gray areas of fibrosis should qualify a patient for resection and which cysts can safely remain under
and vessels’’ for NeuroEndocrine Neoplasms (NEN) and ‘‘field of bright, gray
A130 United European Gastroenterology Journal 4(5S)
surveillance. Our aim was to understand which baseline cyst and patient features male gender, a history of prostate cancer and diabetes, weight loss and initial
predict disease progression and malignant transformation. cyst size 42 cm. A history of prostate cancer, diabetes, weight loss, elevated cyst
Aims & Methods: Patients with clinically suspected IPMN who did not meet fluid CEA and cyst size 42 cm were associated with development of worrisome
consensus criteria for resection at diagnosis and were surveyed for at least 12 features. In logistic regression analysis, a history of prostate cancer (OR 2.9; 95%
months or underwent surgery after a minimum surveillance of 3 months were CI 1.7–7.7) and weight loss (OR 2.47; 95% CI 1.18–6.1) were associated with
included. All patients evaluated by radiologic studies or endoscopic ultrasound development of worrisome features (p 5 0.05). There were no baseline predictors
between 1998 and 2015 were included. We defined progression as either an of cyst size increase alone. Baseline characteristics such as race, smoking or
increase in size of the dominant cyst 20% or 2 mm or the development of alcohol use, a strong family history of PDAC, multifocality and location of
worrisome features (mural nodule or mass, thick septations, main duct involve- cysts were not associated with increased disease progression.
ment or high grade dysplasia or cancer on cytology or surgical pathology). Conclusion: In the largest multicenter surveillance study of low risk IPMNs to
Statistical analysis was performed with the Chi square and Fisher exact tests date, we showed that 41% of suspected IPMNs increased in size only, 9% devel-
for categorical variables and Mann-Whitney U test for continuous variables. oped worrisome features and 2% developed high-grade dysplasia or cancer.
All covariates of interest with p 5 0.05 in the univariate analysis were included Among baseline characteristics, none were predictive of size increase. A personal
in the logistic regression model. history of prostate cancer and weight loss were the strongest predictors of the
Result: development of worrisome features.
Disclosure of Interest: All authors have declared no conflicts of interest.
Progression by
Progression development of
Non- by cyst worrisome
progressors size increase features OP333 MULTIMODALITY TREATMENT OF LOCALLY ADVANCED
(n ¼ 248) (n ¼ 205) (n ¼ 46) PANCREATIC CANCER, INCLUDING FOLFIRINOX
CHEMOTHERAPY, SURGICAL EXPLORATION AND
Age at 1st study, mean 65.3 (11.3) 66.6 (10.7) 68.5 (10.6) IRREVERSIBLE ELECTROPORATION: PROSPECTIVE SERIES OF
(SD) 132 CONSECUTIVE PATIENTS
Male gender, n (%) 95 (38.3%) 80 (39%) 24 (52.2%) J. A. Anne Vogel1, S. J. Rombouts1, T. De Rooij1, O.R. c. Busch1, O. M.
Van Delden2, M. G. Dijkgraaf3, J.E. Van Hooft4, H. W. Van Laarhoven5, R.
Race
C. Martin6, A. Schoorlemmer1, J. W. Wilmink7, K. P. Van Lienden2, M.G. h.
White, n (%) 174 (86.6%) 152 (85.4%) 33 (82.5%) Besselink1
1
Black, n (%) 11 (5.5%) 11 (6.2%) 5 (12.5%) Surgery, Academic Medical Center, Amsterdam/Netherlands
2
Asian, n (%) 9 (4.5%) 8 (4.5%) 0 Radiology, Academic Medical Center, Amsterdam/Netherlands
3
Clinical Research Unit, Academic Medical Center, Amsterdam/Netherlands
Smoker ever, n (%) 100 (43.1%) 86 (44.1%) 22 (51.2%) 4
Gastroenterology, Academic Medical Center, Amsterdam/Netherlands
EtOH use ever, n (%) 108 (47%) 85 (44.7%) 22 (50%) 5
Medical Oncology, Academic Medical Center, Amsterdam/Netherlands
6
CP, n (%) 9 (3.7%) 5 (2.5%) 3 (6.8%) Surgery, University of Louisville, Louisville/United States of America/KY
7
AP, n (%) 18 (7.5%) 10 (5.1%) 2 (4.5%) Medical Oncology, Academic Medical Center Amsterdam, Amsterdam/
Netherlands
Cancer, n (%) 75 (30.5%) 78 (38.4%) 21 (46.7%) *
Colon, n (%) 3 (1.2%) 4 (2%) 3 (6.7%) * Contact E-mail Address: [email protected]
Breast, n (%) 7 (2.8%) 12 (5.9%) 0 Introduction: Novel treatment options in locally advanced pancreatic cancer
(LAPC), including FOLFIRINOX and irreversible electroporation (IRE) have
Prostate, n (%) 6 (2.4%) 12 (5.9%) 8 (17.8%) * shown promising survival-rates. However, outcomes are heavily influenced by
Diabetes, n (%) 56 (23%) 45 (22.4%) 20 (44.4%) * selection bias as most studies were retrospective and excluded patients who did
Family hx of PDAC, 22 (9.5%) 21 (11%) 2 (4.8%) not receive FOLFIRIONX or had progressive disease.
n (%) Aims & Methods: We aimed to describe outcomes of multimodality treatment
Baseline symptoms, 71 (28.6%) 60 (29.3%) 14 (30.4%) with chemotherapy, surgical exploration and IRE in a prospective consecutive
n (%) LAPC-cohort. Patients with histologically proven LAPC (Dutch guideline:
490 arterial and/or 4270 venous involvement) were prospectively registered
Abd pain, n (%) 65 (26.2%) 49 (23.9%) 11 (23.9%) (September 2013–March 2015). After 3 months of chemotherapy
Weight loss, n (%) 11 (4.4%) 18 (8.8%) 6 (13%) * (FOLFIRINOX for WHO physical status 0–1 patients, otherwise gemcitabine),
Jaundice, n (%) 1 (0.4%) 1 (0.5%) 0 restaging was performed by assessing RECIST 1.1-response, resectability, and
Serum CEA, median 1.6 (1, 3) 1.6 (1, 2.2) 1.1 (.8, 2.3) IRE-eligibility (tumor 5 cm, sufficient vascular patency). All patients with non-
(IQR) progressive disease, eligible for IRE proceeded to laparotomy, regardless of
resectability. The study was registered with the Dutch trial registry NTR4230.
Serum CA 19–9, 13.5 (4.8, 37.3) 17 (8, 46) 14 (10.3, 27.5) Result: Of 132 consecutive LAPC-patients, 93 (70%) received chemotherapy (59
median (IQR) (45%) FOLFIRINOX). After 3 months, 59 (45%) had non-progressive disease
Cyst size, mean (SD), 11.8 (6.0) 11.1 (6.4) 16.9 (6.7) * and 36 (27%) were IRE-eligible and underwent laparotomy, resulting in 14
mm (11%) pancreatic resections and 15 (11%) IREs. In 36 patients who underwent
Cyst size 0–1 cm, n (%) 100 (40.3%) 94 (45.9%) 7 (15.2%) * laparotomy, 14 (39%) suffered from Clavien-Dindo grade 3 complications (6/
Cyst size 1–2 cm, n (%) 120 (48.4%) 87 (42.4%) 22 (47.8%) 14 resection, 7/15 IRE, 1/7 palliative exploration). Four patients (11%) died
within 90 days (1/14 resection, 2/15 IRE, 1/7 palliative exploration). Median
Cyst size 2–3 cm, n (%) 28 (11.3%) 24 (11.7%) 17 (37%) * overall survival after resection, IRE, in non-progressive disease without resec-
Multifocality, n (%) 95 (38.3%) 72 (35.1%) 24 (52.2%) tion/IRE and in all 132 patients was 34, 19, 17 and 11 months respectively.
Location Conclusion: This is the first prospective study on multimodality treatment, includ-
Head, Uncinate, Neck, 93 (37.7%) 79 (38.7%) 17 (37%) ing FOLFIRINOX and IRE, in a consecutive LAPC-cohort. An 11% resection-
n (%) rate with a median overall survival of 34 months seems highly promising where
no clear survival benefit was seen after IRE. This study highlights the importance
Body, n (%) 93 (37.7%) 72 (35.3%) 15 (32.6%) of reporting on unselected LAPC-cohorts.
Tail, n (%) 61 (24.7%) 53 (26%) 14 (30.4%) Disclosure of Interest: R.C. Martin: Prof. Dr. Marin is a paid consultant for
Cytopathology AngioDynamics
Benign, n (%) 35 (52.2%) 27 45%) 4 (26.7%) K.P. van Lienden: Dr. Krijn van Lienden is a paid consultant for
AngioDynamics
Non-malignant n (%) 3 (4.5%) 5 (8.3%) 1 (6.7%) All other authors have declared no conflicts of interest.
Atypical, n (%) 3 (4.5%) 4 (6.7%) 3 (20%)
Nondiagnostic, n (%) 26 (38.8%) 24 (40%) 7 (46.7%)
Cyst CEA, median 24 (4.1, 104.5) 101 (14, 333) 2555 (13, 5775) *
(IQR)
Cyst CEA =192 ng/mL, 8 (19.5%) 13 (37.1%) 11 (68.8%) *
n(%)
Cyst amylase, median 2749 (261, 124527) 8660 (634, 32905) 1028 (40.5, 4684)
(IQR)

*Statistically significant difference as compared to non-progressors. We identi-

fied 499 patients who met inclusion criteria. Average surveillance time was 47 (þ/
 28.7) months. 251 (50%) patients showed progression: 205 (41%) progressed
by size alone and 46 (9.2%) developed worrisome features. 55 (11%) met resec-
tion criteria and 21 of these went on to surgery; pathology demonstrated 4
invasive carcinoma, 5 IPMN with high-grade dysplasia, 8 IPMN with low-
grade dysplasia, 2 mucinous cystadenoma, 1 serous cystadenoma and 1 neuroen-
docrine tumor. We then compared predictors of progression. In a univariate
analysis, progression to cancer or high-grade dysplasia was associated with
United European Gastroenterology Journal 4(5S) A131
OP334 NATIONWIDE MULTIDISCIPLINARY ONLINE EXPERTPANEL past the uterine horn tissue implantation). Linaclotide (3 ug/kg/day) was dosed
FOR PANCREATIC CANCER: INITIAL RESULTS chronically for 14 days to measure its effects on plasma extravasation, and the
J. Van Hilst1, M. S. Walma2, J. A. Vogel1, S. J. Rombouts3, B.A. Bonsing4, effects of linaclotide (3 ug/kg/day) on vaginal hyperalgesia were measured after
T. Bollen5, R. Bruijnen6, R. V. Dam7, R. S. Dwarkasing8, M.F. Gerhards9, acute (day 1, 2 hours after dosing) and chronic (day 5) dosing, compared to
B. Groot Koerkamp10, I.D. Hingh11, K. De Jong12, G. Kazemier12, N. C. Krak8, vehicle. Plasma extravasation and EMG measurements were done 10 weeks
H. W. Van Laarhoven14, C. J. Van Laarhoven15, K. P. Van Lienden16, after the first surgical procedure, when rats were in the proestrus stage of their
I.Q. Molenaar17, C..Y. Nio16, S. S. Phoa16, H. C. Van Santvoort18, J. J.J. De reproductive cycle. GC-C mRNA expression was determined by qRT-PCR.
Vries19, J. W. Wilmink20, O.R.c. Busch21, C.H.j. Van Eijck22, M.G.h. Besselink1 Result: Chronic oral dosing of linaclotide (n ¼ 12) significantly (P 5 0.01)
1
Surgery, Academic Medical Center, Amsterdam/Netherlands reduced Evans Blue plasma extravasation in the small intestine compared to
2
Surgery, University Medical Center Utrecht, Utrecht/Netherlands vehicle (n ¼ 12). In contrast, linaclotide did not have an effect on plasma extra-
3
University Medical Center Utrecht, Amsterdam/Netherlands vasation of endometrial cysts and other pelvic organs. Consistent with these
4
Leiden University Medical Center, Leiden/Netherlands findings, expression of GC-C was restricted to the small intestine, and not
5
St. Antonius Ziekenhuis, Nieuwegein/Netherlands detected in endometrial cysts and other pelvic organs. Both, acute and chronic
6
Radiology, University Medical Center Utrecht, Utrecht/Netherlands oral administration of linaclotide significantly (P 5 0.05 (n ¼ 14) and P 5 0.01
7
Surgery, Maastricht Universitair Medisch Centrum, Maastricht/Netherlands (n ¼ 14), respectively) reduced endometriosis-induced vaginal hyperalgesia, com-
8
Radiology, Erasmus Medical Center, Rotterdam/Netherlands pared to vehicle treated animals (n ¼ 9).
9
OLVG, Amsterdam/Netherlands Conclusion: Oral administration of linaclotide significantly reduced visceral pain
10
Surgery, Erasmus Medical Center, Amsterdam/Netherlands in a rat model of endometriosis-induced vaginal hyperalgesia. These data suggest
11
Surgery, Catharina hospital, Eindhoven/Netherlands that GC-C agonism, beyond its established effect of improving abdominal pain in
12
Surgery, Univeristy Medical Center Groningen, Groningen/Netherlands IBS-C patients may also be able to alleviate pain in a spectrum of chronic pelvic
13
VU University Medical Center, Amsterdam/Netherlands pain conditions possibly through common sensory peripheral and central inner-
14
Oncology, Academic Medical Center Amsterdam, Amsterdam/Netherlands vation pathways.
15
Surgery, Radboudumc, Nijmegen/Netherlands Disclosure of Interest: P. Ge: Employee, stock holder and stock options from
16
Radiology, Academic Medical Center, Amsterdam/Netherlands Ironwood pharmaceuticals Inc.
17
Surgery, University medical Center Utrecht, Utrecht/Netherlands J. Ren: Contractor at Ironwood Pharmaceuticals, Inc
18
Surgery, St Antonius Hospital Nieuwegein, Nieuwegein/Netherlands N. Dmitrieva: Contractor at Ironwood Pharmaceuticals, Inc
19
Radiology, VU University Medical Center, Amsterdam/Netherlands A. Silos-Santiago: Employee, stock holder and stock options from Ironwood
20
Oncology, Academic Medical Center Amsterdam, Amsterdam/Netherlands pharmaceuticals Inc and Decibel Therapeutics.
21
Surgery, Academisch Medisch Centrum (AMC), Amsterdam/Netherlands C.B. Kurtz: Employee, stock holder and stock options from Ironwood pharma-
22
Erasmus Medical Center, Rotterdam/Netherlands ceuticals Inc.
G. Hannig: Employee, stock holder and stock options from Ironwood pharma-
Contact E-mail Address: [email protected] ceuticals Inc
Introduction: Due to the centralization of pancreatic cancer treatment, both post-
operative mortality and overall survival are improving. However, a downside of
centralization is the decreasing knowledge on new treatment strategies and clin-
ical trials in non-pancreatic centers. OP336 GUANYLATE CYCLASE-C EXPRESSION IS DOWN-
Aims & Methods: The Dutch Pancreatic Cancer Group (DPCG) aimed to REGULATED IN COLONIC BIOPSIES FROM FEMALE IRRITABLE
develop an online expertpanel to facilitate and tailor rapid expert advice for BOWEL SYNDROME PATIENTS WITH CONSTIPATION
patients with (locally advanced) pancreatic cancer. In collaboration with Aexist S. Garcia-Caraballo1, A. M. Harrington1, J. Castro1, G. Hannig2, C. B. Kurtz2,
(The Hague, the Netherlands) we developed the ImageHubÕ system which A. Silos-Santiago2, L. Chang3, S. M. Brierley4
allows for secure, online review of CT scans. Next, a nationwide multidisciplinary 1
Visceral Pain Group, University of Adelaide, Adelaide/Australia
expertpanel for pancreatic cancer consisting of surgeons, (interventional) radiol- 2
Ironwood Pharmaceuticals, Inc., Cambridge/United States of America
ogists and medical oncologists was installed. This study prospectively analyses 3
Oppenheimer Center Of Neurobiology Of Stress, David Geffen School of
the first patients who were referred to the online expertpanel between June 2015 Medicine, UCLA, Los Angeles/United States of America
and February 2016. 4
Visceral Pain Group, University of Adelaid, Adelaide/Australia
Result: A total of 59 patients from 7 centers were referred to the expertpanel. All
had locally advanced pancreatic cancer and in 46% (27/59) of the patients this led Contact E-mail Address: [email protected]
to an additional treatment or a change in treatment strategy. A resection with Introduction: Linaclotide, a guanylate cyclase-C (GC-C) agonist, reduces abdom-
curative intention was performed in 5 patients (8%) and 21 patients (42%) were inal pain and improves constipation in patients with Irritable Bowel Syndrome
included in a clinical trial, investigating local ablative therapies. In all cases the with Constipation (IBS-C). We have shown that linaclotide activates GC-C
expertpanel advice was provided within one week. expressed on intestinal epithelial cells, resulting in the production and release
Conclusion: The results show that an online expertpanel is feasible and changed of cyclic GMP (cGMP), which accelerates gastrointestinal transit and inhibits
the treatment strategy in almost half of the patients with locally advanced pan- colonic nociceptors. Furthermore distinct alterations in key components of the
creatic cancer. Future studies have to determine the impact of an online expert- GC-C/cGMP signalling pathway across different subtypes of IBS patients from
panel on the accessibility of new treatment strategies, survival and quality of life. the Australian population, have been shown. However, it remains to be deter-
Disclosure of Interest: All authors have declared no conflicts of interest. mined if these changes extend to 1) other components of this pathway, 2) a
separate U.S. cohort of IBS patients, and 3) patients with chronic idiopathic
constipation (CIC).
WEDNESDAY, OCTOBER 19, 2016 08:30–10:00 Aims & Methods: Female Rome III IBS and CIC patients and healthy controls
CONSTIPATION AND FECAL INCONTINENCE: FROM BENCH TO BEDSIDE – ROOM ages 18–55 yrs were recruited mainly by community advertisement in the U.S.
N2_____________________ Recto-sigmoid mucosal biopsies were taken at 30 cm from the anal verge during
sigmoidoscopy. RNA was extracted from all biopsies and Taqman qRT-PCR
OP335 ORAL ADMINISTRATION OF THE GUT-RESTRICTED used to assess mRNA expression of 18 different known components of the GC-
GUANYLATE CYCLASE-C AGONIST, LINACLOTIDE, REDUCES C/cGMP signalling pathway. These targets included GC-C (GUCY2C), its endo-
ENDOMETRIOSIS-INDUCED VAGINAL HYPERALGESIA genous ligands (GUCA2A, GUCA2B), PDZ proteins regulating GC-C activity
P. Ge1, J. Ren1, N. Dmitrieva2, A. Silos-Santiago1, C. B. Kurtz1, G. Hannig1 (PDZD3), cGMP-dependent protein kinases (PRKG2), phosphodiesterases
1
Ironwood Pharmaceuticals, Inc., Cambridge/United States of America (PDE3A, PDE3B), components involved in ionic secretion (PDZK1, SLC9A2,
2
Department Of Psychology, Florida State University, Tallahassee/United States SLC9A3, SLC26A3, CFTR) and transporters of cGMP (ABCC4, ABCC5).
of America Result: We compared female healthy controls (N ¼ 12, mean age 36.4 yrs) with
IBS patients with constipation (N ¼ 12, mean age 32.8 yrs), diarrhea (IBS-D;
Contact E-mail Address: [email protected] N ¼ 11, mean age 30.2 yrs), mixed bowel habits (IBS-M; N ¼ 10, mean age
Introduction: Linaclotide, a locally acting GC-C agonist, is an FDA-approved 40.8 yrs), and patients with CIC (N ¼ 12, mean age 30.7 yrs). In IBS-C biopsies,
guanylate cyclase-C (GC-C) agonist, for the treatment of Irritable Bowel GC-C expression was significantly reduced (2-fold reduction) compared with
Syndrome with Constipation (IBS-C) and Chronic Idiopathic Constipation biopsies from healthy controls (P 5 0.05). However, in these IBS-C biopsies
(CIC). Linaclotide reverses colonic mechanical hypersensitivity in chronic colonic none of the other GC-C/cGMP pathway components were significantly altered
hypersensitive mice, and reduces noxious signaling in vivo to the spinal cord. compared with healthy controls (P 4 0.05). In contrast, biopsies from CIC
Painful Bladder Syndrome/Interstitial Cystitis and Overactive Bladder are patients did not display significant alterations in GC-C or the other GC-C/
common comorbidities of IBS-C. Chronic oral administration of linaclotide in cGMP pathway components compared with healthy controls (P 4 0.05).
a mouse model of bladder overactivity reverses colitis-induced changes in bladder Similarly, biopsies from IBS-D and IBS-M patients did not display any signifi-
function and sensitivity via a proposed mechanism involving viscero-visceral cant alterations in the GC-C/cGMP pathway components tested (P 4 0.05).
organ cross-talk. We hypothesized that linaclotide may be able to similarly Conclusion: In this cohort of female IBS-C patients, GC-C, but not other eval-
reduce visceral pain in other chronic pelvic pain conditions, and tested this uated components of the GC-C cGMP pathway, was significantly reduced. A
hypothesis in a rat model of endometriosis-induced vaginal hyperalgesia. lack of GC-C expression in these patients may result in a lack of cGMP produc-
Aims & Methods: One centimeter segments of the uterine horns of female tion, which may reduce intestinal secretion and the anti-nociceptive actions of
Sprague-Dawley rats were surgically removed and 4 pieces of uterine horn cGMP compared with healthy controls. Given these changes were apparent in
tissue/rat were implanted around the mesenteric arteries adjacent to the cecum IBS-C but not in CIC, IBS-D or IBS-M patients, these changes may help to
(endometrium side down). Pelvic organ/tissue permeability was measured by explain some aspects of the pathophysiology associated with IBS-C.
Evans Blue dye plasma extravasation (vascular permeability). The severity of Disclosure of Interest: G. Hannig: Employee, stock holder, and stock options
vaginal hyperalgesia was accessed by viscero-motor responses (VMR) to vaginal from Ironwood pharmaceuticals Inc.
balloon distension. VMR was recorded by electromyography (EMG) using a C.B. Kurtz: Employee, stock holder and stock options from Ironwood pharma-
wireless telemetry system (telemetric probe was surgically implanted 6 weeks ceuticals Inc.
A132 United European Gastroenterology Journal 4(5S)
A. Silos-Santiago: Employee, stock holder, and stock options from Ironwood OP338 EFFICACY AND SAFETY OF NALDEMEDINE FOR THE
pharmaceuticals Inc and Decibel Therapeutics. TREATMENT OF OPIOID-INDUCED CONSTIPATION IN
L. Chang: Scientific advisory boards or consultation for AstraZeneca, Synergy, SUBJECTS WITH CHRONIC NON-CANCER PAIN RECEIVING
Ardelyx, Irownwood, Bioamerica, Takeda, Allergan, Commonwealth Labs, OPIOID THERAPY: RESULTS FROM TWO PHASE 3 CLINICAL
QOL Medical, Salix, and Drais. TRIALS
S.M. Brierley: Research support: Ironwood Pharmaceuticals Inc., Takeda M. E. Hale1, J. Wild2, J. Reddy3, T. Yamada3, J.C. Arjona Ferreira3
Pharmaceuticals Inc., Key Pharmaceuticals Inc. 1
Gold Coast Research, LLC, Plantation/United States of America/FL
All other authors have declared no conflicts of interest. 2
Upstate Clinical Research Associates, Williamsville/United States of America/NY
3
Shionogi Inc., Florham Park/United States of America/NJ
Contact E-mail Address: [email protected]
OP337 PATIENTS’ PERCEPTIONS OF CONSTIPATION DIFFER Introduction: Opioids effectively treat pain but their use is limited by side effects
STRIKINGLY FROM THOSE OF GASTROENTEROLOGY including opioid-induced constipation (OIC). Naldemedine is an oral, peripher-
SPECIALISTS AND GENERAL PRACTITIONERS, AND THERE IS NO ally-acting m-opioid receptor antagonist that is being evaluated for the treatment
CONSISTENT AGREEMENT WITH THE ROME III CRITERIA of OIC.
E. Dimidi1, D. Wang2, C. Cox1, S. Neville1, S..M. Scott3, K. Whelan1 Aims & Methods: Two identical Phase-3, double-blind, randomized, placebo-
1
King’s College London, London/United Kingdom controlled 12-week studies were conducted. In both studies, subjects 18 to 80
2
Liverpool School of Tropical Medicine, Liverpool/United Kingdom years old, with chronic non-cancer pain and OIC, taking opioids for 3 months
3
Queen Mary University London, London/United Kingdom and on a stable regimen for 1 month, not on laxatives, and meeting all other
eligibility criteria were randomized (1:1) to naldemedine 0.2 mg taken orally QD
Contact E-mail Address: [email protected] or placebo. The primary objective was to evaluate the efficacy of naldemedine vs.
Introduction: Constipation is a prevalent condition with a huge socioeconomic placebo as assessed by the proportion of responders. A responder was defined as
burden. It is unclear whether patients’ and doctors’ perceptions of the definition someone who had 9 positive- response weeks (PRW) out of 12 weeks and 3
of constipation agree with each other or with formal diagnostic criteria proposed PRW out of the last 4 weeks. A PRW was defined as 3 spontaneous bowel
by expert committees (e.g. Rome III). movements (SBMs)/week and 1 SBM/week increase from baseline. The safety
Aims & Methods: A cross-sectional survey was undertaken to compare the symp- and tolerability of naldemedine was also assessed. Studies were approved by an
toms perceived to be important for the diagnosis of constipation within the adult IRB prior to randomization of subjects and conducted in accordance with GCP
general population (with and without constipation), gastrointestinal (GI) specia- Guideline (ClinicalTrials.gov identifier NCT01965158 and NCT01993940).
lists (gastroenterologists, colorectal surgeons) and general practitioners (GPs) in Result: In study 1, 547 subjects were randomized (naldemedine 274; placebo 273)
the UK. Symptoms considered important in diagnosing constipation and their and in Study 2, 553 subjects were randomized (naldemedine 277; placebo 276). In
perceived burden, together with 10 case studies based on the Rome III criteria both studies, there were a significantly greater proportion of responders with
were investigated. Responses were compared between groups using chi squared naldemedine relative to placebo (Study 1: naldemedine 47.6%; placebo 34.6%,
tests. P ¼ 0.0020, Study 2: naldemedine 52.5%; placebo 33.6%, P 5 0.0001). A signifi-
Result: 2,257 members of the general population (1,623 self-reported constipa- cantly greater increase in the frequency of SBMs per week from baseline to Week
tion, 934 without), 365 GI specialists and 411 GPs completed the survey. Only a 1 was observed with naldemedine relative to placebo and this difference remained
minority of the general population considered the Rome III symptoms important generally stable between the two groups throughout the 12-week study period.
for diagnosing constipation (Table 1). Infrequent bowel movements were most The naldemedine group also showed a greater increase, relative to the placebo
frequently reported as important by GI specialists (65%), compared with less group, from baseline to the last 2 weeks of the study period in the frequency of
than half of GPs (41%) and less than a third of the constipated (26%) and non- complete SBMs and the frequency of SBMs without straining. Summary mea-
constipated (28%) general population (P 5 0.001). The symptom most frequently sures of treatment-emergent adverse events (TEAEs) were generally similar
reported as important for diagnosing constipation by the general population was between naldemedine and placebo groups in both studies. The TEAEs reported
straining (40–43%), whereas for GPs it was hard stools (66%). for 45% of subjects and at a higher frequency in naldemedine relative to placebo
were abdominal pain and diarrhea. In both studies, treatment with naldemedine
Table 1: Frequency of symptoms perceived to be important for a diagnosis of was not associated with signs or symptoms of opioid withdrawal, and the analge-
constipation sic effect of opioids was not affected.
Conclusion: Results from two identically designed Phase 3 studies demonstrated a
General Population consistent efficacy and safety profile of naldemedine as a treatment for OIC in
subjects with chronic non-cancer pain. Naldemedine treatment resulted in a sig-
Without With GI nificantly greater proportion of responders than placebo, with improvement early
constipation constipation specialists GPs P value on and throughout the 12-week study period. Naldemedine was generally well
tolerated in these two studies.
Rome III symptoms Disclosure of Interest: M.E. Hale: I was a Principle Investigator for the Clinical
Infrequent bowel 28% 26% 65% 41% 50.001 Trials, and a consultant for Shionogi
movements J. Wild: 1) I was a Principal Investigator on Compose1 trial and 2) I did receive a
Hard stool 26% 32% 57% 66% 50.001 stipend from Shionogi for clinical study review. Otherwise I have no relationship
with the company.
Straining 43% 40% 53% 61% 50.001 J. Reddy: Employee of Shionogi
Sense of incomplete 15% 24% 21% 13% 50.001 T. Yamada: Employee of Shionogi
evacuation J.C. Arjona Ferreira: Employee of Shionogi
Manual disimpaction 14% 15% 32% 34% 50.001
Non-Rome III symptoms
Long time on toilet without 42% 29% 33% 23% 50.001 OP339 PILOT STUDY COMPARING THREE METHODS OF
stool SCREENING FOR FECAL INCONTINENCE
Laxative use 37% 33% 56% 40% 50.001
J. Busby-Whitehead1, W. E. Whitehead2, S. Heymen3, J. S. Kizer4, O. Palsson3,
M. Simrén5
1
Geriatric Medicine, University of North Carolina, Chapel Hill/United States of
The symptoms most frequently considered to be bothersome were different for America/NC
each of the groups: manual disimpaction for the constipated general population, 2
Center For Functional GI And Motility Disorders, University of North Carolina,
bloating for GI specialists and straining for GPs. In the 10 case studies, correct Chapel Hill/United States of America/NC
diagnoses were made by doctors (GPs and GI specialists) on 79–80% of occa- 3
Unc Center For Functional GI And Motility Disorders, University of North
sions. However, on average, the absence of constipation was correctly identified Carolina at Chapel Hill, Chapel Hill/United States of America/NC
by doctors in 85–92% of the six cases without constipation, whereas the presence 4
Geriatric Medicine, University of North Carolina at Chapel Hill, Chapel Hill, NC/
of constipation was correctly identified in only 60–70% of the four cases with United States of America
constipation. 5
Dept Of Internal Medicine, Sahlgrenska University Hospital, Gothenburg/Sweden
Conclusion: There are striking differences in the perceived definition and burden
of symptoms of constipation between the general population, GI specialists and Contact E-mail Address: [email protected]
GPs, and variable agreement with the Rome III criteria. These differences have Introduction: Fecal incontinence (FI) affects 8% of US adults overall including
major implications for patient care, management and satisfaction with treatment. 15% over age 70. However, less than 1/3 of people with FI have discussed this
The findings reinforce the need to re-evaluate current diagnostic criteria for problem with their physicians, and most of these report that they were not
constipation in clinical practice and to ensure these are communicated widely. screened but volunteered this symptom. This suggests many physicians are not
Disclosure of Interest: All authors have declared no conflicts of interest. screening for FI.
Aims & Methods: The goal of this study was to provide preliminary information
on the effectiveness of 3 simple screening interventions for increasing screening
rates in a Geriatric Medicine Clinic (GMC) at the University of North Carolina:
a gastrointestinal (GI) symptom checklist distributed in the clinic waiting room,
screening by the clinic nurse, and screening by the medical provider. The GI
symptom checklist included fecal incontinence [accidental bowel leakage] and 7
other common GI symptoms. Patients checked all they had experienced in the
last month, and gave the checklist to the clinic nurse. To facilitate screening by
nurses and providers, we suggested three screening questions. We also gave
United European Gastroenterology Journal 4(5S) A133
providers and nurses a modified Fecal Incontinence Severity Inventory (FISI) to positive preventative strategies such as the use of medication and scheduling
help them decide whether FI was severe enough to warrant referral to a specialist, bowel movements.
and instructions on how to refer to the GI Medicine Clinic.
All patients attending the GMC during 4 two-week periods were considered Table 1: Prevalence of Coping Strategies and Impact of Faecal Incontinence
subjects. After an initial two-week baseline, all patients were exposed to the Severity on Coping
screening methods in the same sequence for two weeks each: GI symptom check-
list, provider screening, and nurse screening. Three types of outcome data were Coping Strategy % who use Effect of FI Severity
collected: (1) A limited review of electronic medical records of all patients seen
during these 4 two-week periods was used to identify the number of new FI Wear pads 61
diagnoses during these 4 periods. (2) Following the last screening intervention, Schedule BM 49
all 11 clinic providers rated the effort required by each intervention and indicated Antidiarrheal drug 43 .029
whether they believed the benefit outweighed the burden. (3) Telephone inter-
views were conducted 2–4 weeks after the index clinic visit to determine what Avoid food that cause diarrhea 47
proportion of patients had been screened during their clinic visit. A p-value of Locate all toilets in area 31
5.10 accepted as significant in this small pilot study. Fiber or drugs for constipation 30
Result: 1034 unique patients were seen during the 4 two-week periods: 60 had a Take spare clothes when going out 24
diagnosis of FI somewhere in their medical record, and 24 had a diagnosis of FI
at their index visit for this study, including 6 new FI diagnoses. Three of the 6 Avoid leaving home if possible 19 .018
new diagnoses occurred during the GI checklist intervention and 3 during pro- Avoid physical activity 19
vider screening (p 5 .10). None occurred during nurse screening. The GI symp- Avoid eating in restaurants 19 .002
tom checklist was rated the least burdensome by the 11 providers (p ¼ .09). Five Avoid sex 14 .026
of 11 providers said the benefits of screening outweighed the burden, 4 were
undecided, and 2 rated screening as too burdensome (p ¼ .001). Phone interviews Restrict eating before going out 12 .047
were completed by 88 patients: 33/88 (37.5%) confirmed they were screened by Enema before going out 10
their doctor or nurse, 55.7% said no, and 6.8% said they did not know or Shop online or have food delivered 06
declined to answer. Discourage visits from friends 04
Conclusion: Systematically encouraging geriatric medicine providers to screen for
FI significantly increased the number of patients receiving a new diagnosis of FI Average number of coping strategies 3.86 (2.61) 5.001
compared to baseline, and most geriatricians thought the benefits outweighed the
burden. Distributing a GI symptom checklist in the clinic was rated least burden-
some and was as effective as direct screening by the geriatrician. However, these Disclosure of Interest: All authors have declared no conflicts of interest.
interventions to improve screening were only partially effective: 37.5% of
patients remembered being asked about FI at their clinic visit.
Disclosure of Interest: All authors have declared no conflicts of interest. WEDNESDAY, OCTOBER 19, 2016 08:30–10:00
NEW INSIGHTS IN UPPER GI ENDOSCOPY TECHNIQUES – ROOM
L7_____________________

