Therapies for bleeding gastric varices: is the fog starting to clear?

Abstract

Current guidelines recommend endoscopic therapy as first-line treatment for bleeding gastric varices, with the option of a transjugular intrahepatic portosystemic stent-shunt where endoscopic therapy is not available. Current guidelines recommend endoscopic therapy as first-line treatment for bleeding gastric varices, with the option of a transjugular intrahepatic portosystemic stent-shunt where endoscopic therapy is not available. The prevalence of gastric varices is 4% in patients with cirrhosis who have never bled,1Sarin S.K. Lahoti D. Saxena S.P. et al.Prevalence, classification and natural history of gastric varices: a long-term follow-up study in 568 portal hypertension patients.Hepatology. 1992; 16: 1343-1349Crossref PubMed Scopus (831) Google Scholar although it has also been reported that 25% of patients with cirrhosis have gastric varices at screening endoscopy.2Kim T. Shijo H. Kokawa H. et al.Risk factors for hemorrhage from gastric fundal varices.Hepatology. 1997; 25: 307-312Crossref PubMed Scopus (295) Google Scholar The risk of bleeding from gastric varices is also approximately half that of bleeding from esophageal varices.1Sarin S.K. Lahoti D. Saxena S.P. et al.Prevalence, classification and natural history of gastric varices: a long-term follow-up study in 568 portal hypertension patients.Hepatology. 1992; 16: 1343-1349Crossref PubMed Scopus (831) Google Scholar, 3de Franchis R. Primignani M. Natural history of portal hypertension in patients with cirrhosis.Clin Liver Dis. 2001; 5: 645-663Abstract Full Text Full Text PDF PubMed Scopus (276) Google Scholar Conversely, mortality from gastric variceal bleeding is higher than esophageal variceal bleeding, with the worst outcomes for isolated type 1 varices.1Sarin S.K. Lahoti D. Saxena S.P. et al.Prevalence, classification and natural history of gastric varices: a long-term follow-up study in 568 portal hypertension patients.Hepatology. 1992; 16: 1343-1349Crossref PubMed Scopus (831) Google Scholar, 3de Franchis R. Primignani M. Natural history of portal hypertension in patients with cirrhosis.Clin Liver Dis. 2001; 5: 645-663Abstract Full Text Full Text PDF PubMed Scopus (276) Google Scholar The optimal therapy for bleeding gastric varices remains controversial because there are few randomized, controlled studies. Current guidelines recommend endoscopic therapy as first-line treatment for bleeding gastric varices, with the option of transjugular intrahepatic portosystemic stent-shunt (TIPSS) where endoscopic therapy is not available.4de Franchis R. Evolving consensus in portal hypertension. Report of the Baveno IV consensus workshop on methodology of diagnosis and therapy in portal hypertension.J Hepatol. 2005; 43: 167-176Abstract Full Text Full Text PDF PubMed Scopus (935) Google Scholar, 5Garcia-Tsao G. Sanyal A.J. Grace N.D. et al.Prevention and management of gastroesophageal varices and variceal hemorrhage in cirrhosis.Hepatology. 2007; 46: 922-938Crossref PubMed Scopus (1322) Google Scholar When interpreting results from studies, it is important to identify the number of patients with active bleeding at endoscopy. Active bleeding is associated with worse outcomes6Ben Ari Z. Cardin F. McCormick A.P. et al.A predictive model for failure to control bleeding during acute variceal haemorrhage.J Hepatol. 1999; 31: 443-450Abstract Full Text Full Text PDF PubMed Scopus (112) Google Scholar and is particularly challenging with gastric varices, where bleeding can be torrential. Currently, the endoscopic therapeutic options for gastric variceal bleeding include band ligation, tissue adhesives, and thrombin. The greatest evidence exists for tissues adhesives, which are recommended as first-line endoscopic therapies in both the American Association for the Study of Liver Diseases guidelines and by the Baveno IV consensus.4de Franchis R. Evolving consensus in portal hypertension. Report of the Baveno IV consensus workshop on methodology of diagnosis and therapy in portal hypertension.J Hepatol. 