Clinical Gastroenterology and Hepatology 2014;12:919928

PERSPECTIVES IN CLINICAL GASTROENTEROLOGY

AND HEPATOLOGY
Management of Gastric Varices
Juan Carlos GarciaPagn,* Marta Barrufet, Andres Cardenas, and ngels Escorsellk
*Hepatic Hemodynamic Laboratory, and kICU, Liver Unit, Hospital Clinic, Institut dInvestigacions Biomdiques August
Pi-Sunyer (IDIBAPS), Ciber de Enfermedades Hepticas y Digestivas (CIBEREHD), Barcelona; Diagnostic Imaging Center,
Hospital Clinic, Barcelona; GI/Endoscopy Unit, Institut de Malalties Digestives i Metaboliques, Hospital Clnic, University of
Barcelona, IDIBAPS, CIBEREHD, Barcelona, Spain
This article has an accompanying continuing medical education activity on page e52. Learning ObjectivesAt the end of this activity, the successful
learner will understand the prevalence, classication, and therapy of gastric varices in patients with cirrhosis.

According to their location, gastric varices (GV) are classied as gastroesophageal varices and isolated gastric
varices. This review will mainly focus on those GV located
in the fundus of the stomach (isolated gastric varices 1 and
gastroesophageal varices 2). The 1-year risk of GV bleeding
has been reported to be around 10%16%. Size of GV,
presence of red signs, and the degree of liver dysfunction
are independent predictors of bleeding. Limited data suggest that tissue adhesives, mainly cyanoacrylate (CA), may
be effective and better than propranolol in preventing
bleeding from GV. General management of acute GV bleeding
must be similar to that of esophageal variceal bleeding,
including prophylactic antibiotics, a careful replacement of
volemia, and early administration of vasoactive drugs. Small
samplesized randomized controlled trials have shown that
tissue adhesives are the therapy of choice for acute GV
bleeding. In treatment failures, transjugular intrahepatic
portosystemic shunt (TIPS) is considered the treatment of
choice. After initial hemostasis, repeated sessions with CA
injections along with nonselective beta-blockers are recommended as secondary prophylaxis; whether CA is superior to
TIPS in this scenario is not completely clear. Balloonoccluded retrograde transvenous obliteration (BRTO) has
been introduced as a new method to treat GV. BRTO is also
effective and has the potential benet of increasing portal
hepatic blood ow and therefore may be an alternative for
patients who may not tolerate TIPS. However, BRTO obliterates spontaneous portosystemic shunts, potentially
aggravating portal hypertension and its related complications. The role of BRTO in the management of acute GV
bleeding is promising but merits further evaluation.

gastric varices (IGV). GOV are divided as GOV1, which are

esophageal varices that extend below the gastroesophageal
junction along the lesser curve of the stomach, and GOV2,
which are those that extend beyond the gastroesophageal
junction into the fundus of the stomach. IGV includes IGV1,
which are those located in the fundus of the stomach and
also called fundal varices, and IGV2, which refer to ectopic
varices located anywhere in the stomach (Figure 1). This
classication, initially described by Sarin et al,1 has
important clinical implications regarding incidence, risk of
bleeding, and management. According to Sarin et al, GOV1
represent almost 75%, GOV2 21%, IGV1 less than 2%, and
IGV2 4% of all GV. GOV1 are a continuation of esophageal
varices and share the same vascular anatomy and response
to treatment and thus will not be further discussed. This
review will mainly focus on the management of IGV1 and
GOV2, the so-called cardiofundal varices. Data regarding
prevalence, bleeding risk, and management of IGV2 are
scarce, and therefore no specic recommendations are
made on this type of GV. However, in our center the management of IGV2 is similar to that of IGV1. Although recent
studies specically detail the different types of GV, most of
the available data comes from series of patients with mixed
types of GV and portal hypertension etiologies (cirrhotic
and noncirrhotic), and the results may not be applicable to
all types of GV. As a result, the optimal treatment of gastric
fundal varices has not fully been determined.

Primary Prophylaxis
Keywords: Gastric Varices; Variceal Bleeding; Portal Hypertension; Cirrhosis; Cyanoacrylate; Transjugular Intrahepatic Portosystemic Shunt (TIPS); Balloon-occluded Retrograde
Transvenous Obliteration (BRTO).

revalence of gastric varices (GV) in patients with

cirrhosis is estimated to be near 17%. However,
this estimation is based on only one study1; therefore, the
actual magnitude of the problem is not well known.
According to their location within the stomach, GV are
classied as gastroesophageal varices (GOV) and isolated

In a prospective study including 117 patients with

cirrhosis and cardiofundal varices (69% IGV1 and 31%
Abbreviations used in this paper: BRTO, balloon-occluded retrograde
transvenous obliteration; CA, cyanoacrylate; EBL, endoscopic band ligation; EIS, endoscopic injection sclerotherapy; EUS, endoscopic ultrasonography; GOV, gastroesophageal varices; GV, gastric varices; IGV,
isolated gastric varices; RCT, randomized controlled trial; TIPS, transjugular intrahepatic portosystemic shunt.
2014 by the AGA Institute
1542-3565/$36.00
http://dx.doi.org/10.1016/j.cgh.2013.07.015

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Clinical Gastroenterology and Hepatology Vol. 12, No. 6

for End-Stage Liver Disease score were again factors

associated with a high risk of bleeding. In this study, GV
were mainly GOV2, with few IGV1. There were signicant
differences in favor of CA for the prevention of bleeding
and survival when compared with no treatment and only
for prevention of rebleeding when compared with propranolol. However, larger studies are needed before a
formal recommendation in regard to the need and type
of primary prophylaxis for GV can be made. Until then,
our recommendation is not to use primary prophylaxis in
GV or alternatively use nonselective beta-blockers.

Management of Acute Gastric Variceal

Bleeding

Figure 1. Sarins classication of GV. Modied with permission from the American Gastroenterological Association
(AGA) Institute Gastroslides Cirrhosis and Portal
Hypertension.