OP340 COPING WITH FAECAL INCONTINENCE: A POPULATION OP341 NOVEL ENDOLOOP VS. OVER-THE-SCOPE-CLIP (OTSC) IN
STUDY ENDOSCOPIC CLOSURE OF GASTRIC FULL-THICKNESS
1 2 2 3 4 DEFECT: A MULTI-CENTER STUDY
E.V. Carrington , O. Palsson , S. Heymen , S. Gould , M. Simrén , W.
E. Whitehead4 N. Gao, R. Li, D. Shi, D. Zhang, W. Chen
1
Gastroenterology & Hepatology, University of North Carolina, Chapel Hill/ Department of Gestroenterology, First Affiliated Hospital of Soochow University,
United States of America/NC Suzhou, Jiangsu, China, Suzhou/China
2
UNC Center For Functional GI And Motility Disorders, University of North
Carolina at Chapel Hill, Chapel Hill/United States of America/NC Contact E-mail Address: [email protected]
3
Emergency Surgery Department, Northwick Park Hospital, Harrow/United Introduction: Endoscopic full-thickness resection (EFTR) of the gastric lesion
Kingdom using a snaring technique has been applied for gastric subepithelial tumors. We
4
Center For Functional GI And Motility Disorders, University of North Carolina, identified criteria for the use of a novel type of nylon loop device vs. traditional
Chapel Hill/United States of America/NC ’Over the scope’-clip (OTSC) for containing artificial submucosal lesions.
Aims & Methods: One hundred and twenty- eight patients with submucosal
Contact E-mail Address: [email protected] tumors in gastric fundus were randomly divided into two groups, study group
Introduction: Faecal incontinence (FI) is a common and devastating condition with 56 patients and control group with 72 patients, all patients were treated with
that significantly impacts quality of life. Many individuals suffer in silence and endoscopic full-thickness resection. After the resection, novel LeCampTM endo-
population surveys report that fewer than 30% of those affected consult a phy- loop device and OTSC were used respectively to close the gastric defects in the
sician. Little is known about how people prevent or cope with symptoms in the study group and control group. The closure success rate, closure time, complica-
community. tions and the wound-healing rate were compared.
Aims & Methods: This study aimed to describe the most common coping strate-
Result: All lesions were removed by using EFTR technique. The closure success
gies, the impact of FI severity on ways of coping, whether those under a physi-
rates of the two groups were both 100%. Of the total of 128 patients, a compar-
cian’s care cope differently and the perceived overall effectiveness of individuals’
ison between the novel endoloop (n ¼ 56) and OTSC (n ¼ 72) groups demon-
coping efforts. A 54-question survey was designed and distributed online
strated no differences in closure time(14.86  4.93 min vs. 8.04  5.63 min,
(Qualtrics, UT, USA) to individuals in the US general population in March
p 4 0.05) and readmission rate (17.03% vs. 18.2%, p 4 0.05). The average
2016 who reported symptoms of FI occurring at least twice per month.
time of removing the stomach tube in the study group was slightly longer (4.
Respondents were asked to report coping behaviors using both a pre-defined
vs. 1 day, p 5 0.05), and there was a significant differences in the length of
list of 15 coping strategies and free-text fields. Symptom severity was defined
hospital stay for the study group (4.32  2.45 days vs. 2.1  0.63 days). 24
by the Fecal Incontinence and Constipation Assessment (FICA) scale as mild if
hours after the operation, X-ray examination showed minor subdiaphragmatic
6, moderate if 7–10 or severe if 11.
free air. Due to its low quantities and lack of symptoms, abdominal puncture was
Result: A total of 254 complete datasets were received, of which 182 (122 F,
deemed unnecessary. No subcutaneous emphysema, pneumothorax, pneumome-
median age 41, range 18–86) were retained for analysis after eliminating incon-
diastinum were found in 24 hours after the operations. There were no significant
sistent responders. The median FICA score was 9 (4–13) with 149 (82%) respon-
differences in the incidence and severity of complications rate, even though all
dents reporting either moderate or severe symptoms. 103 (57%) had consulted a
patients experienced no postoperative complications such as bleeding, perfora-
physician for FI. The median number of coping strategies used was 3 (range: 1–
tion and abdominal infection in control group. However one case receiving
13). The most commonly reported strategies were the use of pads (111/182, 61%),
treatment of endoloop that induced localized peritonitis resulted in serosal
scheduling of bowel movements (88/182, 49%), the use of anti-diarrheal medica-
inflammation. The patient was managed conservatively with medical therapy,
tion (86/182, 43%) and food avoidance (77/182, 42%). The number of strategies
such as the administration of intravenous fluids and broad-spectrum parenteral
used was significantly related to FI symptom severity (2.69 for those with mild,
antibiotics to cover the colonic bacterial flora until the symptoms subsided. All
4.17 moderate, and 4.89 severe symptom categories, p 5 .001), and consulting
wounds healed in two month after the operations.
status (3.32 for non-consulters vs. 4.28 for consulters, p ¼ .013). Number of
Conclusion: Closure of gastric full-thickness defects with the novel type of endo-
coping strategies was unrelated to sex, age, race/ethnicity, or education. The
loop device is technically feasible and effective. Both techniques should be
coping strategies reported to be most effective were antidiarrheal medications
regarded as equally acceptable reconstructive options following endoscopic
(48/182, 26% of sample), food avoidance / dietary manipulation (27/182, 14%)
full-thickness resection for gastric lesion.
and incontinence pads (21/182, 13%). Individuals who had consulted a physician,
Disclosure of Interest: All authors have declared no conflicts of interest.
compared to those who had not consulted, were more likely to use antidiarrheal
medication (55% vs. 37%; 2 ¼ 6. 23, p ¼ 0.016) and schedule bowel movements
(56% vs. 38%; 2 ¼ 6.02, p ¼ .017). Only 43/182 (24%) reported that their coping
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G. Gyimesi7, A.Z. Szepes7, V. Kovacs8, I. Racz9, Z.G. Szepes10

1
First Department Of Medicine, University of Szeged, Szeged/Hungary
OP342 ENDOSCOPIC SUBMUCOSAL DISSECTION FOR DUODENAL 2
First Department Of Internal Medicine, University of Szeged, Szeged/Hungary
ADENOMA: COMPLICATION RATE AND FOLLOW UP OF 38 CASES 3
Department Of Medical Physics And Informatics, University Of Szeged, Szeged,
W. Margos1, H. Ivekovic2, R.C.P. Yeung3, L. Shaza4, H. Piessevaux5, Hungary, University of Szeged, Szeged/Hungary
4
P.H. Deprez6 Semmelweis University 2nd Dept. of Internal Medicine, Budapest/Hungary
5
1
Depart. D’hepato-gastroente´rologie, Cliniques Universitaires Saint-Luc, Brussels, Gastroenterology, MH Healthcare Center Dept. of Gastroenterology, Budapest/
Belgium, Jambes/Belgium Hungary
6
2
Gastroenterology And Hepatology, Univeristy Hospital Centre Zagreb, Zagreb/ Military Hospital – State Health Centre, Budapest/Hungary
7
Croatia Bács-Kiskun County University Teaching Hospital, Kecskeme´t/Hungary
8
3
Gastroenterology, Clin Univ St.Luc, Universite Catholique Louvain, Monstreux/ 1st Department Of Medicine And Gastroenterology., Petz Aladár County and
00
Belgium Teaching Hospital, Gy o r/Hungary
9
4
University Hospital Saint-Luc, Bruxelles/Belgium 1st Department Of Medicine And Gastroenterology., Petz Aladár County and
5
Hepato-gastroente´rologie, Cliniques Universitaires Saint-Luc, Overijse/Belgium Teaching Hospital, Györ/Hungary
10
6
Dept. De Hepato-gastroenterologie, Cliniques Universitaire Saint-Luc Universite´ First Department Of Szeged, University of Szeged, Szeged/Hungary
de Louvain, Brussels/Belgium Contact E-mail Address: [email protected]
Contact E-mail Address: [email protected] Introduction: Gastric antral vascular ectasia (GAVE) represents a burden both to
Introduction: Endoscopic mucosal resection (EMR) and endoscopic submucosal the healthcare system and the patients’ quality of life as the rate of transfusion
dissection (ESD) are used for endoscopic treatment of superficial duodenal ade- dependence due to occult bleeding might be up to 60–70%. Currently, argon
noma. They can be combine for the resection of a same lesion (Hybrid plasma coagulation (APC) is the gold standard treatment, however its efficacy
Endoscopic Resection, HER). ESD has higher rates of complications than impairs on the long term. Besides, its efficiency depends on the settings, the size
EMR, and is technically challenging. We present results on the adverse events of the area treated, as well as the individual variations in performance.
and clinical outcome of ESD/HER compared to EMR in our cohort of patients. Endoscopic band ligation (EBL) has been proven to be a good and a potentially
Aims & Methods: In a single tertiary center, we cross-examined our database of superior alternative with less variability in the treatment of mucosal and submu-
endoscopic procedures to identify patients with duodenal adenoma treated by cosal lesions. Nevertheless, there is still no consensus regarding the end-point of
ESD, HER and EMR between 2006 and 2016. We included patients with non- the treatment (cessation of the endoscopic lesions or resolution of transfusion
ampullary lesions and familial adenomatous polyposis. Procedure was qualified need), the optimal treatment choice, and the preferable treatment settings.
as ESD when an endoscopic knife was used. When resection was achieved with Aims & Methods: Our retrospective multicentre study aimed to evaluate and
endoscopic knife and resection loop, the procedure was considered as HER. We compare the efficacy of APC and EBL in patients with GAVE both in terms
divided complications in 3 groups (ASGE and ESGE recommendations): intra- of required treatment sessions and hospitalization rates, and changes in haemo-
procedural, early complications (occurring within 15 days) and late complica- globin levels and transfusion need. Four tertiary endoscopic centres were
tions (occurring after 15 days). Results were expressed as medians, and compared involved. Data were collected retrospectively between January 2009 and
with Student’s t-test, Pearson’s chi-squared test. December 2014. APC was performed with 30–70 W power and 2.4 L/min argon
Results: Thirty-eight patients underwent ESD/HER procedure out of a total of gas flow settings. In case of EBL, 5–6 ligation bands were applied per treatment
111 patients. The resection was complete in 38/39 lesions in ESD/HER group, session. The average follow-up period was 18.3 months.
and 141/149 lesions in EMR group (p ¼ 0.182). Histological finding showed 4% Results: A total of 34 patients with GAVE were treated with either APC or EBL
adenocarcinomas, 34% HGD, and 60% LGD. No significant differences were at one of the four centres involved throughout the study period. 26 patients
observed in terms of age, sex, location of lesions or length of hospitalization. presented with diffuse and 8 with linear type of GAVE. Occult gastrointestinal
There were significant differences in the procedure time (108 min ESD/HER, bleeding occurred in 25, acute bleeding in 15 patients. Both acute and occult
79 min EMR), intraprocedural complications (46% ESD/HER, 23% EMR) gastrointestinal bleeding was present in 6 cases. 22 patients were treated with
and early complications (23% ESD/HER, 9% EMR). Intra-procedural compli- APC and 12 with EBL. Both treatment methods increased haemoglobin levels
cations occurred in 46% of ESD/HER vs 23% in EMR (p ¼ 0.015), including and decreased transfusion need significantly (3.01 g/dl and 10.41 blood units in
haemorrhage (ESD/HER 25.6%, EMR 20.1%) and perforation (ESD/HER case of APC, and 2.14 g/dl and 7.78 blood units in case of EBL). The need for
20.5%, EMR 3.4%, p ¼ 0.07). In ESD/HER, perforations occurred between blood transfusions ceased totally in 18 patients after the endoscopic resolution of
2006 and 2010. Early complications (Haemorrhage, perforation, pancreatitis) the lesions. Significantly less treatment sessions were required in case of EBL
occurred in 23% ESD/HER vs 9% in EMR (p ¼ 0.001), managed either by compared to APC (1.50 vs. 5.23, p ¼ 0.011), with a longer interval between each
medical or endoscopic treatment. Five cases of perforation occured (4 ESD/ session (4.50 vs. 2.69 months, p ¼ 0.480). On the other hand, APC resulted in a
HER, p ¼ 0.001) and 2 cases needed surgery. Three cases of late complications higher increase in haemoglobin levels (3.37 g/dl vs. 2.36 g/dl, p ¼ 0.213) and a
(stenosis) occured in the EMR group. No mortality reported during the study. higher decrease in the need for blood transfusion (10.41 vs. 7.78 units,
Conclusion: There is a higher rate of intraprocedural and early complications in p ¼ 0.566), although the differences were not significant. In case of APC, fewer
the ESD/HER group, especially in case of perforation. Those events can be well treatments (4.25) and hospitalizations (2.33) were needed, and higher increase in
managed in a tertiary center, experienced in ESD and HER. Perforation rate haemoglobin level per treatment session (0.76 g/dl) could be observed with the
tends to decrease over time, reflecting the experience acquired in our team. This 50 W power setting compared to the 30 W and 70 W setting (number of treat-
highlight the importance of a learning process in ESD/HER procedure, which ments: 12.5 and 6.13; hospitalizations: 2.5 and 4.63; and increase in haemoglobin
results in better management of intraprocedural and early complications. level/treatment session: 0.38 g/dl and 0.46 g/dl), although the small case number
Disclosure of Interest: All authors have declared no conflicts of interest. was a severe limiting factor. Generally, more treatment sessions were required for
the endoscopic resolution of GAVE lesions compared to the one needed for the
cessation of the transfusion need (3.45 vs. 3; p ¼ 0.037), but the difference was not
References significant in case of APC and EBL separately.
Conclusion: Both APC and EBL are effective in the treatment of GAVE.
1. Joana Marques, Francisco Baldaque-Silva, Pedro Pereira, Urban Arnelo, Although EBL may seem to be superior to APC in terms of the number of
Naohisa Yahagi, Guilherme Macedo. Endoscopic mucosal resection and treatment sessions and hospitalizations, no significant difference was found in
endoscopic submucosal dissection in the treatment of sporadic nonampullary the extent to which the two methods influence the haemoglobin level and trans-
duodenal adenomatous polyps. World J Gastrointest Endosc 2015 June 7(7): fusion need. Optimizing APC setups may also improve the performance and
720–727 25; . efficacy. There is a pressing need for further prospective studies with homoge-
2. Peter John Basford and Pradeep Bhandari. Endoscopic management of non- nized large case number to establish recommendations about the endoscopic
ampullary duodenal polyps. Ther Adv Gastroenterol 2012; 5(2): 127–138. treatment of GAVE.
DOI: 10.1177/1756283X11429590. Disclosure of Interest: All authors have declared no conflicts of interest.
3. Sung Min Park, Joo Ho Ham, Byung-Wook Kim, Joon Sung Kim,
ChangWhan Kim, Jin Il Kim, Chul Hyun Lim, and Jung Hwan Oh.
Feasibility of Endoscopic Resection for Sessile Nonampullary Duodenal
Tumors: A Multicenter Retrospective Study. Hindawi Publishing
Corporation Gastroenterology Research and Practice Volume 2015, Article
ID 692492, 4 pages http://dx.doi.org/10.1155/2015/692492.
4. Sattianayagam Prayman T, et al. Endoscopic submucosal dissection: experi-
ence in an Australian tertiary center. Annals of Gastroenterology 2014; 27:
212–218.
United European Gastroenterology Journal 4(5S) A135
OP344 WATERJET SUBMUCOSAL DISSECTION OF PORCINE and lowers quality of life for patients. Although steroid is generally used to
ESOPHAGUS WITH THE HYBRIDKNIFEÕ AND ERBEJETÕ 2 prevent the stricture by expecting anti-inflammatory actions, complications
SYSTEM and side effects are of concern. Mesenchymal stem cells (MSCs) have been
D. Akutsu1, H. Suzuki1, T. Narasaka1, M. Terasaki1, T. Kaneko1, H. Matsui1, reported to be a valuable cell source in regenerative medicine, and large amounts
Y. Mizokami2, I. Hyodo1 of MSCs can be noninvasively isolated from human amnion, which is discarded
1
Department Of Gastroenterology, University of Tsukuba, Tsukuba/Japan after delivery. Moreover, conditioned medium (CM) obtained from MSCs has
2
Division Of Endoscopy, University of Tsukuba Hospital, Tsukuba/Japan been reported to have anti-inflammatory and anti-fibrotic effects in several
animal models. In this study, we evaluated whether CM obtained from amnion
Contact E-mail Address: [email protected] MSC culture could prevent the stricture after large esophageal ESD in pigs.
Introduction: Esophageal endoscopic submucosal dissection (ESD) is technically Aims & Methods: We resected semicircumference of pig’s esophagus by ESD
difficult because of narrow working spaces and ease of perforation due to the under general anesthesia. We prepared CM gel by mixing CM with carboxy-
lack of serosa. HybridKnifeÕ is a recently developed ESD device that is com- methyl cellulose, and endoscopically applied 20 mL of MSC-CM gel onto the
bined with the high-pressure waterjet ERBEJETÕ 2 system to lift mucosa. We wound bed immediately after ESD, and on day 7 and on day 14 (CM weekly
hypothesized that this waterjet could make submucosal dissection safer and stu- (CM-W) group, n ¼ 3). Standard medium gel was used as a control group (n ¼ 3).
died this in porcine esophagus. We also injected triamcinolone acetonide (80 mg) into the remained submucosa
Aims & Methods: Water pressures of 30–70 bar were tested to determine the immediately after ESD (steroid group, n ¼ 3). In addition, we administered
appropriate waterjet ESD with HybridKnifeÕ (WJ-ESD) pressure in one pig. 40 mL of CM gel orally from day 1 through day 4 after ESD (CM daily (CM-
WJ-ESD safety and completion were compared with those of conventional D) group, n ¼ 3). Finally, we humanely euthanized the pigs on day 21 to measure
ESD using DualKnifeÕ (C-ESD). Each of 3 virtual esophageal lesions in 2 pigs the stricture rate and for histological analysis evaluating fiber thickness and
were resected alternatively using both methods from the lower to upper esopha- muscle fiber atrophy (masson-trichrome staining), re-epithelialization (p63 and
gus. For WJ-ESD, the submucosa, except for hard fibrous tissues, was dissected Ki-67), the number of activated myofibroblasts (a-SMA), capillary density
using water pressure alone. (CD31), infiltration of macrophages (CD107a) and neutrophils (myeloperoxi-
Results: Using 50 bar of water pressure resulted in the best balance between dase). The experimental protocol was approved by the Animal Care and Use
dissection speed and view-disturbing water backflow. The dissection speeds for Committees of Hokkaido University.
the lower, middle, and upper esophagus were 0.2, 0.9, and 0.2 cm2/min in 50 bar Results: Stricture rate in CM-W, CM-D and steroid groups was significantly
WJ-ESD and 1.1, 0.5, and 1.0 cm2/min in C-ESD, respectively. Minor bleeding lower than control group (56.3  7.1%, 52.3  4.7% and 49.3  4.2% vs
was frequent in WJ-ESD, but was easily stopped by electrocoagulation with the 80.0  2.0%, respectively). Histological examination demonstrated that the
same needle. No perforation was observed in either group. Thermal damage of number of activated myofibroblasts and fiber thickness were significantly sup-
dissected tissues appeared mild, and the extent of muscle injury was smaller for pressed in CM-W, CM-D and steroid groups as compared with control group
WJ-ESD (4, 6, and 8%) compared with C-ESD (14, 16, and 7%). (26.8  8.6, 21.5  4.9 and 20.6  2.3 vs 68.3  5.7 cells/HPF; 832.9  26.1,
Conclusion: WJ-ESD spent longer dissection time, but damaged less muscle layer. 987.1  145.1 and 944.3  250.8 vs 1,609  418.2 mm, respectively). There were
It can be combined with electrocautery ESD. no differences in re-epithelialization, capillary density, infiltration of macro-
Disclosure of Interest: All authors have declared no conflicts of interest. phages and neutrophils among four groups; however, muscle fiber atrophy was
References significantly suppressed in CM-W group compared with the control group.
Conclusion: Myofibroblast activation causes fibrosis and contributes to the stric-
1. Guo HM, Zhang XQ, Chen M, et al. Endoscopic submucosal dissection vs ture after ESD, and CM gel prevented the esophageal stricture by suppressing the
endoscopic mucosal resection for superficial esophageal cancer. World J. myofibroblast activation and fibrosis. Oral administration of CM would be a
Gastroenterol 2014; 20: 5540–7. promising treatment to prevent post-ESD esophageal stricture, and it is as effec-
2. Isomoto H, Ymaguchi N, Minami H, et al. Management of complications tive as steroid treatment.
associated with endoscopic submucosal dissection/endoscopic mucosal resec- Disclosure of Interest: All authors have declared no conflicts of interest.
tion for esophageal cancer. Dig. Endosc 2013; 25: 29–38.
3. Sato H, Inoue H, Ikeda H, et al. Clinical experience of esophageal perfora-
tion occurring with endoscopic submucosal dissection. Dis. Esophagus 2014;
27: 617–22. OP346 ENDOSCOPIC ULTRASOUND VS PET-CT IN GASTRIC CANCER
4. Neuhaus H, Wirths K, Schenk M, et al. Randomized controlled study of STAGING BEFORE AND AFTER NEOADJUVANT CHEMOTHERAPY
EMR versus endoscopic submucosal dissection with a water-jet HybridKnife
E. Redondo Cerezo, J. G. Martinez-Cara, R. Jimenez-Rosales, F. Valverde-
of esophageal lesions in a porcine model. Gastrointest. Endosc 2009; 70:
Lopez, A. Caballero-Mateos, P. Jervez-Puente, J.L. Ariza-Fernandez, M. Ubeda-
112–20.
Muñoz, M. Lopez De Hierro, J. De Teresa
5. Lingenfelder T, Fischer K, Sold MG, et al. Combination of water-jet dissec-
Gastroenterology, Hospital Virgen de las Nieves, Granada/Spain
tion and needle-knife as a hybrid knife simplifies endoscopic submucosal
dissection. Surg. Endosc 2009; 23: 1531–5. Contact E-mail Address: [email protected]
6. Yahagi N, Neuhaus H, Schumacher B, et al. Comparison of standard endo- Introduction: Gastric cancer is one of the most common malignant tumors in the
scopic submucosal dissection (ESD) versus an optimized ESD technique for gastrointestinal tract. Treatment is based in an accurate staging. Emerging meth-
the colon: an animal study. Endoscopy 2009; 41: 340–5. ods, as EUS or PET-CT, are increasingly being used for this purpose. With the
7. Fukami N, Ryu CB, Said S, et al. Prospective, randomized study of conven- increasing evolution of those techniques and the expanded clinical experience,
tional versus HybridKnife endoscopic submucosal dissection methods for the studies comparing the most accurate and efficient methods in this setting are
esophagus: an animal study. Gastrointest. Endosc 2011; 6: 1246–53. needed.
8. Schumacher B, Charton JP, Nordmann T, et al. Endoscopic submucosal Aims & Methods: Our aim was to analyze the results of EUS and PET-CT in
dissection of early gastric neoplasia with a water jet–assisted knife: a stating and restaging our patients with gastric cancer, comparing both of them
Western, single-center experience. Gastrointest. Endosc 2012; 6: 1166–74. with the histological results. Patients with a confirmed gastric cancer were pro-
9. Zhou PH, Schumacher B, Yao LQ, et al. Conventional vs. waterjet-assisted spectively enrolled. Only patients who finally received a surgical resection were
endoscopic submucosal dissection in early gastric cancer: a randomized con- included. All patients underwent preoperative TNM staging by means of EUS
trolled trial. Endoscopy 2014; 10: 836–43. and PET-CT within 21 days prior to the surgical treatment. All endoscopic
10. De-la-pena J, Calderon A, Esteban JM, et al. Experimental study of hybrid- ultrasounds were performed by two experienced ultrasonographers (E.R-C, J.
knife endoscopic submucosal dissection (ESD) versus standard ESD in a M-C). For most of the procedures radial echoendoscope (GF-UM160;
Western country. Rev. Esp. Enfem. Dig 2014; 106: 98–102. Olympus Europe) reserving curvilinear echoedoscope for FNA, in the rare
11. Sato C, Nakano T, Nakagawa A, et al. Experimental application of pulsed cases in which we perform it (UCT-180-OL5; Olympus). Every patient received
laser-induced water jet for endoscopic submucosal dissection: Mechanical propofol sedation guided by the endoscopist and by a trained nurse. A systematic
investigation and preliminary experiment in swine. Dig. Endosc 2013; 25: complete US evaluation was performed in each patient. Statistical analysis was
255–63. carried out using the software PAWS Statistics 17.0 (SPSS Inc, Chicago, ILL).
12. Lepilliez V, Robles-Medranda C, Ciocirlan M, et al. Water-jet dissector for The chi-square and the Kappa tests were used to evaluate the consistency
endoscopic submucosal dissection in an animal study: outcomes of the con- between the EUS and histopathological staging of gastric cancer. Chi-square
tinuous and pulsed modes. Surg. Endosc 2013; 27: 2921–7. and Fisher exact tests were used to compare EUS and PET-CT as appropriate.
A p-value less than 0.05 was considered statistically significant.
Results: 256 patients (178 men; aged 67.6  12.1 years) with an endoscopic and
pathologic diagnosis of gastric adenocarcinoma were included between January
OP345 ORAL ADMINISTRATION OF CONDITIONED MEDIUM 2011 and December 2014. The overall accuracy of T staging using EUS was 78%
OBTAINED FROM AMNION-DERIVED MESENCHYMAL STEM in our series. Regarding restaging, the overall accuracy for of T staging was
CELL CULTURE PREVENTS ESOPHAGEAL STRICTURE AFTER 80.2%. Considering lymph node involvement, the accuracy of EUS was
ENDOSCOPIC SUBMUCOSAL DISSECTION IN PIGS 76.2%, very similar to what it was observed for PET-CT (72.5%), but with
T. Mizushima, S. Ohnishi, H. Hosono, M. Tsuda, N. Sakamoto statistical differences (p ¼ 0.02). The accuracy of EUS for preoperative N0, N1,
Gastroenterology And Hepatology, Hokkaido University Graduate School of N2 and N3 staging was 76.2%, 78.6%, 76.2% and 90% respectively. When
Medicine, Sapporo/Japan studying the performance of both techniques in restaging we found that EUS
had a better performance when considering the main staging differences which
Contact E-mail Address: [email protected] can change patients’ management. In this regard, the accuracy in distinguishing
Introduction: Endoscopic submucosal dissection (ESD) for esophageal cancer has T1-T2 tumors vs. T3-T4 tumors was 91.3%, better than in the first staging.
been widely accepted in last decade; however, it often causes postoperative stric- Indeed, similar results were found in N staging with an accuracy of 88.3% for
ture when over three-quarters of the circumference of the esophagus is dissected, N-positive vs. N-negative distinction. By contrast, PET-CT showed an accuracy
A136 United European Gastroenterology Journal 4(5S)
of 69% for lymph node involvement when restaging, inferior to what was found on the expression of membrane markers EpCAM and TROP-2 in HPCs. Human
for EUS and for the initial staging (p 5 0.0001). livers were dissociated and the cell suspension was analysed and separated by
FACS. The sorted cells and the whole liver extracts were evaluated on both
TABLE 1.: Accuracy of EUS and PET vs Histology protein level (immunohistochemical staining) and RNA level (RNA sequencing).
Pathway analysis was performed using KEGG pathways, Ingenuity Pathway
Sensitivity Specificity PPV NPV Accuracy Kappa Analysis and Gene Set Enrichment Analysis.
Results: Immunohistochemical evaluation of the isolated fractions indicated the
T1 50% 98.5% 75% 95.7% 94.5% 0.57 enrichment of HPCs in the SP, EpCAM-positive and TROP-2-positive cell frac-
T2 41.7% 88.5% 41.7% 88.5% 80.8% 0.30 tions. Pathway analysis of the RNA sequencing data from the different isolated
T3 38.5% 86.5% 50% 80% 74% 0.27 HPC fractions shows an enrichment and activation of known HPC pathways like
Wnt/b-catenin and Notch pathways, known for their role in proliferation and
T4 77.3% 61% 61% 77.3% 68% 0.37 differentiation of HPCs. In addition we identified several novel pathways acti-
T4a 76.2% 65.5% 61.5% 75% 70% 0.40 vated in human HPC-enriched cells such as the TNF and IL17A pathways.
T1-T2/T3-T4 87.3% 50% 84.2% 56.3% 78.1% 0.39 Mutual comparison of the different isolation methods indicates some slight dif-
N0 73.9% 78.9% 81% 71.4% 76.2% 0.52 ferences between the different HPC populations, e.g. the ErbB signalling path-
way is activated in the TROP-2 positive cells while this is not the case in the
N1 50% 83.3% 33.3% 90.9% 78.6% 0.28 EpCAM-positive or SP cell populations.
N2 55.6% 81.8% 45.5% 87.1% 76.2% 0.35 Conclusion: Our results indicate that gene signatures of human HPCs are
N3 97.4% 90.2% enriched in pathways already known to be involved in HPC activation in
Nþ/N 78.9% 73.9% 71.4% 81% 76.2% 0.52 human and in animal models, but we also identify previously unknown pathways
like TNF, IL17A and ErbB signalling pathways. Comparison of the 3 isolation
PET Nþ/N 50% 90.9% 81.8% 69% 72.5% 0.42 methods sheds light on the possible existence of different HPC populations resid-
RESTAGING ing in the human liver. The isolated HPC populations will be used to further
T1–T2/T3–T4 95% 66.7% 95% 66.7% 91.3% 0.62 characterize human HPCs and to understand the molecular mechanisms under-
T2 66.7% 95% 66.7% 95% 91.3% 0.62 lying their activation and differentiation, with the ultimate goal of using HPCs
for the treatment of liver diseases.
T3 50% 76.9% 62.5% 66.7 65.2% 0.28 Disclosure of Interest: All authors have declared no conflicts of interest.
T4 70% 61.5% 58.3% 72.7% 65.2% 0.31
N0 56.3% 83.3% 82% 58.8% 67.9% 0.38
N1 75% 87% 50% 95.5% 85.7% 0.52
OP348 SORTILIN DEFICIENCY REDUCES DUCTULAR REACTION,
N2 33.3% 76% 14.3% 90.5% 71.4% 0.06 HEPATOCYTE APOPTOSIS AND LIVER FIBROSIS IN
N3 20% 87% 25% 84% 75% 0.08 CHOLESTATIC-INDUCED LIVER INJURY
Nþ/N 83.3% 92.9% 90.9% 86.7% 88.5% 0.77 I. Zvibel1, E. Hubel2, S. Fishman3, O. Shibolet2
1
PET Nþ/N 41.7% 88.2% 71.4% 68.2% 69% 0.32 Gastroenterology, Tel Aviv Sourasky Medical center, Tel Aviv/Israel
2
Gastroenterology, Tel Aviv Sourasky Medical Center, Tel Aviv/Israel
Contact E-mail Address: [email protected]
Conclusion: Our results, obtained from a real clinical practice, showed that the Introduction: Sortilin, a member of the Vps10 domain receptor family, traffics
overall accuracies of EUS and PET-CT for preoperative N staging were 76.2% newly synthesized proteins from the trans-Golgi network to secretory pathways,
and 72.5%, with significant differences between both techniques. The overall endosomes or to the cell surface. Sortilin trafficked molecules, including acid
accuracy of EUS for T staging was 78% and 80.2% for restaging. More impor- sphingomyelinase (aSMase), cathepsins and IL-6, mediate activation of hepatic
tantly, our results show a significant advantage of EUS over PET-CT in resta- stellate cells (HSC), hepatocyte apoptosis, cholangiocyte proliferation and liver
ging, even in our series, in which the vast majority of suspicious lymph nodes inflammation and fibrosis.
were not sampled. In conclusion, EUS performance in gastric cancer N staging Aims & Methods: We investigated sortilin role in the development of biliary
and restaging is better than PET-CT. Both procedures showed suboptimal damage leading to hepatocellular injury and fibrosis, based on its regulation of
accuracies when considered alone, and more than one single staging method aSMase trafficking and on its involvement in IL-6 secretion.Cholestatic injury
should be used. was induced in wild type (WT) and Sortilin-/- mice by bile duct ligation (BDL).
Disclosure of Interest: All authors have declared no conflicts of interest. Fibrosis was induced both by BDL and by administration of CCl4.Liver inflam-
References mation and cholangiocyte activation and proliferation were assessed by qRT-
PCR for inflammatory cytokines and by immunohistochemistry with Ki67
1. Mocellin S and Pasqualy S. Chocrane. Diagnostic accuracy of endoscopic (marker of proliferation) and with Ly6G (neutrophil marker). Liver damage
ultrasonography (EUS) for the preoperative locoregional staging of primary and hepatocyte apoptosis were determined by serum liver enzymes and by
gastric cancer. Cochrane Database Syst Rev 2015 Feb 6; 2: CD009944. TUNEL assay. Liver fibrosis was assessed by Sirius Red staining quantitation
2. Smyth EC and Shah MA. Role of 18F 2-fluoro-2-deoxyglucose positron and by qRT-PCR for fibrotic markers. ASMase activity was inhibited in vivo by
emission tomography in upper gastrointestinal malignancies. World J amitriptyline administration.IL-6 effect was neutralized by administration of an
Gastroenterol 2011 14; 17: 5059–74. anti-IL-6 antibody to WT mice after BDL.
3. Guo T, Yao F, Yang AM, Li XY, Zhong DR, Wu DS, et al. Endoscopic Results: Sortilin-/- mice displayed strongly attenuated liver fibrosis following
ultrasound in restaging and predicting pathological response for advanced BDL and CCl4 treatment, accompanied by an attenuated in vitro activation
gastric cancer patients after neoadjuvant chemotherapy. Asia Pac J Clin phenotype of Sortilin-/- HSCs. Reduced Sortilin-/-hepatic aSMase activity was
Oncol 2014; 10: e28–32. in line with reduced hepatocyte apoptosis following BDL and CCl4 injury and
reduced susceptibility of hepatocytes from Sortilin-/-mice to bile acid-induced
apoptosis in vitro. The role of aSMase in hepatocyte apoptosis was further
WEDNESDAY, OCTOBER 19, 2016 08:30–10:00
demonstrated using in vivo pharmacological inhibition of aSMase activity after
LIVER CELL BIOLOGY AND FIBROSIS – ROOM L8_____________________ BDL. Strikingly, Sortilin-/- mice displayed impaired inflammation and ductular
OP347 CHARACTERISATION OF DIFFERENTLY ISOLATED HEPATIC reaction three days after BDL, demonstrated by reduced reactive cholangiocytes,
PROGENITOR CELL POPULATIONS IN HUMAN ALCOHOLIC reduced cholangiocyte proliferation and accompanied by reduced serum IL-6.
LIVER Short-term treatment of bile duct-ligated WT mice with a neutralizing antibody
A. Ceulemans1, S. Verhulst2, L. A. Van Grunsven2, T. Roskams1 to IL-6 attenuated hepatic inflammation and expression of reactive cholangio-
1
Department Of Imaging & Pathology, Translational Cell & Tissue Research, KU cyte-derived cytokines and chemokines.
Leuven, Leuven/Belgium Conclusion: Sortilin mediates cholestatic liver damage and fibrosis via its effects
2
Department Of Basic Biomedical Sciences, Liver Cell Biology Lab, Vrije on aSMase activity and serum IL-6.
Universiteit Brussel, Brussels/Belgium Disclosure of Interest: All authors have declared no conflicts of interest.

