Skip to main page content
U.S. flag

An official website of the United States government

Dot gov

The .gov means it’s official.
Federal government websites often end in .gov or .mil. Before sharing sensitive information, make sure you’re on a federal government site.

Https

The site is secure.
The https:// ensures that you are connecting to the official website and that any information you provide is encrypted and transmitted securely.

Access keys NCBI Homepage MyNCBI Homepage Main Content Main Navigation
Meta-Analysis
. 2015 May 12;2015(5):CD010180.
doi: 10.1002/14651858.CD010180.pub2.

Endoscopic injection of cyanoacrylate glue versus other endoscopic procedures for acute bleeding gastric varices in people with portal hypertension

Eddy Ríos Castellanos  1 , Pamela Seron, Javier P Gisbert, Xavier Bonfill Cosp
Affiliations
Meta-Analysis

Endoscopic injection of cyanoacrylate glue versus other endoscopic procedures for acute bleeding gastric varices in people with portal hypertension

Eddy Ríos Castellanos et al. Cochrane Database Syst Rev. .

Abstract

Background: In people with portal hypertension, gastric varices are less prevalent than oesophageal varices. The risk of bleeding from gastric varices seems to be lower than from oesophageal varices; however, when gastric varices bleed, it is often severe and associated with higher mortality. Endoscopic sclerotherapy of bleeding gastric varices with N-butyl-2-cyanoacrylate glue (cyanoacrylate) is considered the best haemostasis with a lower risk of re-bleeding compared with other endoscopic methods. However, there are some inconsistencies between trials regarding mortality, incidence of re-bleeding, and adverse effects.

Objectives: To assess the benefits and harms of sclerotherapy using cyanoacrylate compared with other endoscopic sclerotherapy procedures or with variceal band ligation for treating acute gastric variceal bleeding with or without vasoactive drugs in people with portal hypertension and to assess the best dosage of cyanoacrylate.

Search methods: We searched the Cochrane Hepato-Biliary Controlled Trials Register, the Cochrane Central Register of Controlled Trials (CENTRAL), MEDLINE, EMBASE, and Science Citation Index Expanded from inception to September 2014 and reference lists of articles. We included trials irrespective of trial setting, language, publication status, or date of publication.

Selection criteria: Randomised clinical trials comparing sclerotherapy using cyanoacrylate versus other endoscopic methods (sclerotherapy using alcohol-based compounds or endoscopy band ligation) for acute gastric variceal bleeding in people with portal hypertension.

Data collection and analysis: We performed the review following the recommendations of the Cochrane Handbook for Systematic Reviews of Interventions and the Cochrane Hepato-Biliary Module.We presented results as risk ratios (RR) with 95% confidence intervals (CI), with I(2) statistic values as a measure of intertrial heterogeneity. We analysed data with both fixed-effect and random-effects models, and reported the results with random-effects models. We performed subgroup, sensitivity, and trial sequential analyses to evaluate the robustness of the overall results, risk of bias, sources of intertrial heterogeneity, and risk of random errors.

Main results: We included six randomised clinical trials with three different comparisons: one trial compared two different doses of cyanoacrylate in 91 adults, bleeding actively from all types of gastric varices; one trial compared cyanoacrylate versus alcohol-based compounds in 37 adults with active or acute bleeding from isolated gastric varices only; and four trials compared cyanoacrylate versus endoscopic band ligation in 365 adults, with active or acute bleeding from all types of gastric varices. Main outcomes in the included trials were bleeding-related mortality, failure of intervention, re-bleeding, adverse events, and control of bleeding. Follow-up varied from six to 26 months. The participants included in these trials had chronic liver disease of different severities, were predominantly men, and most were from Eastern countries. We judged all trials at high risk of bias. Application of quality criteria for all outcomes yielded very low quality grade of the evidence in the three analyses, except for the low quality evidence rated for the re-bleeding outcome in the cyanoacrylate versus endoscopic band ligation comparison. Two different doses of cyanoacrylate: we found very low quality evidence from one trial for the effect of 0.5 mL compared with 1.0 mL of cyanoacrylate on all-cause mortality (20/44 (45.5%) with 0.5 mL versus 21/47 (45%) with 1.0 mL; RR 1.02; 95% CI 0.65 to 1.60), 30-day mortality (RR 1.07; 95% CI 0.41 to 2.80), failure of intervention (RR 1.07; 95% CI 0.56 to 2.05), prevention of re-bleeding (RR 1.30; 95% CI 0.73 to 2.31), adverse events reported as fever (RR 0.56; 95% CI 0.32 to 0.98), and control of bleeding (RR 1.04; 95% CI 0.78 to 1.38). Cyanoacrylate versus alcohol-based compounds: we found very low quality evidence from one trial for the effect of cyanoacrylate versus alcohol-based compounds on 30-day mortality (2/20 (10%) with cyanoacrylate versus 4/17 (23.5%) with alcohol-based compound; RR 0.43; 95% CI 0.09 to 2.04), failure of intervention (RR 0.36; 95% CI 0.09 to 1.35), prevention of re-bleeding (RR 0.85; 95% CI 0.30 to 2.45), adverse events reported as fever (RR 0.43; 95% CI 0.22 to 0.80), and control of bleeding (RR 1.79; 95% CI 1.13 to 2.84). Cyanoacrylate versus endoscopic band ligation: we found very low quality evidence for the effect of cyanoacrylate versus endoscopic band ligation on bleeding-related mortality (44/185 (23.7%) with cyanoacrylate versus 50/181 (27.6%) with endoscopic band ligation; RR 0.83; 95% CI 0.52 to 1.31), failure of intervention (RR 1.13; 95% CI 0.23 to 5.69), complications (RR 2.81; 95% CI 0.69 to 11.49), and control of bleeding (RR 1.07; 95% CI 0.90 to 1.27). There was low quality evidence for the prevention of re-bleeding (RR 0.60; 95% CI 0.41 to 0.88). Trial sequential analysis showed that the analyses were underpowered (diversity-adjusted required information size was 5290 participants for bleeding-related mortality).