GOV2), the incidence of bleeding was 16%, 36%, and

44% at 1, 3, and 5 years, respectively. Size of varices,
presence of red signs, and the degree of liver dysfunction
were directly related with the risk of bleeding (ranging
from an annual incidence of bleeding of 4% in patients
with Child class A with small varices without red signs to
65% in patients with Child class C with large varices with
red signs)2 (Figure 2). However, these data must be
cautiously interpreted because of the small number of
patients followed for more than 1 year and the unusually
high prevalence (52%) of concomitant hepatocelullar
carcinoma. The 1-year bleeding risk of the small (n 30)
untreated group of a recent prospective randomized
controlled trial (RCT) comparing cyanoacrylate (CA)
(n 30) vs beta-blockers (n 29) was around 10%.3
Variceal size and liver function evaluated by the Model

Figure 2. A large gastric varix (IGV1) with a recent nipple sign.

Although no studies have been specically devoted to

address this issue in patients with cardiofundal varices,
general consensus is that the initial management is
similar to that of esophageal variceal bleeding, including
the use of prophylactic antibiotics, careful replacement of
volemia with a restrictive transfusion policy, and the
early administration of vasoactive drugs (terlipressin,
somatostatin, or a somatostatin analogue).4,5 IGV1
varices, which often appear as a consequence of large
spontaneous splenorenal shunts, may bleed with portal
pressure gradients lower than those needed for
esophageal varices. It can then be hypothesized that
more powerful vasoconstrictors are needed not only
to decrease portal pressure but also to markedly
reduce portal and collateral blood ow to control acute
cardiofundal variceal bleeding. In our experience,
nearly 40% of patients with bleeding IGV1 who were
only receiving vasoactive drugs require rescue therapy,
mainly transjugular intrahepatic portosystemic shunt
(TIPS), to achieve 5-day control of bleeding.6 Therefore,
we currently do not recommend using vasoactive drugs
alone but always with concomitant endoscopic therapy.
Specic high-quality data on the use of endoscopic
therapy for acute GV bleeding are limited, and in most
published RCTs only half of patients included in the trials
had cardiofundal varices. Despite these limitations, most
uncontrolled series report a high rate of control of
bleeding with the use of tissue adhesives such as CA
(>90%) (Table 1). In addition, small-size RCTs comparing
tissue adhesives vs either endoscopic band ligation (EBL)
or endoscopic injection sclerotherapy (EIS) have shown
that tissue adhesives are equally7 or more8,9 effective than
EBL in the control of acute bleeding and more effective
than both in preventing rebleeding. In addition, tissue
adhesives perform better than sclerotherapy in
achieving initial hemostasis.9,10 GOV1 varices are usually
treated as esophageal varices with EBL, although some
investigators also recommend the use of tissue
adhesives for GOV1 varices.11 Overall, experts agree that
endoscopic therapy with tissue adhesives, mainly CA, is
the therapy of choice for acute bleeding from IGV1 and
GOV2.4,12,13 If tissue adhesive is not available, band

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Management of Gastric Varices

921

Table 1. Results of Published Studies on Endoscopic Treatment of Acute Bleeding From GV

First author, year
(reference)

Design

Ogawa, 199969
Kind, 200070
Huang, 200071
Akahoshi, 200272
Rengstorff, 200473
Mahadeva, 200323

Retros
Obs
Obs
Obs
Pilot
Obs

33
174
90
52
25
43

Cheng, 200730
Mumtaz, 200774
Marques, 200828
Paik, 200875
Procaccini, 200944

Obs
Obs
Obs
Obs
Retros

146
50
48
121
105

Monsanto, 201276
Oho, 19959

Obs
RCT

97
53

Lo, 20018
Sarin, 200210

RCT
RCT

26
17

Tan, 20067

RCT

97

Hou, 200977

RCT

91

Treatment
received (n)
EIS (21) vs glue (12)
Glue
Glue
Glue
Glue
TIPS (20) vs
glue (23)
Glue
Glue
Glue
Glue
TIPS (61) vs
glue (44)
Glue
EIS (24) vs
glue (29)
EBL (11) vs glue (15)
EIS (8) vs
glue (9)
EBL (48) vs
glue (49)
Glue (0.5 vs
1.0 mL)

Initial control (%)

overall (according
to treatment)

Mortality (%)
overall (according to
treatment)

Follow-upa
(mo)

67 (53 vs 100)
97
100
96
100
93 (90 vs 96)

NR
64
40
30
12
20 (25 vs 15)

36
36
12
11
6

95
100
88
91
91 (90 vs 93)

10
12
44
12
NR

36
In-hospital
18
1

96
81 (50 vs 88)

9
53 (67 vs 38)

In-hospital

69 (45 vs 87)
59 (38 vs 78)

42 (48 vs 29)
18 (25 vs 11)

24
16

93 (93 vs 93)

64 (63 vs 65)

36

88

NR

NOTE. All the studies included IGV1, GOV1, and GOV2.

Obs, observational study; Retros, retrospective comparative study.
a
Median.

ligation seems to have some benet in small GOV2 varices.

However, no specic studies have evaluated this issue.5
The standard protocol uses CA and lipiodol in 1:1
ratio, injecting with no more than 1 mL at the varix each
time14 (Supplementary Video). In most cases, CA is
usually extruded into the stomach lumen within 13
months after injection.15 Multiple complications from CA
injection have been reported among published studies. A
recent report of 753 patients indicated that most complications occurred from rebleeding that was due to
extrusion of the glue cast (4.4%), sepsis (1.3%), distant
emboli (pulmonary, cerebral, splenic; 0.7%), gastric ulcer
formation (0.1%), major gastric variceal bleeding (0.1%),
and mesenteric hematoma associated with hemoperitoneum and bacterial peritonitis (0.1%). The complication-related mortality was 0.5%.16 Other studies have
reported a higher incidence of embolism that may occur
in up to 2%3% of cases.13,17
Combination therapy of endoscopy and pharmacologic therapy is considered the standard of care in acute
esophageal variceal bleeding.4,5 However, because of
the paucity of data it is unknown whether this
recommendation also applies to GOV2 or IGV1 variceal
bleeding. Because in most cases drug therapy is
started before diagnostic endoscopy (and therefore
before the identication of the gastric variceal origin
of bleeding), it seems the most rational approach is to
combine drug therapy plus endoscopic treatment

