Metal and glue: best treatment choice for gastric varices?

Variceal bleeding is a serious complication in patients with cirrhosis. Bleeding from gastric varices in particular is associated with high morbidity and mortality, and conventional endoscopic therapy is less effective [1]. Although transjugular intrahepatic portosystemic shunt may be superior to medical therapy in patients with compensated cirrhosis (Child – Pugh class C < 14), it is contraindicated in patients with severe liver disease owing to the risk of precipitating encephalopathy.

“...the most important message from the paper by Zhang et al. is that clipping gastric varices appears to be safer than once thought, particularly in expert hands and when followed by therapy with cyanoacrylate glue.”

Cyanoacrylate-based tissue adhesives have been used throughout the world for treatment of gastric variceal bleeding for over three decades [2]. Although no high quality data are available, most series report control of bleeding rates in excess of 90 %, which appears superior to alternative techniques [6] [7]. Long-term results also appear favorable following secondary prevention and as such, many experts agree that cyanoacrylate should be the therapy of choice for acute bleeding from isolated gastric varices type 1 and gastroesophageal varices type 2. The most dreaded complication of glue injection is embolization, which can lead to venous thrombosis and pulmonary or cerebrovascular infarction, particularly in patients with large gastrorenal shunts [8] [9]. Endoscopic ultrasound-guided sclerotherapy has been proposed as a method to decrease the risk of embolism and improve treatment efficacy [10]. As it is assumed that embolization occurs due to the migration of glue particles via portosystemic shunts, any intervention that decreases the blood flow through the varix should theoretically be associated with a reduced risk of embolization. Anecdotal reports have suggested that clipping the variceal outflow can accomplish this safely and effectively [11].

In this issue of Endoscopy, Zhang et al. report their results with this technique in a retrospective series of 61 patients with cirrhosis, gastric varices, and evidence of gastrorenal shunts on cross-sectional imaging [12]. Patients with malignancy or significant cardiopulmonary comorbidity were excluded. Most patients underwent the procedure for secondary prophylaxis. The vast majority had well-compensated liver disease (Child class A or B) with a median model for end-stage liver disease (MELD) score of 9. Experienced endoscopists deployed hemostatic clips on what was judged to be the inflow or outflow of the gastric varix (or both) prior to the injection of cyanoacrylate sandwiched between two doses of another sclerosing agent (lauromacrogol). The primary end point was all-cause rebleeding and secondary end points were death or liver transplantation. Adverse events including embolization were assessed clinically. The technical success rate was 100 % including hemostasis in 4 patients with acute bleeding; 36 patients required additional cyanoacrylate injections. During a median follow-up of 7 months, rebleeding occurred in 23 % of patients and eradication of gastric varices was noted in 30/33 patients by computed tomography (CT) imaging. Four patients were lost to follow-up and two died of hepatic failure. There were only minor complications from the procedure and no symptomatic embolic events occurred.

At first glance, it appears that clipping prior to glue injection for gastric varices is safe and effective, and the authors should certainly be congratulated for their results using this novel and original technique. When we put the findings in perspective, however, two questions arise: Is clipping prior to cyanoacrylate actually safer or more effective than standard glue injection? Can these outcomes be extrapolated to other patient populations? The answer to the first question is still unknown. The study is relatively small from a safety perspective and there was no control group (historical or not) of patients who underwent glue injection without clips. In addition, the embolic events were assessed symptomatically rather than by imaging. The risk of embolism from glue injection alone in experienced hands is small enough that the confidence interval reported in other relatively large series included zero [11]. There was only one case of symptomatic pulmonary embolism out of 152 patients who underwent sclerotherapy for gastric varices in one of the largest series from North America [8]. If only one of the four patients who were lost to follow-up in the paper by Zhang et al. had an embolism, the presumed safety gain imparted by clipping dissipates. The endoscopists used two interventions not one in addition to the glue: clipping and additional sclerotherapy with lauromacrogol; one has to wonder therefore whether clipping or sandwiching the glue was more important assuming that no embolism occurred. The location of the inflow and outflow as the best area for clipping was guesstimated by the endoscopist using information from the CT image. More than 40 % of patients required two clips and 23 % needed three or more clips, suggesting that this technique is not always straightforward even in “expert eyes.” Although only one clip-induced bleed occurred, other experts have raised concerns about clipping gastric varices because of the potential risks [12]. Finally, from an efficacy perspective, the rebleeding rate in the Zhang et al. study was similar to reports in other nonselected populations [8].

There are additional concerns regarding the generalizability of the results. The vast majority of patients in this study had well-compensated cirrhosis with a median MELD score of 9. In contrast, the mean MELD score in previously published series with glue sclerotherapy was substantially higher [11]. Patients with gastric variceal bleeding seen in practice quite often have severe liver dysfunction or other complications such as portal vein thrombosis or malignancy, which occurred in only a minority or were outright excluded in the Zhang et al. study. Contrast CT to identify large shunts may be a luxury item prior to urgent endoscopy and some patients may not have contrast at all due to renal dysfunction, as a consequence of liver disease or prerenal azotemia. Clipping all patients with acute variceal bleeding may be impractical, unnecessary or risky. As such, for now, clip-assisted glue injection can only be recommended for patients with well-compensated liver disease with no other complications and well-defined portal anatomy.

In conclusion, the most important message from the paper by Zhang et al. is that clipping gastric varices appears to be safer than once thought, particularly in expert hands and when followed by therapy with cyanoacrylate glue. Whether this can reduce the risk of embolization in patients with gastrorenal shunts, above and beyond simple glue injection, is a question that awaits a more definitive answer through prospective studies or larger series with objective safety measurements.

• References

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