Authors' conclusions: This review suggests that endoscopic sclerotherapy using cyanoacrylate may be more effective than endoscopic band ligation in terms of preventing re-bleeding from gastric varices. However, due to the very low quality of the evidence, we are very uncertain about our estimates on all-cause and bleeding-related mortality, failure of intervention, adverse events, and control of bleeding. The trials were at high risk of bias; the number of the included randomised clinical trials and number of participants included in each trial was small; and there was evidence of internal heterogeneity across trials, indirectness of evidence in terms of population, and possible publication bias.The effectiveness of different doses of cyanoacrylate and the comparison of cyanoacrylate versus alcohol compounds to treat variceal bleeding in people with portal hypertension is uncertain due to the very low quality of the evidence.The shortcomings mentioned call for more evidence from larger trials that need to be conducted according to the SPIRIT statement and reported according to CONSORT guidelines.

PubMed Disclaimer

Conflict of interest statement

None known.

Figures

1
1
Study flow diagram.
2
2
Risk of bias graph: review authors' judgements about each risk of bias item presented as percentages across all included studies.
3
3
Risk of bias summary: review authors' judgements about each risk of bias item for each included study.
4
4
Trial sequential analysis of cyanoacrylate versus band ligation for acute bleeding in people with gastric varices on the outcome bleeding‐related mortality. The diversity‐adjusted required information size (DARIS) is 5290 participants. The calculation is based on a proportion of people dying in the control group (Pc) of 59%; a relative risk reduction (RRR) of 20% based on the intervention effect in trials with a high risk of bias; an alpha (a) of 5%; a beta (b) of 20%; and diversity of 59%. The red lines sloping towards a Z‐value of 1.96 and ‐1.96 are the trial sequential monitoring boundaries. The blue line is the cumulative Z‐curve that does not cross the trial sequential monitoring boundaries for benefit, harm, or futility of cyanoacrylate.
5
5
Trial sequential analysis of cyanoacrylate versus band ligation for acute bleeding in people with gastric varices on the outcome failure of intervention. The diversity‐adjusted required information size (DARIS) is 4098 participants. The calculation is based on a proportion of people with failure of the intervention in the control group (Pc) of 10%; a relative risk reduction (RRR) of 40% based on the intervention effect in trials with a high risk of bias; an alpha (a) of 5%; a beta (b) of 20%; and diversity of 65%. The red lines sloping towards a Z‐value of 1.96 and ‐1.96 are the trial sequential monitoring boundaries. The blue line is the cumulative Z‐curve that crosses the conventional boundaries after the first trial and fell under the conventional boundaries and remained there after the second trial. The cumulative Z‐curve does not cross the trial sequential monitoring boundaries for benefit, harm, or futility of cyanoacrylate.
6
6
Trial sequential analysis of cyanoacrylate versus band ligation for acute bleeding in people with gastric varices on the risk of the outcome re‐bleeding. The diversity‐adjusted required information size (DARIS) was 1840 participants. The calculation is based on a proportion of people re‐bleeding in the control group (Pc) of 30%; a relative risk reduction (RRR) of 20%; an alpha (a) of 5%; a beta (b) of 20%; and diversity of 7%. The blue line is the cumulative Z‐curve that crosses the conventional boundarie for benefit during the second trial and remained there adding the third and fourth trials.
7
7
Trial sequential analysis of cyanoacrylate versus band ligation for acute bleeding in people with gastric varices on the outcome control of bleeding. The diversity‐adjusted required information size (DARIS) is 534 participants. The calculation is based on a proportion of people with control of bleeding in the control group (Pc) of 84%; a relative risk reduction (RRR) of 20%; an alpha (a) of 5%; a beta (b) of 20%; and diversity of 61%. The red lines sloping towards a Z‐value of 1.96 and ‐1.96 are the trial sequential monitoring boundaries for benefit or harm. The blue line is the cumulative Z‐curve that does not cross the conventional boundaries or the trial sequential monitoring boundaries for benefit, harm, or futility of cyanoacrylate.
1.1
1.1. Analysis
Comparison 1 Two different doses of cyanoacrylate, Outcome 1 Total mortality.
1.2
1.2. Analysis
Comparison 1 Two different doses of cyanoacrylate, Outcome 2 30‐day mortality.
1.3
1.3. Analysis
Comparison 1 Two different doses of cyanoacrylate, Outcome 3 Failure of intervention.
1.4
1.4. Analysis
Comparison 1 Two different doses of cyanoacrylate, Outcome 4 Re‐bleeding.
1.5
1.5. Analysis
Comparison 1 Two different doses of cyanoacrylate, Outcome 5 Adverse effects (fever).
1.6
1.6. Analysis
Comparison 1 Two different doses of cyanoacrylate, Outcome 6 Control of bleeding.
2.1
2.1. Analysis
Comparison 2 Cyanoacrylate versus alcohol‐based compounds, Outcome 1 Bleeding‐related mortality.
2.2
2.2. Analysis
Comparison 2 Cyanoacrylate versus alcohol‐based compounds, Outcome 2 Failure of intervention.
2.3
2.3. Analysis
Comparison 2 Cyanoacrylate versus alcohol‐based compounds, Outcome 3 Re‐bleeding.
2.4
2.4. Analysis
Comparison 2 Cyanoacrylate versus alcohol‐based compounds, Outcome 4 Adverse effects (fever).
2.5
2.5. Analysis
Comparison 2 Cyanoacrylate versus alcohol‐based compounds, Outcome 5 Adverse effects (ulceration).
2.6
2.6. Analysis
Comparison 2 Cyanoacrylate versus alcohol‐based compounds, Outcome 6 Control of bleeding.
3.1
3.1. Analysis
Comparison 3 Cyanoacrylate versus band ligation, Outcome 1 Bleeding‐related mortality.
3.2
3.2. Analysis
Comparison 3 Cyanoacrylate versus band ligation, Outcome 2 Bleeding‐related mortality stratified by trials with high or unclear risk of bias.
3.3
3.3. Analysis
Comparison 3 Cyanoacrylate versus band ligation, Outcome 3 Bleeding‐related mortality stratified by type of gastric varices.
3.4
3.4. Analysis
Comparison 3 Cyanoacrylate versus band ligation, Outcome 4 Bleeding‐related mortality stratified by full papers or abstracts.
3.5
3.5. Analysis
Comparison 3 Cyanoacrylate versus band ligation, Outcome 5 Bleeding‐related mortality stratified by use of vasoactive drugs.
3.6
3.6. Analysis
Comparison 3 Cyanoacrylate versus band ligation, Outcome 6 Failure of intervention.
3.7
3.7. Analysis
Comparison 3 Cyanoacrylate versus band ligation, Outcome 7 Failure of intervention stratified by trials with high or unclear risk of bias.
3.8
3.8. Analysis
Comparison 3 Cyanoacrylate versus band ligation, Outcome 8 Failure of intervention stratified by full papers or abstracts.
3.9
3.9. Analysis
Comparison 3 Cyanoacrylate versus band ligation, Outcome 9 Re‐bleeding.
3.10
3.10. Analysis
Comparison 3 Cyanoacrylate versus band ligation, Outcome 10 Re‐bleeding stratified by trials with high or unclear risk of bias.
3.11
3.11. Analysis
Comparison 3 Cyanoacrylate versus band ligation, Outcome 11 Re‐bleeding stratified by full papers or abstracts.
3.12
3.12. Analysis
Comparison 3 Cyanoacrylate versus band ligation, Outcome 12 Re‐bleeding stratified by type of gastric varices.
3.13
3.13. Analysis
Comparison 3 Cyanoacrylate versus band ligation, Outcome 13 Re‐bleeding stratified by use of vasoactive drugs.
3.14
3.14. Analysis
Comparison 3 Cyanoacrylate versus band ligation, Outcome 14 Adverse effects (general).
3.15
3.15. Analysis
Comparison 3 Cyanoacrylate versus band ligation, Outcome 15 Adverse effects stratified by trials with high or unclear risk of bias.
3.16
3.16. Analysis
Comparison 3 Cyanoacrylate versus band ligation, Outcome 16 Control of bleeding stratified by full papers or abstracts.
3.17
3.17. Analysis
Comparison 3 Cyanoacrylate versus band ligation, Outcome 17 Complications stratified by use of vasoactive drugs.
3.18
3.18. Analysis
Comparison 3 Cyanoacrylate versus band ligation, Outcome 18 Control of bleeding.
3.19
3.19. Analysis
Comparison 3 Cyanoacrylate versus band ligation, Outcome 19 Control of bleeding stratified by trials with high or unclear risk of bias.
3.20
3.20. Analysis
Comparison 3 Cyanoacrylate versus band ligation, Outcome 20 Control of bleeding stratified by use of vasoactive drugs.
See this image and copyright information in PMC