(preferably tissue adhesives) in patients with acute GV

bleeding.
In massive bleeding with hemodynamic instability,
balloon tamponade can be used as a temporary bridge
(for a maximum of 24 hours) until denitive treatment
can be instituted. Tamponade may achieve hemostasis
in up to 80% of the patients, although more than 50%
of the cases rebleed after balloon deation. A single
study from Teres et al18 comparing the LintonNachlas
vs the SengstakenBlakemore tube demonstrated that
LintonNachlas tube was more effective in fundal variceal bleeding because of the large volume (600 mL) of
its single gastric balloon, allowing an appropriate
compression of the fundal varices. Nevertheless, if the
LintonNachlas balloon is not available, compression
with the gastric balloon of a SengstakenBlakemore
tube maximally inated may be appropriate.
TIPS is considered the treatment of choice in patients
bleeding from GOV2 or IGV1 after failure to control initial
bleeding or rebleeding with combination therapy.19,20
Contrary to what is suggested in esophageal variceal
bleeding, a second-attempt endoscopic therapy is
usually not considered. Embolization of collaterals
feeding GV has been proposed to increase the efcacy of
the TIPS procedure. Two retrospective studies analyzed
the efcacy of embolization combined with TIPS in acute
variceal bleeding. Few patients with cardiofundal
variceal bleeding (2121 and 31,22 respectively) were

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Clinical Gastroenterology and Hepatology Vol. 12, No. 6

included. No rm conclusions can be drawn from these

small studies. However, although evidence on the target
portal pressure gradient to be reached to prevent
rebleeding from fundal GV is not clear and it has been
suggested that fundal varices may rebleed despite a
portal pressure gradient slightly below 12 mm Hg, the
small previous studies suggest that there is not a clear
rationale to perform embolization, particularly if the
portal pressure gradient after TIPS is reduced below 12
mm Hg.
There is no RCT evaluating the use of TIPS as the
initial treatment to achieve hemostasis in patients with
IGV1; a cohort study suggested that it is highly effective
in achieving initial hemostasis in GOV1 and GOV2 varices.23 A recent RCT showed that early (72 hours from
bleeding) polytetrauoroethylene-coated TIPS can be
considered as a rst-line treatment in patients with
esophageal variceal bleeding at high risk of treatment
failure (dened by Child class C less than 14 points or
Child class B with active bleeding) because it reduces the
risk of treatment failure and improves survival in comparison with conventional treatment with drugs plus
endoscopic therapy.24 Although patients with GV were
excluded in the study, it is likely that the benet of the
use of early TIPS may also apply to patients with GV and
the same high-risk criteria; however, this needs to be
studied further.

Secondary Prophylaxis
Rebleeding rates after an acute GV bleeding episode
treated with tissue adhesives (mainly CA) range from
7%65%, with most of the large series reporting rates
below 15%. Thus, after initial hemostasis with tissue
adhesives, repeated sessions are performed on a 2- to
4-week basis until endoscopic obliteration is achieved.
Several case series and controlled studies have specifically evaluated the effect of long-term injections
of tissue adhesives (mainly CA) to prevent GV
rebleeding17,2530 (Table 2). In most of these studies,
eradication is achieved with 24 injections with a
volume ranging from 12 mL per session.
Similar to what occurs with initial hemostasis, CA
has been shown to be superior to both sclerotherapy

and band ligation for secondary prophylaxis. On the

contrary, comparison with nonselective beta-blockers
offers conicting results. In a small randomized study,
41 patients who bled from esophageal (n 31) or GV
(GOV 1 and GOV 2) (n 10) treated initially with CA
were randomized to repeated CA injections (n 21) or
propranolol (80160 mg) (n 20).31 No signicant
differences were observed between the 2 groups in the
incidence of variceal rebleeding and death. The incidence of complications was higher in the CA group
(47% vs 10%). A major limitation of the study was the
small number of patients with GV.31 In a more recent
RCT, 64 patients who bled from GV (54 GOV 2 and
10 IGV1) were allocated to receive either repeated CA
(n 33) or propranolol (n 34) for secondary prophylaxis.32 Rebleeding in the CA group was signicantly
lower than in the beta-blocker group (15% vs 55%,
P .004), and after a 26-month follow-up the mortality
rate was lower as well (3% vs 25%, P .026). The rate
of complications in the CA group was 3%.
A recent report indicates that endoscopic ultrasonography (EUS)guided therapy for fundal GV (IGV1 and
GOV2) with CA and bered coils may improve the efcacy of this technique.33 In this study, 30 patients underwent successful transesophageal EUS-guided therapy
of IGV1 and GOV2. The mean number of GV treated was
1.3 per patient, and the mean volume of CA injected was
1.4 mL per varix. GV were obliterated after a single
treatment session in the vast majority of patients (96%)
who underwent follow-up endoscopy. Rebleeding
occurred in 1 patient who was successfully treated with
a second session. There were no procedure-related
complications. Although this is a small series, EUS-guided
therapy seems to be a promising approach in selected
cases; however, more data are needed to consider it a
routine tool for the management of GV.
Finally, in a recent study, 95 patients with GV (GOV2,
n 77; IGV1, n 18) who bled and were successfully
treated with CA were assigned to receive treatment with
beta-blockers plus repeated CA (every 34 weeks until
the varices were obliterated) or repeated CA injections
alone.34 After a mean follow-up of 19 months, the overall
rebleeding (22 vs 26 patients, P .336) and survival
rates (22 vs 20, P .936) were not different between the
2 groups. One-year rebleeding free survival was also

Table 2. Results of Published Studies on Long-term Injection of Tissue Adhesives in the Prevention of GV Rebleeding
First author, year
(reference)

Eradication/hemostasis (%)

Rebleeding (%)

Follow-up
(median)

Rajoriya, 201125
Mishra, 201032
Choudhuri, 201026
Belletrutti, 200827
Marqus, 200828
Cheng, 200730
Joo, 200717