Contact E-mail Address: [email protected]

Introduction: Hepatic progenitor cells (HPCs) are small cells with a relative large
oval nucleus and a scanty cytoplasm situated in the canals of Hering. OP349 ACTIVATION OF NECROPTOSIS IN HUMAN AND
Phenotypically, HPCs express both markers of (immature) hepatocytes (e.g. - EXPERIMENTAL CHOLESTASIS
fetoprotein) and markers of cholangiocytes (e.g. cytokeratin K7 and K19). The M.B. Afonso1, P. M. Rodrigues1, A. Simão1, H. Cortez-Pinto2, D. Ofengeim3, J.
mechanisms facilitating proliferation and differentiation of human HPCs are still D. Amaral1, R. E. Castro1, J. Yuan4, C. M. P. Rodrigues1
poorly understood. 1
iMed.ULisboa, Faculty of Pharmacy, Universidade de Lisboa, Lisbon/Portugal
Aims & Methods: In this study, we aimed to characterize human HPCs in order to 2
Gastrenterology, Hospital Santa Maria, Lisbon/Portugal
use them as a potential incessant source of cells for cellular transplantation or to 3
Department Of Cell Biology, Harvard Medical School, Boston/United States of
control their activation and differentiation in vivo in chronic liver diseases. America/MA
Therefore we isolated and compared, on both protein and RNA level, HPC- 4
Department Of Cell Biology, Harvard Medical School, Boston/United States of
enriched cell populations from adult human liver tissue using different isolation America/MA
methods: side population (SP), TROP-2 and EpCAM-based cell sorting. Fresh
human liver tissue was collected from alcoholic steatohepatitis explant livers, and Contact E-mail Address: [email protected]
HPC-enriched cells were obtained via three different isolation methods. A first Introduction: Targeting necroptosis, a programmed necrotic cell death pathway
method is the SP which is based on the efflux capacities of the progenitor cells of regulated by receptor-interacting protein 3 (RIP3), is being considered as a pro-
the fluorescent DNA binding dye Hoechst-33342. The other methods are based mising therapeutic approach for inflammation-driven liver diseases. Still, the role
United European Gastroenterology Journal 4(5S) A137
of necroptosis in the pathogenesis of cholestatic liver injury has been poorly Ccrk knockdown. In a complementary experiment, we found that MDSC deple-
explored. tion by specific IA8 antibody significantly reduced CCRK-induced tumorigeni-
Aims & Methods: We aimed to evaluate the role of necroptosis in patients with city. Cytokine profiling analysis revealed that CCRK significantly induced
primary biliary cirrhosis (PBC), a cholestatic chronic liver disease, and in mice hepatocellular interferon-6 (IL-6) expression and production, which mediated
after common bile duct ligation (BDL), a classic experimental model of acute MDSC expansion as shown by IL-6 rescue and antibody neutralization experi-
cholestasis and secondary biliary fibrosis. Thioflavin T staining and immunohis- ments. Mechanistic studies demonstrated that CCRK triggered nuclear factor-
tochemistry of RIP3 and its target phosphorylated-mixed lineage kinase domain- kappa B (NF-B) signaling in an enhancer of zeste homolog 2 (EZH2)-dependent
like protein (p-MLKL) were performed in liver biopsies of patients with PBC and manner. Simultaneously, the phosphorylation of NF-B by CCRK facilitated the
healthy controls. C57BL/6N wild-type (WT) or RIP3-deficient (RIP3-/-) mice co-occupancy of IL-6 promoter by NF-B-EZH2 complex for transcriptional
were subjected to BDL or sham surgeries for 3 and 14 days, with subsequent activation.
histological and biochemical analysis of hepatic damage. Necroptotic markers Conclusion: As we also showed elevation of CD33þCD11bþHLA-DR-MDSCs
and the functional crosstalk between RIP3, antioxidant response and iron home- and concordant over-expression of CCRK/EZH2/NF-B/IL-6 signaling in
ostasis were investigated in vivo and in vitro. human HCCs, our results uncover CCRK to be a critical immune regulator to
Results: In PBC patients, expression of RIP3 and p-MLKL was found increased promote MDSC functions, thereby providing a new mechanistic link between
in hepatocytes surrounded by lymphocytic infiltrates and also in cells morpho- aberrant oncogenic signaling and tumor evasion for therapeutic exploitation.
logically resembling bile duct cells. Moreover, p-MLKL fluorescence co-localized Acknowledgement: This project was supported by the University Grants
in cells with increased thioflavin T staining, suggesting necrosome assembly and Committee through the Collaborative Research Fund C4017-14G and the
necroptosis activation. BDL in mice resulted in progressive bile duct hyperplasia, Health and Medical Research Fund (03141376).
multifocal necrosis, fibrosis and inflammation. Concomitantly, necroptosis was Disclosure of Interest: All authors have declared no conflicts of interest.
activated as evidenced by increased RIP3 expression and activity and sequestra- References
tion of RIP3 and MLKL in the insoluble protein fraction of the liver.
Remarkably, RIP3 deficiency blocked BDL-induced necroinflammation at 3 1. Schrader J. The role of MDSCs in hepatocellular carcinoma–in vivo veritas?
and 14 days post-BDL. Serum hepatic enzymes, fibrogenic liver gene expression J Hepatol. 2013;59(5):921–3.
and oxidative stress decreased in RIP3-/- mice at 3 days after BDL. However, at 2. Feng H, et al. Cell cycle-related kinase is a direct androgen receptor-regu-
14 days, cholestasis aggravated and fibrosis was not ameliorated. RIP3 deficiency lated gene that drives beta-catenin/T cell factor-dependent hepatocarcino-
further associated with increased hepatic expression of heme oxygenease-1 (HO- genesis. J Clin Invest 2011; 121(8): 3159–75.
1) and accumulation of iron in BDL mice. The functional link between HO-1 3. Yu Z, et al. Cell cycle-related kinase mediates viral-host signalling to pro-
activity and bile acid toxicity was established in RIP3-deficient primary hepato- mote hepatitis B virus-associated hepatocarcinogenesis. Gut 2014; 63(11):
cytes. Finally, TUNEL-positive cells and caspase-3/-7 activity increased 14 days 1793–804.
after BDL in both WT and RIP3-/- mice, while remaining at basal levels at day 3, 4. Feng H, et al. A CCRK-EZH2 epigenetic circuitry drives hepatocarcinogen-
indicating that apoptosis is activated at late time-points in the BDL murine esis and associates with tumor recurrence and poor survival of patients.
model, reflecting the peak of liver fibrosis. J Hepatol 2015; 62(5): 1100–11.
Conclusion: In conclusion, necroptosis is triggered in PBC patients and mediates
hepatic necroinflammation in BDL-induced cholestasis. Targeting necroptosis
may provide an opportunity to develop novel therapeutic strategies to attenuate
acute cholestatic liver injury. However, therapeutic strategies to inhibit RIP3- OP351 PROTECTIVE ROLE OF SPECIFIC PATHOGEN FREE
dependent signalling during chronic cholestasis should be undertaken with a MICROBIOTA IN BILE DUCT LIGATED AND CCL4 MICE
complete understanding of the potential duality of this pathway. (Supported S. Moghadamrad1, K. Mccoy2, P. Kellmann3, A. De Gottardi1
by HMSP-ICT/0018/2011, SFRH/BD/91119/2012, SFRH/BD/88212/2012 and 1
Clinical Research, Hepatology, University of Berne, Berne/Switzerland
SFRH/BD/104160/2014, FCT, Portugal). 2
Clinical Research, Gastroenterology, University of Berne, Berne/Switzerland
Disclosure of Interest: All authors have declared no conflicts of interest. 3
Clinical Research, University of Berne, Berne/Switzerland
Contact E-mail Address: [email protected]
Introduction: In chronic liver disease the presence of gut-derived bacterial pro-
OP350 HEPATOMA-INTRINSIC CCRK SIGNALING PROMOTES ducts and the resultant increase in inflammatory cytokines in the splanchnic and
IMMUNOSUPPRESSIVE TUMOR MICROENVIRONMENT BY systemic circulation may contribute to the progression of fibrosis. However, the
REGULATING MYELOID-DERIVED SUPPRESSOR CELL composition of the intestinal microbiota and the host-microbe interaction in the
ACCUMULATION development of liver fibrosis remain largely unknown. We hypothesized that
A.S.L. Cheng1, J. Zhou1, M. Liu1, H. Sun2, Z. Chen3 fibrosis would be attenuated in a gnotobiotic model of limited intestinal coloni-
1
School Of Biomedical Sciences, Chinese University of Hong Kong, Hong Kong/ zation (altered Schaedler flora, ASF) compared to a more complex colonization
Hong Kong PRC with specific pathogen free flora (SPF).
2
Department Of Medicine And Therapeutics, Chinese University of Hong Kong, Aims & Methods: We aimed to investigate the development of fibrosis and portal
Hong Kong/Hong Kong PRC hypertension in ASF and SPF mice. Liver fibrosis was induced by common bile
3
School Of Biomedical Sciences, University of Hong Kong, Hong Kong/Hong Kong duct ligation (BDL) for 14 days or intraperitoneal injection of 20% (dilution in
PRC olive oil) carbon tetrachloride (CCL4) for 10 weeks in ASF or SPF male, C57BL/
6 mice. Hemodynamic measurements were performed after 14 days in BDL or 10
Contact E-mail Address: [email protected] weeks in CCL4 treated mice. Liver histology and collagen deposition were eval-
Introduction: Myeloid-derived suppressor cells (MDSCs) comprise a heteroge- uated using Sirius red staining for determination of fibrosis degree. To assess
neous population of immature myeloid cells that induces the exhaustion of bacterial translocation, mesenteric lymph nodes, spleen and liver were dissected
anti-tumor immune responses. The accumulation of CD33þHLA-DR- MDSCs aseptically and then cultured on Luria Bertani agar and blood agar plates for
correlates with tumor stage and metastatic burden in various cancers including aerobic and anaerobic culture respectively.
hepatocellular carcinoma (HCC) [1]. Cancer cells can secrete a variety of cyto- Result: There were no differences in portal pressure between sham-operated
kines and chemokines to facilitate the peripheral expansion and tumor infiltra- (controls) ASF or SPF mice. After BDL or CCL4 treatment portal pressure
tion of MDSCs to maintain tumor microenvironment. However, the cancer cell- (PP), portosystemic shunts (PSS) and collagen deposition within the liver
specific signaling cascades that promote MDSC expansion and infiltration showed a significant increase in both groups. However, the increase in portal
remain poorly understood. We have recently demonstrated that cell cycle-related pressure and degree of fibrosis was significantly higher in ASF than SPF mice:
kinase (CCRK) acts as a new oncogenic signaling hub in hepatocellular prolif-
eration and transformation [2–4]. ASF- ASF- SPF- SPF- ASF- ASF- SPF- SPF-
Aims & Methods: To investigate whether CCRK regulates tumor microenviron- sham BDL sham BDL control CCL4 control CCL4
ment in hepatocarcinogenesis, we determined the role of CCRK signaling in the
crosstalk between HCC cells and MDSCs. We have used a liver-specific CCRK PP cmH2O 8.4 11.8** 7.2 9.7* 8.5 12.2** 7.4 10.4*
transgenic mouse model and HCC orthotopic model in C57/BL6 immunocom-
petent mice. Molecular techniques including co-immunoprecipitation and ChIP PSS % 0.29 2.91** 0.38 2.42* 0.6 3.5* 0.5 1.8*
assay were used to investigate the underlying mechanisms. Collagen % 0.1 9.6*** 0.3 5.2*** 1.1 7.6*** 0.8 4.3***
Results: Transgenic over-expression of CCRK in murine liver led to expansion of
polymorphonuclear MDSCs in circulation. Moreover, co-culture of human per- *( p 5 0.05 ** p 5 0.005 *** p 5 0.005) Bacterial translocation was significantly
ipheral blood mononuclear cells (PBMCs) with CCRK-over-expressing immor- higher in ASF-BDL than SPF-BDL mice suggesting that bacterial translocation
talized hepatocytes and HCC cells induced the accumulation of occurred more frequently in ASF-BDL mice. The increase in the bile infarcts area
CD33þCD11bþHLA-DR-MDSCs. The CCRK-induced MDSCs possessed was significantly higher in ASF mice (ASF-BDL 13.5% vs. SPF-BDL 4.8%
immune suppressive functions by inhibiting T cell proliferation and interferon P ¼ 0.026). No significant bacterial translocation was observed in CCL4 treated
gamma expression (IFN- ). In contrast, knockdown of CCRK in hepatic cells mice.
reduced the expansion and immune suppression of MDSCs. Using a Hepa1–6 Conclusion: SPF mice presented attenuated fibrosis and portal hypertension com-
orthotopic HCC model in immune-competent C57BL/6 J mice, we demonstrated pared to ASF mice. Contrary to our hypothesis, these findings suggest that a
that knockdown of Ccrk significantly decreased hepatic tumorigenicity and the more complex intestinal bacterial flora may play a hepato-protective role. Our
levels of circulating and tumor-infiltrating MDSCs as well as their T cell sup- results are in line with studies showing that germ free mice are more susceptible
pressive functions. Notably, adoptive transfer of MDSCs rescued the effects of
A138 United European Gastroenterology Journal 4(5S)
to liver injury and fibrosis suggesting the beneficial role of intestinal microbiota results in an altered-function PTPN22 protein product and is associated with
in preventing liver injury1, 2. increased risk to develop autoimmune disorders, including type 1 diabetes, rheu-
Disclosure of Interest: All authors have declared no conflicts of interest. matoid arthritis, systemic lupus erythematous. However, the same variant
References reduces the risk for Crohn’s disease (CD) onset. We have previously shown
that protein and mRNA levels of PTPN22 are reduced in intestinal biopsies
1. Mazagova M, Wang L, Anfora AT, et al. Commensal microbiota is hepa- from CD patients, and that loss of PTPN22 results in enhanced inflammatory
toprotective and prevents liver fibrosis in mice. FASEB J 2014. cytokine secretion from mononuclear cells treated with interferon-gamma or the
2. Tabibian JH, O’Hara SP, Trussoni CE, et al. Absence of the intestinal bacterial product muramyl dipeptide.
microbiota exacerbates hepatobiliary disease in a murine model of primary Aims & Methods: In this study, we addressed how presence of the altered-func-
sclerosing cholangitis. Hepatology 2016; 63: 185–96. tion variant in PTPN22 influences the susceptibility to intestinal inflammation in
mouse models of colitis. For this aim, colitis was induced in 10–12 week old
female mice by administration of 2% DSS for 7 days (acute DSS colitis), admin-
istration of four cycles of DSS (1.5% DSS for 7 days, followed by 10 days normal
OP352 IMPROVING METABOLIC PARAMETERS IN NAFLD BY drinking water each; chronic DSS colitis), or by transferring naı̈ve T cells into
TARGETING NUCLEAR RECEPTORS RAG2-/- recipients. PTPN22 deficient (PTPN22-/-) mice, or mice expressing the
P.M. Rodrigues1, M.B. Afonso1, A. Simão1, M. Caridade1, C. C. Carvalho2, IBD-associated variant in PTPN22 (PTPN22-619 W mice), and their respective
A. Trindade2, A. Duarte3, P. M. Borralho1, M. V. Machado4, H. Cortez-Pinto5, wild-type (WT) littermates were used for the study.
C. M.P. Rodrigues1, R. E. Castro1 Result: PTPN22-/- mice suffered from aggravated acute DSS colitis as character-
1
Research Institute for Medicines (iMed.ULisboa), Faculty of Pharmacy, ized by pronounced weight loss, increased endoscopic and histologic colitis scores
Universidade de Lisboa, Lisbon/Portugal (p 5 0.05 each), while PTPN22-619 W mice reacted only weak to the DSS treat-
2
Reproduction and Development, Interdisciplinary Centre of Research in Animal ment when compared to WT littermates (p 5 0.05 for weigh development,
Health (CIISA), Faculty of Veterinary Medicine, Universidade de Lisboa, Lisbon/ p 5 0.01 for other parameters). In chronic DSS colitis however, PTPN22-/-
Portugal mice suffered from a milder disease course (reduced weight loss [p 5 0.05],
3
Gulbenkian Institute of Science, Oeiras/Portugal decreased histological severity [p 5 0.05]) from the third cycle onwards.
4
Gastrenterology, Hospital Santa Maria, Lisbon/Portugal PTPN22-619 W on the other hand mice tended to show a more pronounced
5
Gastrenterology, Hospital Santa Maria, Lisbon/Portugal disease course in the later phase. In the T cell transfer model, PTPN22-/- T
cells induced an enhanced histological pathology (p 5 0.05), while weight loss
Contact E-mail Address: [email protected] was not affected when compared to mice receiving WT T cells. In contrast, mice
Introduction: Non-alcoholic fatty liver disease (NAFLD) pathogenesis and treat- transfected with PTPN22-619 W T cells were protected from disease development
ment remain unsolved. microRNAs and bile acids were recently suggested to in the first weeks, and later on developed only a mild disease (moderate weight
participate in disease pathogenesis and, as such, constitute potential therapeutic loss [p 5 0.01], reduced shortening of the colon [p 5 0.05], low histological dis-
tools and targets. Moreover, nuclear receptors, namely peroxisome proliferator- ease scores [p 5 0.05]) when compared to mice receiving WT T cells.
activated receptors (PPARs) and the farnesoid X receptor (FXR) are currently Conclusion: Taken together, we here describe for the first time how the IBD-
under scrutiny as modulators of lipid and glucose metabolism in non-alcoholic associated variant in PTPN22 affects colitis development. This helps to explain
steatohepatitis (NASH). why this variant is associated with a reduced risk for CD onset, although it
Aims & Methods: We aimed to elucidate the role of the miR-21/PPAR pathway increases the risk to develop classical autoimmune disorders.
in liver and muscle tissues of murine NASH models and ascertain the therapeutic Disclosure of Interest: All authors have declared no conflicts of interest.
potential of miR-21 abrogation alone or in combination with obeticholic acid
(OCA). Wild-type (WT) and miR-21 KO mice were fed with chow (n ¼ 10) or
methionine and choline-deficient (MCD; n ¼ 10) diets for 2 and 8 weeks.
Alternatively, mice were fed either chow (n ¼ 12) or fast food diet (FF; n ¼ 12) OP354 TOLL LIKE RECEPTOR 2 MODULATES THE INHIBITORY
for 25 weeks. Six animals from each group had their diet supplemented with MOTOR RESPONSE INDUCED BY HYDROGEN SULPHIDE IN
OCA 10 mg/kg/day (Intercept Pharmaceuticals, Inc.). Human liver biopsies MOUSE COLON
were obtained from morbid obese NAFLD patients (n ¼ 28). Liver/muscle sam- R. Forcén Garcı́a1, E. Layunta1, J. Pardo2, J.E. Mesonero1, L. Grasa3
ples were processed for histological analysis and assessment of miR-21, pro- 1
Pharmacology And Physiology Department, University of Zaragoza, Zaragoza/
inflammatory/pro-fibrogenic cytokines, PPAR and metabolic relevant genes, Spain
by qRT-PCR and immunoblotting. A TaqmanÕ Array was performed to eval- 2
Biochemistry And Molecular And Cellular Biology Department, University of
uate modulation of lipid regulated genes. ROS levels were analysed through the Zaragoza, Zaragoza/Spain
use of 2’,7’- dichlorodihydrofluorescein diacetate. 3
Pharmacology And Physiology, Universidad de Zaragoza, Zaragoza/Spain
Results: WT mice fed with the MCD diet developed steatohepatitis and fibrosis,
displaying increased levels of apoptosis, necroptosis and serum ALT and AST. In Contact E-mail Address: [email protected]
contrast, miR-21 KO mice displayed a significant decrease in steatosis severity, Introduction: The recognition of intestinal microbiota is in part carried out by
liver damage, inflammation and did not develop fibrosis. WT FF-fed mice devel- toll-like receptors (TLR), which are responsible for initiating the innate immune
oped hepatomegaly, macrovesicular steatosis, inflammatory infiltrates and response. Alterations in the intestinal microbiota and its recognition may con-
increased oxidative stress. miR-21 levels were increased in WT FF-fed mice, in tribute to the development of intestinal inflammatory pathologies. Otherwise,
both liver and muscle, concomitantly with decreased expression of PPAR, a key hydrogen sulphide (H2S) is an endogenous gaseous signalling molecule and it
miR-21 target. Similar findings were observed in NAFLD patients. Further, WT potentially plays a relevant role in the intestinal motility. In mammals, two
FFþOCA-fed mice exhibited decreased steatosis and miR-21 expression, com- pyridoxalphosphate-dependent enzymes are responsible for H2S synthesis:
pared with WT FF-fed mice. Importantly, KO FFþOCA-fed mice exhibited cystathionine b-synthase (CBS) and cystathionine -lyase (CSE).
significantly reduced liver inflammation, oxidative stress and steatosis, in parallel Aims & Methods: The aim of this study was to investigate the influence of TLR2
with increased expression of PPAR and its metabolic targets, including CPT-1 on the motor response induced by H2S and the enzymes responsible for H2S
and ACOX2. Finally, lipid regulated genes such as ACAT1, ALOX5 and FABP5 synthesis (CBS and CSE) in mouse colon. Colon strips from male C57/BL10
were found to be severely deregulated in WT FF-fed mice and reverted to control wild-type (WT) and TLR2-/- mice of 8–12 weeks old were suspended in an
levels in KO FFþOCA-fed mice. organ bath in the direction of circular smooth muscle. We studied the effect of
Conclusion: In conclusion, activation of PPAR, as a result of miR-21 abroga- NaHS (10 mM–1 mM), D,L-propargylglycine (PAG, 10 mm–10 mM), an inhibitor
tion, together with FXR activation by OCA, significantly improves metabolic of CSE, and amino-oxyacetic acid (AOAA, 10 mm–10 mM), an inhibitor of CBS,
parameters in NASH, highlighting the therapeutic potential of multi-targeting on WT and TLR2-/- mice colonic motility. Gene expression (mRNA) of CSE and
therapies for NAFLD. (Supported by PTDC/BIM-MEC/0873/2012, SFRH/BD/ CBS were determined by real time-PCR and protein expression of CSE and CBS
88212/2012, FCT, Portugal). were quantified by Western blotting in colon from WT and TLR2-/- mice.
Disclosure of Interest: All authors have declared no conflicts of interest. Results: The NaHS, as a source of exogenous H2S, reduced the frequency but not
the amplitude of the spontaneous contractions in colon from WT mice. The
inhibition of CSE or CBS with PAG or AOAA, respectively, increased the fre-
WEDNESDAY, OCTOBER 19, 2016 08:30–10:00 quency but not the amplitude of the spontaneous contractions in colon from WT
MURINE MODELS OF INTESTINAL INFLAMMATION – ROOM 1.86_____________________ mice. The NaHS induced a higher reduction of the frequency of the spontaneous
contractions in TLR2-/- respect to WT mice. The PAG and AOAA did not
OP353 AN AUTOIMMUNITY-ASSOCIATED VARIANT IN PTPN22 modify the spontaneous contractions in colon from TLR2-/- mice. The mRNA
PROTECTS FROM DISEASE ONSET IN MOUSE MODELS OF and protein expression of CBS resulted decreased in colon of TLR2-/- compared
COLITIS with WT mice. The mRNA but not the protein expression of CSE resulted
M. R. Spalinger1, S. H. Kasper1, C. Gottier1, K. Atrott1, S. Lang2, G. Rogler3, decreased in TLR2-/- compared with WT mice.
M. Scharl4 Conclusion: These results suggest that exogenous and endogenous H2S may reg-
1
Gastroenterology And Hepatology, University Hospital Zurich, Zurich/ ulate the colonic spontaneous contractions in WT mouse, reinforcing the hypoth-
Switzerland esis that H2S is a gaseous inhibitory mediator of intestinal motility. TLR2
2
Division Of Gastroenterology And Hepatology, University Hospital Zurich,
Zürich/Switzerland
3
Klinik Für Gastroenterologie, UniversitätsSpital Zürich, Zürich/Switzerland
4
Division Of Gastroenterology And Hepatology, University Hospital Zürich,
Zürich/Switzerland
Contact E-mail Address: [email protected]
Introduction: Presence of the single nucleotide polymorphism (SNP) rs2476601 in
the gene encoding protein tyrosine phosphatase non-receptor type 22 (PTPN22)
United European Gastroenterology Journal 4(5S) A139
regulates the expression of CBS and modulates the inhibitory motor response HPLC system measuring the degradation rate of endomorphin-2 (EM2, natural
induced by H2S in mouse colon. DPP IV substrate) in the presence of the test compound. Anti-inflammatory
Disclosure of Interest: All authors have declared no conflicts of interest. activity of EMDB-1 was investigated in the model of acute and semi-chronic
References colitis induced by trinitrobenzenesulfonic acid (TNBS). Body weight, macro-
scopic score, ulcer score, colon length and thickness, as well as myeloperoxidase
1. Martinez-Cutillas M, Gil V, Mane N, Clave P, Gallego D, Martin MT and (MPO) activity were recorded. Mesalazine was used as a reference drug.
Jimenez M. Potential role of the gaseous mediator hydrogen sulphide (H2S) Results: EMDB-1 is a potent and specific DPP IV inhibitor as shown by signifi-
in inhibition of human colonic contractility. Pharmacol Res 2015; 93: 52–63. cantly decreased degradation rate of EM2 by DPP IV (t0.5 ¼ 1.73 vs. 3.60 min in
2. Gil V, Gallego D and Jimenez M. Effects of inhibitors of hydrogen sulphide the absence and the presence of EMDB-1, respectively). The intracolonic (i.c.)
synthesis on rat colonic motility. Br J Pharmacol 2011; 164: 485–498. administration of EMDB-1 (0.1, 1 and 3 mg/kg, twice daily) attenuated both
3. Li L, Rose P and Moore PK. Hydrogen sulfide and cell signaling. Annu Rev acute and semi-chronic TNBS-induced colitis in mice in a dose-dependent
Pharmacol Toxicol 2011; 51: 169–187. manner, as indicated by significantly reduced macroscopic parameters and
MPO activity. Anti-inflammatory effect of EMDB-1 was not blocked by nalox-
one, thus the opioid receptors are not involved in its mechanism of action.
Conclusion: EMDB-1 is a potent inhibitor of DPP IV in vitro and exhibits sub-
OP355 DIRECT INHIBITION OF HMGB1 BY NEUTRALIZING stantial anti-inflammatory activity in the GI tract in vivo. Results of this study
ANTIBODY AMELIORATES EXPERIMENTAL COLITIS IN MICE validate the EMDB-1 backbone for further development of peptide DPP IV
VIA TLR4-MYD88 PATHWAY inhibitors and suggest their potential use in the treatment of colitis.
F. Xiao1, B. Sun1, J. Li2, H. Mu1, M. Zhang1, D. Li1, H. Huang1, M. Liu1, Disclosure of Interest: All authors have declared no conflicts of interest.
U. Seidler3, D. Tian1 Supported from grants from the Medical University of Lodz [502-03/1-156-02/
1
Gasroeterology Department, Huazhong Unversity Of Science And Technology 502-14-140 to MS and #503/1-156-04/503-01 to J.F.] and National Science
Affiliated Tongji Hospital, Wuhan/China Centre [No. UMO-2013/11/N/NZ7/02354 to M.S., No. UMO-2013/11/B/NZ7/
2
Huazhong Unversity Of Science And Technology Affiliated Tongji Hospital, 01301 and No. UMO-2014/13/B/NZ4/01179 to J.F.]
Nephrology Department, Wuhan/China
3
Gastroenterology Department, Hannover Medical School, Hannover/Germany
Contact E-mail Address: [email protected] OP357 CHROMOFUNGIN (CHR) AMELIORATES EXPERIMENTAL
Introduction: Biologics targeting inflammatory cytokines has reveal a new era in COLITIS IN MICE VIA MODULATION OF MACROPHAGES’
inflammatory bowel disease treatment. High mobility group protein B1 PLASTICITY
(HMGB1) acts as an alarmin in early stage and inflammatory cytokine in late N. Eissa1, F. Rabbi1, M. Metz-Boutigue2, C. Bernstein3, J. Ghia1
stage during inflammation. Direct blockade of HMGB1 can be protective against 1
Immunology & Internal Medicine, University of Manitoba, Winnipeg/Canada
intestinal inflammation. 2
INSERM, Strasbourg/France
Aims & Methods: Potential role of anti-HMGB1 neutralizing antibody (HnAb) in 3
Internal Medicine, Division of Gastroenterology, University of Manitoba,
inhibiting intestinal inflammation and the underlying mechanism is investigated Winnipeg, Canada, Winnipeg/Canada
in DSS-induced mice colitis (DSS-C) models. 200mg HnAb was administrated
intraperitoneally to DSS-C at d0, d3 and d6 in HnAb group, whereas 200mg anti- Contact E-mail Address: [email protected]
IgY was used as control in DSS-C (DSS-C group) or normal control (ctrl group). Introduction: Macrophages play a major role in inflammatory bowel disease
Colon shortening, disease activity index (DAI), histological score of colitis (HS), (IBD) pathogenesis through an inappropriate response to migration, and an
MPO activity and inflammatory cytokines were evaluated to determine the colo- impaired transition from a pro-inflammatory (classical activated macrophages
nic inflammation severity. Mucosa barrier function was assessed by immuno- (CAMs)) to an anti-inflammatory (alternative activated macrophages (AAMs))
fluorescent staining of mucus layer (mucin2) and tight-junction (T-J) protein phenotype. While there is growing awareness of a relationship between
detection. mRNA was detected by qPCR. T-J protein, HMGB1, TLR4, Chromogranin (Cg)-A and a susceptibility to inflammatory conditions, the spe-
MyD88 was detected by Western blotting and measured by Grey-scale value. cific interaction between CgA-derived peptides and macrophage plasticity in IBD
Statistical analysis was performed using one-way ANOVA analysis and the Post is unknown. Recently, we have shown a linear correlation between CgA and
Hoc LSD test or Tamhane’s T2 test. inflammatory markers in patients with active ulcerative colitis, and colitic
Results: Treatment with HnAb significantly suppressed colonic inflammation in CgA-deficient mice demonstrated a significant decrease of colitis associated to
DSS-C mice by improving colon shortening (6.2  0.4 cm vs. 5.3  0.5 cm, a modulation of macrophage activation. As Cg-A is a prohormone, herein, we
p 5 0.05), DAI (2.7  0.5 vs. 3.7  0.3, p 5 0.05) and HS (6.0  0.1 vs. assessed the functional role of a specific CgA-derived peptides (Chromofungin
9.6  0.7, p 5 0.05). Besides, MPO activity (2.6  0.8 vs. 4.8  1.0, p 5 0.05) (CHR): hCg-A47-66) in the regulation of acute colitis and the functional plasti-
and TNF- (1.61  0.05 vs. 3.04  0.11, p 5 0.05), IFN- (2.14  0.06 vs. city of murine macrophages.
7.87  0.21, p 5 0.05) and IL-1b (1.53  0.10 vs. 2.48  0.04, p 5 0.05) mRNA Aims & Methods: Colitis was induced in C57BL/6 mice (7–8 weeks old) by
expression was decreased when treated with HnAb as compared to DSS-C group administrating dextran sulfate sodium (DSS 5%) in drinking water for 5 days.
(mRNA in ctrl group was set to 1). Relatively intact mucus layer was seen in mice Preventive CHR (2.5 mg/kg/day) or vehicle treatments started 1 day before
colon of HnAb group as compare to DSS-C group. Significantly higher expres- induction of colitis and lasted for a total of 6 days. Disease activity index
sion of tight-junction protein ZO-1 (0.38  0.01 vs. 0.15  0.05, p 5 0.0001), clau- (DAI) was evaluated daily and mice were sacrificed on day 5 post-DSS induction
din-5 (0.50  0.09 vs. 0.17  0.07, p 5 0.0001) and occludin (0.85  0.09 vs. to assess the extent of colitis. At sacrifice macroscopic scores were evaluated,
0.39  0.01, p 5 0.0001) was detected in HnAb mice as compared to mice in serum level of C-reactive protein (CRP) was quantified using ELISA, and colonic
DSS-C group. Interestingly, colonic HMGB1 protein in both nucleus interleukin (IL)-1b, IL-6, TNF-, MIP-1, MIP-1b, and ARG-1 were assessed
(0.58  0.02 vs. 0.79  0.03, p 5 0.0001) and cytoplasm (0.23  0.01 vs. using ELISA and RT-qPCR. Naı̈ve peritoneal macrophages were isolated from
0.40  0.03, p 5 0.0001) were all decreased when treated with HnAb as compare non-colitic C57BL/6 mice and treated by CHR (200 ng/ml) then exposed for 6 h
to DSS-C, suggesting that primary inhibition of HMGB1 by HnAb blocked to LPS (100 ng/ml) to promote CAMs, or to IL-4/IL-13 (20 ng/ml) to promote
sequential HMGB1 formation and release. Lastly, TLR4 (0.31  0.03 vs. AAMs. CAMs markers (IL-6, IL-1b, TNF-, MIP-1 & MIP-b) and AAMs
0.77  0.08, p 5 0.0001) and MyD88 (0.30  0.03 vs. 0.78  0.01, p 5 0.0001) markers (ARG-1) were quantified by using ELISA and RT-qPCR.
protein was significantly reduced in HnAb group than mice in DSS-C group Results: Preventive treatment with CHR significantly reduced the DAI onset and
though MyD88 mRNA was relatively higher in HnAb group than DSS-C severity of colitis associated to rectal bleeding, stool consistency and weight loss.
group (0.69  0.04 vs. 0.38  0.01, p 5 0.05). Macroscopic scores, serum-CRP, colonic IL-1b, IL-6, TNF-, MIP-1, MIP-1b
Conclusion: Administration of HnAb ameliorated DSS-C by suppressing inflam- were significantly decreased, while ARG-1 was significantly increased. In vitro,
mation and strengthening mucosa barrier function possibly through inhibition of CHR-conditioned CAMS expressed significantly less IL-1b, IL-6, TNF-, MIP-
HMGB1-TLR4-MyD88 pathway, suggesting a potential interventional target of 1, MIP-b, but, surprisingly, more ARG-1 when compared to LPS control con-
HMGB1 in ulcerative colitis treatment. dition. Moreover, CHR-conditioned AMS expressed significantly more ARG-1
Disclosure of Interest: All authors have declared no conflicts of interest. when compared to IL-4/IL-13 control condition.
Conclusion: These findings suggest that CHR can modulate the severity of experi-
mental colitis. CHR treatment can attenuate the severity of experimental colitis
and the inflammatory process via the modulation of the functional plasticity of
OP356 NEW, PEPTIDE INHIBITOR OF DIPEPTIDYL PEPTIDASE IV, murine macrophages and their functions. Targeting CgA-derived peptides may
EMDB-1 ATTENUATES COLITIS IN MICE AFTER TOPICAL lead to novel therapeutic strategies in ulcerative colitis.
ADMINISTRATION Disclosure of Interest: All authors have declared no conflicts of interest.
M. Salaga, P. Mosinska, H. Zatorski, M. Zielinska, J. Fichna
Dept. Of Biochemistry, Medical University of Lodz, Lodz/Poland
Contact E-mail Address: [email protected] OP358 DEFICIENCY OF PH-SENSING RECEPTOR TDAG8
Introduction: PETIR (PEptidase-Targeted ImunoRegulation) is a novel therapeu- AMELIORATES T-CELL TRANSFER COLITIS
tic strategy which takes for the purpose restoration of the immune balance by I. Tcymbarevich1, C. De Vallière1, J. Cosin-Roger1, M. R. Spalinger1, C.
limiting the activation of immune cells and induction of endogenous protective A. Wagner2, K. Seuwen3, I. Frey-Wagner1, G. Rogler4
mechanisms, such as TGFb and glucagon-like peptide-2 (GLP-2) through inhibi- 1
Gastroenterology And Hepatology, University Hospital Zurich, Zurich/
tion of DPP IV-dependent pathways. Experimental data indicate that PETIR Switzerland
results in suppression of cell proliferation and reduced synthesis of pro-inflam- 2
Institute Of Physiology, University of Zurich, Zurich/Switzerland
matory cytokines without affecting cellular vitality. 3
Novartis Institutes for Biomedical Research, Basel/Switzerland
Aims & Methods: The objective of this study was to test the anti-inflammatory 4
Klinik Für Gastroenterologie, UniversitätsSpital Zürich, Zürich/Switzerland
activity of a novel DPP IV inhibitor EMDB-1 in the mouse models of colitis. The
inhibitory effect of EMDB-1 on DPP IV was characterized in vitro using the Contact E-mail Address: [email protected]
A140 United European Gastroenterology Journal 4(5S)
Introduction: The adaptive immune system plays a crucial role in the pathogenesis Conclusion: Due to unexpected high recurrence rates after both TEM and EMR,
of inflammatory bowel diseases (IBD). Inflammation in IBD is typically asso- non-inferiority of EMR could not be demonstrated. Taking into account the high
ciated with a decrease in local pH. The proton-sensing receptor T-cell death rate of unexpected malignancies, a trend towards more severe complications after
associated gene 8 (TDAG8), also known as G-protein-coupled receptor 65 TEM and the cost-effectiveness of EMR, EMR is the recommended technique in
(GPR65), has been identified as a risk gene for IBD in recent genome wide case of similar expertise of TEM and EMR.
association studies. Disclosure of Interest: All authors have declared no conflicts of interest.
Aims & Methods: We investigated the role of TDAG8 in T cell-mediated patho-
genesis in intestinal inflammation using a murine adoptive transfer colitis model.
Naı̈ve T-cells (CD4þCD62Lþ), from WT and TDAG8-/- donor mice, were
injected into Rag-/- male mice. Injection of PBS was used in a control group. OP360 EFFICACY OF NON-EXPOSED ENDOSCOPIC WALL-
The results of colitis were evaluated by weight change, colonoscopy score, spleen INVERSION SURGERY (NEWS) AS AN ADVANCED METHOD OF
weight, H&E staining, IHC and mRNA expression. FULL-THICKNESS RESECTION FOR GASTRIC TUMOR
Results: Induction of colitis was observed after 3 weeks by weight loss, diarrhea K. Niimi1, T. Mitsui2, S. Aikou2, S. Kodashima1, N. Yamamichi1,
and bloody stool. The WT group showed severe weight loss (p ¼ 0.013), whereas H. Yamashita3, M. Fujishiro4, Y. Seto3, K. Koike1
the TDAG8-/- group displayed only a minor delay in weight gain. No significant 1
Department Of Gastroenterology, Graduate School Of Medicine, The University
differences were observed in colon length, spleen weight and colonoscopy score of Tokyo, Tokyo/Japan
between PBS and the TDAG8-/- groups. H&E staining of distal and proximal 2
Department Of Gastrointestinal Surgery, Graduate School Of Medicine, The
parts of the colon showed severe infiltration and crypt damage in the WT group. University of Tokyo, Tokyo/Japan
The TDAG8-/- group displayed significantly less histopathological signs of colitis 3
Department Of Gastrointestinal Surgery, Graduate School Of Medicine, The
in comparison to PBS and WT groups. CD3þ and IL-17A immunoreactive cells University of Tokyo, Tokyo/Japan
were rarely detected in colonic tissue of TDAG8-/- in comparison to the WT 4
Department Of Endoscopy And Endoscopic Surgery, Graduate School Of
group. Downregulation of mRNA expression of pro-inflammatory cytokines Medicine, The University of Tokyo, Tokyo/Japan
(IFN , TNF, IL17A) was observed in the TDAG8-/- group in comparison with
the WT group. No significant differences were observed in mRNA expression Contact E-mail Address: [email protected]
levels of Foxp3, RORgþand IL18. Introduction: Endoscopic submucosal dissection (ESD) has been widely accepted
Conclusion: Our data demonstrate that TDAG8-deficiency in T-cells ameliorates as an effective treatment for gastrointestinal tumors. However, ESD for early
the development of colitis suggesting an important physiological role of this pH gastric cancer (EGC) with ulcer scarring is still technically difficult. Non-exposed
receptor. endoscopic wall-inversion surgery (NEWS) is an advanced method of endoscopic
Disclosure of Interest: All authors have declared no conflicts of interest. full-thickness resection (EFTR) without transluminal communication, applying
ESD technique.
Aims & Methods: The aim of this study is to clarify the short-term outcomes of
WEDNESDAY, OCTOBER 19, 2016 10:30–12:00 NEWS for gastric tumors. Between July 2011 and March 2016, 26 patients (9
SURGERY MEETS ENDOSCOPY IN THE COLON – ROOM F1_____________________ females, 17 males; mean age 65.9 years, range 49–85 years) underwent NEWS for
gastric tumors. After marking around a tumor on both the mucosal and serosal
OP359 TRANSANAL ENDOSCOPIC MICROSURGERY VERSUS surfaces and submucosal injection of sodium hyaluronate, circumferential sero-
ENDOSCOPIC MUCOSAL RESECTION FOR LARGE RECTAL myotomy and sero-muscular suturing were made laparoscopically, followed by
ADENOMAS (TREND-STUDY) circumferential muco-submucosal incision endoscopically. The resected specimen
R. M. Barendse1, G. D. Musters1, E.J.R. De Graaf2, F. J. c. Van Den Broek3, was perorally retrieved.
E.C. j. Consten4, P.G. Doornebosch2, J. C. h. Hardwick5, I. C. De Hingh6, Results: The mean tumor size and resected specimen were 23.3 mm (range, 7–
C. Hoff7, J.M. Jansen8, A.w.M. Van Milligen De Wit9, G. Van Der Schelling9, 45 mm) and 36.1 mm (range, 20–66 mm), respectively. All lesions were curatively
E.J. Schoon10, M.P. Schwartz11, B.L.a.m. Weusten12, M. G. Dijkgraaf1, resected in an en-bloc fashion. The mean operation time was 219.0 minutes
P. Fockens1, W. A. Bemelman1, E. Dekker1 (range, 98–397 minutes), and the median estimated blood loss was 0 g (range,
1
Academic Medical Center, Amsterdam/Netherlands 0–250 g). Patients started oral intake on mean postoperative day 3.1 (range, 2–4),
2
IJsselland Hospital, Capelle aan den IJssel/Netherlands and the mean length of postoperative hospital stay was 8.2 days (range, 6–14
3
Máxima Medical Center, Eindhoven/Netherlands days). There were no severe postoperative complications. Histopathological
4
Surgery, Meander Medisch Centrum, Amersfoort/Netherlands examination of the tumors showed 21 GISTs, 1 schwannoma and 4 early gastric
5
Dept. Of Gastroenterology, Leiden University Medical Center, Leiden/ cancer. No tumor residual or recurrences was confirmed by performing gastro-
Netherlands scopy and the mean body weight loss was 2.5 kg (range, 3.2–10.9 kg) during a
6
Catherina Hospital, Eindhoven/Netherlands median follow-up of 11 months (range, 0–37 months).
7
Medical Center Leeuwarden, Leeuwarden/Netherlands Conclusion: NEWS is an effective full-thickness resection with minimum possible
8
Department Of Gastroenterology, Onze Lieve Vrouwe Gasthuis, Amsterdam/ margin without contamination and tumor dissemination into the peritoneal
Netherlands cavity, considering the quality of life of patients. NEWS could be utilized as a
9
Amphia Hospital, Breda/Netherlands novel treatment option especially for node-negative EGC difficult to resect by
10
Gastroenterology, Catharina Hospital, Eindhoven/Netherlands ESD, or EGC with possible lymph node metastasis with a combination of senti-
11
Meander Medical Center, Amersfoort/Netherlands nel node navigation surgery.
12
St Antonius Hospital, Nieuwegein/Netherlands Disclosure of Interest: All authors have declared no conflicts of interest.