2005; 43: 167-176Abstract Full Text Full Text PDF PubMed Scopus (935) Google Scholar, 5Garcia-Tsao G. Sanyal A.J. Grace N.D. et al.Prevention and management of gastroesophageal varices and variceal hemorrhage in cirrhosis.Hepatology. 2007; 46: 922-938Crossref PubMed Scopus (1322) Google Scholar Cyanoacrylate (N-butyl-2-cyanoacrylate, “glue”) undergoes rapid polymerization on contact with living tissues. Therefore, meticulous adherence to technique is crucial, not only to ensure successful safe therapy, but also to prevent irreversible damage to endoscopes caused by polymerization. Initial hemostasis rates of 88% to 100% have been achieved in recent uncontrolled studies.7Fry L.C. Neumann H. Olano C. et al.Efficacy, complications and clinical outcomes of endoscopic sclerotherapy with N-butyl-2-cyanoacrylate for bleeding gastric varices.Dig Dis. 2008; 26: 300-303Crossref PubMed Scopus (43) Google Scholar, 8Seewald S. Ang T.L. Imazu H. et al.A standardized injection technique and regimen ensures success and safety of N-butyl-2-cyanoacrylate injection for the treatment of gastric fundal varices (with videos).Gastrointest Endosc. 2008; 68: 447-454Abstract Full Text Full Text PDF PubMed Scopus (125) Google Scholar, 9Cheng L.F. Wang Z.Q. Li C.Z. et al.Treatment of gastric varices by endoscopic sclerotherapy using butyl cyanoacrylate: 10 years' experience of 635 cases.Chin Med J (Engl). 2007; 120: 2081-2085PubMed Google Scholar Two randomized, controlled trials have compared cyanoacrylate with variceal band ligation,10Lo G.H. Lai K.H. Cheng J.S. et al.A prospective, randomized trial of butyl cyanoacrylate injection versus band ligation in the management of bleeding gastric varices.Hepatology. 2001; 33: 1060-1064Crossref PubMed Scopus (384) Google Scholar, 11Tan P.C. Hou M.C. Lin H.C. et al.A randomized trial of endoscopic treatment of acute gastric variceal hemorrhage: N-butyl-2-cyanoacrylate injection versus band ligation.Hepatology. 2006; 43: 690-697Crossref PubMed Scopus (253) Google Scholar with mixed results for initial hemostasis, although the outcome was in favor of cyanoacrylate for rebleeding rates (22% versus 44% and 31% versus 54%).10Lo G.H. Lai K.H. Cheng J.S. et al.A prospective, randomized trial of butyl cyanoacrylate injection versus band ligation in the management of bleeding gastric varices.Hepatology. 2001; 33: 1060-1064Crossref PubMed Scopus (384) Google Scholar, 11Tan P.C. Hou M.C. Lin H.C. et al.A randomized trial of endoscopic treatment of acute gastric variceal hemorrhage: N-butyl-2-cyanoacrylate injection versus band ligation.Hepatology. 2006; 43: 690-697Crossref PubMed Scopus (253) Google Scholar There were no differences in mortality rates. An interesting development is the use of EUS to guide the injection of cyanoacrylate. A recent article reported on the use of EUS to guide injection of feeding perforator veins with excellent results.12Romero-Castro R. Pellicer-Bautista F.J. Jimenez-Saenz M. et al.EUS-guided injection of cyanoacrylate in perforating feeding veins in gastric varices: results in 5 cases.Gastrointest Endosc. 2007; 66: 402-407Abstract Full Text Full Text PDF PubMed Scopus (139) Google Scholar However, great care is required with the technique to prevent damage to expensive equipment, and this risk may alone prevent the widespread use of EUS-guided cyanoacrylate injection. Complications of tissue adhesives include embolization, with case reports of cerebral stroke, portal vein embolization, splenic infarction, coronary emboli, and a series demonstrating nonfatal pulmonary emboli in 4.6% of cases.13Roesch W. Rexroth G. Pulmonary, cerebral and coronary emboli during bucrylate injection of bleeding fundic varices.Endoscopy. 