Update of

  • doi: 10.1002/14651858.CD010180

Similar articles

See all similar articles

Cited by

See all "Cited by" articles

References

References to studies included in this review

El Amin 2010 {published data only}
    1. Amin H, Abdel Baky L, Sayed Z, Abdel Mohsen E, Eid K, Fouad Y, et al. A randomized trial of endoscopic variceal ligation versus cyanoacrylate injection for treatment of bleeding junctional varices. Tropical Gastroenterology 2010;31(4):279‐84. - PubMed
Hou 2009 {published data only}
    1. Hou MC, Lin HC, Lee HS, Liao WC, Lee FY, Lee SD. A randomized trial of endoscopic cyanoacrylate injection for acute gastric variceal bleeding: 0.5 mL versus 1.0 mL. Gastrointestinal Endoscopy 2009;70(4):668‐75. - PubMed
Lo 2001 {published data only}
    1. Lo GH, Lai KH, Cheng JS, Chen MH, Chiang HT. A prospective, randomized trial of butyl cyanoacrylate injection versus band ligation in the management of bleeding gastric varices. Hepatology 2001;33(5):1060‐4. - PubMed
Sarin 2002 {published data only}
    1. Sarin SK, Jain AK, Jain M, Gupta R. A randomized controlled trial of cyanoacrylate versus alcohol injection in patients with isolated fundic varices. American Journal of Gastroenterology 2002;97(4):1010‐5. - PubMed
Tan 2006 {published data only}
    1. Tan PC, Hou MC, Lin HC, Liu TT, Lee FY, Chang FY, et al. A randomized trial of endoscopic treatment of acute gastric variceal hemorrhage: N‐butyl‐2‐cyanoacrylate injection versus band ligation. Hepatology 2006;43(4):690‐7. - PubMed
Zheng 2012 {published data only}
    1. Zheng F, Lin X, Tao L. A randomized trial of endoscopic treatment of acute gastric variceal hemorrhage: N‐butyl‐2‐cyanoacrylate injection versus band ligation. Journal of Gastroenterology and Hepatology 2012;27(Suppl 5):113. - PubMed