Contact E-mail Address: [email protected]

Introduction: Non-randomized studies suggest that endoscopic mucosal resection WEDNESDAY, OCTOBER 19, 2016 10:30–12:00
(EMR) is equally effective in removing large rectal adenomas as transanal endo- UPPER GI BLEEDING – ROOM M_____________________
scopic microsurgery (TEM). EMR might be more cost-effective and safer. This
trial compares the cost-effectiveness and cost-utility of TEM and EMR for large OP361 MEDIUM- AND LONG-TERM RESULTS OF TREATMENT WITH
rectal adenomas. LANREOTIDE IN CASES OF CHRONIC OR RECURRENT OBSCURE
Aims & Methods: For this randomised controlled non-inferiority trial, patients GASTROINTESTINAL BLEEDING OR DUE TO
with rectal adenomas 3 cm, without malignant features, from 20 hospitals were GASTROINTESTINAL ANGIODYSPLASIAS
included and randomised (1:1) to EMR or TEM, allowing endoscopic removal of S. Frago1, L. Ollero1, M. Lazaro1, E. Peña-Galo1, N. De La Llama2, J. Alcedo1
residual adenoma at 3 months. Unexpected malignancies were excluded post 1
Department Of Digestive Diseases, Miguel Servet University Hospital, Saragossa/
randomisation. Primary outcomes were recurrence within 24 months and the Spain
number of recurrence-free days alive and out of hospital, analysed by intention 2
Department Of Pharmacy, Miguel Servet University Hospital, Saragossa/Spain
to treat. The trial was designed to demonstrate non-inferiority of EMR with
regards to recurrence rate with an upper limit of 10%. Secondary outcomes Contact E-mail Address: [email protected]
were complications, quality of life, anorectal function and costs. This trial is Introduction: Somatostatin analogues have been proposed as a rescue therapy in
registered in the Dutch Trial Registry (NTR1422). cases of chronic or recurrent obscure gastrointestinal bleeding (GIB) or attribu-
Results: Between Feb 2009 and Sept 2013, 209 patients were randomised to EMR table to gastrointestinal angiodysplasias (GIADs). The long-term results with
(n ¼ 106) or TEM (n ¼ 103). 4 patients withdrew consent. 1 patient had prostate lanreotide are still very scarce.
carcinoma instead of rectal adenoma. The remaining 204 patients (103 EMR, 101 Aims & Methods: Our aim is to determine the medium and long-term benefit of
TEM) were treated; 27 (13%) had unexpected cancer and were excluded. One lanreotide in cases of chronic or recurrent refractory obscure gastrointestinal
additional patient withdrew consent. Of the remaining 176 (87 EMR, 89 TEM) bleeding or from gastrointestinal angiodysplasias, in terms of savings of health
patients, overall recurrence rates were 15% after EMR and 11% after TEM resources. This was a retrospective single-center study conducted under conven-
(relative risk 1.33, 95% confidence interval (CI) 0.77–2.46). However, EMR tional clinical practice, following a defined management protocol, between 2003
was statistically not non-inferior to TEM. The number of recurrence-free days to 2012. Patients with chronic or recurrent obscure GIB or due to GIADs,
alive and out of hospital was similar (EMR 609  209, TEM 652  188, p ¼ 0.15). refractory to or not candidates for iron therapy, endoscopic, surgical or angio-
Complications (mostly hemorrhage) occurred in 18% (EMR) vs. 26% graphic treatments, were included. Cirrhotic patients and those ones with very
(TEM) (odds ratio (OR) 0.65 (95% CI 0.32–1.33)). Major complications severe comorbidity (IV-V of the American Society of Anesthesiologists
occurred in 1% (EMR) vs. 8% (TEM) (OR 0.14 (95% CI 0.02–1.13), Classification-ASA-) were excluded. The diagnostic protocol included upper
p ¼ 0.064). Quality adjusted life years were equal in both groups. Although and lower endoscopy, abdominal computed tomography, video capsule endo-
EMR patients scored more favourable on disease specific quality of life ques- scopy and/or single balloon enteroscopy. Lanreotide 60 or 90 mg was adminis-
tionnaires, manometries were similar and continence improved after adenoma tered monthly, for at least 6 months. During the previous year and 36 months
resection regardless of treatment. EMR was approximately E3000 cheaper and after starting the drug it was recorded demographics data, comorbidities, chronic
therefore more cost-effective. use of antiplatelets and anticoagulants, hemostatic treatments, side effects, hos-
pital admissions related to GIB, number of transfused red cells units, intravenous
United European Gastroenterology Journal 4(5S) A141

Table (OP361)

Comparison in health resources consumption before and after Lanreotide.

Variable Mean SD p value Variable Mean SD p value

Admission days - 33.4 9.9 10.0 8.5 24.3 11.6 15.7 14.3 50.01 50.01 50.01 Iron iv doses - 4.0 2.0 2.5 2.6 6.1 5.9 4.5 5.5 50.01 0.08 0.02
Prior yr - 1 yr–2 yr– Prior yr–1 yr–2 yr–
3 yr 3 yr
Red cell units - 11.4 4.5 5.9 6.4 11.6 7.1 10.2 12.6 50.01 0.01 0.04 N.Endoscopies - 1.6 0.1 0.6 0.7 1.7 0.3 1.1 1.6 50.01 0.01 0.03
Prior yr–1 yr–2 yr– Prior yr–1 yr–2 yr–
3 yr 3 yr

SD: Standard deviation. Yr: year

iron doses, and non-diagnostic endoscopies. Differences between data from one treated with SST. Fifty percent of patients had angiodysplasias at multiple sites
year before and each one of the three years after starting lanreotide were eval- (small bowel (75%), stomach (45%), and colon (45%)). Endoscopic treatment
uated using Wilcoxon test, with significance level of p 5 0.05. prior to SST was started in 48%. Octreotide LAR 20 mg was the most frequent
Results: Twenty-two patients (median age 76.1 years, range 56–90; 50% male sex) prescribed (81%). Side-effects occurred in 31% (41/131) of the patients, with
were included. Before starting treatment 19 were ASA III, 22.7% consumed gastrointestinal symptoms (19.8%) and erythema / pain at the injection site
antiplatelet and 31.8% anticoagulants drugs. At the end of follow-up only one (8.4%) the most frequent. In 8 patients (6%) SST was discontinued due to
patient had stopped the anticoagulant. The bleeding was attributed to GIAD in side-effects. There was a high SST response with 89% of the patients having
77.3% and 22.7% was obscure. The bleeding was overt in 68.2% and occult in 450% reduction of their parenteral iron and/or RBC transfusion dependency.
31.8%. Before starting lanreotide 4 patients had received endoscopic treatment Sex, age, small bowel and stomach localization, the use of anticoagulants, dose,
using argon plasma coagulation (APC), 2 hormonal therapy and 1 thalidomide. only parenteral iron dependent and prior endoscopic treatment were not asso-
Two patients received APC concomitant to lanreotide, and 1 hormonal therapy ciated with treatment response. Angiodysplasia localization in the colon (OR
after stopping this one without reaching bleeding cessation. The average duration 0.28, 95% CI 0.09–0.88, p ¼ 0.03) and at multiple sites (OR 0.37, 95% CI
of treatment with lanreotide was 28.4 months (range 6–36). Mean follow-up was 0.17–0.77, p ¼ 0.008) were negatively associated with a good response.
32.4 months (range 9–36), with the results shown in the table. Five patients did Conclusion: Based on this pooled analysis of data from individual patients with
not complete the follow-up for not related to GIB deaths. No side effects forced transfusion dependent angiodysplasia bleeding, SST is effective and safe in the
to suspend lanreotide. majority of patients. A decreased SST response is found in patients with angio-
Conclusion: The use of lanreotide for al least 6 months in patients with chronic or dysplasias located at multiple sites or in the colon.
recurrent obscure gastrointestinal bleeding or from gastrointestinal angiodyspla- Disclosure of Interest: All authors have declared no conflicts of interest.
sias, refractory to or not candidates for other therapies, is safe and is associated
with a decrease in consumption of medical resources within the three years
following its indication.
Disclosure of Interest: All authors have declared no conflicts of interest. OP363 ESOPHAGEAL VARICES POST BANDING ULCER BLEEDING -
DETERMINANTS AND IMPACT IN MORTALITY
P. Marques Da Costa1, S. Carvalhana1, J. Lopes1, A. Valente1, M. V. Machado1,
R. Palma1, H. Cortez-Pinto2, J. Velosa3
OP362 SOMATOSTATIN ANALOGUES ARE LESS EFFECTIVE IN 1
Gastroenterology And Hepatology Intensive Care Unit, Hospital de Santa Maria,
PATIENTS WITH ANGIODYSPLASIAS AT MULTIPLE SITES OR Lisboa/Portugal
LOCATED IN THE COLON: A POOLED ANALYSIS OF INDIVIDUAL 2
Gastroenterology And Hepatology Department, Hospital de Santa Maria, Lisboa/
PATIENT DATA Portugal
K. Grooteman1, W. Kievit2, A. Rocco3, G. Holleran4, P. S. Salgueiro5, 3
Faculdade de Medicina da Universidade de Lisboa, Lisboa/Portugal
T. Aparicio6, G. Scaglione7, R. Manzano8, D. Sautereau9, S. Michopoulos10,
J.P. h. Drenth11, E.J. m. Van Geenen11 Contact E-mail Address: [email protected]
1
Gastroenterology And Hepatology, Radboud University Medical Center, Utrecht/ Introduction: Endoscopic band ligation (EBL) is the choice for both prophylaxis
Netherlands and treatment of esophageal varices hemorrhage. Post-EBL ulcer bleeding is a
2
Health Evidence, Radboudumc, Nijmegen/Netherlands deemed complication for which risk factors and impact in mortality are not
3
University of Parma, Parma/Italy clearly understood.
4
Trinity Academic Gastroenterology Group, Trinity College Dublin, Dublin/Ireland Aims & Methods: We aimed at identifying risk factors for variceal post-EBL ulcer
5
Hospital Santo António, Porto/Portugal bleeding and determine its impact in short and long-term mortality. We con-
6
Hospital Avicenne, Bobigny/France ducted a case control study. Cases: all admissions for post-EBL ulcer bleeding,
7
A. O. G. Rummo, Benevento/Italy in a tertiary gastrointestinal service, from January 2003 to December 2015.
8
Hospital San Pedro de Alcántara, Cáceres/Spain Controls: EBL treated patients without post-therapeutic ulcer bleeding.
9
CHU Limoges Gastroente´rologie, Limoges/France Matching was made for Child-Pugh-Turcotte (CPT) score and indication
10
Dept. Of Gastroenterology, Alexandra Hospital, Athens/Greece (bleeding vs elective) in a 1 case for 2 controls ratio. Patient’s demographics,
11
Gastroenterology And Hepatology, Radboudumc, Nijmegen/Netherlands comorbidities and endoscopic findings were reviewed from medical records.
Endpoints were re-bleeding from post therapeutic ulcer and mortality assessed
Contact E-mail Address: [email protected] at 28, 90, 180 and 360 days post-therapeutic.
Introduction: Cohort studies have shown a beneficial effect of octreotide in Results: A total of 50 post-EBL ulcer bleeding cases and 100 controls were
decreasing the rebleeding rates in patients with gastrointestinal angiodysplasias, included. Mean age (57.1  12.0); male:female ratio (4.1:1). Cirrhosis etiologies:
however with large variation among individuals. Most studies have a small alcoholic (70.7%), HCV (29.3%) and HBV (15.7%). CPT distribution: A
sample size and different primary outcomes, such as haemoglobin and rebleed, (17,3%) B (46%) and C (36.7%); mean MELD was 14.5  6.1. All patients
which makes it difficult to estimate the true effect on clinical relevant outcomes underwent EBL and 7.3% also received a sclerosing agent. Mean time to rebleed:
such as transfusion dependency and to investigate predictors for good clinical 12.6  5.4 days. A higher number of rubber bands (5.8  1.7 vs 5.0  2.1
response. p ¼ 0.003), lower baseline hemoglobin (10.7  1.5 vs 11.5  2.1 g/dL p ¼ 0.007),
Aims & Methods: The aim of this individual patient data meta-analysis is to hemodynamic instability (OR:2.0 p ¼ 0.048) portal vein thrombosis (OR:2.8,
investigate efficacy of SST on transfusion dependency and identify subgroups p ¼ 0.022), HBV cirrhosis (OR:6.2, p ¼ 0.007), and endoscopic stigmata of
of patients that benefit most from SST. A systematic review was performed to active or recent bleeding (OR:5.0 p 5 0.001) correlated with rebleeding. In multi-
identify articles reporting the effect of SST in gastrointestinal angiodyplasias. We variate logistic regression analysis HBV cirrhosis, multiple concomitant aetiolo-
collected individual patient data of included articles. Patients with only oral iron gies of cirrhosis and endoscopic stigmata of recent bleeding were independently
dependency were excluded. The primary outcome was response to SST, defined associated with rebleeding. Post-EBL ulcer bleeding did not significantly
as good: 50% reduction of parenteral iron and/or red blood cell (RBC) trans- impacted overall short and long term mortality. However CPT class B patients
fusions; or poor: 550% reduction of parenteral iron and/or RBC transfusions. with post-EBL ulcer bleeding showed a trend for lower survival which was sig-
We used univariate logistic regression to determine the effects of patient and nificant at 180 days (16% vs 6% log rank p ¼ 0.04).
disease characteristics on SST. The variable ‘‘study’’ was included in the univari- Conclusion: We identified both patient’s and endoscopic features correlating with
ate analysis to correct for study-effect. post-EBL ulcer bleeding, namely HBV infection related cirrhosis, higher number
Results: We identified 7 studies and obtained individual data from 6 (n ¼ 180) of concomitant aetiologies/aggressors, and endoscopic stigmata of recent/active
studies. We analyzed data of 159 patients (mean age 70 years, 56% men) with bleeding. Though overall patient’s short and long-term mortality was not
transfusion dependency due to gastrointestinal angiodysplasia bleeding that were affected by post-EBL ulcer bleeding, CPT class B patients showed a trend for
A142 United European Gastroenterology Journal 4(5S)
lower survival. Thus, we hypothesize that CPT class B patients may be a cluster OP365 PROGNOSTIC FACTORS FOR SECOND ENDOSCOPIC
of patients with low hepatic reserve, to whom post-EBL bleeding may impose an THERAPY FAILURE IN PEPTIC ULCER BLEEDING
additional risk for disease progression, that can significantly impact on survival. A.G. G. Antunes1, A. Vaz2, P. Queirós3, T. Gago1, J. Roseira1, B.M. Santos
Disclosure of Interest: All authors have declared no conflicts of interest. Peixe1, H. Guerreiro1
1
References Dept. Of Gastroenterology, Centro Hospitalar do Algarve, Faro/Portugal
2
Gastrenterologia, Hospital de Faro, Faro/Portugal
1. Vanbiervliet G, Giudicelli-Bornard S, Piche T, et al. Predictive factors of 3
Gastroenterology, Centro Hospitalar do Algarve, Faro/Portugal
bleeding related to post-banding ulcer following endoscopic variceal ligation
in cirrhotic patients: a case-control study. Alimentary Pharmacology & Contact E-mail Address: [email protected]
Therapeutics 2010; 32: 225–32. Introduction: According to current guidelines a second endoscopic therapy is
2. Petrasch F, Grothaus J, Mossner J, Schiefke I and Hoffmeister A. generally encouraged for patients with rebleeding secondary to peptic ulcer dis-
Differences in bleeding behavior after endoscopic band ligation: a retrospec- ease (PUD). Although risk factors for endoscopic hemostasis failure are well
tive analysis. BMC Gastroenterology 2010; 10: 5. defined in the setting of the first endoscopic therapy, literature lacks studies
3. Xu L, Ji F, Xu QW and Zhang MQ. Risk factors for predicting early variceal that focused on the risk factors for rebleeding after the second endoscopic
rebleeding after endoscopic variceal ligation. World Journal of therapy.1
Gastroenterology: WJG 2011; 17: 3347–52. Aims & Methods: To assess risk factors related to the failure of the second
endoscopic therapy in patients with upper gastrointestinal bleeding (UGIB) sec-
ondary to PUD, in order to define high-risk patients that could benefit from
alternative methods like angiography or surgery. Retrospective analysis of all
OP364 INTERNATIONAL PROSPECTIVE STUDY OF UPPER GI cases of UGIB secondary to PUD that were submitted to two endoscopic thera-
HAEMORRHAGE: DOES WEEKEND ADMISSION AFFECT pies between 2010 and 2014 in a tertiary center. We recorded demographic,
OUTCOME? clinical, analytical and endoscopic data. Comorbidities were evaluated according
I. A. Murray1, A. Stanley2, H. R. Dalton3, J.H. J. Ngu4, S. B. Laursen5 to the age adjusted charlson comorbidity index (ACCI). The main endpoint was
1
Gastroenterology, Royal Cornwall Hospital, Truro, Truro/United Kingdom rebleeding, defined as: objective evidence of UGIB, with hemodynamic instability
2
Gastroenterology, Glasgow Royal Infirmary, Glasgow/United Kingdom and Hb decrease 2g/dL, or need for more than 3 units of blood in the 72-hour
3
Gastroenterology, Royal Cornwall Hospital, Truro/United Kingdom period after the endoscopic treatment.
4
Dept. Of Gastroenterology And Hepatology, Singhealth, Singapore/Singapore Results: We identified 56 patients who underwent a second endoscopic therapy.
5
Gastroenterology, Odense Universitetshospital, Odense/Denmark The mean age was 76 years (males: 63%) and the mean ACCI was 7 (3.1). The
most common location of PUD was duodenal (80.4%) and 26.8% were classified
Contact E-mail Address: [email protected] as having a high-risk location (small gastric curvature / posterior wall of the
Introduction: Weekend admissions have been associated with higher mortality. bulb); the estimated mean size of PUD was 13.3 mm (6.8). The mean number
For upper gastrointestinal haemorrhage (UGIH) some studies show significantly of blood units transfused was 3 (2.4). Rebleeding occurred in 23% and in-
increased mortality1 and delayed endoscopy while the UK UGIH audit reported hospital mortality was 20%. In univariate analysis the female gender
no difference2. We studied whether out of hours (OOH) admissions had more co- (p ¼ 0.041), presence of active non gastrointestinal neoplasia (p ¼ 0.021), high-
morbidity, were less stable and/or had higher mortality. risk location (p ¼ 0.001), large-ulcers (p ¼ 0.045), Idiopathic-PUD (p ¼ 0.006)
Aims & Methods: Prospective study over 12 months (from March 2014) from 2 were associated with hemostatic failure. The number of red blood cells (RBC)
UK and 2 international centres. Admission time, demographics, pulse, BP, lab units that were transfused was correlated to hemostatic failure (Rs ¼ 0.548;
results, endoscopy findings, further procedures and 30d mortality were recorded. p ¼ 0.000). Drug-induced peptic ulcers (presence of anticoagualation or antiag-
3 pre-endoscopy scores (Glasgow Blatchford (GBS), AIMS65 and admission gregation agents, non-steroidal anti-inflammatory drugs and no evidence of
Rockall scores) and 2 post-endoscopy scores (PNED and full Rockall scores) Helicobacter pylori infection) were associated with a successful hemostatic treat-
were determined. Chi-squared, Fisher’s exact and Kruskal-Wallis tests were used ment (p ¼ 0.027). The variables ACCI, presence of hemodynamic instability,
as appropriate. A two-tailed significance level of 5% was used. Forrest classification of the PUD in the second endoscopic therapy, gastric or
Results: 2118 consecutive patients, 60% male, median age 66 years were seen. duodenal location, were not statistically significant different between groups
There were no significant differences in mortality, need for endoscopic therapy, when evaluated the hemostatic success. In the multivariate analysis, large
surgery/embolisation or rebleeding in both UK and non-UK centres. There were ulcers (p ¼ 0.014; OR ¼ 7.08) and transfusion of 4 blood units (p ¼ 0.030;
no differences in comorbidity, mean ASA 2.3, pulse or BP although weekday OR ¼ 1.71) were independent risk factors for rebleeding.
admissions had a lower Hb (110 g/l vs 118 g/l (weeknight) vs 117 g/l (weekend) Conclusion: In patients with UGIB secondary to PUD that require a second
p 5 0.001 and higher GBS (p 5 0.05). No difference in peptic ulcer disease or endoscopic therapy for rebleeding, the need for higher blood transfusion (4)
varices incidence between periods although more weekday admissions had and large ulcers (420 mm) were independent risk factors for hemostasis failure.
normal endoscopy(p ¼ 0.002). OOH admissions were less likely to have an endo- Early surgery or angiography should be considered in this group of patients.
scopy (30% not endoscoped vs 23% for weekday admission p 5 0.005). Time to Disclosure of Interest: All authors have declared no conflicts of interest.
endoscopy was less for weeknight admissions (13 h vs 17 h for weekend and 20 h Reference
for weekday admissions p ¼ 0.0001). 67% weekday, 75% weeknight and 60%
weekend admissions had their endoscopy within 24 hours 1. Gralnek IM, Dumonceau JM, Kuipers EJ, et al. Diagnosis and management
of nonvariceal upper gastrointestinal hemorrhage: European Society
Outcome of patients with UGIH and time of presentation ofGastrointestinal Endoscopy (ESGE) Guideline. Endoscopy 2015 Oct;
47(10): a1–46. doi: 10.1055/s-0034-1393172.
Weekdays: Weekdays:
working time overnight Weekends Total