1998; 30: S89-S90PubMed Google Scholar, 14Hwang S.S. Kim H.H. Park S.H. et al.N-butyl-2-cyanoacrylate pulmonary embolism after endoscopic injection sclerotherapy for gastric variceal bleeding.J Comput Assist Tomogr. 2001; 25: 16-22Crossref PubMed Scopus (105) Google Scholar, 15Palejwala A.A. Smart H.L. Hughes M. Multiple pulmonary glue emboli following gastric variceal obliteration.Endoscopy. 2000; 32: S1-S2Crossref PubMed Google Scholar, 16Yu L.K. Hsu C.W. Tseng J.H. et al.Splenic infarction complicated by splenic artery occlusion after N-butyl-2-cyanoacrylate injection for gastric varices: case report.Gastrointest Endosc. 2005; 61: 343-345Abstract Full Text Full Text PDF PubMed Scopus (36) Google Scholar When embolic phenomena occur, fatalities have been reported.7Fry L.C. Neumann H. Olano C. et al.Efficacy, complications and clinical outcomes of endoscopic sclerotherapy with N-butyl-2-cyanoacrylate for bleeding gastric varices.Dig Dis. 2008; 26: 300-303Crossref PubMed Scopus (43) Google Scholar, 17Joshi D. Wendon J. Auzinger G. Stroke after injection of gastric varices.Liver Int. 2009; 29: 374Crossref PubMed Scopus (8) Google Scholar, 18Marion-Audibert A.M. Schoeffler M. Wallet F. et al.Acute fatal pulmonary embolism during cyanoacrylate injection in gastric varices.Gastroenterol Clin Biol. 2008; 32: 926-930Crossref PubMed Scopus (21) Google Scholar Thrombin is a promising agent, and this journal recently published a small UK-based study that used bovine thrombin for gastric varices.19Ramesh J. Limdi J.K. Sharma V. et al.The use of thrombin injections in the management of bleeding gastric varices: a single-center experience.Gastrointest Endosc. 2008; 68: 877-882Abstract Full Text Full Text PDF PubMed Scopus (56) Google Scholar The initial hemostasis rate was 92%, and remarkably there were no patients who rebled from gastric varices. Other uncontrolled studies also had promising results.20Datta D. Vlavianos P. Alisa A. et al.Use of fibrin glue (beriplast) in the management of bleeding gastric varices.Endoscopy. 2003; 35: 675-678Crossref PubMed Scopus (54) Google Scholar, 21Heneghan M.A. Byrne A. Harrison P.M. An open pilot study of the effects of a human fibrin glue for endoscopic treatment of patients with acute bleeding from gastric varices.Gastrointest Endosc. 2002; 56: 422-426Abstract Full Text Full Text PDF PubMed Google Scholar, 22McAvoy N.C. Hayes P.C. The use of human thrombin for the treatment of gastric and ectopic varices.Gut. 2006; 55: A5Google Scholar, 23Przemioslo R.T. McNair A. Williams R. Thrombin is effective in arresting bleeding from gastric variceal hemorrhage.Dig Dis Sci. 1999; 44: 778-781Crossref PubMed Scopus (63) Google Scholar, 24Snobl J. Van Buuren H.R. Van Blankenstein M. Endoscopic injection using thrombin: An effective and safe method for controlling oesophagogastric variceal bleeding.Gastroenterology. 1992; 102 ([abstract]): A891Google Scholar, 25Williams S.G. Peters R.A. Westaby D. Thrombin—an effective treatment for gastric variceal haemorrhage.Gut. 1994; 35: 1287-1289Crossref PubMed Scopus (91) Google Scholar, 26Yang W.L. Tripathi D. Therapondos G. et al.Endoscopic use of human thrombin in bleeding gastric varices.Am J Gastroenterol. 2002; 97: 1381-1385Crossref PubMed Google Scholar Clearly, comparison with other therapies in controlled studies is required before thrombin is universally accepted, although the published studies so far have included more than 200 patients.19Ramesh J. Limdi J.K. Sharma V. et al.The use of thrombin injections in the management of bleeding gastric varices: a single-center experience.Gastrointest Endosc. 