Endoscopic ultrasound-guided intervention for gastric varices: sticky stuff might not (yet) be enough

Bleeding gastroesophageal varices remain a devastating and life-threatening clinical condition that requires immediate and urgent intervention, with the ultimate goal being hemostasis. While esophageal varices (80 % – 85 %) form the bulk of all variceal bleedings in patients with cirrhotic portal hypertension (PHT), gastric varices should not be ignored as a trivial remainder. The second, albeit less frequent, scenario in which gastric varices are found relates to prehepatic conditions (so-called left-sided PHT), such as noncirrhotic thrombosis of the portal/splenic vein [1].

Gastric varices are classically divided into gastroesophageal varices (GOV) or isolated gastric varices (IGV), according to Sarin [1] [2]. This editorial focuses specifically on fundal type varices (GOV2 and IGV1), as they follow a different natural history course and represent the true endoscopic stalemate compared with GOV1 gastric varices, which are esophageal varices extending into the gastric lesser curvature and are treated similarly to esophageal varices, by endoscopic band ligation.

Bleeding gastric varices, irrespective of their etiology, tend to bleed less frequently than esophageal varices; however, when they do bleed, the clinical situation is vastly more disheartening [1] [2] [3]. The reasons for this apparent discrepancy relate to greater difficulties in achieving hemostasis and, thus, greater propensity to rebleed, which in turn both lead to increased bleeding-related mortality. Multiple factors are considered essential in this situation, including the large submucosal component typical of gastric varices, the vascular anatomy feeding and draining the gastric varix, and most important – but amenable – the lack of widespread treatment options and expertise available for this condition.

“...from an endoscopic point of view, the EUS-assisted delivery of combined coil and glue represents a genuine and promising step forward in endoscopic hemostasis for bleeding gastric varices”

As is often the case when there is a lack of robust data or tools to address a certain medical situation, general consensus turns to analogy, which for bleeding gastric varices was found in the management of esophageal variceal hemorrhage, which is far better characterized. Although this comparison is appropriate for the use of prophylactic antibiotics, careful replacement of volemia (with restrictive transfusion policy), and the early administration of vasoactive drugs (which should be able to markedly reduce portal and collateral blood flow), it is not appropriate for the type of hemostatic endoscopic intervention. Whereas endoscopic band ligation is the undisputed standard of care for esophageal varices, it is not when applied to bleeding gastric varices given the lower rate of immediate hemostasis and higher rebleeding rates (2.6 – 4.1-fold higher risk), particularly when compared with endoscopic cyanoacrylate (“glue”) injection [1] [3].

For this reason, cyanoacrylate injection using standard endoscopy is now considered the “gold standard” endoscopic hemostatic treatment for gastric variceal hemorrhage and secondary prophylaxis [1] [3] [4]. However, it also carries several, potentially severe, flaws, and would perhaps be better categorized as “best available gold standard.” Primarily, and most strikingly, efficacy data are scarce, with only half of the patients included in the few published randomized controlled trials (RCTs) having cardiofundal varices. Keeping this in mind, initial hemostasis was reported in over 90 % of patients, but rebleeding rates were still high at 15 % – 20 %, with a clear impact on morbidity and mortality. The rate of variceal obliteration is unclear and varies from 44 % to 100 %, the latter figure being untrustworthy [1] [3] [4]. Secondly, the procedure is not without risks, including systemic glue emboli (0.5 % – 4.3 %), ulcerative extrusion of glue with bleeding (4.4 %), and sepsis with or without thrombophlebitis [4]. These latter phenomena might relate to the combination of a rather untargeted approach, the size and complexity of the underlying portosystemic shunts, and the aliquot(s) of glue injected per injection. In view of these limitations, endoscopic hemostasis of bleeding gastric varices or secondary prophylaxis has remained challenging and far from satisfactory compared with esophageal variceal hemorrhage.

Attempts to improve this stalemate in recent years are almost nonexistent, except for endoscopic ultrasound (EUS)-guided glue and/or coil injection. Binmoeller et al. were the first to report on this technique, which aims to improve the efficacy of the direct glue injection technique using standard endoscopy and to reduce the risk of systemic complications [5]. More specifically, EUS allows not only precise targeting of the vessels responsible for feeding and perforating the gastric varix but also directly monitors, via Doppler, the effect of therapy on variceal flow in real time, as well as the theoretical risk of embolization [4] [5].