References to studies excluded from this review

Akahoshi 2002 {published data only}
    1. Akahoshi T, Hashizume M, Shimabukuro R, Tanoue K, Tomikawa M, Okita K, et al. Long‐term results of endoscopic histoacryl injection sclerotherapy for gastric variceal bleeding: a 10‐year experience. Surgery 2002;131:S176‐81. - PubMed
Bazeed 2013 {published data only}
    1. Bazeed SEE, El‐Khyate HR, Swiffy YM, Nafeh HM. Results of endoscopic sclerotherapy with N‐butyl‐2‐cyanoacrylate and ethanolamine oleate in treatment of bleeding gastric varices. Hepatology International 2013;7(Suppl 1):S508.
Huang 2000 {published data only}
    1. Huang YH, Yeh HZ, Chen GH, Chang CS, Wu CY, Poon SK, et al. Endoscopic treatment of bleeding gastric varices by N‐butyl‐2‐cyanoacrylate (Histoacryl) injection: long‐term efficacy and safety. Gastrointestinal Endoscopy 2000;52(2):160‐7. - PubMed
Kim 2006 {published data only}
    1. Kim JW, Baik SK, Kim KH, Kim HJ, Jo KW, Hong JH, et al. Effect of endoscopic sclerotherapy using N‐butyl‐2‐cyanoacrylate in patients with gastric variceal bleeding. Korean Journal of Hepatology 2006;12(3):394‐403. - PubMed
Ljubicic 2011 {published data only}
    1. Ljubicic N, Biscanin A, Nikolic M, Supanc V, Hrabar D, Pavic T, et al. A randomized‐controlled trial of endoscopic treatment of acute esophageal variceal hemorrhage: N‐butyl‐2‐cyanoacrylate injection vs. variceal ligation. Hepato‐Gastroenterology 2011;58(106):438‐43. - PubMed
Maluf‐Filho 2001 {published data only}
    1. Maluf‐Filho F, Sakai P, Ishioka S, Matuguma SE. Endoscopic sclerosis versus cyanoacrylate endoscopic injection for the first episode of variceal bleeding: a prospective, controlled, and randomized study in Child‐Pugh class C patients. Endoscopy 2001;33(5):421‐7. - PubMed
Maluf‐Filho 2008 {published data only}
    1. Marques P, Maluf‐Filho F, Kumar A, Matuguma SE, Sakai P, Ishioka S. Long‐term outcomes of acute gastric variceal bleeding in 48 patients following treatment with cyanoacrylate. Digestive Diseases and Sciences 2008;53(2):544‐50. - PubMed
Mishra 2010 {published data only}
    1. Mishra SR, Sharma BC, Kumar A, Sarin SK. Endoscopic cyanoacrylate injection versus beta‐blocker for secondary prophylaxis of gastric variceal bleed: a randomised controlled trial. Gut 2010;59(6):729‐35. - PubMed
Mishra 2011 {published data only}
    1. Mishra SR, Sharma BC, Kumar A, Sarin SK. Primary prophylaxis of gastric variceal bleeding comparing cyanoacrylate injection and beta‐blockers: a randomized controlled trial. Journal of Hepatology 2011; Vol. 54, issue 6:1161‐7. - PubMed
Ogawa 1999 {published data only}
    1. Ogawa K, Ishikawa S, Naritaka Y, Shimakawa T, Wagatsuma Y, Katsube A, et al. Clinical evaluation of endoscopic injection sclerotherapy using N‐butyl‐2‐cyanoacrylate for gastric variceal bleeding. Journal of Gastroenterology and Hepatology 1999;14(3):245‐50. - PubMed
Oho 1995 {published data only}
    1. Oho K, Iwao T, Sumino M, Toyonaga A, Tanikawa K. Ethanolamine oleate versus butyl cyanoacrylate for bleeding gastric varices: a nonrandomized study. Endoscopy 1995;27(5):349‐54. - PubMed
Santos 2011 {published data only}
    1. Santos MM, Tolentino LH, Rodrigues RA, Nakao FS, Rohr MR, Paulo GA, et al. Endoscopic treatment of esophageal varices in advanced liver disease patients: band ligation versus cyanoacrylate injection. European Journal of Gastroenterology & Hepatology 2011; Vol. 23, issue 1:60‐5. - PubMed
Shiha 2010 {published data only}
    1. Shiha G, Khalil E, Elfakhry A. Endoscopic band ligation compared to cyanoacrylate injection for management of gastric varices: a randomized controlled study. Hepatology International 2010;4(1):264‐5.
Sugimoto 2007 {published data only}
    1. Sugimoto N, Watanabe K, Watanabe K, Ogata S, Shimoda R, Sakata H, et al. Endoscopic hemostasis for bleeding gastric varices treated by combination of variceal ligation and sclerotherapy with N‐butyl‐2‐cyanoacrylate. Journal of Gastroenterology 2007;42(7):528‐32. - PubMed
Thakeb 1995 {published data only}
    1. Thakeb F, Salama Z, Salama H, Abdel Raouf T, Abdel Kader S, Abdel Hamid H. The value of combined use of N‐butyl‐2‐cyanoacrylate and ethanolamine oleate in the management of bleeding esophagogastric varices [see comments]. Endoscopy 1995; Vol. 27, issue 5:358‐64. - PubMed