Number 858 603 642 2118 OP366 A HISTORY OF ISCHEMIC HEART DISEASE, HIGH BLOOD
Units blood transfused 1.4 [0–6] 1.3 [0–6] 1.4 [0–6] 1.4 [0–6] UREA NITROGEN AND C-REACTIVE PROTEIN LEVELS, AND
Endoscopic therapy 185 (22) 116 (19) 126 (20) 430 (20) LOW HEMOGLOBIN LEVELS: AS PREDICTIVE CLINICAL
FACTORS FOR EARLY DEATH AFTER PERCUTANEOUS
Surgery/embolisation 4 (0.5) 6 (1.0) 6 (0.9) 16 (0.8) ENDOSCOPIC GASTROSTOMY
Rebleeding 49 (5.8) 33 (5.7) 43 (6.9) 126 (6.1)
T. Nishimura1, T. Kuwai2, T. Takasago2, Y. Miyasako2, Y. Sumida2, S. Iio2,
30 d mortality 61 (7.1) 43 (7.1) 48 (7.5) 153 (7.2) H. Imagawa2, T. Yamaguchi2, A. Yamaguchi2, H. Kouno2, H. Kohno2
1
Gastroenterology, Kure Medical Center and Chugoku Cancer Center, kure/Japan
2118 consecutive patients admitted March 2014-March 2015 from Glasgow 2
Gastroenterology, Kure Medical Center and Chugoku Cancer Center, Kure/Japan
(600), Truro (544), Odense (541) and Singapore (433). Data shown are mean
[95% CI] or number (%). Contact E-mail Address: [email protected]
Conclusion: There is no difference in mortality in patients admitted with UGIH Introduction: Percutaneous endoscopic gastrostomy (PEG) is accepted as the
OOH compared to weekday admissions although weekday admissions had a method that enables enteral feeding in patients with swallowing difficulties.
lower haemoglobin and higher GBS. There was no evidence of delay in time to However, complications and early death are considerably prevalent after PEG.
endoscopy with OOH admissions. The severity of UGIH was not related to time To decrease the incidence of early mortality after PEG, it is very important to
of admission. Similar findings were noted in all four centres. identify risk factors of this procedure.
Disclosure of Interest: All authors have declared no conflicts of interest. Aims & Methods: The aim of our study was to determine factors that could
References predict early death within 30 days following PEG. A retrospective analysis of
the records of all patients who underwent PEG at Kure Medical Center and
1. Ahmed A, Armstrong M, Robertson I, Morris AJ, Blatchford O and Stanley Chugoku Cancer Center from April 2008 to March 2016 were performed. We
A. Upper gastrointestinal bleeding in Scotland 2000–2010: improved out- examined clinical and preoperative laboratory data and extracted predictive fac-
comes but a significant weekend effect. World J Gastroenterol 2015; 21: tors of early death after PEG by using univariate and multivariate analyses.
10890–10897. Results: A total of 1077 patients [502 female (46.7%) and 575 male (53.3%);
2. Jairath V, Kahan BC, Logan RF, Hearnshaw SA, Travis SP, Murphy MF mean age 78 y.o.] were assessed. Predictors of poor survival after PEG included
and Palmer KR. Mortality from acute upper gastrointestinal bleeding in the history of ischemic heart disease (odds ratio [OR] 2.32, 95% confidence interval
United Kingdom: does it display a ‘‘weekend effect’’? Am J Gastroenterol. [CI] 1.2–4.3, P 5 0.01), blood urea nitrogen level 30 mg/dl (OR 3.14, 95% CI
2011 106: 1621–1628. 1.8–5.5, P 5 0.0001), C-reactive protein level 2.6 mg/dl (OR 4.04, 95% CI 2.2–
7.3, P 5 0.0001), albumin level 2.7 mg/dl (OR 4.2, 95% CI 2.1–8.2, P 5 0.0001),
and hemoglobin level 11.2 g/dl (OR 4.0, 95% CI 2.0–8.0, P 5 0.0001).
Multivariate analysis on predictive factors of early death revealed a significant
correlation between early death and each of the following: history of ischemic
United European Gastroenterology Journal 4(5S) A143
heart disease (P 5 0.01), high blood urea nitrogen (P ¼ 0.02) and C-reactive pro- OP368 MOLECULAR DISSECTION OF TUMOR ANGIOGENESIS IN
tein levels (P 5 0.01), and anemia (P50.0001). COLORECTAL CANCER
E. Yamamoto1, A. Yorozu2, H. Aoki3, T. Nishidate4, H. Yamano5, T. Sugai6,
odds ratio (95% CI) p-Value H. Suzuki2, H. Nakase1
1
Department Of Gastroenterology And Hepatology, Sapporo Medical University,
History of ischemic heart disease 2.32 (1.2–4.3) 50.01 Sapporo/Japan
2
Blood urea nitrogen level  30 mg/dl 3.14 (1.8–5.5) 50.0001 Department Of Molecular Biology, Sapporo Medical University, Sapporo/Japan
3
Department Of Molecular Biology, Sapporo Medical University, sapporo/Japan
C-reactive protein level  2.6 mg/dl 4.04 (2.2–7.3) 50.0001 4
Department Of Surgery, Surgical Oncology And Science, Sapporo Medical
Albumin level  2.7 mg/dl 4.2 (2.1–8.2) 50.0001 University, Sapporo/Japan
5
Hemoglobin level  11.2 g/dl 4.0 (2.0–8.0) 50.0001 Akita Red Cross Hospital, Akita/Japan
6
Iwate Medical University, Morioka/Japan
Conclusion: A history of ischemic heart disease and laboratory data, such as high
blood urea nitrogen and C-reactive protein levels and low hemoglobin levels may Contact E-mail Address: [email protected]
be useful predictive clinical factors for early death after PEG. If patients have a Introduction: Angiogenesis is a hallmark of cancer development and is considered
history of ischemic heart disease, high blood urea nitrogen, high C-reactive pro- as an attractive therapeutic target.
tein, or anemia, PEG should be considered carefully. Aims & Methods: In this study, we aimed to unravel the molecular mechanism
Disclosure of Interest: All authors have declared no conflicts of interest. underlying tumor angiogenesis in colorectal cancer (CRC). We isolated endothe-
lial and epithelial cells from surgically resected 14 CRC tissues and corresponding
normal colonic tissues using antibodies against endothelial (CD146) and epithe-
WEDNESDAY, OCTOBER 19, 2016 10:30–12:00 lial markers (EpCAM). RNA sequencing (RNA-seq) was carried out in 3 pairs of
IMMUNOTHERAPY IN CANCER – ROOM 1.61/1.62_____________________ normal and tumor endothelial cells. Gene expression was validated by quantita-
tive RT-PCR (RT-qPCR) and immunohistochemistry. Functions of a selected
OP367 GLUTAMINOLYSIS INHIBITION AS A THERAPEUTIC gene were analyzed by tumor conditioned medium (TCM) experiments, in vitro
STRATEGY IN GLUTAMINE-ADDICTED KRAS MUTANT tube formation assay, cell cycle analysis, gene expression microarray and xeno-
COLORECTAL CANCER graft experiments.
C.C. Wong1, J. Xu2, Q. Yun3, X. Li4, W. Kang5, J.J.Y. Sung6, Z. Cai4, J. Yu7 Results: Through RNA-seq analysis, we identified a series of 18 genes which were
1
Department Of Medicine And Therapeutics, Chinese University of Hong Kong, upregulated in the endothelial cells isolated from CRC tissues. We further vali-
Hong Kong/Hong Kong PRC dated the results by qRT-PCR and immunohistochemistry in a larger number of
2
Medicine And Therapeutics, Chinese University of Hong Kong, Hong Kong/Hong clinical samples, and identified gene A as a novel candidate of the tumor endothe-
Kong PRC lium-related gene. Expression of gene A was also upregulated in human umbilical
3
Gastroenterology, Zhejiang University, Hangzhou/China vein endothelial cells (HUVECs) treated with TCM obtained from CRC cell
4
Hong Kong Baptist University, Hong Kong/Hong Kong PRC lines. Knockdown of gene A suppressed in vitro tube formation and induced
5
Department Of Anatomical And Cellular Pathology, The Chinese University of G1 cell cycle arrest in HUVECs. Microarray analysis revealed that knockdown
Hong Kong, Hong Kong/Hong Kong PRC of gene A induced expression changes of approximately 300 genes in HUVECs,
6
Department Of Medicine & Therapeutics, The Chinese University of Hong Kong, and gene ontology analysis showed that cell cycle-related genes were significantly
Hong Kong/China enriched in the affected genes. To confirm our findings in vivo, we co-trans-
7
Institute Of Digestive Disease And Department Of Medicine And Therapeutics, planted CRC cells with HUVECs into nude mice. We found that knockdown
The Chinese University of Hong Kong, Hong Kong/Hong Kong PRC of gene A in HUVECs resulted in reduced micro vessel formations in the xeno-
graft tissues. Finally, we evaluated the clinical implication of gene A in colorectal
Contact E-mail Address: [email protected] cancer. The Cancer Genome Atlas (TCGA) datasets of primary CRCs (n ¼ 411)
Introduction: Colorectal cancer (CRC) with KRAS mutations represents an revealed that higher expression of gene A is associated with worse overall survi-
unmet clinical need due to the lack of effective therapies. A defining characteristic val, suggesting that upregulation of gene A in tumor endothelial cells may pro-
of oncogenic KRAS-driven cancers is an altered cellular metabolism, in which mote aggressiveness of CRC.
glucose and glutamine metabolism are extensively rewired satisfy their anabolic Conclusion: Our results suggest that gene A may play an important role in the
needs. In this study, we investigated the metabolic dependencies of KRAS- angiogenesis in colorectal cancer, and that it could be a potential therapeutic
mutant CRC, established the role of glutaminolysis in KRAS-mutant CRC target.
growth and evaluated the synergism between glutaminolysis inhibition and che- Disclosure of Interest: All authors have declared no conflicts of interest.
motherapy in this subset of CRC.
Aims & Methods: Metabolic dependencies of KRAS mutant CRC cell lines were
assessed by colony formation and apoptosis assays. Glutamine metabolism in WEDNESDAY, OCTOBER 19, 2016 10:30–12:00
KRAS mutant CRC cells were traced using stable U13C5-glutamine labeling COMPLICATIONS OF LIVER CIRRHOSIS: BEYOND BLEEDING AND ASCITES – ROOM
and Ultra-high Performance Liquid Chromatography-Mass Spectrometry N1_____________________
(UPLC-MS). Role of glutaminase (GLS1) and the mitochondrial glutamate
transporter (SLC25A22) in mediating glutaminolysis was evaluated. Finally, OP369 RANDOMIZED CONTROLLED TRIAL OF BACLOFEN IN
the functional effect of glutaminolysis inhibition (via GLS1 or SLC25A22 block- TREATMENT OF MUSCLE CRAMPS IN PATIENTS WITH LIVER
ade) and its synergy with chemotherapeutic agents were tested. CIRRHOSIS
Results: Deprivation of glucose, glutamine or their combination in six KRAS S. Abd-Elsalam1, L. Abo Ali1, S. Soliman1, S. Zakaria2, I. Shehab El-Din1,
mutant CRC (DLD1, HCT116, LOVO, SW480, SW620 and SW1116) and four A. Elfert1
KRAS wild type CRC cell lines (CACO-2, COLO205, HT29 and SW48) revealed 1
Tropical Medicine Department, Tanta university, Tanta/Egypt
that KRAS mutant CRC cells were profoundly sensitive to glutamine depletion 2
Pharmacy, Damanhour university, Damanhour/Egypt
as compared with KRAS wild type CRC cells; whilst exhibiting resistance to
glucose depletion. This indicates that supply of glutamine is obligatory for Contact E-mail Address: [email protected]
KRAS mutant CRC survival. U13C5-glutamine labeling in DLD1 cells and Introduction: Muscle cramps adversely inFuence the quality of life of patients
UPLC-MS revealed that a majority of glutamine was metabolized into gluta- with liver cirrhosis. However, despite the obvious association of muscle cramps
mate, aspartate and the intermediates of the tricarboxylic acid (TCA) cycle, with liver disease, there is a paucity of information regarding pathogenesis and
indicating that glutamine-derived carbons were channeled to the mitochondria treatment in these patients.
for the replenishment of TCA cycle (a process known as glutaminolysis). We Aims & Methods: This is the first randomized placebo controlled trial of baclofen
further revealed that glutamine was first converted to glutamate by GLS1 at the in the treatment of muscle cramps in patients with liver cirrhosis. One hundred
outer side of inner mitochondrial membrane, which is coupled to SLC25A22 for patients with liver cirrhosis and suffering from muscle cramps signed informed
the import of glutamate into the mitochondrial matrix. Consistent with this consent to participate in this study. They were recruited from Department of
model, the silencing of GLS1 or SLC25A22 significantly suppressed cell prolif- Tropical Medicine-Tanta University hospital. They were randomized to receive
eration in KRAS mutant CRC cells, indicating that their coupled action is indis- either baclofen or placebo for 3 months. Patients were followed monthly and one
pensable for cell growth. U13C5-glutamine tracing in DLD1 cells with month after withdrawal. Each visit, the clinico-epidemiological data were
SLC25A22 knockdown showed an attenuated entry of glutamine-derived car- recorded, muscle cramp questionnaire was filled, and any drug related side effects
bons into the TCA cycle, confirming its involvement in glutaminolysis. were reported.
Inhibition of SLC25A22-dependent glutaminolysis triggered metabolic stress, Results: In the baclofen group, the frequency of muscle cramps was significantly
suppressed ATP production and promoted oxidative stress. Moreover, a combi- decreased after one and three months of treatment (p 5 0.005), with a significant
natorial approach utilizing SLC25A22- shRNA plus 5-Fluorouracil synergisti- rebound after withdrawal (P 5 0.001). Patients receiving baclofen had a signifi-
cally suppressed KRAS mutant CRC growth in vitro and in subcutaneous cant decrease in the severity and duration of muscle cramps (P 5 0.001). After
xenograft models. three months of baclofen therapy at dose of 30 mg/day, muscle cramps disap-
Conclusion: KRAS mutant CRC cells are addicted to glutamine and the blockade peared completely in 72%, reduced in 20%, and no change in 8% of patients. No
of glutaminolysis enzymes GLS1 and SLC25A22 suppressed cell survival. significant changes in the frequency, severity and duration of muscle cramps were
SLC25A22 represents a novel therapeutic target in KRAS mutant CRC and its noted in the placebo group. There were few but non-significant side effects in the
synergistic effect with chemotherapy warrants further investigation. baclofen group when compared to placebo group.
Disclosure of Interest: All authors have declared no conflicts of interest. Conclusion: Baclofen was well tolerated, safe, and effective in the treatment of
muscle cramps in Egyptian patients with post-hepatitis C liver cirrhosis.
A144 United European Gastroenterology Journal 4(5S)
Disclosure of Interest: All authors have declared no conflicts of interest. years. Significant increases over time were found for ADRs, which rose from a
References mean of 22.2% (SD 10.7%) in 2007–2008 to 24.2% (11.6%) in 2013–2014, cor-
responding to an average increase of þ1.5% per two-year-period (95% confi-
1. Mehta SS and Fallon MB. Muscle cramps in liver disease. Clin. dence interval [95%CI] þ0.9%, þ2.2%, p 5 0.001). Likewise, proximal lesion
Gastroenterol. Hepatol 2013; 11(11): 1385–91. detection rates rose from 15.8% (SD 9.8%) to 21.7% (SD 13.3%, þ2.5% per
2. Chatrath H, Liangpunsakul S, Ghabril M, et al. Prevalence and morbidity two-year-period, 95%CI þ1.9%, 3.1%, p 5 0.001). Adverse events occurred in
associated with muscle cramps in patients with cirrhosis. Am J Med 2012; 0.3%, 63% thereof were associated with polypectomy. There was a decline in
125(10): 1019–25. complication rates of 7.3 per 10,000 endoscopies per two-year-period (95%CI
13.1, 1.5 per 10,000 endoscopies per two-year-period, p ¼ 0.013). Sedation
increased the probability of adverse events (0.24% in sedated and 0.16% in
unsedated patients, p ¼ 0.025). Notably, all perforations occurred under
OP370 SPONTANEOUS BACTERIAL PERITONITIS – DOES THE sedation.
INFECTION ACQUISITION SITE MATTER? Conclusion: This study showed a strong improvement in quality of screening
A.G. G. Antunes1, C. Teixeira2, P. Costa3, B.M. Santos Peixe1, A. Alves2, colonoscopies performed within a quality assurance program in Austria between
S. Santos3, C. Chagas3, A. P. Oliveira2, H. Guerreiro1 2007 and 2014. Both overall adenoma detection rate and detection rate of prox-
1
Dept. Of Gastroenterology, Centro Hospitalar do Algarve, Faro/Portugal imal lesions increased strongly in the investigated study period. Interestigly, the
2
Dept. Of Gastroenterology, Centro Hospitalar de Setúbal, Setúbal/Portugal detection rate of advanced adenomas decreased.
3
Dept. Of Gastroenterology, Centro Hospitalar de Lisboa Ocidental, Lisboa/ Disclosure of Interest: All authors have declared no conflicts of interest.
Portugal
Contact E-mail Address: [email protected]
Introduction: Spontaneous bacterial peritonitis (SBP) develops in up to 25% of OP372 ENDORINGSTM INCREASES ADR EVEN IN HIGH-RISK
patients with cirrhosis and its associated with significant short and long-term SCREENING COLONOSCOPY: RESULTS OF A SINGLE CENTRE
morbidity and mortality. With the ambulatorization of medical care, the use of PILOT STUDY
antibiotics for primary and secondary prophylaxis of SBP, there is some con- B. Hayee1, G. Chung-Faye2
troversial concerning whether the acquisition site of the infection has an effect on 1
Gastroenterology, Kings College Hospital, London/United Kingdom
the prognosis of SBP and if the international guidelines for antibiotic therapy 2
Gastroenterology, King’s College Hospital, London/United Kingdom
(mainly based on the acquisition site) are still considered to be the best practice.
Aims & Methods: 1) To compare clinical, analytical and microbiological features Contact E-mail Address: [email protected]
between nosocomial and community-acquired SBP; 2) to assess the influence of Introduction: Colonoscopy remains the gold standard procedure for screening
the infection acquisition site when evaluated in-hospital mortality and 1 year- and polyp detection, with adenoma detection rate (ADR) being a widely accepted
mortality. Retrospective cohort study, conducted in 3 tertiaries centers that eval- key performance indicator (KPI). It has long been recognised that even experi-
uated all cases of SBP between 2010 and 2014. Medical records and laboratory enced endoscopists incur an appreciable ‘miss-rate’ and a number of novel
data were reviewed. For defining the acquisition site of the infection, we followed devices have been marketed to assist this aspect of practice. The EndoringsTM
the criteria described by European Center for Disease Prevention and Control device is a simple soft silicone, single-use device consisting of a series of rings
(ECDC). Healthcare-Associated infections and Nosocomial infections were ana- arranged around a central tubular core. As the colonoscope is inserted the rings
lyzed as the same variable. Multiresistant bacteria (MDR) was defined according fold backward to allow intubation and flare on withdrawal to flatten colonic
to the ECDC criteria (resistant to 3 antibiotic families, including beta-lactam folds and aid inspection.
antibiotics). Aims & Methods: This was a single-centre pilot study to determine the effect of
Results: We identified 222 episodes of SBP, from which 110 were considered as Endorings used in a high-risk cancer screening population (national), when used
community-acquired; in-hospital mortality was 28,8% and 1 year-mortality was by experienced operators with an established ADR already 445%. Prospective
56,9%. In 85 episodes we obtained microbiological isolation (MDR ¼ 28), with a data was collected during screening colonoscopy (performed by two accredited
predominance of gram negative (53,6%). Community-acquired SBPs were more colonoscopists) when the EndoringsTM device was used and compared the results
frequently caused by gram negative bacteria and Nosocomial-acquired SBPs to outcomes from the previous few months, for the same two colonoscopists)
were more frequently by gram positive bacteria (p ¼ 0,033); SBPs secondary to when the device was not in use (ie. historical controls).
MDR-bacteria were more frequent in Nosocomial-acquired group (19,64 vs Results: The ADR without EndoringsTM (n ¼ 85) was 49.4% with a per-proce-
6,36%; p ¼ 0,003). No statistically significant differences were noticed between dure detection rate (ppr) of 0.97. With the device (n ¼ 66), ADR was 66.7%
centers when analysed microbiological isolation rate, gram staining of MDR (p ¼ 0.0006) with ppr of 1.625. This represents a 35% increase in ADR and a
isolations. There were no statistically significant differences between 68% increase in the number of polyps detected at any given procedure. There
Community-acquired SBP and Nosocomial-acquired SBPs for the variables were no significant differences in completion rates, withdrawal time, use of seda-
age, gender, Child-Pugh, MELD, Hb, leukocytes, platelets, CRP, Na, INR, tion or comfort scores. The device was removed in 5/66 procedures due to inter-
bilirubin, albumin, ascites fluid characteristics, gastrointestinal bleeding, acute ference with intubation (in the presence of either an angulated sigmoid or
kidney injury and hemodynamic instability at diagnosis. Nosocomial-acquired diverticulosis). No complications were recorded.
SBPs were associated with longer hospitalizations (17,8 vs 11,7 days; p ¼ 0,007). Conclusion: Use of the EndoringsTM device was associated with a significant
No statistically significant difference was detected when analyzed in-hospital increase in ADR. Qualitatively, the three-ring design was felt to interfere with
mortality (Nosocomial-acquired ¼ 29,5 vs Community-acquired ¼ 28,2%; normal intubation such that insertion technique had to be modified. An updated
p ¼ 0,833). When assessed 1 year-mortality, Nosocomial-acquired SBPs were design iteration with two rings in slightly different positions along the central
associated with a worse prognosis (63,0 vs 51,7%; p ¼ 0,025). tube, has been produced and appears to offer a significant advantage in this
Conclusion: Nosocomial-acquired SBPs were associated with higher rates of regard. Furthermore, the central tube can be pushed further along the distal
MDR-bacteria, longer hospitalization lengths and higher 1 year-mortality. end of the colonoscope to allow the terminal ileum to be intubated with the
Clinical and laboratorial features were not significantly different between SBP device in place. The EndoringsTM may offer an advantage in screening colono-
according to the infection acquisition site; 6,36% of community-acquired SBPs scopy and, in this cohort, further prospective investigation is warranted.
were secondary to MDR-bacteria and so in a relevant percentage of our sample, Disclosure of Interest: All authors have declared no conflicts of interest.
empiric antibiotic therapy according to the current guidelines would eventually
fail.
Disclosure of Interest: All authors have declared no conflicts of interest.
OP373 THE FIRST RANDOMISED CONTROLLED TRIAL OF
ENDOCUFF VISIONÕ ASSISTED COLONOSCOPY VERSUS
WEDNESDAY, OCTOBER 19, 2016 10:30–12:00 STANDARD COLONOSCOPY FOR POLYP DETECTION IN BOWEL
IMPROVING QUALITY OF SCREENING COLONOSCOPY – ROOM N2_____________________ CANCER SCREENING PATIENTS (E-CAP STUDY)
R. Bhattacharyya1, F.J.Q. Chedgy2, K. Kandiah2, C. Fogg3, B. Higgins3,
OP371 SEVEN YEARS OF QUALITY ASSURANCE IN SCREENING B. Haysom-Newport4, L. Gadeke1, F. Thursby-Pelham2, R. Ellis1, P. Goggin1,
COLONOSCOPY IN AUSTRIA G. Longcroft-Wheaton5, P. Bhandari2
E. Waldmann1, I. Gessl2, D. Sallinger2, P. Jeschek1, M. Britto-Arias1, 1
Dept. Of Gastroenterology, Queen Alexandra Hospital Dept. of Gastroenterology,
E. Fasching3, W. Weiss1, M. Gschwantler1, M. Trauner1, M. Ferlitsch4 Portsmouth/United Kingdom
1 2
Austrian Society of Gastroenterology and Hepatology (OEGGH): Quality Gastroenterology, Queen Alexandra Hospital, Portsmouth/United Kingdom
3
assurance working group, Vienna/Austria University of Portsmouth, Portsmouth/United Kingdom
2 4
Department of Internal Medicine III, Division of Gastroenterology & Hepatology, Queen Alexandra Hospital Dept. of Gastroenterology, Portsmouth/United
Medical University of Vienna, Vienna/Austria Kingdom
3 5
Main Association of the Austrian Social Insurance Institutions, Vienna/Austria Gastroenterology, Portsmouth Hospitals NHS trust, Hampshire/United Kingdom
4
Department of Internal Medicine III, Division of Gastroenterology & Hepatology,
Medical University of Vienna, Wien/Austria Contact E-mail Address: [email protected]
Introduction: Up to 25% of colonic polyps are missed during colonoscopy. The
Contact E-mail Address: [email protected] Endocuff VisionÕ is a cap with soft flexible arms which attaches to the end of a
Introduction: Screening colonoscopy only effectively prevents from colorectal colonoscope and improves views during withdrawal. We have performed the first
cancer if performed with high quality. randomised controlled trial to identify the role of Endocuff VisionÕ in improving
Aims & Methods: Austria implemented a quality assurance program in screening polyp detection.
colonoscopy in 2007. This study provides a report on 8 years of quality assured Aims & Methods: Our aim was to investigate the impact of Endocuff VisionÕ-
screening colonoscopy. assisted colonoscopy on polyp detection, as compared to standard colonoscopy,
Results: In the investigated time period, 301 endoscopic units provided data of in the UK Bowel Cancer Screening Programme (BCSP). This was a single-centre,
159,246 screening colonoscopies. 49.1% were female patients. Mean age was 61.1 parallel group, randomised controlled trial. Ethics approval was obtained (ref:
United European Gastroenterology Journal 4(5S) A145
14/SC/0207). Patients attending for BCSP colonoscopy were stratified based on for screening, surveillance, following positive FOBT, or due to change in
whether they were attending for index screening colonoscopy or for polyp sur- bowel habits were randomized to either G-EYE colonoscopy or SC. Detected
veillance. Within each stratum participants were randomised to either Standard polyps were removed and sent for pathology. Polyp and adenoma detection rates
or Endocuff assisted colonoscopy. All procedures were performed by experi- were calculated.
enced, nationally accredited BSCP endoscopists, who had carried out 45000 Result: 480 patients were enrolled in the study, of which 238 subjects were ran-
colonoscopies and had cecal intubation rates of 490%. domized to SC and 242 subjects were randomized to G-EYETM colonoscopy.
Result: 534 patients were recruited from Sep 2014 to Sep 2015. 3 were excluded Baseline parameters and indication for colonoscopy were similar in both groups.
due to new diagnosis of polyposis syndrome, to avoid skewing of results. 531 The ADR, adenoma per patient, number of adenomas by size and advanced
were included and randomised to the 2 study arms. No significant difference was adenomas for each group are presented in Table 1. G-EYE colonoscopy
seen between the 2 groups for the primary endpoint of number of polyps per improved ADR by 45.6% when compared to SC. More specifically, the G-
patient. Secondary endpoints: No significant difference was observed between the EYE endoscope increased the number of advanced adenomas and large-size
2 groups for adenoma detection rate (ADR) or number of adenomas per patient adenomas by 96.9% and 96.2%, respectively. Procedural times were similar in
(Table 1). Endpoints were also evaluated separately for: screening group, surveil- both groups.
lance group, and the individual 4 endoscopists. In all these analyses, no signifi-
cant difference was found between the 2 study arms for any of the study Table 1: Results Summary
endpoints. No significant adverse events were encountered during the study in
either arm. The cecal intubation time was not prolonged and patients did not SC G-EYE % Increase
experience any additional discomfort due to the Endocuff Vision.
ADR 33.8% 49.2% 45.6%
Table 1: E-CAP results Adenoma per patient 0.57 0.93 63.2%
Diminutive adenomas (2–5 mm) 67 105 56.7%
Standard Endocuff
Small adenomas (6–9 mm) 19 26 36.8%
Patients 265 266 Large adenomas (10 mm) 26 51 96.2%
Polyps 470 436 Advanced adenomas 32 63 96.9%
Polyps/patient 1.77 1.64 p ¼ 0.441
Adenomas 359 336
Adenomas/patient 1.35 1.26 p ¼ 0.536 Conclusion: Our study shows that the G-EYE endoscope can substantially
PDR 185/265 ¼ 69.8% 187/266 ¼ 70.3% p ¼ 0.925 improve ADR when compared to SC. In addition to diminutive and small ade-
ADR 167/265 ¼ 63% 162/266 ¼ 60.9% p ¼ 0.851 nomas, the G-EYE endoscope detects a larger number of advanced and large-size
adenomas. Consequently, we conclude that the G-EYE endoscope can signifi-
Cancer detection rate 15/265 ¼ 5.7% 14/266 ¼ 5.3% p ¼ 0.851 cantly enhance the quality of CRC screening and thus reduce colonoscopic miss
rates and interval cancer incidents.
Disclosure of Interest: H. Jacob: Board of directors
Conclusion: In the UK, bowel cancer screening is performed by highly experi- All other authors have declared no conflicts of interest.
enced endoscopists with special accreditation. Our results suggest that in expert
hands, ADR exceeds 60% even without Endocuff. In such settings, Endocuff
Vision did not improve polyp detection rates (PDR) or ADR. However,
Endocuff did not cause any adverse events, prolong procedure duration or OP375 EFFICACY AND SAFETY OF THE NOVEL 1L PEG AND
cause additional discomfort. These data demonstrate the safety and feasibility ASCORBATE BOWEL PREPARATION NER1006 VERSUS
of Endocuff. However, no additional gain was demonstrated in expert hands. TRISULFATE SOLUTION IN OVERNIGHT SPLIT-DOSING
Disclosure of Interest: All authors have declared no conflicts of interest. ADMINISTRATION: RESULTS FROM THE PHASE 3 STUDY NOCT
M. Demicco1, L. B. Clayton2, R. Ng Kwet Shing2, M. S. Epstein3
1
Anaheim Clinical Trials LLC, Anaheim/United States of America/CA
2
Clinical Development, Norgine, Harefield/United Kingdom
OP374 INCREASED ADENOMA DETECTION RATE BY G-EYE HIGH 3
Investigative Clinical Research, Annapolis/United States of America/MD
DEFINITION COLONOSCOPY IN COMPARISON TO STANDARD
HIGH DEFINITION COLONOSCOPY- A PROSPECTIVE Contact E-mail Address: [email protected]
RANDOMIZED MULTICENTRE STUDY Introduction: Successful colon cleansing enables effective colonoscopy. PEG
H. Shirin1, B. Shpak2, J. Epshtein3, P. Vilmann4, A. Hoffman5, S. Sanduleanu6, based split dosing preparations are traditionally seen as the gold standard in
S. Ishaq7, P.A. Testoni8, S.A. Gross9, H. Neumann10, M. Goetz11, cleansing, but many still require a high preparation volume intake. NER1006
P.D. Siersema12, D. Abramowich13, M. Shnell2, M. Mizrahi3, J. Hendel4, is the first 1L PEG3350 and ascorbate bowel preparation in phase 3 clinical
J.W. Rey5, R. De Ridder6, E. Viale8, M. Pochapin9, M. Yair1, N. Gluck2, development. The low volume of NER1006 is achieved through the use of ascor-
S. Yaari3, T. Stigaard4, R. Simantov1, M. Moshkowitz2, E. Israeli3, S. Sloth4, bate in the second dose only.
S. Matalon1, A. Vilkin2, A. Benson3, A. Maliar1, A. Waizbard2, T. Hershcovici3, Aims & Methods: This phase 3, randomised, multicentre, colonoscopist-blinded,
E. Shachar1, S. Rochberger2, E. Tsvang3, M. Braverman1, H. Jacob3, non-inferiority study assessed the efficacy, safety and tolerability of a 2-day
Y. Brachman1, J.G. Karstensen4, D. Teubner5, R.M. m. Bogie6, R. Kiesslich5 overnight split-dosing regimen of either NER1006 (N2D) or trisulfate solution
1
Assaf Harofeh Medical Center, Tzrifin/Israel (TS) in patients undergoing colonoscopy. Two alternative primary endpoints
2
Laniado Hospital, Netanya/Israel were evaluated: overall bowel cleansing success and ‘Excellent plus Good’ cleans-
3
Hadassah Medical Center, Jerusalem/Israel ing rate in the colon ascendens using the Harefield Cleansing Scale (HCS).
4
Copenhagen University Hospital Herlev, Herlev/Denmark Secondary endpoints included hierarchical evaluation of lesion detection rates
5
HSK Dr. Horst-Schmidt-Kliniken, Wiesbaden/Germany (key), and cleansing assessment using the Boston Bowel Preparation Scale
6
UMC Maastricht, Maastricht/Netherlands (BBPS; supportive). Patient tolerability, acceptability and compliance were
7
Russell’s Hall, Dudley/United Kingdom assessed using questionnaires. Safety was monitored through adverse events
8
San Raffaele Hospital, Milano/Italy and clinical laboratory evaluation. The threshold for statistical significance in
9
NYU Langone Medical Center, New York/United States of America this study was P 5 0.025. The confidence interval (CI) for the difference between
10
University Hospital Erlangen, Erlangen/Germany the groups used a 10% margin to demonstrate non-inferiority vs. TS.
11
Universitätsklinikum Tübingen, Tübingen/Germany Result: Patients were randomised to receive either N2D (n ¼ 310) or TS (n ¼ 311).
12
Radboud University Medical Center, Nijmegen/Netherlands For N2D and TS, respectively, the mean age (SD) was 57.7 (10.36) and 57.3
13
Asaf Harofeh Medical Center, Tzrifin/Israel (10.56) years. The distribution of males vs. females was 158 (51.0%) vs. 152
(49.0%) for N2D and 169 (54.3%) vs. 142 (45.7%) for TS. High successful
Contact E-mail Address: [email protected] overall bowel cleansing efficacy was achieved in both treatment groups (Table
Introduction: Colorectal cancer (CRC) detection is attributed to the early detec- 1). N2D demonstrated non-inferiority (lower CI limit  10%) to TS for both
tion and removal of polyps and adenomas during colonoscopy procedures. alternative primary endpoints. Numerically, more patients on N2D achieved an
Although colonoscopy is considered to be the ‘‘gold standard’’ for CRC preven- ‘Excellent plus Good’ cleansing rate in the colon ascendens compared with TS.
tion, a significant number of polyps and adenomas go undetected during stan- Non-inferiority for N2D in adenoma detection rate in the colon ascendens was
dard procedures. This is largely due to polyps that are hidden behind colonic not demonstrated; other key secondary endpoints were not formally tested.
folds that obscure endoscopic optics and result in interval cancers. The G-EYE Tolerability and acceptability as assessed by the Bowel Cleansing Impact
endoscope (Smart Medical Systems Ltd., Ra’anana, Israel) comprises a standard Review (BOCLIR) Questionnaire were comparable for N2D and TS (Table 1).
forward-viewing endoscope with a permanently integrated balloon at the distal Compliance rates were high in both treatment groups. There were no deaths.
end. Upon withdrawal of the endoscope, the G-EYE balloon is inflated to a NER1006 was not associated with any serious treatment-emergent adverse events
partial pressure allowing for the flattening of haustral folds, centralization of (TEAEs). The most frequently reported related TEAEs in both treatment groups
the endoscope optics, and reduction in bowel slippage, thus providing improved were nausea and vomiting.
visualization of the colon anatomy and increased detection of polyps and Conclusion: When administered as a 2-day split dosing regimen, and compared to
adenomas. trisulfate solution, NER1006 was non-inferior in overall bowel cleansing success
Aims & Methods: This prospective, randomized, multicentre study compares the and in achieving an ‘Excellent plus Good’ cleansing rate in the colon ascendens.
adenoma detection rate (ADR) of the G-EYE HD colonoscopy with that of Both treatments were well tolerated; most TEAEs were mild or moderate in
standard HD colonoscopy (SC). Patients (age 4 50) referred to colonoscopy severity and reflected the expected safety profile of respective treatments. The
A146 United European Gastroenterology Journal 4(5S)