2008; 68: 877-882Abstract Full Text Full Text PDF PubMed Scopus (56) Google Scholar, 20Datta D. Vlavianos P. Alisa A. et al.Use of fibrin glue (beriplast) in the management of bleeding gastric varices.Endoscopy. 2003; 35: 675-678Crossref PubMed Scopus (54) Google Scholar, 21Heneghan M.A. Byrne A. Harrison P.M. An open pilot study of the effects of a human fibrin glue for endoscopic treatment of patients with acute bleeding from gastric varices.Gastrointest Endosc. 2002; 56: 422-426Abstract Full Text Full Text PDF PubMed Google Scholar, 22McAvoy N.C. Hayes P.C. The use of human thrombin for the treatment of gastric and ectopic varices.Gut. 2006; 55: A5Google Scholar, 23Przemioslo R.T. McNair A. Williams R. Thrombin is effective in arresting bleeding from gastric variceal hemorrhage.Dig Dis Sci. 1999; 44: 778-781Crossref PubMed Scopus (63) Google Scholar, 24Snobl J. Van Buuren H.R. Van Blankenstein M. Endoscopic injection using thrombin: An effective and safe method for controlling oesophagogastric variceal bleeding.Gastroenterology. 1992; 102 ([abstract]): A891Google Scholar, 25Williams S.G. Peters R.A. Westaby D. Thrombin—an effective treatment for gastric variceal haemorrhage.Gut. 1994; 35: 1287-1289Crossref PubMed Scopus (91) Google Scholar, 26Yang W.L. Tripathi D. Therapondos G. et al.Endoscopic use of human thrombin in bleeding gastric varices.Am J Gastroenterol. 2002; 97: 1381-1385Crossref PubMed Google Scholar The ease of injection and lack of embolic phenomena are potential benefits. Interventional radiologists have come to the rescue of many endoscopists when managing bleeding varices. TIPSS has revolutionalized the management of esophageal varices, and the evidence so far suggests that TIPSS is effective in the prevention of rebleeding from gastric varices.27Tripathi D. Therapondos G. Jackson E. et al.The role of the transjugular intrahepatic portosystemic stent shunt (TIPSS) in the management of bleeding gastric varices: clinical and haemodynamic correlations.Gut. 2002; 51: 270-274Crossref PubMed Scopus (178) Google Scholar It has been demonstrated that patients with large gastric varices have lower portal pressure than those with esophageal varices,27Tripathi D. Therapondos G. Jackson E. et al.The role of the transjugular intrahepatic portosystemic stent shunt (TIPSS) in the management of bleeding gastric varices: clinical and haemodynamic correlations.Gut. 2002; 51: 270-274Crossref PubMed Scopus (178) Google Scholar, 28Chao Y. Lin H.C. Lee F.Y. et al.Hepatic hemodynamic features in patients with esophageal or gastric varices.J Hepatol. 1993; 19: 85-89Abstract Full Text PDF PubMed Scopus (41) Google Scholar, 29Stanley A.J. Jalan R. Ireland H.M. et al.A comparison between gastric and oesophageal variceal haemorrhage treated with transjugular intrahepatic portosystemic stent shunt (TIPSS).Aliment Pharmacol Ther. 1997; 11: 171-176Crossref PubMed Scopus (58) Google Scholar possibly as a result of the development of gastrorenal portosystemic shunts.30Watanabe K. Kimura K. Matsutani S. et al.Portal hemodynamics in patients with gastric varices. A study in 230 patients with esophageal and/or gastric varices using portal vein catheterization.Gastroenterology. 1988; 95: 434-440Abstract PubMed Google Scholar Sanyal et al31Sanyal A.J. Freedman A.M. Luketic V.A. et al.The natural history of portal hypertension after transjugular intrahepatic portosystemic shunts.Gastroenterology. 