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Editorial Has the Time Come for Cyanoacrylate Injection to Become the Standard-Of-Care for Gastric Varices?

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Editorial Has the Time Come for Cyanoacrylate Injection to Become the Standard-Of-Care for Gastric Varices? Tropical Gastroenterology 2010;31(3):141–144 Editorial Has the time come for cyanoacrylate injection to become the standard-of-care for gastric varices? Radha K. Dhiman, Narendra Chowdhry, Yogesh K Chawla The prevalence of gastric varices varies between 5% and 33% among patients with portal Department of Hepatology, hypertension with a reported incidence of bleeding of about 25% in 2 years and with a higher Postgraduate Institute of Medical bleeding incidence for fundal varices.1 Risk factors for gastric variceal hemorrhage include the education Research (PGIMER), size of fundal varices [more with large varices (as >10 mm)], Child class (C>B>A), and endoscopic Chandigarh, India presence of variceal red spots (defined as localized reddish mucosal area or spots on the mucosal surface of a varix).2 Gastric varices bleed less commonly as compared to esophageal Correspondence: Dr. Radha K. Dhiman, varices (25% versus 64%, respectively) but they bleed more severely, require more blood E-mail: [email protected] transfusions and are associated with increased mortality.3,4 The approach to optimal treatment for gastric varices remains controversial due to a lack of large, randomized, controlled trials and no clear clinical consensus. The endoscopic treatment modalities depend to a large extent on an accurate categorization of gastric varices. This classification categorizes gastric varices on the basis of their location in the stomach and their relationship with esophageal varices.1,5 Gastroesophageal varices are associated with varices along the lesser curve (type 1), or along the cardia (type 2); isolated gastric varices are present in the fundus (type 1) or at ectopic sites in the stomach or the first part of the duodenum (type 2).1,5 Although, endoscopic variceal band ligation is the undisputed gold standard therapy for bleeding esophageal varices, this approach has been less successful for the treatment of bleeding gastric varices.6 Treatment options for gastric varices includes the radiological insertion of a transjugular intrahepatic portosystemic stent shunt (TIPSS) and the endoscopic injection of sclerosing agents, such as absolute alcohol, ethanol oleate, sodium tetradecyl sulfate, tissue adhesives and thrombin.7 N-butyl-2-cyanoacrylate (NBC) is the most commonly used tissue adhesive for the treatment of gastric varices in clinical practice and is superior to intravariceal injections using ethanol oleate or absolute alcohol.7 American Association for the Study of Liver Diseases guidelines1 and the Baveno V consensus5 recommend endoscopic therapy with NBC as first-line treatment for bleeding isolated gastric varices and gastroesophageal varices type 2. Endoscopic variceal ligation or sclerosing agents can be used in bleeding from gastroesophageal varices type 1. A transjugular intrahepatic portosystemic stent shunt (TIPSS) should be considered in patients in whom hemorrhage from fundal varices cannot be controlled or in whom bleeding recurs despite combined pharmacological and endoscopic therapy or where endoscopic therapy is not available. NBC is a liquid with a consistency similar to water and therefore it can be given by intravariceal injection. When added to a physiologic medium such as blood, NBC rapidly polymerizes, forming a hard substance. Hence, after injection into a varix, NBC plugs the lumen resulting in rapid hemostasis in cases of active bleeding and eradication of gastric varices. NBC is commonly used in Europe and Asia for the treatment of gastric varices but is not approved by FDA in the United States. © Tropical Gastroenterology 2010 142 Tropical Gastroenterology 2010;31(3):141–144 In this issue of Tropical Gastroenterology, Choudhuri et al8 switched from diluted NBC to undiluted NBC midway through from India report impressive results using NBC, Nectacryl, for the study, after noticing embolic complications with diluted the treatment of bleeding fundal gastric varices (mostly isolated NBC, and thereafter reported absence of embolic complications gastric varices and gastroesophageal varices type 2) as an with undiluted NBC.21 emergency procedure for active bleeding in 62 patients and as Most evidence for the use of cyanoacrylate in gastric an elective procedure for prevention of rebleeding in 108 variceal bleeding comes from series based in India, Japan, patients. The overall hemostasis rate at 48hours was 82.3 % in Europe, and the United States, which report good initial actively bleeding group. Overall bleeding recurred in 14.5% of hemostasis rates of over 93% (range, 71-100), rebleeding rates the patients. Definitive success was achieved in 89.9% of of 23% (range, 7.6-52) and mortality of 28% (range, 3.7-82.5) in patients with a complete follow up who had been followed. No 24 trials.7 Both studies have shown efficacy of NBC on above- significant complications were noticed except for injection site mentioned parameters according to the literature. Case series ulceration in 32 patients. The major