Additional references

Alexander 2006
    1. Alexander S, Korman MG, Sievert W. Cyanoacrylate in the treatment of gastric varices complicated by multiple pulmonary emboli. Internal Medicine Journal 2006;36(7):462‐64. - PubMed
Arakaki 2003
    1. Arakaki Y, Murakami K, Takahashi K, Sato R, Okimoto T, Ishitobi H, et al. Clinical evaluation of combined endoscopic variceal ligation and sclerotherapy of gastric varices in liver cirrhosis. Endoscopy 2003;35(11):940‐5. - PubMed
Balshem 2011
    1. Balshem H, Helfand M, Schunemann HJ, Oxman AD, Kunz R, Brozek J, et al. GRADE guidelines: 3. Rating the quality of evidence. Journal of Clinical Epidemiology 2011;64(4):401‐6. [PUBMED: 21208779] - PubMed
Belletrutti 2008
    1. Belletrutti PJ, Romagnuolo J, Hilsden RJ, Chen F, Kaplan B, Love J, et al. Endoscopic management of gastric varices: efficacy and outcomes of gluing with N‐butyl‐2‐cyanoacrylate in a North American patient population. Canadian Journal of Gastroenterology 2008;22(11):931‐6. - PMC - PubMed
Bonilha 2011
    1. Bonilha DQ, Correia LM, Monaghan M, Lenz L, Santos M, Libera ED. Prospective study of bacteremia rate after elective band ligation and sclerotherapy with cyanoacrylate for esophageal varices in patients with advanced liver disease. Arquivos De Gastroenterologia 2011;48(4):248‐51. - PubMed
Brok 2008
    1. Brok J, Thorlund K, Gluud C, Wetterslev J. Trial sequential analysis reveals insufficient information size and potentially false positive results in many meta‐analyses. Journal of Clinical Epidemiology 2008;61(8):763‐9. - PubMed
Brok 2009
    1. Brok J, Thorlund K, Wetterslev J, Gluud C. Apparently conclusive meta‐analyses may be inconclusive ‐ trial sequential analysis adjustment of random error risk due to repetitive testing of accumulating data in apparently conclusive neonatal meta‐analyses. International Journal of Epidemiology 2009;38(1):287‐98. - PubMed
Cheng 2007
    1. Cheng LF, Wang ZQ, Li CZ, Cai FC, Huang QY, Linghu EQ, et al. Treatment of gastric varices by endoscopic sclerotherapy using butyl cyanoacrylate: 10 years' experience of 635 cases. Chinese Medical Journal 2007;120(23):2081‐5. - PubMed
Chun 1995
    1. Chun HJ, Hyun JH. A new method of endoscopic variceal ligation‐injection sclerotherapy (EVLIS) for gastric varices. Korean Journal of Internal Medicine 1995;14:730‐5. - PMC - PubMed
Cipolletta 1998
    1. Cipolletta L, Bianco MA, Rotondano G, Piscopo R, Prisco A, Garofano ML. Emergency endoscopic ligation of actively bleeding gastric varices with a detachable snare. Gastrointestinal Endoscopy 1998;47(5):400‐3. - PubMed
D'Amico 2010
    1. D'Amico G, Pagliaro L, Pietrosi G, Tarantino I. Emergency sclerotherapy versus vasoactive drugs for bleeding oesophageal varices in cirrhotic patients. Cochrane Database of Systematic Reviews 2010, Issue 3. [DOI: 10.1002/14651858.CD002233.pub2] - DOI - PMC - PubMed
de Franchis 2010
    1. Franchis R, On behalf of the Baveno V Faculty. Revising consensus in portal hypertension: Report of the Baveno V consensus workshop on methodology of diagnosis and therapy in portal hypertension. Journal of Hepatology 2010;53(4):762‐8. - PubMed
Egger 1997
    1. Egger M, Davey‐Smith G, Schneider M, Minder C. Bias in meta‐analysis detected by a simple, graphical test. BMJ (Clinical Research Ed.) 1997;315:629‐34. - PMC - PubMed
Evrard 2003
    1. Evrard S, Dumonceau JM, Delhaye M, Golstein P, Deviere J, Moine O. Endoscopic histoacryl obliteration versus propranolol in the prevention of esophagogastric variceal rebleeding: a randomized trial. Endoscopy 2003;35:729‐35. - PubMed
Garcia‐Pagán 2013
    1. Garcia‐Pagán JC, Barrufet M, Cardenas A, Escorsell À. Management of Gastric Varices. Clinical Gastroenterology and Hepatology 2013;12(6):919‐28. - PubMed
Garcia‐Tsao 2007
    1. Garcia‐Tsao G, Sanyal AJ, Grace ND, Carey W. Prevention and management of gastroesophageal varices and variceal hemorrhage in cirrhosis. Hepatology 2007;46(3):922‐38. - PubMed
Garcia‐Tsao 2008
    1. Garcia‐Tsao G, Bosch J, Groszmann RJ. Portal hypertension and variceal bleeding ‐ unresolved issues. Summary of an American Association for the study of liver diseases and European Association for the study of the liver single‐topic conference. Hepatology 2008;47(5):1764‐72. - PubMed
Gimson 1991
    1. Gimson AE, Westaby D, Williams R. Endoscopic sclerotherapy in the management of gastric variceal haemorrhage. Journal of Hepatology 1991;13:274‐8. - PubMed
Gluud 2012