31
33
108
34
48
613
85

90
100
89
84
87
77
98

10
10
10
12
20
8
29

4y
26 mo
30.7 17.2 mo
11 mo
18 mo
25 mo
24 mo

Survival (%)
65 (1 y)
90 (2 y)
NA
82 (1 y)
56 (NA)
95 (1 y)
NA

Complications (%)
6.4
3
NA
3
6
5
3.5

June 2014

similar (77% vs 76.5%). The results of this study suggest

that contrary to what has been demonstrated for
esophageal variceal bleeding, adding beta-blocker therapy to repeated sessions of CA provides no important
benet for prevention of rebleeding and mortality in
patients with GV bleeding. Despite these ndings and
because nonselective beta-blockers are effective in patients with concomitant esophageal varices, until larger
studies with longer follow-up are available, we still
recommend the use of nonselective beta-blockers as an
adjunct to endoscopic therapy in the prevention of GV
rebleeding.

Other Endoscopic Therapies

Other endoscopic treatments have also been used to
prevent rebleeding. Sclerotherapy has been abandoned
because of high rebleeding rates (50%90%). Variceal
band ligation may be used for those patients with GOV1
and in some cases of small GOV2, and it is generally
performed every 2 weeks until apparent endoscopic
obliteration. However, band ligation is limited by the fact
that it cannot be used in large GOV2 or IGV1.7 Detachable
loop snares to treat large GV (>2 cm) along with propranolol have resulted in low rebleeding rates; however,
data are very scarce, and the procedure is labor intensive. This approach has not been further evaluated and
has not been compared with other modalities and thus
cannot be routinely recommended.

Thrombin
Thrombin converts brinogen to a brin clot, thus
forming a clot inside the GV and occluding blood ow.
The use of bovine thrombin was banned because of the
risk of potential prion transmission. This is not the case
when using commercially available human thrombin.
Each vial is reconstituted with 5 mL distilled water for a
concentration of 250 U/mL.35 The average dose of
injected thrombin ranges between 1500 and 2000 U.
Available data indicate that thrombin is safe and effective
in the treatment of acute GV bleeding, with hemostasis
rates of 70%100%; however, rebleeding rates may
range from 7%50%.3641 There are scarce data in
regard to follow-up and eradication rates. After initial
hemostasis,
repeated
thrombin
injections
are
performed every 23 weeks until eradication. Because
of the paucity of data mostly coming from case series,
the routine use of thrombin cannot be routinely
recommended.

Transjugular Intrahepatic Portosystemic

Shunt
The role of TIPS vs CA in preventing GV bleeding has
been evaluated in 3 small studies (2 retrospective

Management of Gastric Varices

923

observational studies and 1 prospective). Remarkably, in all

3 studies most patients included had GOV1, a few GOV2, and
only anecdotal IGV1 varices. In addition, the stents used
were uncoated, which has been shown to be associated with
lower TIPS patency, efcacy, and survival than coated
stents.42 Two of these studies23,43 showed a higher
rebleeding rate in the CA group (30% and 59%) vs the
TIPS group (15% and 40%) (Supplementary Table 1).
Frequency of complications was similar in the 2 groups,
but TIPS-treated patients showed a higher incidence of
hepatic encephalopathy23,43,44 and long-term morbidity
requiring hospitalization44 than endoscopically treated
patients. The studies found no signicant differences in
survival. Mahadeva et al23 analyzed the costs after 6
months of therapy and found that CA injections were
more cost-effective than TIPS in a small group of 43
patients with GV bleeding. In summary, TIPS is a very
effective therapy to prevent GV rebleeding. Nevertheless,
because of the previously mentioned drawbacks, more
data are needed to clarify the role of TIPS in the
secondary prophylaxis of GV bleeding and determine
whether this therapy must be universally applied or
reserved as a rescue therapy after failure of more
conservative approaches.

Surgery
Surgery has currently fallen out of favor for patients
with portal hypertension because of the wide availability of less invasive techniques such as endoscopy
and interventional radiology. In selected cases, patients with GV and segmental/left-sided portal hypertension that is due to isolated splenic vein thrombosis
may be candidates for splenectomy or splenic embolization as a means of denitive therapy; however, data
are scarce.

Balloon-occluded Retrograde
Transvenous Obliteration
Balloon-occluded retrograde transvenous obliteration
(BRTO) has been introduced as a treatment method that
aims to directly obliterate the GV. Since its introduction
by Kanagawa et al,45 BRTO has become widely accepted
in Japan and in some centers in the United States as a
minimally invasive and highly effective treatment for GV.
The technical difculty of BRTO relies on the anatomy of
the afferent and draining veins of the GV. Accurate
assessment, which is mainly based on imaging studies of
the variceal hemodynamic pattern, is the most important
factor in ensuring successful treatment. This anatomy
and how it alters the approach have been thoroughly
reviewed by Hirota et al,46 Kiyosue et al,47,48 and
Al-Osaimi et al.49
In most cases, there is a gastrorenal or gastrocaval
shunt. In this situation under uoroscopic guidance, a
balloon catheter is inserted into the outlet of the

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Clinical Gastroenterology and Hepatology Vol. 12, No. 6

Figure 3. (A) Basic portosystemic venous anatomy

of GV with the classic gastrorenal or splenorenal
shunts. (B) Conventional
BRTO procedure through
transfemoral approach with
balloon in the gastrorenal
shunt. IVC, inferior vena
cava; LGV, left gastric vein;
LRV, left renal vein; MV,
mesenteric vein; PGV,
posterior gastric vein(s);
PV, main portal vein; SGV,
short gastric vein(s); SV,
splenic vein. Afferent vein
(thin arrows). Drainage vein
(thick arrow).

gastrorenal or gastrocaval shunt through a sheath placed

in the right femoral vein. Immediately afterward,
venography is performed with an injection of 1015 mL
contrast medium via the inated balloon catheter, and
GV are slowly, intermittently, and completely lled with
a sclerosant (Figure 3).45,46,5063 Thirty to 50 minutes
after the injection, as much of the remaining sclerosant

as possible is aspirated via the catheter. Finally, the

balloon is deated, and the catheter is withdrawn.
Ethanolamine oleate is the predominant and traditional
sclerosant agent used in the BRTO procedure,
particularly in Asia.45,46,5060 Detergent sclerosants in a
foam or froth have also been studied in both Japan
(polidocanol)61,62 and the United States (3% STS).63

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925

Figure 4. Suggested algorithm for management of

GV. *EBL in small GV if
tissue
adhesives
not
available. HE, hepatic
encephalopathy.