Table 1 (OP375): Efficacy and safety endpoints

NER1006 2-day Comparator: CI for the

split-dosing trisulfate solution difference [P value]
Abstract legend N2D TS N2D vs. TS

EFFICACY Primary analysis set, n ¼ 276 Primary analysis set, n ¼ 280

Primary endpoint: Patients with successful 235 (85.1%) 238 (85.0%) 8.15%* [0.528]
overall bowel cleansing efficacy (HCS) [n]
Supportive secondary endpoint: Patients with 228 (82.6%) 227 (81.1%) n.a.
successful overall bowel cleansing efficacy
(BBPS) [n]
Primary endpoint: Excellent plus Good cleans- 99 (35.9%) 82 (29.3%) 1.69%* [0.059]
ing rate in colon ascendens [n]
Key secondary endpoint: Adenoma detection 14.1% 17.1% 11.36%, 5.28%** [0.863]
rate, colon ascendens
Key secondary endpoint: Adenoma detection 33.7% 35.0% n.a.
rate, overall colon
Key secondary endpoint: Polyp detection rate, 18.5% 23.9% n.a.
colon ascendens
Key secondary endpoint: Polyp detection rate, 45.7% 48.6% n.a.
overall colon
Compliance rate (min 75% of both doses taken) 255 (92.4%) 255 (91.1%) n.a.
[n]
BOCLIR score [mean (SD)] 39.9 (17.70) 39.6 (17.51) n.a.
SAFETY Safety set, n ¼ 262 Safety set, n ¼ 265
All treatment-emergent adverse events [n] 118 67 n.a.
Patients with any related treatment-emergent 39 (14.9%) 25 (9.4%) n.a.
adverse event [n]

* ¼ 97.5% 1-sided CI; ** ¼ 95% 2-sided CI; n.a. ¼ not applicable

1L NER1006 showed high efficacy and safety in overnight split-dosing in each segment of the colon) in 215/224 (96.0%). No significant differences
administration. between group A and B were observed with regards to adherence to preparation
Disclosure of Interest: M. DeMicco: Contractor for Norgine through Anaheim scheme, which were both optimal, (98.1% vs 97.5%, p ¼ 0.693) and to the ade-
Clinical Trials LLC; Principal Investigator for the NOCT study. quacy of bowel prep (BBPS 4 2 in each segment) (97.2% vs 94.9%, p ¼ 0.785).
L.B. Clayton: Employee of Norgine No variable was significantly associated with split-dose uptake at logistic regres-
R. Ng Kwet Shing: Employee of Norgine sion analysis.
M.S. Epstein: Contractor for Norgine through Investigative Clinical Research. Conclusion: Present data show an excellent compliance with split-dose prescrip-
Investigator for the NOCT study. tion for early morning colonoscopy in both written only and oral and written
instruction groups, leading to very satisfactory levels of colon cleansing. This
finding underlines that the adoption of a self-explanatory booklet clearly describ-
ing the benefits of split-dose marginalizes the need of additional oral instructions.
OP376 THE USE OF A SELF-EXPLANATORY BOOKLET FOR BOWEL This result is relevant in an open-access system, where routine oral education is
PREPARATION WITHOUT ORAL INSTRUCTIONS OVERCOMES unfeasible, and does not support ESGE indications, which recommend both oral
BARRIERS AGAINST SPLIT-DOSE ADOPTION FOR EARLY and written explanation by healthcare professionals.
MORNING COLONOSCOPY: A RANDOMIZED CONTROLLED Disclosure of Interest: All authors have declared no conflicts of interest.
TRIAL Reference
A. Andrealli, S. Paggi, A. Amato, E. Rondonotti, G. Imperiali, N. Lenoci,
1. Radaelli F, Paggi S, Repici A et al. Barriers against split-dose bowel pre-
G. Mandelli, N. M.L. Terreni, G. Spinzi, F. Radaelli
paration colonoscopy. Gut 2016 [Epub ahead of print].
Digestive Endoscopy And Gastroenterology, Valduce Hospital, Como/Italy
Contact E-mail Address: [email protected]
WEDNESDAY, OCTOBER 19, 2016 10:30–12:00
Introduction: Split-dose cleansing regimen for colonoscopy is recommended over
day-before preparation by practice guidelines and it has been shown to increase BURDEN OF LIVER DISEASE – ROOM L7_____________________
the adenoma detection rate. Nevertheless, the compliance with split-dose pre- OP377 THE BURDEN OF OVERT AND OCCULT LIVER CIRRHOSIS IN
scription for early-morning colonoscopy (8–10 am) is poor [1]. PATIENTS WITH METABOLIC SYNDROME: ANALYSIS FROM A
Aims & Methods: Present randomized study was aimed at evaluating weather the LARGE GENERAL PRACTITIONERS DATABASE
addition of oral instructions to a self-explanatory booklet for bowel preparation A. Martini1, E. Ceranto1, A. Gatta2, P. Pontisso3
increases compliance with split-dose. We prospectively enrolled consecutive 50– 1
Department Of Medicine, University of Padua, Padova/Italy
70 yr-old outpatients undergoing screening colonoscopy from 8:00 to 10:00 am. 2
Dept of Medicine, Internal Medicine and Hepatology, University of Padova,
Exclusion criteria were inability to provide consent and contraindications to the Padova, Italy, Padova/Italy
preparation adopted in the study. All patients received a low-volume prepara- 3
Dept Of Medicine, Internal Medicine And Hepatology, University of Padova,
tion. We designed a dedicated booklet underlying the advantages of split-dose Padova/Italy
regimen including: 1. reduction of the risk of missing neoplastic lesions; 2.
improvement of colon cleansing and lower risk of rescheduling the procedure; Contact E-mail Address: [email protected]
3. increase of bowel prep tolerability; 4. reduction in procedure duration. Day- Introduction: Liver cirrhosis represents the end stage of chronic liver disease,
before preparation was left as an alternative and discouraged, secondary option. characterized by high mortality and morbidity (1,2) with relevant health and
In order to evaluate whether additional oral explanation, aimed at reinforcing the social costs (3). Metabolic syndrome represents one of the major risk factors
benefits of split-dose, may further improve compliance, patients were rando- of liver disease in western countries (4). The real prevalence of this condition is
mized in two groups: group A-only booklet delivered; group B-oral explanation difficult to assess, since liver disease is silent until clinical decompensation of
along with booklet. Patients’ data (demography, education, socioeconomic cirrhosis occurs.
status), along with prep-related and procedural data, were collected by a struc- Aims & Methods: The aim of this study was to estimate the prevalence of occult
tured questionnaire on colonoscopy day. Colon cleansing was evaluated by liver disease in the Veneto region and to compare the results with the burden of
Boston Bowel Preparation Scale (BBPS). Proportions were compared by chi- patient with overt diagnosis in the same geographic area. For the epidemiological
squared test or chi-squared for trend, as appropriate. A logistic regression ana- analysis the MilleinRete dataset was used, where medical records of 139,104
lysis was performed to disclose factors associated with compliance to split-dose subjects were stored by 99 general practitioners in the Veneto region. As indica-
prescription. A p-value 50.05 was considered significant for all comparisons. tors, transaminases elevation (42 nv in at least two occasions) for liver disease
Results: During the study period (January–April 2016), 286 patients were and thrombocytopenia (5120,000 m/L) for liver cirrhosis were used. Patients
enrolled (mean age 59.8  7, males 53.7%), 143 in group A and 143 in group with thrombocytopenia due to hematologic disorders were excluded.
B; of them 266 have undergone colonoscopy (group A: 130, group B: 136). The Prevalence of patients with already diagnosed chronic hepatitis, cirrhosis and
two groups were well balanced as concerns age, gender, education, employment comorbidities was assessed using ICD9-CM-1997 codes.
and marriage status. Split-dose was adopted by 106/130 and by 118/136 patients Result: Among 11.540 patients with elevated transaminases, 35% were already
in group A and B, respectively (81.5% vs 86.8%, p ¼ 0.317). Among patients who diagnosed as patients with liver disease of known etiology (viral hepatitis, alcohol
complied with split-dose the quality of bowel cleansing was adequate (BBPS 4 2 abuse or hepatic steatosis), while in the remaining 65% no liver disease diagnosis
United European Gastroenterology Journal 4(5S) A147
was recorded. Sex distribution of these patients was similar to that of the patients spent by Social Security in France for HE hospitalisations with a mean cost per
without liver enzymes alteration (M/F:0.91 vs 0.9, respectively), while age was hospital admission estimated at E5,535 (  SD E6,411).
higher in patients with elevated transaminases [mean age (yrs) ¼ 55.5 vs 48.9, Conclusion: The mean length of stay in patients with HE was high (15  19 days).
p 5 0.0001]. Patients with overt diagnosis of cirrhosis were 0.3% of the overall The binomial model confirmed the significant longer length of stay induced by
population, while thrombocytopenia, as indicator of occult cirrhosis, was patients with comorbidity such as malnutrition, renal insufficiency, bacterial
detected in 1.3% of the remaining patients. The epidemiological profile of infection and respiratory disease. The annual economic burden of HE hospitali-
these two groups was similar [M/F:1.59; mean age (yrs) ¼ 65.6 vs M/F:1.67; sations in France amounted to E40 million.
mean age (yrs) ¼ 65, p ¼ ns], but significantly different (p 5 0.0001) compared Disclosure of Interest: H. Hagege: Herve Hagege has acted as a medical expert for
to the normal population and to subjects with only liver enzyme alterations. Norgine and Alfa Wassermann
Patients with occult and overt cirrhosis presented a similar prevalence of meta- R. Benamouzig: Robert Benamouzig has acted as a medical expert for Norgine
bolic syndrome profile (49% and 56% respectively), while these figures were and Alfa Wassermann
lower in patients without signs of liver disease (33%, p 5 0.0001). C. Bureau: Cristophe Bureau has acted as a medical expert for Norgine and Alfa
Conclusion: In conclusion, a large proportion of patients with biochemical signs Wassermann
of chronic hepatitis and cirrhosis are still undiagnosed. Metabolic syndrome C. Blein: Cécile Blein is an employee of HEVA, who were contracted by Norgine
seems to be the major risk factor that characterizes patients with more severe and Alfa Wassermann to participate in this study.
liver disease. C. Amaz: CAMILLE Amaz is an employee of HEVA, who were contracted by
Disclosure of Interest: All authors have declared no conflicts of interest. Norgine and Alfa Wassermann to participate in this study.
References E. Ribot-Mariotte: Emmanuelle Ribot-Mariotte was an employee of Alfa
Wassermann at the time the study was undertaken.
1. Tsochatzis EA, et al. Lancet. 2014 May 17;383(9930):1749–61. I. Leurs: Irina Leurs was an employee of Norgine at the time the study was
2. Blachier M, et al. J Hepatol. 2013 Mar;58(3):593–608. undertaken.
3. Moorman AC, et al. Hepatology. 2015 May;61(5):1479–84. All other authors have declared no conflicts of interest.
4. Rinella ME. JAMA 2015;313:2263–2273.

OP379 THE IMPACT OF RIFAXIMIN-ALPHA ON NHS HOSPITAL

OP378 THE NATIONAL BURDEN IN FRANCE OF HOSPITAL CARE RESOURCE USE IN UK PATIENTS WITH HEPATIC
FOR PATIENTS WITH HEPATIC ENCEPHALOPATHY: DATA ENCEPHALOPATHY: A RETROSPECTIVE OBSERVATIONAL
FROM THE FRENCH NATIONAL HOSPITAL DATABASE (PMSI) STUDY (IMPRESS)
A. Abergel1, H. Hagege2, R. Benamouzig3, C. Bureau4, C. Blein5, C. Amaz5, R. Aspinall1, A. Radwan2, G. Shaya3, H. Sodatonou2, R. Cipelli4, M. Hudson5
E. Ribot-Mariotte6, I. Leurs7 1
Queen Alexandra Hospital, Portsmouth/United Kingdom
1 2
CHU de Clermont-Ferrand, Clermont-Ferrand/France Medical Affairs, Norgine, Harefield/United Kingdom
2 3
Creteil Gastroenterologie, CHI Creteil Gastroente´rologie, Cre´teil cedex/France Uk & Ireland Medical & Regulatory Affairs, Norgine, Harefield/United Kingdom
3 4
Service De Gastroenterologie, Hopital Avicenne, Bobigny/France pH Associates, Marlow/United Kingdom
4 5
CHU Purpan, Toulouse/France Freeman Hospital, Newcastle/United Kingdom
5
HEVA, Lyon/France
6
Alfa-Wassermann Pharma, Levallois-Perret/France,7Medical Dept., Norgine Contact E-mail Address: [email protected]
Medical Department, Rueil Malmaison/France Introduction: In clinical trials rifaximin- (RFX) has been shown to reduce the
risk of an overt episode of hepatic encephalopathy (HE) and the number of HE-
Contact E-mail Address: [email protected] related hospitalisations, but there are limited data describing its impact on
Introduction: Hepatic encephalopathy (HE) is a complication of cirrhosis char- healthcare resource use in real-world UK practice. This study compared hospital
acterized by a broad spectrum of neuropsychiatric manifestations. According to resource use pre- and post-RFX initiation in UK patients.
the clinical symptoms there are two types of HE: covert HE and overt HE Aims & Methods: A retrospective observational study in 11 specialist National
(OHE). In general, the prevalence of OHE is estimated at 10%–14% in cirrhotic Health Service (NHS) centres of 145 patients prescribed RFX for HE between
patients and at 10%–50% in patients with transjugular intrahepatic portosyste- July 2008 and May 2014. Local clinical staff reviewed patients’ medical records
mic shunt (TIPS). In France, the prevalence of OHE was estimated at 25,000 for demographics, RFX prescribing and adverse drug reactions (ADRs) to RFX.
patients (21,000 to 30,000 patients). Yet little is published on the national burden Details of inpatient hospitalisations and hospital visits in the 12 months pre- and
of hospitalisation of patients with hepatic encephalopathy. The first objective of post-RFX initiation were extracted from NHS Trust electronic databases. Ethics
this study was to use the retrospective national PMSI data (Programme reference 14/WS/1017.
Médicalisé des Systèmes d’Information) to assess the public health burden of Results: Of the 145 patients evaluated, 89 (61%) were male. At RFX initiation,
hospitalisations for OHE, documenting its incidence rate but also to analyse mean age was 61 years (standard deviation [SD] ¼ 11), 119 patients (82%) were
the characteristics of hospitalisations. The second objective was to study the on lactulose. Child-Pugh score was recorded for 67 (46%) patients (10% Class A,
factors independently associated with length of stay in patients with HE. 54% B, 36% C). Resource use in the 6/12 months pre- and post-RFX initiation is
Aims & Methods: A retrospective cohort was performed from the national PMSI shown in Table 1; to avoid nonsurvivor confounding this analysis includes the
database from 2012 and 2013. Given the absence of coding specificity of hepatic 114 patients (78%) who were alive at 6 months and 102 (70%) alive at 12 months
encephalopathy via ICD 10 code "K72 *" Hepatic failure, not elsewhere classi- post-RFX initiation. 3 patients (2%) had ADRs and 4 (3%) developed C.difficile
fied", an algorithm of patients hospitalised for HE was implemented according to infection (none of whom discontinued treatment).
a medical expertise from the expression of the main symptoms of the disease. A Conclusion: In UK clinical practice, treatment with RFX for HE is well-tolerated
negative binomial regression model was used to estimate the link between lengths and associated with significant reductions in hospitalisation frequency, bed occu-
of stay and HE patient’s characteristics like age, sex, comorbidities (malnutrition, pancy (including critical care) and emergency room visits; reductions are
renal failure, bacterial infection and respiratory diseases), stays in reanimation, observed within 6 months of treatment initiation and sustained at 12 months.
intensive care units and death. This is the first study to demonstrate a reduction in critical care bed occupancy
Result: The study collected respectively 13,484 patients on 2012 corresponding to with RFX.
17,001 hospitalisations and 13,672 patients in 2013 corresponding to 17,491 Disclosure of Interest: R. Aspinall: Consultant and UK advisory board member
hospitalisations. The mean age was 63.1  13.8 years in 2013 and 62.7  13.9 for Norgine
years in 2012. Thirty percent of patients were admitted to the intensive care A. Radwan: Employee of Norgine
units. In nearly all hospital stays, the illness was medically managed (87% of G. Shaya: Employee of Norgine
stays in 2013 and 89% in 2012). Nevertheless, there are 12% of surgical stays H. Sodatonou: Employee of Norgine
(1,664 stays in 2013 and 1,514 stays in 2012). The mean length of HE stay was 15 R. Cipelli: Consultant for Norgine. Employee of pH Associates which was com-
days (SD 19 days) and the median was 10 days. The length of stay was 48% missioned by Norgine Pharmaceuticals to provide support with study design and
longer for patients with malnutrition, and 52% longer in case of a bacterial management, data analysis and scientific editorial services.
infection. The length of stay was 12% and 14% longer for patients with renal M. Hudson: Consultant for Norgine. Attended advisory board and has given
failure and respiratory diseases, respectively. More 40 million euros per year are sponsored lectures (national or international) on behalf of Norgine.

Table 1 (OP379): All-cause resource use pre- and post-RFX initiation

6 months (n ¼ 114) 12 months (n ¼ 102)