    1. Gluud LL, Krag A. Banding ligation versus beta‐blockers for primary prevention in oesophageal varices in adults. Cochrane Database of Systematic Reviews 2012, Issue 8. [DOI: 10.1002/14651858.CD004544.pub2] - DOI - PMC - PubMed
Gluud 2015
    1. Gluud C, Nikolova D, Klingenberg SL. Cochrane Hepato‐Biliary. About Cochrane (Cochrane Review Groups (CRGs)) 2015, Issue 2. Art. No.: LIVER.
Grace 1997
    1. Grace ND. Diagnosis and treatment of gastrointestinal bleeding secondary to portal hypertension. American College of Gastroenterology Practice Parameters Committee. American Journal of Gastroenterology 1997;92(7):1081‐91. - PubMed
GRADEpro 2008 [Computer program]
    1. Brozek J, Oxman A, Schünemann H. GRADEpro. Version 3.2 for Windows. Grade Working Group 2004‐2007, 2008.
Greig 1990
    1. Greig JD, Garden OJ, Anderson JR, Carter DC. Management of gastric variceal haemorrhage. British Journal of Surgery 1990;77:297‐9. - PubMed
Guo 2009
    1. Guo Z, Wu Z, Wang Y. Antacids for preventing oesophagogastric variceal bleeding and rebleeding in cirrhotic patients. Cochrane Database of Systematic Reviews 2009, Issue 1. [DOI: 10.1002/14651858.CD005443.pub2] - DOI - PMC - PubMed
Guyatt 2008
    1. Guyatt GH, Oxman AD, Kunz R, Vist GE, Falck‐Ytter Y, Schünemann HJ, GRADE Working Group. Rating quality of evidence and strength of recommendations: what is "quality of evidence" and why is it important to clinicians?. BMJ (Clinical Research Ed.) 2008;336(7653):1106‐10. - PMC - PubMed
Guyatt 2011a
    1. Guyatt G, Oxman AD, Akl EA, Kunz R, Vist G, Brozek J, et al. GRADE guidelines: 1. Introduction ‐ GRADE evidence profiles and summary of findings tables. Journal of Clinical Epidemiology 2011;64(4):383‐94. [PUBMED: 21195583] - PubMed
Guyatt 2011b
    1. Guyatt GH, Oxman AD, Kunz R, Atkins D, Brozek J, Vist G, et al. GRADE guidelines: 2. Framing the question and deciding on important outcomes. Journal of Clinical Epidemiology 2011;64(4):395‐400. [PUBMED: 21194891] - PubMed
Guyatt 2011c
    1. Guyatt GH, Oxman AD, Vist G, Kunz R, Brozek J, Alonso‐Coello P, et al. GRADE guidelines: 4. Rating the quality of evidence ‐ study limitations (risk of bias). Journal of Clinical Epidemiology 2011;64(4):407‐15. [PUBMED: 21247734] - PubMed
Guyatt 2011d
    1. Guyatt GH, Oxman AD, Montori V, Vist G, Kunz R, Brozek J, et al. GRADE guidelines: 5. Rating the quality of evidence ‐ publication bias. Journal of Clinical Epidemiology 2011;64(12):1277‐82. [PUBMED: 21802904] - PubMed
Guyatt 2011e
    1. Guyatt GH, Oxman AD, Kunz R, Brozek J, Alonso‐Coello P, Rind D, et al. GRADE guidelines 6. Rating the quality of evidence ‐ imprecision. Journal of Clinical Epidemiology 2011;64(12):1283‐93. [PUBMED: 21839614] - PubMed
Guyatt 2011f
    1. Guyatt GH, Oxman AD, Kunz R, Woodcock J, Brozek J, Helfand M, et al. GRADE guidelines: 7. Rating the quality of evidence ‐ inconsistency. Journal of Clinical Epidemiology 2011;64(12):1294‐302. [PUBMED: 21803546] - PubMed
Guyatt 2011g
    1. Guyatt GH, Oxman AD, Kunz R, Woodcock J, Brozek J, Helfand M, et al. GRADE guidelines: 8. Rating the quality of evidence ‐ indirectness. Journal of Clinical Epidemiology 2011;64(12):1303‐10. [PUBMED: 21802903] - PubMed
Guyatt 2011h
    1. Guyatt GH, Oxman AD, Sultan S, Glasziou P, Akl EA, Alonso‐Coello P, et al. GRADE guidelines: 9. Rating up the quality of evidence. Journal of Clinical Epidemiology 2011;64(12):1311‐6. [PUBMED: 21802902] - PubMed
Guyatt 2013a
    1. Guyatt G, Oxman AD, Sultan S, Brozek J, Glasziou P, Alonso‐Coello P, et al. GRADE guidelines: 11. Making an overall rating of confidence in effect estimates for a single outcome and for all outcomes. Journal of Clinical Epidemiology 2013;66(2):151‐7. [PUBMED: 22542023] - PubMed
Guyatt 2013b
    1. Guyatt GH, Oxman AD, Santesso N, Helfand M, Vist G, Kunz R, et al. GRADE guidelines: 12. Preparing summary of findings tables ‐ binary outcomes. Journal of Clinical Epidemiology 2013;66(2):158‐72. [PUBMED: 22609141] - PubMed
Guyatt 2013c
    1. Guyatt GH, Thorlund K, Oxman AD, Walter SD, Patrick D, Furukawa TA, et al. GRADE guidelines: 13. Preparing summary of findings tables and evidence profiles ‐ continuous outcomes. Journal of Clinical Epidemiology 2013;66(2):173‐83. [PUBMED: 23116689] - PubMed
Harada 1997
    1. Harada T, Yoshida T, Shigemitsu T, Takeo Y, Tada M, Okita K. Therapeutic results of endoscopic variceal ligation for acute bleeding of oesophageal and gastric varices. Journal of Gastroenterology and Hepatology 1997;12:331‐5. - PubMed
Higgins 2003
    1. Higgins JP, Thompson SG, Deeks JJ, Altman D. Measuring inconsistency in meta‐analyses. BMJ (Clinical Research Ed.) 2003;327:557‐60. - PMC - PubMed