1997; 112: 889-898Abstract Full Text Full Text PDF PubMed Scopus (237) Google Scholar studied the effect of TIPSS on gastric (isolated type 1) and esophageal varices. Despite a significant reduction in the size of esophageal varices and decrease in the portal pressure gradient (PPG) to less than 12 mm Hg, half of the patients with gastric varices had persistent isolated varices, mainly as a result of splenorenal shunts. These differences may reflect the fact that gastric varices are true veins with a large volume, which contributes to increased wall tension.32Polio J. Groszmann R.J. Hemodynamic factors involved in the development and rupture of esophageal varices: a pathophysiologic approach to treatment.Semin Liver Dis. 1986; 6: 318-331Crossref PubMed Scopus (184) Google Scholar The latter may explain why gastric varices bleed despite lower portal pressures. The efficacy of TIPSS for bleeding gastric varices is likely to be related to a decrease in the PPG rather than a decrease in the size of varices at endoscopy. Indeed, it may be necessary to aim for a lower a PPG after TIPSS insertion for gastric variceal bleeding. This is supported by a study in which most patients who rebled from gastric varices after TIPSS insertion had a PPG greater than 7 mm Hg.27Tripathi D. Therapondos G. Jackson E. et al.The role of the transjugular intrahepatic portosystemic stent shunt (TIPSS) in the management of bleeding gastric varices: clinical and haemodynamic correlations.Gut. 2002; 51: 270-274Crossref PubMed Scopus (178) Google Scholar In the past decade, uncontrolled studies have investigated the use of TIPSS in the management of variceal bleeding either from gastric varices alone33Barange K. Peron J.M. Imani K. et al.Transjugular intrahepatic portosystemic shunt in the treatment of refractory bleeding from ruptured gastric varices.Hepatology. 1999; 30: 1139-1143Crossref PubMed Scopus (147) Google Scholar or gastric compared with esophageal varices.27Tripathi D. Therapondos G. Jackson E. et al.The role of the transjugular intrahepatic portosystemic stent shunt (TIPSS) in the management of bleeding gastric varices: clinical and haemodynamic correlations.Gut. 2002; 51: 270-274Crossref PubMed Scopus (178) Google Scholar, 34Chau T.N. Patch D. Chan Y.W. et al.“Salvage” transjugular intrahepatic portosystemic shunts: gastric fundal compared with esophageal variceal bleeding.Gastroenterology. 1998; 114: 981-987Abstract Full Text PDF PubMed Google Scholar In a study of 28 patients with cirrhosis with bleeding fundal varices, the 96% success rate at initial hemostasis and the 29% rebleeding rate were similar to those with esophageal variceal bleeding.34Chau T.N. Patch D. Chan Y.W. et al.“Salvage” transjugular intrahepatic portosystemic shunts: gastric fundal compared with esophageal variceal bleeding.Gastroenterology. 1998; 114: 981-987Abstract Full Text PDF PubMed Google Scholar Barange et al33Barange K. Peron J.M. Imani K. et al.Transjugular intrahepatic portosystemic shunt in the treatment of refractory bleeding from ruptured gastric varices.Hepatology. 1999; 30: 1139-1143Crossref PubMed Scopus (147) Google Scholar studied 32 cirrhotic patients with bleeding gastric varices and observed a high rate of hemostasis of 90% with a 1-year cumulative rebleeding rate of 31%. In another small study of predominantly fundal variceal bleeding, there was no significant difference in the rate of hemostasis between gastric and esophageal variceal bleeding.35Rees C.J. Nylander D.L. Thompson N.P. et al.Do gastric and oesophageal varices bleed at different portal pressures and is TIPS an effective treatment?.Liver. 