Mean (SD) n* Pre-RFX Post-RFX P n* Pre-RFX Post-RFX P

Hospitalisations with 101 2.2 (1.9) 1.0 (1.3) 50.001 99 2.7 (2.8) 1.7 (2.0) 0.002
overnight stay per patient
Total bed days 101 2890 1206 - 99 3138 1621 -
Total bed days per inpatient 101 28.6 (31.4) 11.9 (23.2) 50.001 99 31.7 (35.9) 16.4 (29.1) 50.001
Critical care bed days per inpatient 19 7.9 (10.1) 2.0 (5.1) 0.046 18 11.3 (11.8) 2.4 (6.0) 0.017
Emergency room visits per patient 63 1.9 (2.3) 1.0 (1.0) 50.001 65 2.4 (3.4) 1.8 (2.6) 0.099
A148 United European Gastroenterology Journal 4(5S)
0.48–0.75) vs 0.40 (0.32–0.47), p ¼ 0.028) and Ang (1–7) (mean 22.8 (20.1–25.4)
vs 14.1 (10.8–17.4) pg/ml, p 5 0.001) were higher, and ACE and Ang II similar in
OP382 PREGNANCY OUTCOME IN MORE THAN 5000 BIRTHS TO participants with IBD compared with controls. No significant correlations
WOMEN WITH VIRAL HEPATITIS IN A POPULATION-BASED between circulating RAS components and markers of disease activity (faecal
COHORT STUDY IN SWEDEN calprotectin, C-reactive protein, platelet or white cell counts, or albumin) were
K. Stokkeland1, J.F. Ludvigsson2, R. Hultcrantz1, A. Ekbom3, J. Höijer4, noted. Amongst patients undergoing colonoscopy (20 CD, 15 UC, 14 non-IBD
M. Bottai4, O. Stephansson5 controls) and intestinal resection (5 each with CD, UC and non-IBD), angioten-
1
Department Of Medicine, Karolinska Institutet, Stockholm/Sweden sinogen, renin, ACE, ACE2, Ang II, Ang (1–7), AT1R, AT2R and Mas receptor
2
Division Of Epidemiology And Public Health, University of Nottingham, were identified by qRT-PCR and/or immunohistochemistry in healthy and dis-
Nottingham/Sweden eased bowel, with significantly higher gene expression of angiotensinogen (3–4
3
Department Of Medicine Solna, Clinical Epidemiology Unit, Karolinska fold), ACE (30–40 fold) and ACE2 (10 fold) expressed in the terminal ileum than
Institutet, Stockholm/Sweden colon (p 5 0.0001 for all). RAS components were consistently localised to the
4
Unit Of Biostatistics, Karolinska Institutet, Stockholm/Sweden epithelium; variably in the lamina propria and submucosa, especially microvas-
5
School Of Public Health, University of California, Berkley/United States of cular endothelium; and circular muscle myocytes. Expression of mRNA of angio-
America tensinogen was two-fold higher in inflamed IBD and non-inflamed IBD or non-
IBD control colonic segments (p 5 0.001, Kruskall-Wallis); immunohistochem-
Contact E-mail Address: [email protected] ical staining intensity for ACE2 was higher in the colon in patients with CD
Introduction: Previous studies have shown inconsistent results with respect to (p ¼ 0.002), and that for Ang (1–7) lower (p ¼ 0.001) in the colon in patients with
hepatitis B (HBV), Hepatitis C (HCV) and pregnancy outcome. IBD than non-IBD controls. Staining intensity of Mas receptor was higher in
Aims & Methods: The aim of this study was to investigate pregnancy outcome in non-inflamed colon in patients with IBD than in inflamed colon or healthy
women with HBV or HCV. In a nationwide cohort of pregnancies between 1997 control tissue (p ¼ 0.045, Kruskall-Wallis).
and 2011 we investigated the risks of adverse pregnancy outcomes in 3 077 births Conclusion: All of the components of the classical and alternative RAS pathways
to women with HBV and 2 150 births to women with HCV using data from are present in healthy intestinal tissue suggesting a role in normal physiology,
Swedish healthcare registries. Births to women without HBV (n ¼ 1 428 238), and especially in epithelial cells. Circulating and mucosal components of the alter-
births without HCV (n ¼ 1 429 165) served as population controls. Crude and native RAS axis are upregulated in patients with IBD, but mucosal Ang (1–7) is
adjusted relative risks (RR) were calculated using Poisson regression analysis. reduced, suggesting dysregulation and a potential role of the RAS in pathogen-
Results: Women with HCV were more likely to smoke (47.62% vs. 8.65%) and to esis or perpetuation of inflammation in IBD. Novel therapies that increase muco-
have alcohol dependence (18.79 vs. 1.07) compared with population controls. sal Ang (1–7) may have a role in IBD.
Most women with HBV were born in non-Nordic countries. HCV was associated Disclosure of Interest: All authors have declared no conflicts of interest.
with a decreased risk of preeclampsia (aRR: 0.42, 95% CI: 0.25–0.65), an
increased risk of late neonatal death (7–27 days: aRR: 4.47, 95% CI: 1.01–
12.44) and an increased risk of preterm birth (aRR: 1.31, 95% CI: 1.08–1.59).
HBV was associated with an increased risk for preterm birth (aRR: 1.21, 95% OP384 BLOCKADE OF AEB7 INTEGRIN CONTROLS TRAFFICKING OF
CI: 1.01–1.44). CD8þ AND TH9 LYMPHOCYTES FROM IBD PATIENTS TO THE
Conclusion: Both HBV and HCV are risk factors for preterm births, while HCV INFLAMED GUT IN VIVO
seems to be associated with a protective effect against preeclampsia. Future S. Zundler1, A. Fischer1, R. Atreya1, R. Lopez-Posadas1, A. Watson2,
studies should corroborate these findings. C. Neufert1, I. Atreya1, M.F. Neurath1
Disclosure of Interest: All authors have declared no conflicts of interest. 1
Department Of Medicine 1University Erlangen-Nuremberg, Erlangen/Germany
2
Norwich Medical School, University of East Anglia Dept. of Medicine, Norwich/
WEDNESDAY, OCTOBER 19, 2016 10:30–12:00 United Kingdom
TRANSLATIONAL ASPECTS OF IBD – ROOM L8_____________________ Contact E-mail Address: [email protected]
Introduction: The anti-4b7 antibody vedolizumab (VDZ), which inhibits gut
OP383 ALTERATION OF THE RENIN-ANGIOTENSIN SYSTEM IN THE homing of lymphocytes via interaction of 4b7 with MAdCAM-1, has greatly
CIRCULATION, TERMINAL ILEUM AND COLON IN PATIENTS increased therapeutic options in patients with IBD. However, lymphocyte
WITH INFLAMMATORY BOWEL DISEASE: A POTENTIAL NOVEL homing may also occur via other homing molecules like the 4b1 integrin1 and
THERAPEUTIC TARGET a considerable portion of patients does not respond to VDZ therapy2. The anti-
M. Garg1, S. Royce2, C. Tikellis3, C. Shallue1, P. Sluka4, H. Wardan5, D. Batu6, b7 antibody etrolizumab3 (ETZ) is currently tested in phase III trials and addi-
E. Velkoska7, L. M. Burrell7, M. Thomas8, A. Mcfarlane1, P. R. Gibson9, tionally blocks the binding of Eb7 to E-Cadherin, which is believed to mediate
J. Lubel1 epithelial retention of homed lymphocytes4.
1
Gastroenterology, Eastern Health, Box Hill, Melbourne/Australia/VIC Aims & Methods: We aimed to compare lymphocyte trafficking upon blockade of
2
Pharmacology, Monash University, Clayton, Melbourne/Australia/VIC b7 vs. 4b7 integrin. Hence, 4b7 and Eb7 expression was determined on per-
3
Biochemistry Of Diabetic Complications, Baker IDI, Melbourne/Australia/VIC ipheral blood and lamina propria lymphocyte subsets of UC and CD patients
4
Eastern Health Clinical School, Monash University, Box Hill, Victoria/Australia/ and healthy donors by flow cytometry or immunofluorescence staining, respec-
VIC tively. The regulation of Eb7 expression upon lymphocyte stimulation and
5
Eastern Health Clinical School, Monash University, Box Hill, Melbourne/ incubation with cytokines was studied. In in vitro adhesion assays the adhesive
Australia capacities of lymphocytes to MAdCAM-1 and E-Cadherin and the inhibitory
6
Baker IDI, Melbourne/Australia/VIC potential of VDZ and the ETZ surrogate antibody FIB504 (ETZs) were tested.
7
Medicine, Austin Hospital, University of Melbourne, Heidelberg, Melbourne/ Finally, lymphocytes from UC patients were treated with either of the com-
Australia/VIC pounds, fluorescence labelled and injected into the ileocolic artery of immuno-
8
Biochemistry Of Diabetic Complications, Baker IDI, Melbourne/Australia suppressed mice. Gut homing was assessed by in vivo confocal microscopy and
9
Medicine, Monash University, Melbourne/Australia/VIC flow cytometry of lamina propria cells.
Results: AEb7 expression was significantly higher on CD8þ lymphocytes than on
Contact E-mail Address: [email protected] CD4þ lymphocytes both in the peripheral blood and the gut. Among both sub-
Introduction: The renin-angiotensin system (RAS) has well-recognised roles in sets Eb7 expression was correlated with IL-9 secretion, while CD4þIL9þ cells
cardiovascular and renal homeostasis, but may also regulate inflammation, fibro- expressed less 4b7 than other CD4þ subsets. At the same time, CD8þ cells
sis and angiogenesis in multiple other organs, including the gastrointestinal tract. exhibited a notably greater potential to increase Eb7 expression upon T cell
The recently recognised alternative RAS axis comprising angiotensin converting receptor stimulation and TGF-b treatment, while butyric and retinoic acid
enzyme 2 (ACE2), the effector peptide angiotensin (Ang) (1–7) and the Mas decreased Eb7 expression on CD8þ cells. ETZs markedly inhibited binding of
receptor, mediate anti-inflammatory and anti-fibrotic effects as opposed to the CD4þ and CD8þ lymphocytes to rhE-Cadherin and blocked the adhesion of
classical axis comprising ACE, Ang II and the AT1 receptor. This study aimed to CD4þ and CD8þlymphocytes to rhMAdCAM-1 to a degree comparable with
prospectively characterise the RAS in the circulating and intestinal compart- VDZ. Fewer lymphocytes bound to a mix of both ligands upon treatment with
ments in patients with inflammatory bowel disease (IBD) and non-IBD controls. ETZs compared with VDZ. In our humanized mouse model the portion of
Aims & Methods: Circulating components of the RAS were measured in patients human CD8þ cells in the murine gut was significantly reduced three hours
with Crohn’s disease (CD), ulcerative colitis (UC) and non-IBD controls, and after injection when cells were treated with ETZs vs. VDZ. Among CD4þ
associations with markers of disease activity evaluated. Terminal ileum, ascend- cells, the fraction of PU.1þ cells was decreased. The expression of Eb7 on
ing and sigmoid colon from patients undergoing intestinal resection and colono- CD8þ cells from IBD patients treated with VDZ was higher in the maintenance
scopy were surveyed for these components by mRNA expression by qRT-PCR, than in the induction phase of treatment.
and immunohistochemical localisation and semi-quantification of particle den- Conclusion: VDZ may not equally cover all pathogenetically relevant lymphocyte
sity using microscope image processing software. ACE2 activity was measured in subsets leading to insufficient therapeutic response in predisposed patients. ETZ
biopsy samples. seems to offer superior reduction of intestinal lymphocyte infiltration especially
Results: 56 patients with CD (mean age 41 [range 21–76] y, 27 females), 45 with concerning CD8þ and Th9 cells.
UC (44 [22–82] y, 19 females) and 39 non-IBD controls (46 [22–83] y, 21 females) Disclosure of Interest: S. Zundler: The etrolizumab Surrogate antibody was pro-
were studied. No significant differences in demographic features were noted vided by Genentech, San Francisco, CA, USA. The company was neither
across the three groups. Circulating renin (mean 25.4 (95% CI 21.6–29.1) vs involved in conception and design of the study nor in analysis and interpretation
18.6 (13.9–23.3) mIU/L, p ¼ 0.026), ACE2:ACE ratio (mean 0.61 (95% CI of the results. SZ received funding from Takeda.
United European Gastroenterology Journal 4(5S) A149
M.F. Neurath: M.F.N. has served as an advisor for Abbvie, MSD, Boehringer, presenting cells and may promote either tolerogenic or inflammatory T cell
Takeda, Pentax and Giuliani. responses to mucosal antigens. DC are also capable of imprinting tissue specific
All other authors have declared no conflicts of interest. homing markers on T cells which direct T cell migration to sites including the
References skin, gut and lymphoid tissue. We characterised homing marker profile and
ongoing cytokine production of circulating DC subsets from patients with
1. Rivera-Nieves J, et al. L-selectin, alpha 4 beta 1, and alpha 4 beta 7 integrins Crohn’s disease and from healthy controls.
participate in CD4þ T cell recruitment to chronically inflamed small intes- Aims & Methods: DC within peripheral blood mononuclear cells from adults with
tine. J. Immunol 2005; 174: 2343–2352. active luminal Crohn’s disease or from healthy controls were characterised using
2. Feagan BG, et al. Vedolizumab as induction and maintenance therapy for flow cytometry. DC were identified as HLA-DRþ and negative for markers of
ulcerative colitis. N. Engl. J. Med 2013; 369: 699–710. other cell lineages (CD3, CD14, CD16, CD19, CD34). Myeloid DC (mDC,
3. Vermeire S, et al. Etrolizumab as induction therapy for ulcerative colitis: a CD11cþCD123-) and plasmacytoid DC (pDC, CD11c-CD123þ) were assessed
randomised, controlled, phase 2 trial. Lancet Lond. Engl 2014; 384: 309–318. for phenotype (maturation status, homing markers and pattern recognition
4. Cepek KL, et al. Adhesion between epithelial cells and T lymphocytes receptors) and on-going cytokine production by surface and intracellular stain-
mediated by E-cadherin and the alpha E beta 7 integrin. Nature 1994; 372: ing, respectively.
190–193. Results: In patients with Crohn’s disease (n ¼ 20), a greater proportion of mye-
loid DC expressed a gut-homing profile (CLA-b7þ, p ¼ 0.0011) compared to
healthy controls (n ¼ 13) where most myeloid DC were not tissue-specific
(CLAþb7þ, p ¼ 0.0016). In both Crohn’s and controls, myeloid DC were largely
OP385 VITAMIN D REGULATES DENDRITIC CELL ACTIVITY AND gut-homing (CLA-b7þ, p ¼ 0.001) whilst plasmacytoid DC were strongly skin
TRAFFICKING IN CROHN’S DISEASE (CLAþb7-) and lymph node (CCR7þ) homing (p 5 0.0001). Production of pro-
P. Hendy1, D. Reddi2, D. Bernardo3, L. Durant2, A. Noble4, N. English2, S. inflammatory cytokines was up-regulated in Crohn’s, with myeloid DC produ-
C. Knight4, A. L. Hart5 cing higher levels of TNF and plasmacytoid DC producing higher levels of IL-6
1
St. Mark’s Hospital, Harrow/United Kingdom than controls (p ¼ 0.0042 and p ¼ 0.013 respectively). Expression of maturation
2
Antigen Presentation Research Group, Imperial College, London/United Kingdom marker CD86 was increased on myeloid DC in Crohn’s but not on plasmacytoid
3
Gastroenterology Unit, Hospital U. La Princesa, IP, and CIBERehd, Madrid/ DC (p ¼ 0.027 and p ¼ 0.13 respectively). Expression of IFN-, Il-1b, Il-12,
Spain CD40, CD80, TLR2 and TLR4 on DC did not differ between Crohn’s and
4
Antigen Presentation Research Group, Imperial College, London/United Kingdom controls for either DC subset.
5
Gastroenterology, St Marks Hospital, Harrow/United Kingdom Conclusion: The increased myeloid DC expression of gut homing phenotype
markers and production of TNF in Crohn’s disease compared with controls
Contact E-mail Address: [email protected] highlights the central role that this dendritic cell subset plays in the pathogenesis
Introduction: Dendritic cells (DC) can determine whether the mucosal immune of Crohn’s disease. Differences between homing markers on myeloid DC (gut
system mounts an inflammatory or regulatory response to antigen and likely homing) and plasmacytoid DC (skin homing) suggest that they may have differ-
contributes to the pathogenesis of Crohn’s disease. Vitamin D down-regulates ent roles in different manifestations of Crohn’s, with myeloid DC being central to
DC inflammatory responses and could prove beneficial as a treatment adjunct in gut inflammation whilst plasmacytoid DC might be involved in cutaneous
Crohn’s. Vitamin D also modulates DC homing marker expression. This study Crohn’s disease and the skin sequelae of anti-TNF therapy.
assessed the effect of high dose parenteral vitamin D treatment on circulating DC Disclosure of Interest: P. Hendy: Advisory board for: Falk, AbbVie
phenotype and function in patients with active luminal Crohn’s disease receiving All other authors have declared no conflicts of interest.
anti-TNF therapy.
Aims & Methods: Peripheral blood mononuclear cells were isolated from 14
patients with active luminal Crohn’s disease and suboptimal vitamin D levels
(575 nmol/L) prior to and 6 weeks after starting anti-TNF (infliximab) ther- OP387 A PROTEOMIC APPROACH TO EXPLORE THE PROTECTIVE
apy. Patients with low vitamin D (550 nmol/L) were also given a single high ROLE OF INULIN IN PREVENTING LPS-INDUCED HUMAN
dose of parenteral vitamin D (300,000 international units 1,25(OH)2vitamin D3). COLONIC SMOOTH MUSCLE IMPAIRMENT
Flow cytometry was used to identify total DC, (HLA-DRþ cells negative for A. Altomare1, C. Vannini2, M. P.L. Guarino1, S. Barera3, V. Locato4, S. Cocca1,
markers of other cell lineages (CD3, CD14, CD16, CD19 & CD34)). DC were G. Arrigoni3, R. Alloni5, L. De Gara4, M. Cicala1
further subtyped as myeloid (mDC, CD11cþCD123-) and plasmacytoid (pDC, 1
Gastroenterology Unit, Campus Bio Medico University, Rome/Italy
CD123þCD11c-). Expression of phenotypic markers (including maturation and 2
Department Of Biotechnology And Life Science, University of Insubria, varese/
homing markers and pattern recognition receptors) and on-going intracellular Italy
DC cytokine production during 4 hours’ culture were assessed. 3
Department Of Biotechnology And Life Science, University of Insubria, Varese/
Results: Production of TNF by myeloid DC was significantly reduced Italy
(p ¼ 0.016) in those patients who received vitamin D alongside anti-TNF ther- 4
Food Sciences And Human Nutrition Unit, Campus Bio Medico University, Rome/
apy, beyond that of those who received anti-TNF therapy alone (mean post- Italy
treatment expression of TNF 24.9% v 39.1% respectively). There was a signifi- 5
Surgery Unit, Campus Bio Medico University, Rome/Italy
cant correlation between increase in vitamin D level and decrease in TNF
production by myeloid DC (p ¼ 0.025; R2 ¼ 0.76). An increase of serum Contact E-mail Address: [email protected]
25(OH)vitamin D greater than 20 nmol/L was associated with a decrease in Introduction: Fructans, such as inulin, are dietary fibers which stimulate gastro-
myeloid DC TNF production. Anti-TNF therapy alone induced a significant intestinal function acting as prebiotics. We recently demonstrated the protective
upregulation of the skin homing marker cutaneous lymphocyte antigen (CLA) on effect of inulin on LPS-induced damage of colonic smooth muscle in an ex vivo
myeloid DC (p ¼ 0.0055), an effect which was not seen in patients receiving experimental model, which seems to be related to presence of oxidative stress.
adjunctive vitamin D. Aims & Methods: In the present study, the protective role of inulin against LPS-
Conclusion: High dose parenteral vitamin D, given as an adjunct to anti-TNF induced oxidative stress was evaluated on colonic mucosa using a proteomic
therapy in Crohn’s, promotes down-regulation of circulating myeloid DC pro- approach. Human colonic mucosa and submucosa, obtained from disease-free
duction of TNF. This may influence the subsequent interaction of DC and T margins of resected segments for cancer, were sealed between two chambers
cells. TNF promotes a TH-17 response characteristic of Crohn’s inflammation; containing Krebs solution, with the luminal side of the mucosa overlayed with
thus the ability of vitamin D to further block TNF production may promote a 5 ml of Krebs, or 100 mg/mL LPS solution, or 100 mg/mL LPS þ100 mg/mL
more regulatory T cell response and improve outcomes when used as an adjunct inulin Fructafit IQ (LPS þ INU). The biological system was kept oxygenated
to anti-TNF therapy. The upregulation of the skin homing marker CLA follow- for 30 min at 37 C. The solutions on the submucosal side were collected following
ing anti-TNF therapy may explain the high rates of cutaneous side effects to this mucosal exposure to Krebs in the absence (N-undernatant) or presence of LPS
drug class. The down-regulation of CLA by vitamin D in this setting may be (LPS-undernatant) or LPS þ inulin (LPS þ INU-undernatant). Undernatants
clinically useful in those patients suffering cutaneous sequelae of anti-TNF were tested for the effects on human colonic smooth muscle strips contractility
therapy. using an organ bath system. Proteomic analysis (iTRAQ based analysis) was used
Disclosure of Interest: P. Hendy: Advisory board: DrFalk; AbbVie to separate and compare the total soluble proteomes from human colonic
All other authors have declared no conflicts of interest. mucosa and submucosa treated. Each sample was labelled by one of four
reagents of the iTRAQ 4-plex and then combined into one aliquote. Triplicate
labelling was performed, which showed a high level of reproducibility.
Results: Inulin exposure was able to restore, in human colonic mucosa, the LPS-
OP386 CIRCULATING DENDRITIC CELL SUBSETS IN CROHN’S dependent alteration of some proteins involved in the host response and in the
DISEASE SHOW ALTERATIONS IN TISSUE HOMING AND intestinal smooth muscle contraction (ZG16, CALM1/MLCK/MYL signaling
CYTOKINE PRODUCTION pathway) and to reduce the upregulation of two proteins involved in the radi-
P. Hendy1, D. Reddi2, D. Bernardo3, L. Durant2, A. Noble4, N. English2, S. cal-mediated oxidative stress induced by LPS (APEX1, CCT7). Moreover the
C. Knight4, A. L. Hart5 administration of inulin entails a higher level of some detoxification enzymes
1
St. Mark’s Hospital, Harrow/United Kingdom (MT2A, GSTK1, and UGT2B4) with respect to LPS treatment. Following expo-
2
Antigen Presentation Research Group, Imperial College, London/United Kingdom sure to the LPS-undernatant, a significant decrease in maximal Ach-induced
3
Gastroenterology Unit, Hospital U. La Princesa, IP, and CIBERehd, Madrid/ contraction was observed when compared to the contraction induced in control
Spain muscle strips incubated with the N-undernatant (49  5% vs 10  1% respec-
4
Antigen Presentation Research Group, Imperial College, London/United Kingdom tively, P 5 0.05.) and this was completely prevented by pre-incubation of the
5
Gastroenterology, St Marks Hospital, Harrow/United Kingdom LPS with Inulin (12  2%, P ¼ ns versus N-undernatant)
Conclusion: Our data suggest that the exposure of colonic mucosa to inulin is able
Contact E-mail Address: [email protected] to prevent LPS-dependent altered expression of some key proteins which pro-
Introduction: Crohn’s disease is characterised by an exaggerated immune mote intestinal motility and the host response, reducing the radical-mediated
response to mucosal antigen. Dendritic cells (DC) are the primary antigen oxidative stress
A150 United European Gastroenterology Journal 4(5S)
Disclosure of Interest: All authors have declared no conflicts of interest. unclear whether this also reflects the molecular phenotype and hence how this
Reference stratification might influence therapy and prognosis in an era of personalised
medicine.
1. Pasqualetti V, Altomare A, Guarino MP, et al. Antioxidant activity of inulin Aims & Methods: The aim of this study was to determine the molecular pheno-
and its role in the prevention of human colonic muscle cell impairment types of GOJ tumours and to relate this to the Siewert classification. The gene
induced by lipopolysaccharide mucosal exposure. PLoS One 2014; 16;9: expression profile of 107 treatment naı̈ve gastro-oesophageal adenocarcinomas
e98031. was assessed by the Illumina HTv4.0 beadchip array (GOJ1: 35, GOJ2: 31,
GOJ3: 18, true gastric comparators: gastric fundus/proximal body: 6, distal
body: 9, antrum: 8). Only tumours of intestinal Lauren type were included.
Differential gene expression analysis was done using limma in R, unbiased sub-
OP388 TLR4 IS STILL ACTIVE IN GP96-DEFICIENT MACROPHAGES group assignment was performed applying a model-based algorithm using
J. Cosin Roger, C. Stanzel, A. Terhalle, S. Lang, L. Wolfram, I. Frey-Wagner, MCLUST in R. Gene-set enrichment based pathway analysis was done using
M. Hausmann, M. Fried, M. Scharl, G. Rogler GAGE in R based on KEGG and Gene Ontology terms. Whole genome sequen-
Division Of Gastroenterology And Hepatology, University Hospital Zurich, cing data was analysed for a subset of 45 GOJ tumours (50x for tumours and 30x
Zürich/Switzerland for matched germline) to assess mutational burden, recurrently mutated genes,
copy number aberrations, and mutational signatures in the identified subgroups.
Contact E-mail Address: [email protected] Results: The Siewert classification did not reveal differential gene expression
Introduction: Gp96 is an endoplasmic reticulum chaperone for multiple protein apart from the gene REC8, a member of the meiotic recombination proteins,
substrates which plays an important role in innate and adaptive immunity. Lack which was upregulated in GOJ3 compared with GOJ1 (p ¼ 0.003). Unbiased
of this protein in intestinal macrophages (iMACs) of Crohn’s Disease (CD) assignment of the gene expression profiles instead revealed three distinct
patients is correlated with a loss of tolerance against the host gut flora, triggering groups which were not correlated with Siewert type, tumour stage or grade
a chronic and persistent inflammation. iMACS are crucial for pathogen recogni- (p 4 0.05). Group 1 showed strong expression of MUC5AC, CTSE, and
tion at the mucosal surface of the gastrointestinal tract and Toll-like receptors CLDN18, and was enriched for pathways involved in cell metabolism and cell
(TLR), one of the best investigated family of pattern recognition receptors, lead turnover. Group 2 was positive for CDX1, CDX2 and CDH17, and was enriched
to the phosphorylation of NFB after their activation. Previous studies of our for digestive and absorptive processes. Group 3 showed high expression of genes
group revealed a strong expression of TLR2 and 4 on inflammatory iMACS involved in immune-cell function including CXCL10, IDO1 and HLA-genes, and
leading to a higher susceptibility of CD patients to LPS, in parallel with a specific was enriched for pathways involved in immune response and cell-cell-commu-
loss of gp96. nication. Immunohistochemistry for a subset of the above mentioned genes con-
Aims & Methods: We aim to study the impact of the gp96-knockdown on TLR- firmed expression of these genes within the respective subgroups. Comparison of
function in the human monocytic cell line MM6 and in a conditional gp96- whole-genome sequencing data showed comparable features across all groups
LysMcre knock-out mice. MM6 cells were stably transduced with lentiviral with the expected recurrent mutations and trinucleotide mutational context.
gp96-knockdown vector. The lentiviral vector particles were produced by co- Survival was significantly different between groups: Group 1 had the worst over-
transfection of HEK293T cells with transfer, packaging and envelope plasmids all survival (group 1: 25.9 m, group 2: 45.2 m, group 3: 83.5 m; p ¼ 0.019) and
using Fugene HD Transfection Kit. After transduction, cells were treated with shorter recurrence-free survival in patients undergoing curative treatment path-
LPS (100 ng/ml) for 2 hours. Furthermore, in order to analyze the relevance ways (group 1: 24.3 m, group 2: 73.5 m, group 3: 86.2 m; p ¼ 0.051).
in vivo, conditional LysMcre-gp96 knock-out (KO) mice were also generated Conclusion: Adenocarcinomas at the GOJ comprise three distinct molecular phe-
after crossing gp96flox-mice with LysMCre mice. Peritoneal macrophages were notypes, which are not reflected by the anatomical location. These subgroups
isolated from both, wild-type (WT) and KO mice, and treated with LPS (100 ng/ have differences in biological pathways and survival and may thus have implica-
ml) for 2 hours. In transduced MM6 cells and peritoneal macrophages, TLR2 tions for prognosis and targeted therapy.
and TLR4 expression was analyzed by flow cytometry and the expression of Disclosure of Interest: All authors have declared no conflicts of interest.
NFB, IB-, IL-8, IL-6 and TNF- were analyzed by Western blot, qPCR
and ELISA. Results are expressed as percentage or fold induction  SEM. All
experiments were performed with an n  3.
Results: After checking that the efficiency of lentiviral knockdown was more than OP391 SRGAP1, A CO-TARGET OF MIR-340 AND MIR-124, FUNCTIONS
90% by Western blot, flow cytometry experiments revealed that the number of AS A POTENTIAL ONCOGENE WITH AMPLIFICATION AND
TLR4þ and TLR2þ gp96 shRNA transduced cells were slightly decreased, 81% RECURRENT MUTATION IN GASTRIC TUMORIGENESIS
and 77% respectively, compared with mock-transduced MM6 cells, 92% and W. Kang1, T. Huang1, Y. Zhou1, Y. Dong2, J.H. m. Tong1, K.F. To1
97% respectively. In line with this, the analysis of the expression of TLR4 and 1
Anatomical And Cellular Pathology, The Chinese University of Hong Kong, Hong
TLR2 receptors in peritoneal macrophages showed a similar slight decrease in Kong/Hong Kong PRC
KO mice (74.4% and 77.0% respectively) compared with WT mice (78.2% and 2
Institute Of Digestive Disease And Department Of Medicine And Therapeutics,
90.5% respectively). The functionality of TLR4 receptor was also analyzed and The Chinese University of Hong Kong, Hong Kong/Hong Kong PRC
treatment with LPS induced a significant increase in the ratio pIB-/IB- in
gp96 shRNA cells (1.6 fold induction) and in KO peritoneal macrophages Contact E-mail Address: [email protected]
(5  1.5); and in protein expression of pNFB in both gp96 shRNA (1.7) and Introduction: SRGAP1 (Slit-Robo GTPase-activating protein 1) functions as a
in KO peritoneal macrophages (1.5  0.6) compared with non-treated mock- GAP for Rho-family GTPases and downstream of Slit-Robo signaling. However,
transduced cells and WT peritoneal macrophages. Furthermore, LPS induced a the involvement of SRGAP1 activation and functional role in gastric carcinogen-
significant increase in the mRNA and protein expression of IL-8 (9 fold induc- esis has not been investigated.
tion and 800 pg/ml respectively) in gp96 shRNA compared with mock-trans- Aims & Methods: We aim to investigate the biological functions of SRGAP1 and
duced cells. These results were strongly reinforced since LPS also induced a comprehensively reveal its regulation by deregulated miRNAs in gastric carcino-
significant increase in the mRNA expression of IL-8 (11.7  2.6), IL-6 genesis. The mRNA and protein expression of SRGAP1 were examined by qRT-
(12.3  3.9) and TNF- (7.9  1.9) in KO peritoneal macrophages compared PCR and Western blot. The biological role of SRGAP1 in GC was demonstrated
with non-treated macrophages. by MTT proliferation, monolayer colony formation, cell invasion and migration
Conclusion: TLR4 receptor is still active and functional even in the absence of assays through siRNA-mediated knockdown. The prediction of miRNAs which
gp96 in macrophages. potentially target SRGAP1 was performed by TargetScan (http://www.targets-
Disclosure of Interest: All authors have declared no conflicts of interest. can.org/) and miRDB (http://mirdb.org). miR-340 and miR-124 were screened
out for further validation. The regulation of SRGAP1 by miRNAs was con-
firmed by qRT-PCR, Western blot and dual luciferase activity assays by ectopic
WEDNESDAY, OCTOBER 19, 2016 10:30–12:00 expression of miR-340 and miR-124.
GASTRIC AND JUNCTIONAL CANCERS – ROOM 1.86_____________________ Results: SRGAP1 is over-expressed in 9 out of 12 (75.0%) GC cell lines both
from the mRNA and protein level. In clinical samples form TCGA cohort,
OP389 A NEW, BIOLOGICALLY RELEVANT CLASSIFICATION FOR SRGAP1 shows gene amplification in 5/258 (1.9%) cases and its mRNA upre-
ADENOCARCINOMA AT THE GASTRO-OESOPHAGEAL gulation shows positive correlation with the copy number change. The mutation
JUNCTION rate of SRGAP1 in primary GC is 8/258 (3.1%) Knockdown of SRGAP1 in
J. Bornschein1, J. Perner2, L. Wernisch3, M. Secrier2, S. Macrae1, A. Miremadi4, MKN28, MGC-803 and SGC-7901 cells exhibited significant anti-oncogenic
M. O’Donovan5, M. Selgrad6, M. Venerito7, L. Bower2, M. Eldridge2, effect in vitro. SRGAP1 downregulation suppressed cell proliferation, reduced
P. Malfertheiner7, R.C. Fitzgerald1 monolayer colony formation, and inhibited at least 50% of the cell invasion and
1
MRC Cancer Unit, University of Cambridge, Cambridge/United Kingdom migration ability. Moreover, luciferase activity experiments revealed SRGAP1
2
Cancer Research UK, Cambridge Institute, Cambridge/United Kingdom knockdown significantly inhibited Wnt/b-catenin pathway, which was further
3
Biostatistics Unit, University of Cambridge, Cambridge/United Kingdom confirmed by the inactivation of b-catenin and downregulation of CCND1 and
4
Department Of Pathology, Cambridge University Hospitals, Cambridge/United c-Myc. In addition, SRGAP1 was confirmed to be a direct target of miR-340 and
Kingdom miR-124 in GC. These two miRNAs showed decreased expression compared
5
Histopathology, Cambridge University Hospitals, Cambridge/United Kingdom with adjacent normal epithelium cells and the downregulation of miR-340 and
6
Internal Medicine I, University of Regensburg, Regensburg/Germany miR-124 were associated with poor survival. Enforced overexpression of miR-
7
Gastroenterology, Hepatology & Infectious Diseases, Otto-von-Guericke 340 and miR-124 in GC cells also exerted tumor-suppressive function by inhibit-
University, Magdeburg/Germany ing cell proliferation and inducing G1 phase cell cycle arrest. In 28 paired GC
samples, the expression of SRGAP1 protein showed negative correlation with the
Contact E-mail Address: [email protected] expression of miR-340 and miR-124.
Introduction: Adenocarcinomas at the gastro-oesophageal junction (GOJ) are Conclusion: SRGAP1 is over-expressed and plays an oncogenic role in GC
currently stratified according to the Siewert classification by location of the through activating Wnt/b-catenin pathway. Apart from gene amplification and
main tumour mass (GOJ1: 1–5 cm proximal to the junction, GOJ2: 1 cm prox- mutation, the activation of SRGAP1 in GC is partly due to the downregulation
imal to 2 cm distal to the junction, GOJ3: 2–5 cm distal to the junction). It is of tumor suppressor miRNAs, miR-340 and miR-124. These findings provided
United European Gastroenterology Journal 4(5S) A151
clinical implications that targeting SRGAP1 might have therapeutic potential for OP394 PALLIATIVE CHEMOTHERAPY AND TARGETED THERAPIES
GC. FOR ESOPHAGEAL AND GASTRO-ESOPHAGEAL JUNCTION
Disclosure of Interest: All authors have declared no conflicts of interest. CANCER
V. T. Janmaat1, M.J. Bruno2, M. Peppelenbosch3, R. H.j. Mathijssen4, A. Van
Der Gaast1, E.W. Steyerberg1, E.J. Kuipers5, M.C.w. Spaander6
1
Gastroenterology & Hepatology, Erasmus Medisch Centrum, Rotterdam/
OP392 HOXB7 PROMOTES EPITHELIAL-MESENCHYMAL Netherlands
TRANSITION AND METASTASIS IN GASTRIC CANCER 2
Department Of Gastroenterology & Hepatology, University Medical Center
Y.R. Sim1, J. Park1, T. Kim2, W. Choi2, J.A. Lee2, M.K. Joo1, B.J. Lee2, Rotterdam, Rotterdam/Netherlands
H.J. Chun3, S.W. Lee4, Y.T. Bak2 3
Gastroenterology & Hepatology, Universitair Medisch Centrum, Rotterdam/
1
Division Of Gastroenterology, Department Of Internal Medicine, Korea Netherlands
4
University College of Medicine Guro Hospital, Seoul/Korea, Republic of ErasmusMC, Academic Medical Center Rotterdam, Rotterdam/Netherlands
2 5
Korea University College of Medicine Guro Hospital, Seoul/Korea, Republic of Department Of Gastroenterology And Hepatology, Erasmus MC University
3
Division Of Gastroenterology, Department Of Internal Medicine, Korea Medical Center, Rotterdam/Netherlands
6
University College of Medicine Anam, Seoul/Korea, Republic of Gastroenterology & Hepatology, Erasmus Medical Center Gastroenterology and
4
Korea University College of Medicine Ansan Hospital, Seoul/Korea, Republic of Hepatology, Rotterdam/Netherlands
Contact E-mail Address: [email protected] Contact E-mail Address: [email protected]
Introduction: In the previous study we observed that HOXB7 is highly expressed Introduction: More than 50% of patients with esophageal (EC) or gastro-esopha-
in gastric cancer and promote migration or invasion, and inhibit apoptosis in geal junction cancer (GEJC) have metastatic disease at the time of diagnosis.
gastric cancer cells. Chemotherapy and targeted therapies are increasingly used for palliative treat-
Aims & Methods: We aimed in this study to demonstrate the roles of HOXB7 in ment with the intent to control tumor growth, improve quality of life, and pro-
development of epithelial-mesenchymal transition (EMT) and metastasis in gas- long survival. To date, scientific proof is lacking.
tric cancer using in vitro and in vivo model. We established HOXB7-expression Aims & Methods: Therefore, the aim of this study was to systematically review
stable cell lines (MKN45-B7) and mock cells (MKN45-mock). Western blot was and compare the effectiveness of chemotherapy and targeted therapy to best
performed to validate EMT markers and phospho-Akt/PTEN activity. By injec- supportive care (BSC) and, to compare the addition of a cytostatic or targeted
tion of stable cell lines, xenograft tumors were produced on the 8-week old male therapeutic to a control arm in patients with EC/GEJC. This abstract is based on
Balb/C nude mice (nu/nu). 4 weeks after injection, we extracted xenograft a pre-peer review of a formal Cochrane Review. Upon completion and approval,
tumors, and implanted fragment of tumors on the stomach of another 8-week the final version is expected to be published in the Cochrane Database of
old nude mice. 6 weeks after implantation, mice were sacrificed and their peri- Systematic Reviews. We searched the Cochrane Central Register of Controlled
toneal metastasis, perigastric lymph node and volume of gastric tumor were Trials, MEDLINE and EMBASE, and searched reference lists of studies. The
compared between both groups. search was not restricted to English language publications only. Randomized
Results: MKN45-B7 cells frequently showed fibroblast-like mesenchymal pheno- controlled trials on palliative chemotherapy and/or targeted therapy, versus
type, whereas most of MKN45-mock cells showed epithelial phenotype. BSC or versus a control arm, in patients with esophageal or gastro-esophageal
Mesenchymal markers (snail, vimentin) were up-regulated and epithelial junction cancer were included. Two authors independently extracted data.
marker (E-cardherin) was down-regulated in MKN45-B7 cells, as well as phos- Results: For the comparison of palliative chemotherapy or targeted therapy
pho-Akt level was increased and PTEN expression was decreased compared by versus BSC, five trials with a total of 751 patients were included in the meta-
MKN45-mock cells. The volume of xenograft tumor was significantly increased analysis for overall survival (OS). This analysis demonstrated a significant benefit
in MKN45-B7 cell-injected mice than MKN-mock cell injected mice. Mean in OS in favor of the group receiving palliative chemotherapy and/or targeted
number of peritoneal metastasis/perigastric lymph node and volume of gastric therapy compared to BSC (hazard ratio (HR) 0.81 (0.71 to 0.92)). A similar trend
tumor were also significantly increased in MKN45-B7 tumor-implanted mice. was observed for progression free survival (PFS), including two trials and 541
When we transiently transfected siAkt on MKN45-B7 cells, snail and vimentin participants, with a HR of 0.58 (95%CI 0.28 to 1.18). For the comparison of
expression were down-regulated, whereas E-cadherin expression was up-regu- adding a cytostatic and/or targeted agent to a control arm, ten trials, with 1288
lated, compared by siControl-transfected MKN45-B7 cells. patients in total were included for the meta-analysis of OS. This analysis demon-
Conclusion: Our findings suggest that HOXB7 may play crucial role in inducing strated a significant benefit in OS in favor of the arm with an additional cyto-
EMT and promoting metastasis in gastric cancer via modulating Akt/PTEN axis. static or targeted therapeutic with a HR of 0.77 (95% CI 0.70 to 0.85). The
Disclosure of Interest: All authors have declared no conflicts of interest. median increased survival time was limited, one month for adding an additional
cytostatic or targeted therapeutic to the control arm. Subanalysis with second
line therapies showed a similar benefit as first line therapies. Ramucirumab was
the only agent, investigated more than once, that significantly improved both OS
OP393 SIGNIFICANCE OF COLONOSCOPY IN PATIENTS WITH and PFS. Palliative chemotherapy and/or targeted therapy increased the fre-
GASTRIC HIGH GRADE DYSPLAIS OR EARLY GASTRIC CANCER quency of treatment related toxicity of at least grade 3. However, treatment
R. Daegon, D. Kang, H. Kim, C. Choi, S. Park, S. Kim, H. Nam, J. Jeon, J. Cho, related deaths did not occur more frequently. Quality of life, for the studies
J. Park, S. Lee that reported this outcome, often improved in the arm with an additional agent.
Division Of Gastroenterology, Department Of Internal Medicine, Pusan National Conclusion: Palliative chemotherapy and/or targeted therapy significantly
University Yangsan Hospital, Yangsan/Korea, Republic of increase OS compared to BSC in patients with esophageal or gastroesopha-
geal-junction carcinoma. Additionally, patients who receive multiple chemother-
Contact E-mail Address: [email protected] apeutic or targeted therapeutic agents have an increased OS, PFS and
Introduction: Relationship of gastric cancer and colon cancer, it is not yet clearly improvement of quality of life, on the expense of treatment-associated toxicity
identified. But usually there is high risk of colorectal cancer known as gastric of at least grade 3. Based on this meta-analysis, palliative chemotherapy and/or
cancer patients. targeted therapy should be considered standard care for esophageal and gastro-
Aims & Methods: The purpose of this study was to discuss the development risk esophageal junction carcinoma.
of colorectal neoplasmand colon cancer in patients with gastric category 4 lesion Disclosure of Interest: All authors have declared no conflicts of interest.
(high-grade dysplasia, HGD and early gastric cancer, EGC) who underwent
endoscopic submucosal dissection (ESD) compared to healthy controls. We
also investigated the associated risk factors for colorectal neoplasm and colon WEDNESDAY, OCTOBER 19, 2016 10:30–12:00
cancer. The study group included a total of 209 patients with gastric category ABSTRACTS ON FIRE: NEW APPROACHES TO COLORECTAL DISEASE –
4 lesion (95 HGD and 114 EGC) that underwent ESD. And 610 healthy controls HOTSPOT_____________________
were included. All of the patients underwent concurrent screening colonoscopy
between January 2009 and May 2014. High risk colorectal neoplasm was defined OP395 ECONOMIC EVALUATION OF ANTIBIOTIC THERAPY VS
as 41 cm, adenoma with villous component, adenoma with HGD, three or more APPENDECTOMY FOR TREATMENT OF UNCOMPLICATED
polyps or adenocarcinoma. ACUTE APPENDICITIS: RESULTS OF THE APPAC RANDOMIZED
Results: High-risk colorectal neoplasm was found in 50/209 patients (23.9%) in CLINICAL TRIAL
patient group and 47/610 (7.7%) in controls (p 5 0.05). Colon cancer was diag- P. Salminen1, S. Sippola1, R. Tuominen2, H. Paajanen3, T. Rautio4,
nosed in 16/209 patients (7.6%) in patient group and 18/610 (2.9%) in controls P. Nordström5, M. Aarnio6, T. Rantanen7, S. Hurme8, J. Virtanen9, J. Mecklin10,
(p 5 0.05). The risk factors of high-risk colorectal neoplasm were associated with J. Sand5, A. Jartti11, J. Grönroos1
age, DM, colon cancer family history, and presence of gastric category 4 lesion. 1
Division Of Digestive Surgery And Urology, Turku University Hospital, Turku/
The risk factors of colon cancer were associated age, and colon cancer family Finland
history, and presence of gastric category 4 lesion. 2
Department Of Public Health, Turku University, Turku/Finland
Conclusion: The incidence of high-risk colorectal neoplasm and colon cancer in 3
University of Eastern Finland, Kuopio/Finland
patient group who underwent gastric ESD was higher than that in the control 4
Department Of Surgery, Oulu University Hospital, Oulu/Finland
group. Therefore, patients undergoing ESD with category 4 lesions may need 5
Division Of Surgery, Gastroenterology And Oncology, Tampere University
screening colonoscopy. Hospital, Tampere/Finland
Disclosure of Interest: All authors have declared no conflicts of interest. 6
Department Of Surgery, Jyväskylä Central Hopsital, Jyväskylä/Finland
7
Department Of Surgery, Kuopio University Hospital, Kuopio/Finland
8
Department Of Biostatistics, Turku University, Turku/Finland
9
Department Of Radiology, Turku University Hospital, Turku/Finland
10
University of Eastern Finland, Jyväskylä/Finland
11
Department Of Radiology, Oulu University Hospital, Oulu/Finland
Contact E-mail Address: [email protected]
A152 United European Gastroenterology Journal 4(5S)
Introduction: Appendectomy has been the standard treatment for acute appendi- leakage. Among patients treated conservatively, 13 (23.2%) ultimately under-
citis for over a century and more than 300 000 appendectomies are performed went elective resection due to ongoing abdominal complaints. There was no
annually in the United States1. Although appendectomy is generally well toler- mortality.
ated, it is a major surgical intervention and can be associated with postoperative Conclusion: Elective sigmoidectomy is superior to conservative managements in
morbidity. Our APPAC trial2 comparing antibiotic therapy with appendectomy terms of quality of life in patients with recurrent and persisting abdominal com-
for treatment of uncomplicated acute appendicitis showed that the majority of plaints after an episode of diverticulitis.
CT-proven uncomplicated acute appendicitis patients were successfully treated Disclosure of Interest: All authors have declared no conflicts of interest.
with antibiotics. Most patients randomized to antibiotic treatment did not References
require appendectomy during the 1-year follow-up period, and those who
required appendectomy did not experience significant or increased complications. 1. Peppas G, Bliziotis LA, Oikonomaki D and Falagas ME. Outcomes after
Aims & Methods: The objective of this study was to compare the treatment costs medical and surgical treatment of diverticulitis: A systematic review of the
of antibiotic therapy and appendectomy for treatment of uncomplicated acute available evidence. J Gastroenterol Hepatol 2007; 22: 1369–1368.
appendicitis in our Appendicitis Acuta (APPAC) randomized clinical trial. The 2. Vennix S, Morton DG, Hahnloser D, Lange JF and Bemelman WAResearch
APPAC multicenter, open-label, non-inferiority randomized clinical trial was Committee of the European Society of Coloproctocology. Systematic review
conducted in Finland from November 2009 until June 2012. A total of 530 of evidence and consensus on diverticulitis: an analysis of national and inter-
adult patients aged 18 to 60 years with CT-scan confirmed uncomplicated national guidelines. Colorectal Dis 2014 Nov; 16(11): 866–78. doi: 10.1111/
acute appendicitis were enrolled in six Finnish hospitals. Patients were randomly codi.12659.
assigned to early appendectomy (n ¼ 273) or antibiotic treatment (n ¼ 257). The 3. Andeweg CS, Felt-Bersma R, Verbon A, Stoker J, Boermeester M and
cost estimates were based on the cost levels of the final quarter of year 2012. All Bleichrodt R. Summary of the practice guideline on diverticulitis in the
costs were recorded, whether generated by the initial visit and subsequent treat- colon: diagnostics and treatment in specialty care. Ned Tijdschr Geneeskd
ment or possible recurrent appendicitis during the one-year follow-up period. 2013; 157(15): A6124.
Results: In the operative group, the overall societal costs were 16 times higher 4. Pasternak I, Wiedemann N, Basilicata G and Melcher GA. Gastrointestinal
than in the antibiotic group. In both groups productivity losses represented a quality of life after laparoscopic-assisted sigmoidectomy for diverticular dis-
slightly higher proportion of overall societal costs than all treatment costs ease. Int J Colorectal Disease 2012; 27: 781–787.
together, with diagnostics and medicines having a minor role. Patients in the
operative group were prescribed significantly more sick leave days (16.96, SD
8.30) compared with the antibiotic group (9.17, SD 6.89) (p 5 0.001). When the
age and sex of the patient as well as the hospital of care were controlled simulta- OP397 PREVALENCE OF SESSILE SERRATED ADENOMAS/POLYPS
neously, the operative treatment option generated significantly more costs in all IN DISTAL COLON DURING SCREENING COLONOSCOPY/
models. FLEXIBLE SIGMOIDOSCOPY: A SINGLE BOWEL CANCER
Conclusion: To our knowledge, this is the first randomized study comparing SCREENING CENTRE EXPERIENCE FROM UK
antibiotic therapy and appendectomy in uncomplicated acute appendicitis to R. Rameshshanker1, F. Purchiaroni1, A. Wilson1, Z.P. Tsiamoulos2,
report thorough cost analysis. Avoiding unnecessary appendectomies in our A. Rajendran3, P. Tekkis4, B.P. Saunders5
study resulted in major cost savings. Although 27% of the antibiotic group 1
Wolfson Endoscopy Unit, St Mark’s Hospital, London/United Kingdom
patients underwent surgery, the differences in costs both to the service providers 2
St Mark’s Hospital And Academic Institute, St. Marks Hospital Wolfson Unit for
and to the society overall strongly support evaluating antibiotic therapy as the Endoscopy, London/United Kingdom
first alternative for uncomplicated acute appendicitis. Further studies evaluating 3
Wolfson Endoscopy Unit, St Mark’s Hospital, Harrow, London/United Kingdom
the optimal treatment of acute uncomplicated appendicitis are strongly encour- 4
Professor Of Colorectal Surgery And Consultant Colorectal Surgeon, Department
aged also from an economic standpoint. of Colorectal Surgery, Royal Marsden Hospital, London/United Kingdom
Disclosure of Interest: P. Salminen: Research grant / a government research grant 5
Wolfson Unit For Endoscopy, St. Mark’s Hospital/Academic Institute, London/
(EVO) awarded to Turku University hospital United Kingdom
All other authors have declared no conflicts of interest.
References Contact E-mail Address: [email protected]
Introduction: Sessile Serrated Adenomas/Polyps (SSA/P) are responsible for
1. Livingston EH, Fomby TB, Woodward WA and Haley RW. nearly 20% of colorectal cancer (CRC). Despite the utility of novel image enhan-
Epidemiological similarities between appendicitis and diverticulitis suggest- cing techniques including narrow band imaging it is difficult to differentiate
ing a common underlying pathogenesis. Archives of Surgery 2011 Mar; hyperplastic (HP) polyps from SSA/Ps. Vast proportion of endoscopists leave
146(3): 308–14. the diminutive and possibly small HP polyps in situ in the recto sigmoid area
2. Salminen P, Paajanen H, Rautio T, et al. Antibiotic Therapy vs (diagnose and disregard approach). Hence there is a possibility of leaving SSA/P
Appendectomy for Treatment of Uncomplicated Acute Appendicitis: The in the recto sigmoid region which could potentially lead to CRC later in life.
APPAC Randomized Clinical Trial. JAMA 2015 Jun 16; 313(23): 2340–8. Aims & Methods: We aim to estimate the prevalence of SSA/P in recto sigmoid
colon at screening colonoscopy and flexible sigmoidoscopy (FS). Patients aged
455 years underwent a screening colonoscopy (n ¼ 500) or a flexible sigmoido-
scopy (n ¼ 500) at our institution between August 2014 and April 2015 were
OP396 SURGERY VERSUS CONSERVATIVE TREATMENT FOR included. Data collected from 500 consecutive patients who underwent a colono-
RECURRENT AND ONGOING DIVERTICULITIS; RESULTS OF A scopy or a FS. Demographic, procedural and polyp data were retrieved from our
MULTICENTER RANDOMIZED CONTROLLED TRIAL (DIRECT- endoscopy database.
TRIAL) Results: 99.6% of (498/500) colonoscopy and 97.6% of flexible sigmoidoscopy
M. Stam1, B. Wall Vd1, W.A. Draaisma1, W. A. Bemelman2, M.A. Boermeester3, procedures were completed. Screening colonoscopy detected 1006 polyps and FS
I.A. m.j. Broeders4, E. Belgers5, B. Toorenvliet6, H.A. Prins7, E.C.j. Consten8 detected 249 polyps. Polyp size ranged between 1–80 mm (colonoscopy mean size
1
Surgery, Meander MC, Amersfoort/Netherlands 6 mm, SD 7.2 mm; FS mean 3.4 mm, SD 3.9 mm). While colonoscopy detected 43
2
Department Of Surgery, Academisch Medisch centrum Dept. of Surgery, SSA/Ps (4.3%), FS detected only 6 SSA/Ps (2.4%) which equates to an overall
Amsterdam/Netherlands prevalence of 3.9% (49/1255). Table 1 summarises the SSA/Ps prevalence data
3
Dept. Of Surgery, Academic Medical Center Amsterdam, Amsterdam/ from our cohort. In rectum there were 8 SSA/Ps detected and resected which
Netherlands equals to a 3.6% of all rectal polyps. All SSA/Ps detected in rectum were less than
4
Surgery, Meander Medical Center, Amersfoort/Netherlands 10 mm in size (range 2–9 mm). Prevalence of SSA/Ps in proximal colon was 4.5%.
5
Surgery, Atrium MC Parkstad, Heerlen/Netherlands
6
Surgery, Ikazia, Rotterdam/Netherlands Total number Number of Prevalence
7
Surgery, Jeroen Bosch Hospital, Den Bosch/Netherlands Site of polyps SSA/Ps of SSA/Ps
8
Meander Medisch Centrum Dept. of Surgery, Amersfoort/Netherlands
Rectum 222 08 3.6%
Contact E-mail Address: [email protected]
Introduction: Patients with recurrent or persisting complaints following an epi- Sigmoid colon 320 13 4%
sode of diverticulitis are managed with either conservative measures or elective Descending colon 133 02 1.5%
sigmoidectomy. To date no studies have been done comparing these two treat- Splenic flexure 37 00 0%
ment modalities. We aimed to determine which treatment is superior in terms of Transverse colon 217 07 3.2%
improving quality of life. (DIRECT trial,NTR1478 (www.trialregister.nl)).
Aims & Methods: An open-label, multicenter, randomized clinical trial was per- Hepatic flexure 37 01 2.7%
formed in 24 teaching and 2 academic hospitals in the Netherlands (DIRECT Ascending colon 168 09 5.4%
trial). Patients presenting with either recurrent or persistent abdominal com- Caecum 114 09 7.9%
plaints after an objectified episode of diverticulitis were included. Patients were Site not specified 07 00 0%
randomly assigned to either conservative treatment, according to current day
practice, or elective (laparoscopic) sigmoidectomy using a stratified digital en- Conclusion: Our cohort showed a slightly higher prevalence of SSA/Ps in rectum
block randomization system. Primary endpoint was quality of life measured by and sigmoid colon. Therefore, it becomes clinically relevant to differentiate SSA/
the Gastro-intestinal Quality of life Index (GIQLI) after six months. Ps from HP polyps in recto sigmoid before adapting a diagnose and disregard
Results: Between July 1, 2010 and April 1, 2014, 109 patients were randomized approach for small (6–9 mm) hyperplastic looking polyps in this location.
when the data safety and monitoring board prematurely terminated the trial Disclosure of Interest: All authors have declared no conflicts of interest.
because off increasing difficulties in recruitment. Fifty-three patients were ran-
domized to resection and 56 to conservative treatment. The GIQLI score was
significantly higher among patients randomized to resection (114.4 (SD 22.3) vs
100.4 (SD 22.7) p ¼ 0.0001). Seven (13.2%) patients developed anastomotic
United European Gastroenterology Journal 4(5S) A153
OP398 SERRATED POLYPOSIS SYNDROME: A SURGICAL
PERSPECTIVE
S.A.Q. Rana1, J. Ijspeert2, N. Atkinson3, Y. Van Herwaarden4, I.D. Nagtegaal5, OP399 IMPROVED RISK CLASSIFICATION FOLLOWING
S.K. Clark6, J.E. East7, E. Dekker8, A. Latchford9 COLORECTAL ADENOMA REMOVAL
1
Surgery, St. Mark’s Hospital, London/United Kingdom P. Wieszczy1, M.F. Kaminski2, R. Franczyk3, M. Loberg4, J. Kobiela5,
2
Gastroenterology, Academic Medical Centre, Amsterdam-Zuidoost/Netherlands M. Rupinska6, B. Kocot1, M. Rupinski7, Ø. Holme2, U. Wojciechowska8,
3
Translational Gastroenterology Unit, Oxford University Hospitals, Oxford/ J. Didkowska8, M. Bretthauer4, D. Ransohoff9, M. Kalager2, J. Regula10
1
United Kingdom Department Of Gastroenterology, Hepatology And Clinical Oncology, Medical
4
Gastroenterology, Radboudumc, Nijmegen/Netherlands Center for Postgraduate Education, Warsaw/Poland
5 2
Radboud University Nijmegen Medical Center, Radboud University Nijmegen Clinical Effectiveness Research Group, Institute Of Health And Society,
Medical Center Dept. of Pathology, Nijmegen/Netherlands University of Oslo, Oslo/Norway
6 3
Department Of Surgery, St Marks Hospital, London/United Kingdom Departement Of Oncological Gastroenterology, The Maria Sklodowska-Curie
7
Department Of Gastroenterology, Gastroenterology Unit John Radcliffe Hospital, Memorial Cancer Center and Institute of Oncology, Warsaw/Poland
4
Oxford/United Kingdom Department Of Transplantation Medicine And K. G. Jebsen Center For Colorectal
8
Gastroenterology & Hepatology, AMC, Amsterdam/Netherlands Cancer Research, Oslo University Hospital, Oslo/Norway
9 5
Department Of Gastroenterology, St. Mark’s Hospital, London/United Kingdom Department Of General, Endocrine And Transplant Surgery, Medical University
of Gdansk, Gdansk/Poland,6Department Of Gastroenterology, Hepatology And
Contact E-mail Address: [email protected] Clinical Oncology, Medical Centre for Postgraduate Education, Warsaw/Poland
Introduction: Serrated Polyposis Syndrome (SPS) is associated with an increased 7
Department Of Gastroenterological Oncology, The Maria Sklodowska-Curie
risk of colorectal cancer (CRC). Some patients may require colonic surgery but Memorial Cancer Center And Institute Of Oncology, Warsaw, Poland, Warsaw/
the literature regarding indication, procedure performed, outcomes and surgical Poland
decision making is sparse. We aimed to address these issues. 8
National Cancer Registry of Poland, the Maria Sklodowska-Curie Memorial
Aims & Methods: 434 patients with SPS, were retrospectively enrolled from 7 Cancer Center and Institute of Oncology, Warsaw/Poland
centers in the Netherlands and 2 in the UK. Data were retrieved from medical 9
Departments Of Medicine And Epidemiology, University of North Carolina at
charts, pathology and endoscopy reports and collected in a centralized database. Chapel Hill, Chapel Hill NC/United States of America
Data relating to surgical resection and surveillance outcomes were assessed. 10
Department Of Gastroenterology, Maria Sklodowska-Curie Memorial Cancer
Results: A total of 164 (38%) patients underwent colorectal surgery; 114 (70%) Centre and Institute o Oncology, Warsaw/Poland
for CRC, 31 (19%) for high polyp burden and 14 (9%) for unresectable polyps.
Surgery for SPS Cancer Twenty seven (25%) SPS cancers were managed with Contact E-mail Address: [email protected]
total colectomy and ileorectal anastomosis (IRA), with the remaining 87 (75%) Introduction: Current colonoscopy surveillance recommendations after polyp
patients having a more limited resection. 90% of those undergoing IRA had a removal are arbitrary and resource demanding. We developed a novel risk clas-
formal diagnosis of SPS at the time of their surgery compared with only 39% of sification system for colorectal cancer following adenoma removal.
those undergoing more conservative resections. Fifty eight (50%) patients had a Aims & Methods: We included all individuals who underwent screening colono-
resection for cancer before a diagnosis of SPS was made. Total polyp burden scopy with adequate bowel cleansing and caecum intubation in the Polish
(median 40 v 22.5, p 5 0.01) and proximal polyp numbers (median 20 v 12, National Colorectal Cancer Screening Program between January 2000 and
p 5 0.019) were significantly higher in those having more extensive surgery. In December 2008. They were followed for colorectal cancer incidence and death
the limited resection group eight (9%) patients developed metachronous through national registries until December 2013. We estimated adjusted hazard
tumours; of these only three have recorded formal post-operative endoscopic ratios (HR) for individuals with different adenoma characteristics compared to
surveillance. None of these patients met SPS criteria at the time of index surgery. individuals without adenomas and derived a novel risk classification system.
Three had total IRA as management of their second tumour. The median interval Results: Among 159,928 individuals (median age 56 years; 37.6% males) with a
to development of second CRC was 24 months. In the limited resection group median follow-up of 7.1 years we identified 82 colorectal cancers after adenoma
seven (8%) patients required further surgical intervention for endoscopically removal (0.31%) and 194 in individuals without adenomas (0.15%). The stron-
unmanageable polyp load. All had IRA as their second procedure. Total polyp gest predictors for colorectal cancer risk were adenoma size 20 mm in diameter
burden (median 40 v 25, p 5 0.01), proximal polyp burden (median 25 v 15, (HR 8.70; 95% CI 5.43–13.95, P 5 0.001), high-grade dysplasia (HR 4.15; 95%
p ¼ 0.002) and number of proximal polyps 410 mm (median 10 v 2, p ¼ 0.005) CI 2.05–8.43, P 5 0.001) and 3 adenomas (HR 3.13; 95% CI 1.60–6.12,
were higher in this group compared with those having surgery for CRC alone. P ¼ 0.001). In a novel risk classification system using only these three predictors
Surgery for High Polyp Burden All 31 patients had a diagnosis of SPS and under- the number of individuals in the high-risk group was reduced by 56% with no
went IRA. The median total polyp count was 43 (IQR 34–56.5) and median increased risk of overlooked cancer (absolute risk difference per 10,000 indivi-
proximal polyp burden was 31 (IQR 26.8–47.5). Surgery for Unresectable duals: 2.2; 95% CI 11.9–16.3).
Polyp Fourteen patients had unresectable polyps and had segmental resections. Conclusion: Limiting surveillance recommendations to patients with adenomas
None have developed CRC to date. Polyp burden in this group was equivalent to 20 mm in diameter or high-grade dysplasia or 3 adenomas significantly
those having CRC surgery. reduces the need of surveillance colonoscopies without increasing the risk for
Conclusion: 1. Over one-third of SPS patients required colorectal resection. The cancer.
vast majority for CRC, of whom only half were known to fulfil criteria for SPS at Disclosure of Interest: All authors have declared no conflicts of interest.
the time of their cancer resection. 2. Developing metachronous cancer is uncom-
mon. Segmental resection and close endoscopic surveillance may be appropriate
for at least some of this patient cohort and more extensive surgery reserved for
those whose SPS cancers present concurrently with higher polyp counts. Surgical OP400 COST-EFFECTIVENESS ANALYSIS OF POST-POLYPECTOMY
decision making should be guided by the endoscopic assessment of the SPS. COLONOSCOPY SURVEILLANCE USING JAPANESE DATA: RISK-
Disclosure of Interest: All authors have declared no conflicts of interest. STRATIFIED SURVEILLANCE BASED ON POLYP RESULTS IS
MORE COST-EFFECTIVE
M. Sekiguchi1, T. Matsuda1, A. Igarashi2, H. Takamaru1, M. Yamada1,
T. Sakamoto1, T. Nakajima1, Y. Kakugawa3, Y. Saito4
1
Endoscopy Division, National Cancer Center Hospital, Tokyo/Japan
2
Graduate School Of Pharmaceutical Sciences, the University of Tokyo, Tokyo/
Japan
3
Cancer Screening Center, National Cancer Center Hospital, Tokyo/Japan
4
Endoscopy Division, National Cancer Center Hospital Endoscopy Division,
Tokyo/Japan
Contact E-mail Address: [email protected]
Introduction: To maximize the usefulness of total colonoscopy (CS) in reducing
deaths from colorectal cancer (CRC), it is essential that cost-effective post-poly-
pectomy CS surveillance programs are implemented. However, this has not been
well examined. European Union and United States guidelines for post-polypect-
omy surveillance recommend risk-stratified programs based on initial CS
results.1,2 Japanese guidelines, however, recommend that post-polypectomy sur-
veillance CS should be performed within 3 years of polypectomy, regardless of
the results of resected polyps.3 Given that different surveillance programs are
recommended in different settings, it is important to determine the most cost-
effective surveillance program.
Aims & Methods: The aim of this study was to determine the most cost-effective
post-polypectomy CS surveillance program by performing a Markov model ana-
lysis using Japanese data. The model was developed by simulating the clinical
course of CRC as a transition from normal epithelium, low-risk adenomatous
polyps sized 1–4 mm and 5–9 mm, high-risk adenomatous polyps, CRC, and
finally to death from CRC.4 High-risk polyps included intramucosal cancers
and adenomas with a diameter  10 mm, with high-grade dysplasia, or with vil-
lous histology (25%). The initial population comprised 100,000 average-risk
individuals aged 40 years. Parameters of transition probabilities, costs, and test
characteristics were determined based on Japanese data.4 Four surveillance
A154 United European Gastroenterology Journal 4(5S)
18
strategies were evaluated for costs, gained quality-adjusted life-years (QALYs), Kinki University, Osaka/Japan
19
and the required number of CS procedures. In strategy 1, post-polypectomy Osaka Medical Center for Cancer and Cardiovascular Diseases, Osaka/Japan
20
surveillance CSs were performed 1 year after polypectomy regardless of the Machida Gastrointestinal Hospital, Osaka/Japan
21
polyp results. In strategy 2, the interval between surveillance CSs and polypect- Kyoto Katsura Hospital, Kyoto/Japan
22
omy was 3 years regardless of the polyp results. Strategy 3 was a risk-stratified Kyoto Prefectural University of Medicine, Kyoto/Japan
23
one; surveillance CSs were performed 3 years after the resection of high-risk Fujita Health University, Aichi/Japan
24
polyps and 5 years after that of low-risk polyps. In strategies 1, 2 and 3, surveil- Terai Clinic, Tokyo/Japan
25
lance CSs were performed 10 years after normal CSs. Strategy 4 was also a risk- Akita Red Cross Hospital, Akita/Japan
26
stratified one with more intense use of CS than strategy 3; the interval between National Cancer Cener Hospital East, Tokyo/Japan
27
surveillance CSs and the resection of high-risk polyps, low-risk polyps, and no Tokura Yamaguchi Clinic, Shizuoka/Japan
28
polyps were 1, 3 and 5 years, respectively. In all strategies, a fecal immunochem- Toho University, Tokyo/Japan
29
ical test-based CRC screening program was provided before surveillance, and Aomori Prefectural Central Hospital, Aomori/Japan
30
uptake rates were set at 60% in the base-case analysis. A probabilistic sensitivity Endoscopy Division, National Cancer Center Hospital Endoscopy Division,
analysis (PSA) was also performed for all model parameters. Tokyo/Japan
Results: QALYs and costs per person in strategy 1–4 were as follows: strategy 1,
23.004 QALYs and US$1,024.88; strategy 2, 23.000 QALYs and $1,009.02; strat- Contact E-mail Address: [email protected]
egy 3, 23.013 QALYs and $977.40; strategy 4, 23.046 QALYs and $970.31. The Introduction: There have been many narrow-band imaging (NBI) magnifying
required numbers of CS procedures per person in strategy 1, 2, 3 and 4 were endoscopic classifications advocated (Sano, Hiroshima, Showa, and Jikei classi-
2.143, 1.664, 1.617 and 2.548, respectively. Risk-stratified strategies (strategies 3 fications) so far in Japan. NBI magnifying endoscopy for qualitative and quan-
and 4) yielded higher QALYs with lower costs than strategies 1 and 2. titative diagnosis for colorectal lesions is useful, however, some discussion in
Comparing strategy 3 with strategy 4, yielded QALYs were higher and required Japan has raised issues such as i) the presence of multiple terms for the same
cost was lower in strategy 4. Strategy 4 was most-cost-effective, showing simple or similar findings, ii) the necessity of including surface patterns in magnifying
dominance over the other strategies, followed by strategy 3; however, strategy 4 endoscopic classifications, and iii) differences in the NBI findings between poly-
required the most CS procedures. The PSA showed that the probability of strat- poid and superficial lesions. To resolve these issues and unify the classifications,
egy 4 being chosen as the most cost-effective at the willingness-to-pay value of the Japan NBI Expert Team (JNET) was set up in 2011. The aim of this study is
$50,000 was 67.8%. to scientifically evaluate the NBI scale and determine the NBI findings and
Conclusion: After polypectomy, risk-stratified CS surveillance programs based on diagnostic criteria used in the unified classification (The JNET classification).
the polyp results should be recommended owing to higher expected effectiveness Aims & Methods: The JNET classification, which is a modification of NICE
and cost-effectiveness. Furthermore, more intense use of CS procedures in risk- classification, consists of 4 categories (Types 1, 2A, 2B, and 3) based on vessel
stratified surveillance can heighten the effectiveness and cost-effectiveness in the and surface patterns without color. We made a hypothesis that each of them are
Japanese setting. However, it does require a larger number of CS procedures; correlated with the histopathological findings of hyperplastic polyp/sessile ser-
thus, it would be preferable to determine the most appropriate use of CS proce- rated polyp (SSP), low grade intramucosal neoplasia, high grade intramucosal
dures in risk-stratified surveillance programs depending on the nationwide avail- neoplasia/shallow submucosal invasive cancer, and deep submucosal invasive
ability of CS resources. cancer, respectively. A web image interpretation study using the modified
Disclosure of Interest: All authors have declared no conflicts of interest. Delphi (UMIN000010292: Multicenter study for developing universal NBI mag-
References nifying endoscopic classification of colorectal tumors in Japan) was conducted.
25 specialists in magnification evaluated NBI magnifying findings and histology
1. Hassan C, et al. Endoscopy. 2013; 45: 842–51. with 100 NBI still images on the web.
2. Lieberman DA, et al. Gastroenterology. 2012; 143: 844–57. Results: Univariate and multivariate analyses and analysis on diagnosability
3. Tanaka S, et al. J Gastroenterol. 2015; 50: 252–60. from 5 candidate NBI magnifying findings such as 1) loose vessel areas, 2)
4. Sekiguchi M, et al. Jpn J Clin Oncol. 2016; 46: 116–25. interruption of thick vessels, 3) scattered vessels, 4) thick, linearized/meandering
atypical vessels in the tumor, and 5) amorphous areas of surface patterns for
Type 3, and i) variable caliber of vessels, ii) thick vessels iii) irregular distribution
of vessels, iv) vessel meandering, and v) irregular or obscure surface pattern for
OP401 NEW NBI MAGNIFYING ENDOSCOPIC CLASSIFICATION FOR type 2B. Among the five candidate NBI findings, three findings such as 1) loose
COLORECTAL TUMORS PROPOSED BY THE JAPAN NBI EXPERT vessel areas, 2) interruption of thick vessels, and 5) amorphous areas of surface
TEAM (JNET) patterns were identified as the diagnosis of type 3. In addition, three findings such
K. Sumimoto1, S. Tanaka2, Y. Sano3, S. Kudo4, N. Hayashi2, S. Oka2, as I) variable caliber of vessels, III) irregular distribution of vessels, and V)
M. Iwatate3, S. Saito5, T. Matsuda6, Y. Wada7, T. Fujii8, H. Ikematsu9, irregular or obscure surface pattern were selected for the diagnosis of type 2B.
T. Uraoka10, N. Kobayashi11, H. Nakamura12, K. Hotta13, T. Horimatsu14, Conclusion: Subclassification of NICE Type 2 (2A & 2B) could be performed
N. Sakamoto15, O. Tsuruta16, H. Kawano17, H. Kashida18, Y. Takeuchi19, scientifically with NBI magnifying findings without color using web image inter-
H. Machida20, T. Kusaka21, N. Yoshida22, I. Hirata23, T. Terai24, H. Yamano25, pretation study, which could conduct differentiatial diagnosis between low grade
K. Kaneko26, T. Nakajima9, T. Sakamoto6, Y. Yamaguchi27, N. Tamai5, intramucosal neoplasia and high grade intramucosal neoplasia/shallow submu-
N. Maruyama23, H. Ishikawa22, Y. Murakami28, S. Yoshida29, Y. Saito30 cosal invasive cancer.
1
Department Of Gastroenterology And Metabolism, Hiroshima University hospital, Disclosure of Interest: All authors have declared no conflicts of interest.
Hiroshima/Japan
2
Hiroshima University Hospital, Hiroshima/Japan
3
Sano Hospital, Kobe/Japan
4
Showa University Northern Yokohama Hospital, kanagawa/Japan
5
The Jikei University School of Medicine, Tokyo/Japan
6
National Cancer Center Hospital, Tokyo/Japan
7
Tokyo Medical and Dental University, Tokyo/Japan
8
Takahiro Fujii Clinic, Tokyo/Japan
9
National Cancer Center Hospital East), Tokyo/Japan
10
Dept. Of Gastroenterology, Keio University School of Medicine Res and
Developm. for Minimally, Tokyo/Japan
11
Tochigi Cancer Center, Tochigi/Japan
12
Department of Gastroenterology, Chofu Surgical Clinic, Tokyo/Japan
13
Shizuoka Cancer Center, Shizuoka/Japan
14
Kyoto University, Kyoto/Japan
15
Juntendo University, Tokyo/Japan
16
Kurume University, Fukuoka/Japan
17
St. Mary’s Hospital, Tokyo/Japan