The advantage of foam is that it reduces the sclerosantto-volume ratio, requiring less sclerosant per procedure.
In cases that involve complex types of afferent or
draining veins, the use of additional techniques is required
for successful treatment. These techniques include stepwise injection of the sclerosing agent, selective injection of
the agent via a microcatheter, coil embolization of the
afferent gastric veins, double-balloon catheterization, and
BRTO performed with percutaneous transhepatic portal
venous access or transileocolic venous access.48
Epigastric and back pain (76%),56 fever (26%),56,60
and transient hematuria (53%) are the most common
complications of BRTO. Bacterial peritonitis was found in
8% of patients in one study, but these patients recovered
after only conservative therapy,45 and this complication is
otherwise rarely mentioned in the literature. Portal
(4.3%) and renal vein thrombosis (5%) can be found in a
small number of patients, and both are usually clinically
silent.46,50,59 Pulmonary embolism,59 pulmonary edema,61
coil migration,46 and anaphylaxis to ethanolamine oleate46
have also been reported.
Technical success, dened by complete obliteration of
the GV with sclerosant, occurs in 77%100% of patients.64 In some studies, repeat BRTO was necessary to
achieve such high percentages.46,52,60 GV bleeding after a
successful BRTO ranges from 0%15%46,50,52,55,56,5961,65
or from 0%31.6%66 when factoring in an intent-to-treat
basis (including technical failures). Some authors suggest
that BRTO might be better than TIPS67 or glue65 in the
prevention of GV bleeding. However, the fact that in

most patients, treatment was administered as primary

prophylaxis for high-risk GV, the studies had a small
sample size, and the efcacy of the comparative groups
(either TIPS or glue therapy) was poorer than expected
precludes denitive conclusions. There is only a small
study54 that randomized 15 patients with acute GV
bleeding to receive TIPS (n 7) or BRTO (n 8)
without observing signicant differences in rebleeding,
hepatic encephalopathy, or survival.
BRTO has the potential advantage of increasing portal
blood ow and potentially improving liver function.52,54,57
Therefore, it may represent an alternative in patients who
may otherwise not tolerate TIPS.59 In that regard, in 4
studies including patients with hepatic encephalopathy,
there was resolution or signicant reduction in
encephalopathy in all patients after BRTO.46,50,51,58 By
contrast, BRTO obliterates a spontaneous portosystemic
shunt and therefore aggravates portal hypertension and
its related complications. An increase in the size of
esophageal varices and the risk of esophageal variceal
bleeding after BRTO has been reported (between 7.3%
and 27% after 1 year).52,55,56 Other complications related
to the increase of portal hypertension after BRTO are the
development of portal hypertensive gastropathy (in 5%
13% of cases), ascites (0%44%),65 and hydrothorax/
pleural effusion (0%72%). As a consequence of the
worsening of portal hypertension, in some cases TIPS has
been performed after BRTO.68
In conclusion, although BRTO seems to be a feasible
technique that is able to successfully control and prevent

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GV bleeding, there is a lack of good quality data to

routinely recommend BRTO in the management of GV. In
our opinion, BRTO could be considered in patients with
GV bleeding and large gastrorenal shunts in whom TIPS
may be contraindicated (such as those with refractory
hepatic encephalopathy or elderly patients).

Summary
The best management strategy for GV has not been
completely established because of a paucity of data of
RCTs in this area. Specic treatments such as CA injection and BRTO are not widely available in all centers.
Another limitation is the fact that tissue adhesives such
as CA are not approved by the Food and Drug Administration in the United States, and thus, recommendations
arising from published studies, guidelines, and expert
opinion cannot be extrapolated to routine practice. We
recommend a stepped care approach to the management
of GV as described in Figure 4. There are scarce data on
the role of CA or beta-blockers for primary prophylaxis
of GV bleeding, and thus, specic recommendations
cannot be made; however, patients should receive betablockers if they have concomitant esophageal varices.
After initial resuscitation and implementation of vasoconstrictors and antibiotics, endoscopic therapy with CA
should be the rst line of therapy if available. After the
acute episode, patients should receive beta-blockers
along with repeated sessions of CA injection if available.
TIPS is very effective in controlling active GV bleeding
and for secondary prophylaxis. However, it carries a risk
of hepatic encephalopathy. TIPS is the best treatment
strategy for patients who fail endoscopic therapy.

Supplementary Material
Note: To access the supplementary materials accompanying this article, visit the online version of Clinical
Gastroenterology and Hepatology at www.cghjournal.org,
and at http://dx.doi.org/10.1016/j.cgh.2013.07.015.

References
1. Sarin SK, Lahoti D, Saxena SP, et al. Prevalence, classication
and natural history of gastric varices: a long-term follow-up
study in 568 portal hypertension patients. Hepatology 1992;
16:13431349.
2. Kim T, Shijo H, Kokawa H, et al. Risk factors for hemorrhage
from gastric fundal varices. Hepatology 1997;25:307312.
3. Mishra SR, Sharma BC, Kumar A, et al. Primary prophylaxis of
gastric variceal bleeding comparing cyanoacrylate injection and
beta-blockers: a randomized controlled trial. J Hepatol 2011;
54:11611167.
4. de Franchis R. Revising consensus in portal hypertension:
report of the Baveno V consensus workshop on methodology of
diagnosis and therapy in portal hypertension. J Hepatol 2010;
53:762768.
5. Garcia-Tsao G, Sanyal AJ, Grace ND, et al. Prevention and
management of gastroesophageal varices and variceal hemorrhage in cirrhosis. Hepatology 2007;46:922938.