2000; 20: 253-256Crossref PubMed Scopus (36) Google Scholar In a large retrospective series, TIPSS was used in 40 cirrhotic patients with predominantly fundal variceal bleeding and in 232 patients with esophageal variceal bleeding.27Tripathi D. Therapondos G. Jackson E. et al.The role of the transjugular intrahepatic portosystemic stent shunt (TIPSS) in the management of bleeding gastric varices: clinical and haemodynamic correlations.Gut. 2002; 51: 270-274Crossref PubMed Scopus (178) Google Scholar The rates of variceal rebleeding were similar (20% vs 15%). The complications of TIPSS, such as encephalopathy and shunt dysfunction, were also similar. A noteworthy finding was a lower mortality rate in patients who bled from gastric varices (5-year mortality of 49.5% vs 74.9%, P < .05). Furthermore, the difference in mortality was confined to those patients who bled from gastric varices at a PPG greater than 12 mm Hg. The reason for this difference was not clear, but one possibility is that the PPG may be a direct predictor of mortality. The patients in this study who bled from gastric varices had a significantly lower PPG. Studies indicate a favorable outcome in patients who bleed at lower portal pressures, particularly if measured shortly after a variceal bleed.36Moitinho E. Escorsell A. Bandi J.C. et al.Prognostic value of early measurements of portal pressure in acute variceal bleeding.Gastroenterology. 1999; 117: 626-631Abstract Full Text Full Text PDF PubMed Scopus (356) Google Scholar It is clear that both tissue adhesives and TIPSS can be highly effective in the management of bleeding gastric varices. However, to date, there is only one randomized, controlled trial comparing both therapies.37Lo G.H. Liang H.L. Chen W.C. 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: 679-685Crossref PubMed Scopus (233) Google Scholar This is in contrast to more than 10 controlled studies comparing endoscopic therapies with TIPSS for esophageal variceal bleeding, with results favoring TIPSS for rebleeding at the expense of increased encephalopathy.38Zheng M. Chen Y. Bai J. et al.Transjugular intrahepatic portosystemic shunt versus endoscopic therapy in the secondary prophylaxis of variceal rebleeding in cirrhotic patients: meta-analysis update.J Clin Gastroenterol. 2008; 42: 507-516Crossref PubMed Scopus (98) Google Scholar Lo et al37Lo G.H. Liang H.L. Chen W.C. 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: 679-685Crossref PubMed Scopus (233) Google Scholar randomized patients after control of gastric variceal bleeding to TIPSS (n=35) or cyanoacrylate (n=37). Despite greater variceal eradication in the cyanoacrylate arm, the rebleeding rate was significantly higher with endoscopic therapy (38% vs 11%). There was no difference in survival or complication rates. It is important to emphasize that the efficacy of the treatments for secondary prophylaxis was studied and not initial hemostasis of actively bleeding varices. There is another United Kingdom-based retrospective study that provides more information on efficacy of therapies in active bleeding.39Mahadeva S. Bellamy M.C. Kessel D. et al.Cost-effectiveness of N-butyl-2-cyanoacrylate (histoacryl) glue injections versus transjugular intrahepatic portosystemic shunt in the management of acute gastric variceal bleeding.Am J Gastroenterol. 2003; 98: 2688-2693Crossref PubMed Scopus (99) Google Scholar This study compared cyanoacrylate (n=23) with TIPSS (n=20) in patients with cirrhosis who bled from gastric varices. Active bleeding was noted in 21 patients in total. Both therapies were highly effective in initial hemostasis. The main difference was the reduced rebleeding rate with TIPSS (35% vs 20%). There was no difference in survival. Severe encephalopathy was noted in 2 patients after TIPSS, and 1 patient died after embolization of cyanoacrylate to the chest. However, TIPSS was significantly more expensive. A major limitation of this study is the short follow-up of just 6 months with cyanoacrylate and 12 months with TIPSS, which must be taken into account when interpreting the findings. Therefore, the somewhat limited early evidence suggested that, compared with cyanoacrylate, TIPSS had the advantage of reduced rebleeding, although it can be considerably more expensive. The study by Procaccini et al40Procaccini N.J. Al-Osaimi A.M.S. Northup P. et al.Endoscopic cyanoacrylate versus transjugular intrahepatic portosystemic shunt for gastric variceal bleeding: a single-center U.S. analysis.Gastrointest Endosc. 