Higgins 2011
    1. Higgins JPT, Green S (editors). Cochrane Handbook for Systematic Reviews of Interventions Version 5.1.0 [updated March 2011]. The Cochrane Collaboration, 2011. Available from www.cochrane‐handbook.org.
ICH‐GCP 1997
    1. International Conference on Harmonisation Expert Working Group. International conference on harmonisation of technical requirements for registration of pharmaceuticals for human use. ICH harmonised tripartite guideline. Guideline for good clinical practice CFR & ICH Guidelines. Vol. 1, Pennsylvania: Barnett International/PAREXEL, 1997.
Irani 2011
    1. Irani S, Kowdley K, Kozarek R. Gastric varices: an updated review of management. Journal of Clinical Gastroenterology 2011;45(2):133‐48. - PubMed
Kitano 1989
    1. Kitano S, Hashizume M, Yamaga H, Wada H, Iso Y, Iwanaga T, et al. Human thrombin plus 5 per cent ethanolamine oleate injected to sclerose oesophageal varices: a prospective randomized trial. British Journal of Surgery 1989;76:715‐8. - PubMed
Kjaergard 2001
    1. Kjaergard LL, Villumsen J, Gluud C. Reported methodologic quality and discrepancies between large and small randomized trials in meta‐analyses. Annals of Internal Medicine 2001;135(11):982‐9. - PubMed
Korula 1991
    1. Korula J, Chin K, Ko Y, Yamada S. Demonstration of two distinct subsets of gastric varices. Observations during a seven‐year study of endoscopic sclerotherapy. Digestive Diseases and Sciences 1991;36(3):303‐9. - PubMed
Laine 1995
    1. Laine L, Cook D. Endoscopic ligation compared with sclerotherapy for treatment of esophageal variceal bleeding. A meta‐analysis. Annals of Internal Medicine 1995;123(4):280‐7. - PubMed
Lee 2002
    1. Lee MS, Cho JY, Cheon YK, Ryu CB, Moon JH, Cho YD, et al. Use of detachable snares and elastic bands for endoscopic control of bleeding from large gastric varices. Gastrointestinal Endoscopy 2002;56(1):83‐8. - PubMed
Lundh 2012
    1. Lundh A, Sismondo S, Lexchin J, Busuioc OA, Bero L. Industry sponsorship and research outcome. Cochrane Database of Systematic Reviews 2012, Issue 12. [DOI: 10.1002/14651858.MR000033.pub2] - DOI - PubMed
McCormick 1994
    1. McCormick PA, Dick R, Panagou EB, Chin JKT, Greenslade L, Burroughs AK. Emergency transjugular intrahepatic portasystemic stent shunting as salvage treatment for uncontrolled variceal bleeding. British Journal of Surgery 1994;81:1324‐7. - PubMed
Moher 1998
    1. Moher D, Pham B, Jones A, Cook DJ, Jadad AR, Moher M, et al. Does quality of reports of randomised trials affect estimates of intervention efficacy reported in meta‐analyses?. Lancet 1998;352:609‐13. - PubMed
Mustafa 2013
    1. Mustafa RA, Santesso N, Brozek J, Akl EA, Walter SD, Norman G, et al. The GRADE approach is reproducible in assessing the quality of evidence of quantitative evidence syntheses. Journal of Clinical Epidemiology 2013;66(7):736‐42. [PUBMED: 23623694] - PubMed
Rengstorff 2004
    1. Rengstorff DS, Binmoeller KF. A pilot study of 2‐octyl cyanoacrylate injection for treatment of gastric fundal varices in humans. Gastrointestinal Endoscopy 2004;59:553‐8. - PubMed
RevMan 2014 [Computer program]
    1. The Nordic Cochrane Centre, The Cochrane Collaboration. Review Manager (RevMan). Version 5.3. Copenhagen: The Nordic Cochrane Centre, The Cochrane Collaboration, 2014.
Rosch 1998
    1. Rosch W, Rexroth G. UCTN: pulmonary, cerebral and coronary emboli during bucrylate injection of bleeding fundic varices. Endoscopy 1998;30:S89‐90. - PubMed
Royle 2003
    1. Royle P, Milne R. Literature searching for randomized controlled trials used in Cochrane reviews: rapid versus exhaustive searches. International Journal of Technology Assessment in Health Care 2003;19(4):591‐603. - PubMed
Sarin 1992
    1. Sarin SK, Lahoti D, Saxena SP, Murthy NS, Makwana UK. Prevalence, classification and natural history of gastric varices: a long‐term follow‐up study in 568 portal hypertension patients. Hepatology 1992;16:1343‐9. - PubMed
Sarin 1997
    1. Sarin SK. Long‐term follow‐up of gastric variceal sclerotherapy: an eleven‐year experience. Gastrointestinal Endoscopy 1997;46:8‐14. - PubMed
Sarin 2001
    1. Sarin SK, Jain AK, Jain M, Gupta R. A randomized controlled trial of cyanoacrylate versus alcohol injection in patients with isolated fundic varices. American Journal of Gastroenterology 2002;97:1010‐5. - PubMed
Savović 2012a
    1. Savović J, Jones HE, Altman DG, Harris RJ, Jüni P, Pildal J, et al. Influence of reported study design characteristics on intervention effect estimates from randomized, controlled trials. Health Technology Assessment 2012;16(35):1‐82. - PubMed