Clinical Gastroenterology and Hepatology Vol. 12, No. 6

6. Escorsell A, Abraldes JG, Pipa-Muiz M, et al. Prognosis of
acute bleeding from isolated fundal varices in patients with
cirrhosis: a European cohort. Hepatology 2012;56(Suppl):748A.
7. Tan PC, Hou MC, Lin HC, et al. A randomized trial of endoscopic
treatment of acute gastric variceal hemorrhage: N-butyl-2cyanoacrylate injection versus band ligation. Hepatology 2006;
43:690697.
8. Lo GH, Lai KH, Cheng JS, et al. A prospective, randomized trial
of butyl cyanoacrylate injection versus band ligation in the
management of bleeding gastric varices. Hepatology 2001;
33:10601064.
9. Oho K, Iwao T, Sumino M, et al. Ethanolamine oleate versus
butyl cyanoacrylate for bleeding gastric varices: a nonrandomized study. Endoscopy 1995;27:349354.
10. Sarin SK, Jain AK, Jain M, et al. A randomized controlled trial of
cyanoacrylate versus alcohol injection in patients with isolated
fundic varices. Am J Gastroenterol 2002;97:10101015.
11. Lo GH, Lai KH. Should GOV1 be treated as for esophageal
varices? Gastroenterology 2004;127:10141015.
12. Greenwald BD, Caldwell SH, Hespenheide EE, et al. N-2-butylcyanoacrylate for bleeding gastric varices: a United States pilot
study and cost analysis. Am J Gastroenterol 2003;98:19821988.
13. Caldwell SH, Hespenheide EE, Greenwald BD, et al. Enbucrilate
for gastric varices: extended experience in 92 patients. Aliment
Pharmacol Ther 2007;26:4959.
14. Seewald S, Ang TL, Imazu H, et al. A standardized injection
technique and regimen ensures success and safety of N-butyl2-cyanoacrylate injection for the treatment of gastric fundal
varices (with videos). Gastrointest Endosc 2008;68:447454.
Edson Guzman

Firmado digitalmente por Edson Guzman

Nombre de reconocimiento (DN): cn=Edson Guzman, o, ou=HNERM, [email protected], c=PE
Fecha: 2014.05.26 20:01:59 -05'00'

15. Wang YM, Cheng LF, Li N, et al. Study of glue extrusion after
endoscopic N-butyl-2-cyanoacrylate injection on gastric variceal bleeding. World J Gastroenterol 2009;15:49454951.
16. Cheng LF, Wang ZQ, Li CZ, et al. Low incidence of complications from endoscopic gastric variceal obturation with butyl
cyanoacrylate. Clin Gastroenterol Hepatol 2010;8:760766.
17. Joo HS, Jang JY, Eun SH, et al. [Long-term results of endoscopic histoacryl (N-butyl-2-cyanoacrylate) injection for treatment of gastric varices: a 10-year experience]. Korean J
Gastroenterol 2007;49:320326.
18. Teres J, Cecilia A, Bordas JM, et al. Esophageal tamponade
for bleeding varices: controlled trial between the SengstakenBlakemore tube and the Linton-Nachlas tube. Gastroenterology
1978;75:566569.
19. Chau TN, Patch D, Chan YW, et al. Salvage transjugular
intrahepatic portosystemic shunts: gastric fundal compared with
esophageal variceal bleeding. Gastroenterology 1998;114:
981987.
20. Azoulay D, Castaing D, Majno P, et al. Salvage transjugular
intrahepatic portosystemic shunt for uncontrolled variceal
bleeding in patients with decompensated cirrhosis. J Hepatol
2001;35:590597.
21. Gaba RC, Bui JT, Cotler SJ, et al. Rebleeding rates following
TIPS for variceal hemorrhage in the Viatorr era: TIPS alone versus
TIPS with variceal embolization. Hepatol Int 2010;4:749756.
22. Xiao T, Chen L, Chen W, et al. Comparison of transjugular
intrahepatic portosystemic shunt (TIPS) alone versus TIPS
combined with embolotherapy in advanced cirrhosis: a retrospective study. J Clin Gastroenterol 2011;45:643650.
23. Mahadeva S, Bellamy MC, Kessel D, et al. Cost-effectiveness of
N-butyl-2-cyanoacrylate (histoacryl) glue injections versus transjugular intrahepatic portosystemic shunt in the management of

June 2014
acute gastric variceal bleeding. Am J Gastroenterol 2003;
98:26882693.
24. Garcia-Pagan JC, Caca K, Bureau C, et al. Early use of TIPS in
patients with cirrhosis and variceal bleeding. N Engl J Med 2010;
362:23702379.
25. Rajoriya N, Forrest EH, Gray J, et al. Long-term follow-up of
endoscopic Histoacryl glue injection for the management of
gastric variceal bleeding. QJM 2011;104:4147.
26. Choudhuri G, Chetri K, Bhat G, et al. Long-term efcacy and
safety of N-butylcyanoacrylate in endoscopic treatment of
gastric varices. Trop Gastroenterol 2010;31:155164.

Management of Gastric Varices

927

41. Williams SG, Peters RA, Westaby D. Thrombin: an effective

treatment for gastric variceal haemorrhage. Gut 1994;35:
12871289.
42. Yang Z, Han G, Wu Q, et al. Patency and clinical outcomes
of transjugular intrahepatic portosystemic shunt with polytetrauoroethylene-covered stents versus bare stents: a metaanalysis. J Gastroenterol Hepatol 2010;25:17181725.

27. Belletrutti PJ, Romagnuolo J, Hilsden RJ, et al. Endoscopic

management of gastric varices: efcacy and outcomes of gluing
with N-butyl-2-cyanoacrylate in a North American patient population. Can J Gastroenterol 2008;22:931936.

43. Lo GH, Liang HL, Chen WC, et al. A prospective, randomized

controlled trial of transjugular intrahepatic portosystemic shunt
versus cyanoacrylate injection in the prevention of gastric variceal rebleeding. Endoscopy 2007;39:679685.
44. Procaccini NJ, Al-Osaimi AM, Northup P, et al. Endoscopic
cyanoacrylate versus transjugular intrahepatic portosystemic
shunt for gastric variceal bleeding: a single-center US analysis.
Gastrointest Endosc 2009;70:881887.