2009; 70: 881-887Abstract Full Text Full Text PDF PubMed Scopus (99) Google Scholar in this issue of Gastrointestinal Endoscopy comparing TIPSS with cyanoacrylate in the management of gastric variceal bleeding is a welcome addition to the literature. Despite the limitations of a retrospective study, it is the largest such series reported to date and has the longest follow-up. The main aims were to compare rates of rebleeding, survival, and morbidity. Patients with bleeding gastric varices or stigmata of bleeding were treated with TIPSS (n=44) or cyanoacrylate (n=61). Although baseline characteristics were matched, the follow-up for cyanoacrylate was significantly longer (74 vs 48 months). This relates to the use of glue from 1997 to 2004, and the majority of TIPSS procedures performed after 2004, when cyanoacrylate was not available. Despite the potential to bias the results in favor of TIPSS because of advances in the management of bleeding varices over time, the results show similar efficacy for rebleeding (10% and 25% at 1 year for cyanoacrylate and TIPSS, respectively). There was no difference in mortality. There were not enough data to assess the efficacy in actively bleeding patients, which is unfortunate. Likewise, details of PPG reduction after TIPSS insertion were not presented. The significant finding of this study was that of increased morbidity requiring hospitalization after TIPSS, with a striking difference in encephalopathy (11 patients vs 1 patient for cyanoacrylate). It is not clear from the study how many patients were encephalopathic before TIPSS because this is a recognized risk factor for post-TIPSS encephalopathy.41Tripathi D. Helmy A. Macbeth K. et al.Ten years' follow-up of 472 patients following transjugular intrahepatic portosystemic stent-shunt insertion at a single centre.Eur J Gastroenterol Hepatol. 2004; 16: 9-18Crossref PubMed Scopus (75) Google Scholar This information would also have allowed a clear distinction between de novo encephalopathy and deterioration of preexisting encephalopathy after TIPSS insertion. The use of polytetrafluoroethylene-coated stents in 66% of patients is noteworthy and did not seem to influence the results on subgroup analysis. Seven patients treated with cyanoacrylate were later treated with TIPSS, mainly because of refractory bleeding. One patient died after embolization of cyanoacrylate. What can we conclude from this study? With careful attention to technique, cyanoacrylate is effective for the treatment of gastric varices and more resource-efficient than TIPSS. It is also associated with a small but clear risk of mortality caused by embolization, despite expert hands. TIPSS has a definite role and should be used when endoscopic therapies fail in the presence of a patent portal vein. Careful patient selection can reduce the risk of post-TIPSS encephalopathy. The experience with endoscopic therapies for gastric variceal bleeding in recent times makes TIPSS more likely to be a second-line therapeutic modality. Perhaps 10 years ago we may have had a lower threshold for the use of TIPSS in bleeding gastric varices. Clearly, more controlled studies are necessary to make valid conclusions. Studies comparing different endoscopic modalities such as thrombin and tissue adhesives would also be welcome. Such studies should also focus on efficacy in acute gastric variceal bleeding. The author disclosed no financial relationships relevant to this publication.