Savović 2012b
    1. Savović J, Jones HE, Altman DG, Harris RJ, Jüni P, Pildal J, et al. Influence of reported study design characteristics on intervention effect estimates from randomized, controlled trials. Annals of Internal Medicine 2012;157(6):429‐38. - PubMed
Schulz 1995
    1. Schulz KF, Chalmers I, Hayes RJ, Altman DG. Empirical evidence of bias. Dimensions of methodological quality associated with estimates of treatment effects in controlled trials. JAMA 1995;273:408‐12. - PubMed
Schuman 1987
    1. Schuman BM, Beckman JW, Tedesco FJ, Griffin JW Jr, Assad RT. Complications of endoscopic injection sclerotherapy: a review. American Journal of Gastroenterology 1987;82(9):823‐30. - PubMed
Sharara 2001
    1. Sharara AI, Rockey DC. Gastroesophageal hemorrhage. New England Journal of Medicine 2001;345:669‐81. - PubMed
Shiha 1999
    1. Shiha G, El‐Sayed SS. Gastric variceal ligation: a new technique. Gastrointestinal Endoscopy 1999;49:437‐41. - PubMed
Soehendra 1986
    1. Soehendra N, Nam VC, Grimm H, Kempeneers I. Endoscopic obliteration of large esophagogastric varices with bucrylate. Endoscopy 1986;18:25‐6. - PubMed
Takeuchi 1996
    1. Takeuchi M, Nakai Y, Syu A, Okamoto E, Fujimoto J. Endoscopic ligation of gastric varices. Lancet 1996;348:1038. - PubMed
Thorlund 2009
    1. Thorlund K, Devereaux PJ, Wetterslev J, Guyatt G, Ioannidis JP, Thabane L, et al. Can trial sequential monitoring boundaries reduce spurious inferences from meta‐analyses. International Journal of Epidemiology 2009;38(1):276‐86. - PubMed
Thorlund 2010
    1. Thorlund K, Anema A, Mills E. Interpreting meta‐analysis according to the adequacy of sample size. An example using isoniazid chemoprophylaxis for tuberculosis in purified protein derivative negative HIV‐infected individuals. Clinical Epidemiology 2010;2:57‐66. - PMC - PubMed
Thorlund 2011
    1. Thorlund K, Engstrøm J, Wetterslev J, Brok J, Imberger G, Gluud C. User manual for Trial Sequential Analysis (TSA). ctu.dk/tsa/files/tsa_manual.pdf 2011 (accessed 27 January 2015).
TSA 2011 [Computer program]
    1. Copenhagen Trial Unit. TSA ‐ Trial Sequential Analysis. Version 0.9 Beta. Copenhagen: Copenhagen Trial Unit, 2011.
Turler 2001
    1. Turler A, Wolff M, Dorlars D. Embolic and septic complications after sclerotherapy of fundic varices with cyanoacrylate. Gastrointestinal Endoscopy 2001;53:228‐30. - PubMed
Upadhyay 2005
    1. Upadhyay AP, Ananthasivan R, Radhakrishnan S, Zubaidi G. Cortical blindness and acute myocardial infarction following injection of bleeding gastric varices with cyanoacrylate glue. Endoscopy 2005;37(10):1034. - PubMed
Wetterslev 2008
    1. Wetterslev J, Thorlund K, Brok J, Gluud C. Trial sequential analysis may establish when firm evidence is reached in cumulative meta‐analysis. Journal of Clinical Epidemiology 2008;61(1):64‐75. - PubMed
Wetterslev 2009
    1. Wetterslev J, Thorlund K, Brok J, Gluud C. Estimating required information size by quantifying diversity in random‐effects model meta‐analyses. BMC Medical Research Methodology 2009;9:86. - PMC - PubMed
Wood 2008
    1. Wood L, Egger M, Gluud LL, Schulz KF, Jüni P, Altman DG, et al. Empirical evidence of bias in treatment effect estimates in controlled trials with different interventions and outcomes: meta‐epidemiological study. BMJ (Clinical Research Ed.) 2008;336(7644):601‐5. - PMC - PubMed
Wu 2002
    1. Wu CY, Yeh HZ, Chen GH. Pharmacologic efficacy in gastric variceal re bleeding and survival: including multivariate analysis. Journal of Clinical Gastroenterology 2002;35:127‐32. - PubMed
Yang 2002
    1. Yang WL, Tripathi D, Therapondos G, Todd A, Hayes PC. Endoscopic use of human thrombin in bleeding gastric varices. American Journal of Gastroenterology 2002;97:1381‐5. - PubMed
Yoshida 1999
    1. Yoshida T, Harada T, Shigemitsu T, Takeo Y, Miyazaki S, Okita K. Endoscopic management of gastric varices using a detachable snare and simultaneous endoscopic sclerotherapy and O‐ring ligation. Journal of Gastroenterology and Hepatology 1999;14(7):730‐5. - PubMed

References to other published versions of this review

Castellanos 2012
    1. Castellanos ER, Seron P, Gisbert JP, Bonfill Cosp X. Endoscopic injection of cyanoacrylate glue versus other endoscopic procedures for acute bleeding gastric varices in patients with portal hypertension. Cochrane Database of Systematic Reviews 2012, Issue 10. [DOI: 10.1002/14651858.CD010180] - DOI - PMC - PubMed

Publication types

MeSH terms