Learning Outcomes

Is ultrasound an effective way of diagnosing acute

cholecystitis?
IMU Learning Outcome : Psychomotor skills
It has been recommended that all patients with suspected acute
cholecystitis to have a Hepatobiliary system ultrasound to confirm the
diagnosis.1 But is ultrasound sensitive enough in detecting acute
cholecystitis? A study was done by Bingener et al 2 to evaluate
ultrasounds ability to predict acute cholecystitis in patients with clinical
symptoms. In this study, a total of 55 patients with symptoms suggestive
of acute cholecystitis was sent for ultrasound imaging with interpretation
before and after surgery by 2 blind radiologists. The diagnosis of acute
cholecystitis was confirmed during surgery that was done within 48 hours.
Intra-op findings that were considered diagnostic of acute cholecystitis
were gallbladder wall oedema, vascular injection, and distention of gall
bladder. This study concluded that the ultrasound has positive predictive
value of 94% and negative predictive value was only 75%. Thus it is
concluded that ability of diagnose acute cholecystitis is limited. The
author emphasized in the notes section that this conclusion does not
mean that ultrasound should be disregarded as the imaging of choice for
acute cholecystitis but the study was mainly to prove that clinical
symptoms and signs should be relied upon heavily but not ultrasound
findings in diagnosing acute cholecystitis.
A systematic review by Jordy J et al echoed similar conclusion3. They
reported that ultrasound has a substantial margin of error, comparable to
that of MR imaging. In their paper, 5859 patients from 57 studies were
included. Surgical finding was used as a reference standard for presence
of acute cholecystitis. Patients in intensive care unit were excluded due to
predominance of acute acalculous cholecystitis seen in that group of
patients. This systematic review concluded that Cholescintigraphy has the
highest sensitivity (96%) and specificity (90%). Ultrasound on the other
hand reported to have a sensitivity of 81% and specificity of 84%. This
means that in 100 patients with acute cholecystitis, only 81 will have
positive ultrasound findings suggestive of acute cholecystitis.

Meanwhile,in 100 patients without the disease, 16 patients will be

diagnosed as having the disease. Of course observer variability plays a
role in this imaging interpretation. This might lead to small but significant
room for error and unnecessary cholecystectomies or delayed diagnoses. I
have seen a patient who was diagnosed to have cholelithiasis, and acute
cholecystitis but during operation did not have any stones in the gall
bladder.
According to Tokyo Guidelines4, patients who are exhibiting ONE of local
signs of inflammation such as Murphys sign, pain/tenderness in right
upper quadrant WITH one of systemic signs of inflammation such as fever,
elevated white blood cell count, and elevated C-Reactive protein to be
diagnosed as having acute cholecystitis. In conclusion, ultrasound findings
in suspected acute cholecystitis should be taken cautiously and be used
as a diagnostic adjunct.

1. What are the benefits of early cholecystectomy as recommended by Tokyo Guidelines as the
treatment of choice?
IMU Outcome : Critical thinking, problem solving & research
EVIDENCE BASED MEDICINE WORKSHEET FOR STUDIES ON THERAPY
CLINICAL QUESTION
Patient (P): Patients with acute cholecystitis
Intervention (I): Early Cholecystectomy
Comparison (C): Delayed Cholecystectomy
Outcome (O): Intra-op and Post op complications

ACCESSING EVIDENCE THE SEARCH PATH

How was the article identified: Cochrane Library

Search keywords : Randomized Controlled Trial;Time-To-Treatment;Time Factors;

Female;Cholecystecomy;Laparoscopic/adverse effects

Citation: Kolla S, Aggarwal S, Kumar A, Kumar R, Chumber S, Parshad R et al. Early versus delayed
laparoscopic cholecystectomy for acute cholecystitis: a prospective randomized trial. Surgical
Randomisation
Endoscopy. 2004;18(9):1323-1327 5

i).Randomised trial?

Yes

ii).Randomisation methods:
a. Well-documented?
b. Adequate?
iii). Evidence that assigned groups
(e.g. intervention and control) similar
in characteristics at the start of study?

iv). Evidence that assigned groups

(e.g. intervention and control) treated
equally throughout the study?

Yes
Yes

Remarks:

40 patients were chosen that fulfils criteria of

acute cholecystitis. All patients were similar in
characteristics. Randomization was done
between early (within 24 hours) or delayed (6 to
12 weeks) by a third party using computer
generated number list.

Yes
Patients were not treated equally. In delayed
cholecystectomy group patients were treated
with intravenous fluids and antibiotics including
ampicillin, gentamicin, and metronidazole.
No

Accountability
i).Could we trace the progress of ALL
participants throughout the study?

Yes

ii). Was there mention of the use of

intention-to-treat analysis?

Yes

ii). Was the drop-out rate acceptable

(< 20%)?

Yes

Remarks:

No patients dropped out during this study. There

was no specific mention about intention to treat
but the total number of participants at
randomization and at the end of analysis
remained same. Thus it can be assumed that
intention to treat manner was used.

Measurement
i). Was the main outcome
measurement objective?

Yes

Remarks:

a).Patients?