In this issue of Endoscopy, the RCT by Robles-Medranda et al. [6] substantiates for the first time the superiority of combining coils with glue vs. coils alone under EUS guidance in terms of variceal obliteration (86.7 % vs. 13.3 %) and rebleeding rate (3.3 % vs. 20 %) in a single procedure (83.3 % vs. 60 %). Notably, these data have been further confirmed and reinforced by a systematic review by Mohan et al. [7], also published in this issue. The authors compared EUS with coil, EUS with glue, EUS with coil and glue vs. glue via the standard endoscopy approach. EUS-guided therapy with combined coil and glue was the best modality, with a pooled treatment efficacy rate of 97 %, obliteration rate of 86 %, recurrence rate of 5 %, and early and late rebleeding rates of 8 % and 9 %, respectively. And, as if these studies were not enough, another supportive independent meta-analysis has recently been published by McCarthy et al. [8].

These data provide clear reasons to be optimistic about progress in the endoscopic management of gastric varices but also underscore the indispensable and growing therapeutic impact of EUS in hepatopancreatobiliary pathology. Nevertheless, our enthusiasm to unleash this technique temerariously on all gastric varices should be somewhat restrained, as major issues remain. First, high quality confirmatory RCTs, though difficult to perform, should be pursued to validate the currently reported outcomes and further delineate the patient groups most likely to benefit from this kind of procedure, as the current data include a mixture of patients in the setting of active bleeding and secondary prophylaxis but also primary prophylaxis. In particular, the benefit of endoscopic intervention in the latter group is still under debate, as the latest BAVENO consensus report advises against any endoscopic gastric variceal obliteration (by means of endoscopic cyanoacrylate injection) in primary prophylaxis due to insufficient data and thus, unclear risk/benefit. Second, as an endoscopist, one should remember that endoscopic hemostasis for variceal bleeding is not the end but merely the beginning, as gastric variceal bleeding represents a symptom of the much larger syndrome of PHT, most frequently in the context of cirrhosis. Management of these patients should therefore incorporate a multidisciplinary approach to consider the best possible option, which does not necessarily extend to EUS-assisted coil and glue delivery alone, but might also involve pharmacological (i. e. nonselective beta-blockers), radiological (including transjugular intrahepatic portosystemic shunt and balloon-occluded retrograde transvenous obliteration) or surgical intervention (e. g. shunt surgery or liver transplantation).

So, overall and in conclusion, sticky stuff might just not be enough when treating gastric varices but, at least from an endoscopic point of view, the EUS-assisted delivery of combined coil and glue represents a genuine and promising step forward in endoscopic hemostasis for bleeding gastric varices and should definitely be explored further.

Publication History

Article published online:
25 March 2020

• References

• 1 Garcia-Pagan JC, Barrufet M, Cardenas A. et al. Management of gastric varices. Clin Gastroenterol Hepatol 2014; 12: 919-928
• 2 Sarin SK, Lahoti D, Saxena SP. et al. Prevalence, classification and natural history of gastric varices: a long-term follow-up study in 568 portal hypertension patients. Hepatology 1992; 16: 1343-1349
• 3 de Franchis R. BAVENO VI Faculty. Expanding consensus in portal hypertension: report of the BAVENO VI consensus workshop: stratifying risk and individualizing care for portal hypertension. J Hepatol 2015; 63: 743-752
• 4 Fujii-Lau LL, Law R, Wong Kee Song LM. et al. Novel techniques for gastric variceal obliteration. Dig Endosc 2015; 27: 189-196
• 5 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: 1019-1025
• 6 Robles-Medranda C, Oleas R, Valero M. et al. Endoscopic ultrasonography-guided deployment of embolization coils and cyanoacrylate injection in gastric varices versus coiling alone: a randomized trial. Endoscopy 2020; 52: 268-275
• 7 Mohan BP, Chandan S, Khan SR. et al. Efficacy and safety of endoscopic ultrasound-guided therapy versus direct endoscopic glue injection therapy for gastric varices: systematic review and meta-analysis. Endoscopy 2020; 52: 259-267
• 8 McCarthy TR, Bazarbashi AN, Hathorn KE. et al. Combination therapy versus monotherapy for EUS-guided management of gastric varices: a systematic review and meta-analysis. Endosc Ultrasound 2019;
• 9 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: 1161-1167