Table (OP401)

JNET Type 1 Type 2A Type 2B Type 3

Vessel pattern Invisible Regular caliber Regular distri- Variable caliber Irregular Loose vessel areas
bution (meshed/spiral distribution Interruption of thick vessels
pattern)
Surface pattern Regular dark or white spots Regular (tubular/branched / Irregular or obscure Amorphous areas
Similar to surrounding papillary
normal mucosa
Most likely histology Hyperplastic polyp/ Sessile ser- Low grade intramucosal High grade intramucosal neo- Deep submucosal invasive
rated polyp neoplasia plasia/ Shallow submucosal cancer
invasive cancer
United European Gastroenterology Journal 4(5S) A155

OP402 SUBCLASSES OF TYPE-II PIT PATTERN REVEAL OP403 ARTIFICIAL INTELLIGENCE (AI) IN ENDOSCOPY–DEEP
ALTERNATIVE TUMORIGENIC PATHWAYS OF COLORECTAL LEARNING FOR OPTICAL BIOPSY OF COLORECTAL POLYPS IN
SERRATED LESIONS REAL-TIME ON UNALTERED ENDOSCOPIC VIDEOS
H. Aoki1, E. Yamamoto2, H. Yamano3, K. Yoshikawa4, H. Matsushita5, M. F. Byrne1, D. K. Rex2, N. Chapados3, F. Soudan4, C. Oertel4, M. Linares
R. Takagi6, E. Harada5, Y. Tanaka7, T. Sugai8, H. Suzuki1 Perez5, R. Kelly6, N. Iqbal7, F. Chandelier8
1 1
Dept. Of Molecular Biology, Sapporo Medical University, Sapporo/Japan Gastroenterology, Vancouver General Hospital, Vancouver/Canada/BC
2 2
Dept. Of Gastroenterology, Sapporo medical university, Sapporo/Japan Gastroenterology And Hepatology, Indiana University Medical Center,
3
Dept. Of Gastroenterology, Akita Red Cross Hospital, Akita/Japan Indianapolis/United States of America/IN
4 3
Dept. Of Gastroenterology, Akita Red Cross Hospital, Akita/Japan École Polytechnique de Montre´al, Montreal/Canada/QC
5 4
Department Of Gastroenterology, Akita Red Cross Hospital, Akita/Japan Imagia, Montreal/Canada/QC
6 5
Department Of Gastroenterology, Akita Red Cross Hospital, Akita/Japan University of Buenos Aires, Buenos Aires/Argentina
7 6
Gastroenterology, Akita Red Cross Hospital, Akita-Shi/Japan University College Cork, Cork/Ireland
8 7
Dept. Of Molecular Diagnostic Pathology, Iwate Medical University, Morioka/ St Luke’s Hospital, Kilkenny/Ireland
8
Japan Cadens Imaging, Montreal/Canada/QC
Contact E-mail Address: [email protected] Contact E-mail Address: [email protected]
Introduction: Colorectal serrated lesions (SLs) include hyperplastic polyp (HP), Introduction: ASGE-PIVI guidelines support a ‘‘resect and discard’’ strategy for
traditional serrated adenoma (TSA) and sessile serrated adenoma/polyp (SSA/P). diminutive colon polyps, provided that the predictive value of technology allow-
Emerging evidences suggest that SSA/Ps are precursor lesions of colorectal can- ing for ‘‘optical biopsy’’ depicts at least 90% agreement in assignment of post-
cers (CRCs) with BRAF mutation and the CpG island methylator phenotype polypectomy surveillance intervals using pathology as standard. In addition, in
(CIMP). We have previously reported that Type II-Open (Type II-O) pit pat- order for a technology to be used to guide the decision to leave suspected diminu-
terns, which is highly specific to SSA/P. However, clinicopathological and mole- tive rectosigmoid hyperplastic polyps in place (without resection), the technology
cular features of SLs without Type II-O pits remain unclear. should provide 90% negative predictive value for adenomatous histology. Such
Aims & Methods: We aimed to identify clinicopathological and molecular fea- standards with optical biopsy might be achievable with experts (although even
tures of SLs without Type II-O pits. We analyzed the methylation of CIMP that is unclear) but do not cross over into general clinical practice. Several groups
markers (MINT1, 2, 12, 31, p16 and MLH1) and BRAF and KRAS muta- have looked at supporting the process of optical biopsy decision making on
tion in 448 premalignant and malignant colorectal tumors. By using magnifying endoscopic assessment of the histology of diminutive colorectal polyps using
endoscopy, surface microstructures of colorectal lesions were classified into Type traditional machine learning, but to date there are significant limitations in
II pit or tumor pit (Type III, IV or V pit) according to the Kudo’s pit pattern terms of (1) using still images only, and non-realtime computer support, both
classification system. Type II pit was subcategorized into classical Type-II pit, of which are not clinically efficient or effective, and (2) often involving magnifi-
Type II-O pit and Type II-Long (Type II-L) pit. CIMP status (CIMP-high, -low cation endoscopy that is not yet a widespread clinical practice. Deep learning is a
and -negative) was determined by using the five methylation markers. branch of artificial intelligence which is a siginificant advance on traditional
Results: Endoscopic findings were classified as 41 Type II pit, 8 Type II-L pit, 92 machine learning, and with huge computational power, machines can now recog-
Type II-O pit, 21 Type II plus tumor pit, 22 Type II-L plus tumor pit, 50 Type II- nize objects in real time. We sought to apply novel deep learning techniques to
O plus tumor pit and 214 tumor pit. We identified Type II-L plus tumor pit, optical biopsy for colon polyps.
which was specific to TSA with KRAS mutation and CIMP-low (sensitivity, Aims & Methods: We aimed to evaluate deep learning applied to the classification
60%; specificity, 96%). As compared to lesions with only Type II-L pit, of colorectal polyps into NICE types 1 and 2, in real-time on unaltered endo-
KRAS mutation and CIMP-low were more frequent in lesions with Type II-L scopic videos, for the support of clinically efficient optical biopsy. We used 92
plus tumor pits. Progression of Type II-L pit lesions to TSA was associated with videos of small colorectal polyps (510 mm) under white light (WL) and narrow-
KRAS mutation and accumulation of moderate DNA methylation. In contrast, band imaging (NBI) (38 NICE type 1, 52 NICE type 2), using Olympus 190 series
BRAF mutation was frequently observed in colonic tumors with Type II plus colonoscopes. ‘‘Optical biopsy’’ was done on all polyps by an expert with 495%
tumor pit. These results suggest that lesions with Type II-L pit and those with accuracy (using pathology as the reference standard) prior to removal and his-
Type II pit appear to develop through distinct tumorigenic pathways, though the tological confirmation.
majority of lesions with Type II or Type II-L pit were the same HP. We investigated a Deep Learning Artificial Intelligence model with a proprietary
Conclusion: Our data suggest that Type II-L plus tumor pit is a useful hallmark of deep convolutional neural network (DCNN) for the computer-assisted NICE
the premalignant stage of CRCs with KRAS mutation and CIMP-low. type 1&2 differentiation. We designed a 3-class model representing Types 1, 2,
Disclosure of Interest: All authors have declared no conflicts of interest. and unsuitable (frames without statistically representative information–blur,
bubbles, liquid). The model operated at the individual frame level, without
prior segmentation.
For model training purposes, each frame was manually tagged. The final dataset
was split into training and validation sets, without overlap. Finally, the analysis
was performed separately for NBI and WL frames, allowing for reporting of
frame processing time and classification performance.
Results: A total of 33,954 training frames were used, split equally across NBI &
WL, and type 1, type 2, & unsuitable classes. We performed a 5-fold cross-
validation on the tagged frames for quality control. The trained DCNN model
was then used to evaluate the unaltered videos in real-time, with an accuracy for
polyp classification of 90% for NBI, and 83% for WL. The confusion matrix on
whole-video classification of colorectal polyps gives a sensitivity of 93% and
specificity of 85% for NBI. Finally, the processing time of our DCNN model
ran at between 25 and 30 frames per second (fps) using a decent gamer-grade
GPU (NVIDIA Titan-X) on an unaltered video feed of 60 fps, delivering near-
realtime computer support.
A156 United European Gastroenterology Journal 4(5S)
Conclusion: To our knowledge, this is the first application of deep learning to the Disclosure of Interest: U. Pape: Has received grant/research support and served
optical biopsy challenge for polyp differentiation into NICE types 1&2 using as an advisory board member or speaker’s bureau for NPS Pharmaceuticals, Inc.,
non-magnification colonoscopy and NBI, specifically in a clinically representa- Shire plc, and Fresenius Kabi GmbH; served as a study investigator for NPS
tive workflow where computer support is provided in realtime on unaltered Pharmaceuticals, Inc.
endoscopic video streams. Although the present investigation was carried on a P.B. Jeppesen: Has received grant/research support and served as a consultant,
limited datasets of 92 videos, our deep learning model has shown clinically effi- advisory board member, and study investigator for NPS Pharmaceuticals, Inc.
cient and relevant performance for optical biopsy, well aligned with PIVI guide- H. Lee: Employee and stockholder of Shire plc.
lines and the performance of experts. Ongoing work will determine if such a A.A. Grimm: Employee of Shire plc.
computer support solution could aid in the widespread adoption of a ‘‘resect S.J. O’Keefe: Has received research funding support from NPS Pharmaceuticals,
and discard’’ strategy, and reduce the economic burden of pathological evalua- Inc.
tion of benign diminutive colon polyps. This clinical trial was funded by NPS Pharmaceuticals, Inc., Bedminster, NJ.
Disclosure of Interest: M.F. Byrne: Chairman of Satis Operations Inc NPS Pharmaceuticals, Inc., is a wholly owned indirect subsidiary of Shire plc.
D.K. Rex: Olympus consulting and research support This analysis research was funded by Shire plc
N. Chapados: Imagia has commercial interests in artificial intelligence
F. Soudan: Imagia has commercial interests in artificial intelligence
C. Oertel: Imagia has commercial interests in artificial intelligence
M. Linares Perez: research support from Satis Operations Inc
R. Kelly: research support from Satis Operations Inc
F. Chandelier: Shareholder in Cadens Medical Imaging
All other authors have declared no conflicts of interest.

Age, mean (SD), y 48 (7) 48 (7) 50 (17) 52 (14)

Women, n (%) 5 (63) 5 (46) 19 (54) 17 (53)

Body mass index, mean (SD), 22.6 (3.6) 23.3 (4.1) 22.2 (3.1) 22.2 (2.8)*
kg/m2
Stoma present, n (%) 7 (88) 11 (100) 10 (29) 10 (32)*
Colon-in-continuity, n (%) 1 (13) 1 (9) 22 (63) 24 (77)*
Estimated small bowel length, 128 (98) 129 (77)y 54 (43)z 73 (56)x
mean (SD), cm
Baseline PS, mean (SD), L/wk 21.6 (8.1) 15.9 (10.4) 11.5 (5.9) 11.2 (6.4)*
Baseline PS duration, mean 7.2 (7.4) 8.1 (8.0) 5.6 (5.3) 6.1 (5.7)*
(SD), y

*n ¼ 31, yn ¼ 9, zn ¼ 32, xn ¼ 30.