No

As the outcome measurement was objective, it

is not necessary to have blinding of intervention
to patients /clinicians.

b).Clinicians?

No

c). Assessors?

No

Ii). Was there blinding of intervention

to:

OVERALL VALIDITY OF THIS STUDY: ACCEPTABLE WITH SOME CONCERNS

Results

i). What is the main result that I am interested in

Remarks:

I am looking for incidents of intra-operative and post

operative complications in between the two groups.

There were 2 intra-operative complications in the

early cholecystectomy group, and none in the
delayed cholecystectomy group. The complications
were bile duct injury and injury to Hartmans pouch.

ii). Was there a big enough difference between the

intervention and control groups in terms of this
result?

Post-operatively, patients who went through early

cholecystectomy had lesser complications than the
delayed cholecystectomy group.

No

Overall, patients who went through early

cholecystectomy had more intra-op complications
compared to delayed cholecystectomy. But the
difference is not statistically significant (p= 0.456)

Application
i). My patient is similar to the
study participants (i.e. not within
the exclusion criteria)

Yes

ii). The treatment is available and

feasible in my setting

Maybe

iii). The treatment is likely to be

acceptable for my patient and
his/her family

Yes

Remarks:
Early cholecystectomy might not be possible in
Malaysian government hospital setting due to
logistics reason. But complications wise the delayed
vs early interventions do not give any benefits over
one another. The only statistically significant
advantage seen in early cholecystectomy was total
hospital stay which was 3 days in early
cholecystectomy vs 10 days for delayed
cholecystectomy. Thus it would definitely be a better
option for the patient as patients would be able to be
back home and indirectly reduce the overall cost of
admission.
It is also beneficial to the hospital as cost reduction
could be done.

My conclusions
This article provides a good evidence of superiority of early cholecystectomy in comparison with delayed
cholecystectomy in patients with acute cholecystitis. Overall the benefits are mainly for economical purposes rather
than of any medical benefits. Thus logistical convenience should be taken into account before mandating early
cholecystectomy in patients with acute cholecystitis. In our centre where operation theatre is always busy and
booked, delayed elective cholecystectomy provides a safe and feasible alternative.

2. What are types of peritoneal approaches available and how

do they differ?
IMU Learning Outcome: Self-directed lifelong learning with skills in
information and resource management.
Before any laparoscopic procedure, the peritoneum must be
accessed to allow creation of pneumoperitoneum and insertion of
other ports. First we would insert the infraumbilical port for gas
insufflation and camera insertion. Namely two techniques are
available for this crucial first step. In our centre, for laparoscopic
cholecystectomy we use Hasson technique which is an open
technique that was introduced by Hasson in 1971. In Hasson
technique, skin incision is made in the infraumbilical region and
dissected up to the peritoneum where the blunt ended trocar is
inserted prior to carbon dioxide insufflation. Meanwhile in Verress
technique, a 5mm skin incision is made, and the sharp verress
needle is passed through until two clicks are heard indicating needle
has passed through the abdominal fascia and parietal peritoneum.
The choice between both techniques have been widely debated in
the past. Major concerns over closed method are injuries to major
vessels (Abdominal aorta) and major viscera. Closed laparoscopy
has been traditionally associated with more injuries and thus many
post-placement confirmatory tests were derived to prevent further
injuries during the procedure.
A meta-analysis done by Larobina et al6 reviewed 22,465 open
laparoscopic surgeries, and 760,890 closed laparoscopic surgeries.
336 major vascular injuries were reported in the case studies of
closed laparoscopic procedure (Verress needle), whereas in Hasson
none was reported. The injury rate between open and closed
laparoscopy is significant statistically (p= 0.003). Meanwhile the
meta-analysis revealed that there were no statistically significant
difference in major visceral injuries in between open and closed
laparoscopy. In the closed procedure, one major visceral injury was
reported for every 1430 procedures. Whereas in open technique 1
injury is reported in only 2000 procedures. Hasson et al7 reported

similar findings in the review of 5284 laparoscopic procedures

conducted from year 1970 to 1999. They concluded that open
laparoscopy was associated with no method failure of life
threatening complications. However in closed laparoscopy, minor
or medium risk complications happened at the rate of 0.5%. Another
meta-analysis on the same topic was done by Jiang et al8. Their
review included 7 randomized controlled trials, and a total of 4
cases of major complications were reported in the closed
laparoscopy compared to none in open laparoscopy which however
were not statistically significant. Major complications encountered
includes hepatic injuries, ileal perforation and mesenteric
lacerations. Minor complications such as pre-peritoneal insufflations
were also reported and minor complicates were more in closed
technique compared to open and it was statistically significant. In
regards to laparoscopic cholecystectomy, Yerdel MA et al9
performed a cross-sectional study including 1500 patients
undergoing the procedure. Their study reported a significantly
higher complication rates in closed laparoscopic technique (p <0.01)
which includes gastric perforation and iliac artery laceration.
In conclusion, open technique appears to be safer in nature
compared to Verress needle. However, FDA10 recommends Veress
needle technique except in certain cases for example in patients
with previous abdominal surgery, children, thin adults, and patients
with atrophic abdominal musculatures in which injuries rate might
be higher. More randomized controlled trial would be required before
we could confidently decide that one technique is superior to other.