limitations of this study have also highlighted the utility of cyanoacrylate treatment in were a retrospective nature, 9% of patients were lost to follow- specific clinical situations such as pregnancy,22 in children22,23 up and there was only one intervention group. and in infants.24 Repeated injections are required to obliterate In another study from India, recently published in the varices and secondary bleeding. In a recent study, b- Gastrointestinal Endoscopy, Kumar et al9 reported a success blocker were compared with NBC injection for the prevention rate of initial hemostasis in 84.8% among 46 patients with of secondary bleed. Patients with gastroesophageal varices actively bleeding gastric varices. Rebleeding was seen in 23.4% type 2 with eradicated esophageal varices or isolated gastric patients over a mean follow-up of 16 months. Large gastric varices type 1 who had bled from gastric varices were variceal size, fundal location, and large esophageal variceal randomised to NBC injection (n=33) or b-blocker treatment size were predictive of gastric variceal bleed. The mortality was (n=34). The probability of gastric variceal rebleeding rate in the 8.8% for all varices and Child-Pugh status was the only predictor NBC group was significantly lower than in the b-blocker group of mortality. The only limitation of this study was that it had (15% vs 55%, p=0.004) and the mortality rate was lower (3% vs only one intervention group. 25%, p=0.026) during a median follow-up of 26 months. This The technique of NBC injection was important in these 2 study further confirms the findings reported earlier that gastric studies.8,9 While former has used minimally diluted NBC with variceal eradication should be the aim with NBC injections on a lipiodol in 4:1 ratio, the later used undiluted glue. Further, to regular follow-up.25 Weeks to months after the injection, the prevent embolization, Kumar et al9 limited maximum amount of mucosa overlying the glue cast sloughs off and the plug is cyanoacrylate per injection to 1 to 2 mL per varix and per session extruded into the stomach; this may be followed by bleed in a to 4 mL. Similarly, Choudhuri et al8 have used 0.5 to 4ml of rare patient due to ulcer formation at the extrusion site. We cyanoacrylate glue per aliquot that was primarily decided by minimize the chances of ulcer bleed of this kind by giving proton the size of varix. These approaches have been taken in an attempt pump inhibitors in a single dose; however the efficacy of this to reduce the embolic complications of cyanoacrylate glue. The approach needs to be confirmed with a prospective randomized rationale for diluting cyanoacrylate glue with lipiodol is to delay controlled trial. the otherwise early polymerization reaction in order to complete Three studies have compared endoscopic NBC injection the injection and remove the needle. Previous studies have with TIPPS placement for the management of gastric variceal used varied dilution with lipiodol (0.5:1.5 to 2:1).10,11 There are bleeding.26-28 Lo et27 found that TIPSS was more effective than several case reports of severe complications related to NBC injection in preventing rebleeding from gastric varices, embolization including cerebral stroke,12 pulmonary embolism,13 with similar survival and frequency of complications. Mahadeva portal vein embolism,14 splenic infarction,15 retro-gastric and colleagues26 retrospectively analyzed that NBC injection abscess16 and septicemia17 which have raised concern about was more cost effective than TIPSS in the management of acute its safety. When embolic phenomena occur, fatalities have also gastric variceal bleeding. A major limitation of this study was been reported.18-20These two studies are important for the short follow-up of just 6 months with cyanoacrylate and 12 eliminating the risk of embolization by using undiluted or months with TIPSS, which must be taken into account when minimally diluted NBC. In another study, the endoscopists interpreting the findings. Procaccini et al28 compares TIPSS Has the time come for cyanoacrylate injection 143 insertion versus NBC injection with TIPSS insertion as a rescue Has the time come for cyanoacrylate injection to become treatment and concluded that in patients with similar the standard treatment for gastric varices? The answer is ‘Yes’. characteristics, therapy with NBC performed as well as a TIPSS However, issues related to the role of NBC in the primary in controlling and preventing gastric variceal hemorrhage with prophylaxis and the place of TIPSS in the management of gastric no significant differences in survival. Patients receiving varices need further large multicenter randomized trials. cyanoacrylate therapy experienced significantly less long-term morbidity related to therapy than patients who received a TIPSS References and was primarily attributable to the development of hepatic encephalopathy. However there was no information whether 1. Garcia-Tsao G, Sanyal AJ, Grace ND, Carey W: Practice the hepatic encephalopathy occurred de novo or it resulted Guidelines Committee of the American Association for the Study from deterioration of preexisting encephalopathy after TIPSS of Liver Diseases; Practice Parameters Committee of the American insertion.
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