28. Marques P, Maluf-Filho F, Kumar A, et al. Long-term outcomes

of acute gastric variceal bleeding in 48 patients following
treatment with cyanoacrylate. Dig Dis Sci 2008;53:544550.

45. Kanagawa H, Mima S, Kouyama H, et al. Treatment of gastric

fundal varices by balloon-occluded retrograde transvenous
obliteration. J Gastroenterol Hepatol 1996;11:5158.

29. Fry LC, Neumann H, Olano C, et al. Efcacy, complications and

clinical outcomes of endoscopic sclerotherapy with N-butyl-2cyanoacrylate for bleeding gastric varices. Dig Dis 2008;26:
300303.

46. Hirota S, Matsumoto S, Tomita M, et al. Retrograde transvenous

obliteration of gastric varices. Radiology 1999;211:349356.

30. Cheng LF, Wang ZQ, Li CZ, et al. Treatment of gastric varices by
endoscopic sclerotherapy using butyl cyanoacrylate: 10 years
experience of 635 cases. Chin Med J (Engl) 2007;120:
20812085.
31. Evrard S, Dumonceau JM, Delhaye M, et al. Endoscopic histoacryl obliteration vs propranolol in the prevention of esophagogastric variceal rebleeding: a randomized trial. Endoscopy
2003;35:729735.
32. Mishra SR, Chander SB, Kumar A, et al. Endoscopic cyanoacrylate injection versus beta-blocker for secondary prophylaxis of
gastric variceal bleed: a randomised controlled trial. Gut 2010;
59:729735.
33. Binmoeller KF, Weilert F, Shah JN, et al. EUS-guided transesophageal treatment of gastric fundal varices with combined
coiling and cyanoacrylate glue injection (with videos). Gastrointest Endosc 2011;74:10191025.
34. Hung HH, Chang CJ, Hou MC, et al. Efcacy of non-selective
beta-blockers as adjunct to endoscopic prophylactic treatment for
gastric variceal bleeding: a randomized controlled trial. J Hepatol
2012;56:10251032.
35. McAvoy NC, Plevris JN, Hayes PC. Human thrombin for the
treatment of gastric and ectopic varices. World J Gastroenterol
2012;18:59125917.
36. Krystallis C, McAvoy NC, Wilson J, et al. EUS-assisted thrombin
injection for ectopic bleeding varices: a case report and review
of the literature. QJM 2012;105:355358.

47. Kiyosue H, Mori H, Matsumoto S, et al. Transcatheter obliteration of gastric varices: part 2strategy and techniques based
on hemodynamic features. Radiographics 2003;23:921937.
48. Kiyosue H, Mori H, Matsumoto S, et al. Transcatheter obliteration of gastric varices: part 1anatomic classication. Radiographics 2003;23:911920.
49. Al-Osaimi AM, Sabri SS, Caldwell SH. Balloon-occluded retrograde transvenous obliteration (BRTO): preprocedural evaluation and imaging. Semin Intervent Radiol 2011;28:288295.
50. Cho SK, Shin SW, Lee IH, et al. Balloon-occluded retrograde
transvenous obliteration of gastric varices: outcomes and
complications in 49 patients. AJR Am J Roentgenol 2007;
189:W365W372.
51. Sonomura T, Sato M, Kishi K, et al. Balloon-occluded retrograde
transvenous obliteration for gastric varices: a feasibility study.
Cardiovasc Intervent Radiol 1998;21:2730.
52. Fukuda T, Hirota S, Sugimura K. Long-term results of balloonoccluded retrograde transvenous obliteration for the treatment
of gastric varices and hepatic encephalopathy. J Vasc Interv
Radiol 2001;12:327336.
53. Kitamoto M, Imamura M, Kamada K, et al. Balloon-occluded
retrograde transvenous obliteration of gastric fundal varices with
hemorrhage. AJR Am J Roentgenol 2002;178:11671174.
54. Choi YH, Yoon CJ, Park JH, et al. Balloon-occluded retrograde
transvenous obliteration for gastric variceal bleeding: its feasibility compared with transjugular intrahepatic portosystemic
shunt. Korean J Radiol 2003;4:109116.

37. Ramesh J, Limdi JK, Sharma V, et al. The use of thrombin

injections in the management of bleeding gastric varices: a singlecenter experience. Gastrointest Endosc 2008;68:877882.

55. Ninoi T, Nishida N, Kaminou T, et al. Balloon-occluded retrograde transvenous obliteration of gastric varices with gastrorenal shunt: long-term follow-up in 78 patients. AJR Am J
Roentgenol 2005;184:13401346.

38. Heneghan MA, Byrne A, Harrison PM. An open pilot study of the
effects of a human brin glue for endoscopic treatment of patients with acute bleeding from gastric varices. Gastrointest
Endosc 2002;56:422426.

56. Hiraga N, Aikata H, Takaki S, et al. The long-term outcome of

patients with bleeding gastric varices after balloon-occluded
retrograde transvenous obliteration. J Gastroenterol 2007;
42:663672.

39. Yang WL, Tripathi D, Therapondos G, et al. Endoscopic use of

human thrombin in bleeding gastric varices. Am J Gastroenterol
2002;97:13811385.

57. Akahoshi T, Hashizume M, Tomikawa M, et al. Long-term results

of balloon-occluded retrograde transvenous obliteration for
gastric variceal bleeding and risky gastric varices: a 10-year
experience. J Gastroenterol Hepatol 2008;23:17021709.
58. Kumamoto M, Toyonaga A, Inoue H, et al. Long-term results
of balloon-occluded retrograde transvenous obliteration for

40. Przemioslo RT, McNair A, Williams R. Thrombin is effective in

arresting bleeding from gastric variceal hemorrhage. Dig Dis Sci
1999;44:778781.