3. Could acute cholecystitis be prevented in patients with

impacted stone presenting as biliary colic?
IMU Learning Outcome : Disease prevention and Health Promotion
This patient had symptoms suggestive of biliary colic 3 days before
the onset of fever longer lasting abdominal pain that were
suggestive of biliary colic. Approximately 20% patients with biliary
colic would eventually develop acute cholecystitis.11 If there is a way
of preventing the gall bladder inflammation, we could prevent long
term admission and usage of other medications.
Akriviadis et al12 did a randomized controlled trial in which 53
patients with biliary colic seen and divided into two groups. One
group of patients received one dose of intramuscular diclofenac
sodium 75mg and another group received a place (n=27), 3ml of
Normal Saline (n=26). In the group of patients treated with
diclofenac sodium, complete relief of pain was obtained in 21 and
only 7 patients were pain free in the placebo group. More
importantly in the diclofenac sodium group, only 4 progressed to
acute cholecystitis, compared to 11 patients in the placebo group.
Thus Akriviadis et al concluded that one dose of 75mg intramuscular
diclofenac sodium could substantially reduce the progression rate
from biliary colic to acute cholecystitis. Goldman et al reported
similar findings in his study. His study included 60 patients with
biliary colic, and he reported that none of the patients who were
treated with diclofenac sodium progressed to acute cholecystitis.13
He postulates that anti-inflammatory properties of diclofenac
sodium plus its smooth muscle relaxant properties lead to
prevention of acute cholecystitis. Tokyo guidelines also recommends
usage of NSAIDS for prevention of acute cholecystitis in patients
with impacted stones while advising caution for usage in patients
with liver cirrhosis or increased risk of acute upper gastrointestinal
bleeding.

References
1. Miura F, Takada T, Kawarada Y, Nimura Y, Wada K, Hirota M, et al.
Flowcharts for the diagnosis and treatment of acute cholangitis and
cholecystitis: Tokyo Guidelines. J Hepatobiliary Pancreat Surg. 2007;14:27
34.

2. Bingener J, Schwesinger W, Chopra S, Richards M, Sirinek K. Does the

correlation of acute cholecystitis on ultrasound and at surgery reflect a
mirror image?. The American Journal of Surgery. 2004;188(6):703-707.

3. Kiewiet J, Leeuwenburgh M, Bipat S, Bossuyt P, Stoker J, Boermeester M. A

Systematic Review and Meta-Analysis of Diagnostic Performance of
Imaging in Acute Cholecystitis. Radiology. 2012;264(3):708-720.

4. Hirota M, Takada T, Kawarada Y, et al.. Diagnostic criteria and severity

assessment of acute cholecystitis: Tokyo Guidelines. J Hepatobiliary
Pancreat Surg 2007;14(1):7882

5. Kolla S, Aggarwal S, Kumar A, Kumar R, Chumber S, Parshad R et al. Early

versus delayed laparoscopic cholecystectomy for acute cholecystitis: a
prospective randomized trial. Surgical Endoscopy. 2004;18(9):1323-1327.

6. Larobina M, Nottle P. Complete Evidence Regarding Major Vascular Injuries

During Laparoscopic Access. Surgical Laparoscopy, Endoscopy &
Percutaneous Techniques. 2005;15(3):119-123.

7. Hasson H, Rotman C, Rana N, Aruna Aruna Kumari N. Open Laparoscopy:

29-Year Experience. Obstetric and Gynecologic Survey. 2001;56(2):85-86.

8. Jiang X, Anderson C, Schnatz P. The Safety of Direct Trocar Versus Veress

Needle for Laparoscopic Entry: A Meta-Analysis of Randomized Clinical
Trials. Journal of Laparoendoscopic & Advanced Surgical Techniques.
2012;22(4):362-370.

9. Yerdel M, Karayalcin K, Koyuncu A, Akin B, Koksoy C, Turkcapar A et al.

Direct trocar insertion versus veress needle insertion in laparoscopic
cholecystectomy. The American Journal of Surgery. 1999;177(3):247-249.

10.US Food and Drug Administration. Laparoscopic Trocar Injuries: A report

from a U.S. Food and Drug Administration (FDA) Center for Devices and
Radiological Health (CDRH) Systematic Technology Assessment of Medical
Products (STAMP) Committee: FDA Safety Communication. Rockville; 2015.

11.Strasberg SM.Acute Calculous Cholecystitis. New England Journal of

Medicine. 2008;359(3):325-325.
12.Akriviadis E, Hatzigavriel M, Kapnias D, Kirimlidis J, Markantas A, Garyfallos
A. Treatment of biliary colic with diclofenac: A randomized, double-blind,
placebo-controlled study. Gastroenterology. 1997;113(1):225-231.
13.Goldman G, Kahn P, Alon R, Wiznitzer T. Biliary colic treatment and acute
cholecystitis prevention by prostaglandin inhibitor. Digest Dis Sci.
1989;34(6):809-811