928

GarciaPagan et al

Clinical Gastroenterology and Hepatology Vol. 12, No. 6

gastric fundal varices: hepatic deterioration links to portosystemic shunt syndrome. J Gastroenterol Hepatol 2010;25:
11291135.

69. Ogawa K, Ishikawa S, Naritaka Y, et al. Clinical evaluation of endoscopic injection sclerotherapy using n-butyl-2-cyanoacrylate for
gastric variceal bleeding. J Gastroenterol Hepatol 1999;14:245250.

59. Sabri SS, Swee W, Turba UC, et al. Bleeding gastric varices
obliteration with balloon-occluded retrograde transvenous
obliteration using sodium tetradecyl sulfate foam. J Vasc Interv
Radiol 2011;22:309316.

70. Kind R, Guglielmi A, Rodella L, et al. Bucrylate treatment of

bleeding gastric varices: 12 years experience. Endoscopy 2000;
32:512519.

60. Akahoshi T, Tomikawa M, Kamori M, et al. Impact of balloonoccluded retrograde transvenous obliteration on management
of isolated fundal gastric variceal bleeding. Hepatol Res 2012;
42:385393.
61. Choi SY, Won JY, Kim KA, et al. Foam sclerotherapy using
polidocanol for balloon-occluded retrograde transvenous obliteration (BRTO). Eur Radiol 2011;21:122129.
62. Clements W, Cavanagh K, Ali F, et al. Variant treatment for
gastric varices with polidocanol foam using balloon-occluded
retrograde transvenous obliteration: a pilot study. J Med Imaging Radiat Oncol 2012;56:599605.
63. Saad WE. The history and evolution of balloon-occluded
retrograde transvenous obliteration (BRTO): from the United
States to Japan and back. Semin Intervent Radiol 2011;28:
283287.
64. Patel A, Fischman AM, Saad WE. Balloon-occluded retrograde
transvenous obliteration of gastric varices. AJR Am J Roentgenol 2012;199:721729.
65. Hong CH, Kim HJ, Park JH, et al. Treatment of patients with
gastric variceal hemorrhage: endoscopic N-butyl-2-cyanoacrylate injection versus balloon-occluded retrograde transvenous
obliteration. J Gastroenterol Hepatol 2009;24:372378.
66. Saad WE, Sabri SS. Balloon-occluded retrograde transvenous
obliteration (BRTO): technical results and outcomes. Semin
Intervent Radiol 2011;28:333338.
67. Ninoi T, Nakamura K, Kaminou T, et al. TIPS versus transcatheter sclerotherapy for gastric varices. AJR Am J Roentgenol
2004;183:369376.
68. Saad WE, Al-Osaimi AM, Caldwell SH. Pre- and post-balloonoccluded retrograde transvenous obliteration clinical evaluation, management, and imaging: indications, management
protocols, and follow-up. Tech Vasc Interv Radiol 2012;15:
165202.

71. Huang YH, Yeh HZ, Chen GH, et al. Endoscopic treatment of
bleeding gastric varices by N-butyl-2- cyanoacrylate (Histoacryl)
injection: long-term efcacy and safety. Gastrointest Endosc
2000;52:160167.
72. Akahoshi T, Hashizume M, Shimabukuro R, et al. Long-term
results of endoscopic Histoacryl injection sclerotherapy for
gastric variceal bleeding: a 10-year experience. Surgery 2002;
131(Suppl):S176S181.
73. Rengstorff DS, Binmoeller KF. A pilot study of 2-octyl cyanoacrylate injection for treatment of gastric fundal varices in
humans. Gastrointest Endosc 2004;59:553558.
74. Mumtaz K, Majid S, Shah H, et al. Prevalence of gastric varices
and results of sclerotherapy with N-butyl 2 cyanoacrylate for
controlling acute gastric variceal bleeding. World J Gastroenterol 2007;13:12471251.
75. Paik CN, Kim SW, Lee IS, et al. The therapeutic effect of
cyanoacrylate on gastric variceal bleeding and factors related to
clinical outcome. J Clin Gastroenterol 2008;42:916922.
76. Monsanto P, Almeida N, Rosa A, et al. Endoscopic treatment of
bleeding gastric varices with histoacryl (N-butyl-2-cyanoacrylate): a South European single center experience. Indian J
Gastroenterol 2012;32:227231.
77. Hou MC, Lin HC, Lee HS, et al. A randomized trial of endoscopic
cyanoacrylate injection for acute gastric variceal bleeding: 0.5 mL
versus 1.0 mL. Gastrointest Endosc 2009;70:668675.
Reprint requests
Address requests for reprints to: Juan Carlos Garcia-Pagn, MD, Hepatic
Hemodynamic Laboratory, Liver Unit, Hospital Clinic, Villarroel 170, 08036
Barcelona, Spain. e-mail: [email protected]; fax: 34-93-227-98-56.
Conicts of interest
These authors disclose the following: Juan Garcia-Pagn received grant support from GORE. Andres Cardenas has been a consultant to Limmedx LLC,
Frontier Medex, and BMJ Publishing Group. The remaining authors disclose no
conicts.

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Management of Gastric Varices

928.e1

Supplementary Table 1. Studies That Used TIPS or CA in Bleeding GV

First author,
year (reference)

Design

Mahadeva, 200323 Cohorts retrospective

(GOV1 and GOV2)
Lo, 200743

Procaccini, 200944

Treatment
received (n)

Initial
control (%)

Mortality (%)

Any source
of rebleeding (%)

43 TIPS (20)
TIPS (90)
At 6 months:
At 6 months: TIPS (15)
vs glue (23)
vs glue (96)
TIPS (25) vs
vs glue (30)
glue (15)
72 TIPS (35)
NA
TIPS (30) vs
TIPS (43) vs glue (59)
vs glue (37)
glue (17)

Randomized prospective
(mostly GOV1 and
GOV2 and few IGV1)
Cohorts retrospective
105 TIPS (44)
(GV type not specied)
vs glue (61)

NA

At 1 year:
At 1 year: TIPS
TIPS (33) vs
(25) vs glue (10)
glue (28)

Followup (mo)
6

33

TIPS (48),
glue (74)