Response:

Abstract

We appreciate the opportunity to respond to the comments of Drs. Matsumo, Takimoto, Kuchide, Yamauchi, and Takemura. One of the main issues regarding the use of cyanoacrylate injection for treatment of gastric varices is proper polymerization time. If the glue polymerizes too quickly, the injector needle will clog and possibly become affixed to the varix. This has been reported with the use of n-butyl 2-cyanoacrylate.1.Dhiman R.K. Chawla Y. Taneja S. Biswas R. Shatma T.R. Dilawari J.B. Endoscopic sclerotherapy of gastric variceal bleeding with n-butyl-2-cyanoacrylate.J Clin Gastroenterol. 2002; 35: 222-227Crossref PubMed Scopus (87) Google Scholar If polymerization occurs too slowly, the glue will not solidify within the varix and may lead to embolization. The slower polymerization time of 2-octyl cyanoacrylate compared with n-butyl 2-cyanoacrylate allows for undiluted injection without the worry of premature polymerization and related complications. Our injection technique uses a very slow, small aliquot injection after the catheter has been primed with saline solution. The saline solution acts to accelerate polymerization compared with Lipiodol, which slows polymerization. This was demonstrated in an ex vivo analysis we performed (unpublished) before initiation of our pilot study comparing the polymerization properties of 2-octyl cyanoacrylate and n-butyl cyanoacrylate in human whole blood. With these injection techniques, we feel that 2-octyl cyanoacrylate can be used safely in the majority of patients with gastric varices. The three patients in our pilot study with active gastric variceal bleeding had type 1 IGV fundal varices.2.Rengstorff D.S. Bimnoeller K.F. A pilot study of 2-octyl cyanoacrylate injection for treatment of gastric fundal varices in humans.Gastrointest Endosc. 2004; 59: 553-558Abstract Full Text Full Text PDF PubMed Scopus (101) Google Scholar None of these patients had clinical signs of embolization after injection. Since our pilot study was published, we have injected over 40 patients, with more than 1 year median follow-up. Included in this group are 7 patients with no history of gastric variceal bleeding who were treated prophylactically. These patients have had no variceal bleeding during follow-up and no evidence of embolic events. One patient with recent bleeding with a type 1 IGV was diagnosed with a pulmonary embolism 5 days after glue injection when she developed dyspnea. This patient had a known history of hypercoaguable state with portal and mesenteric vein thrombosis requiring chronic anticoagulation with Coumadin (Bristol-Myers Squibb, Princeton, NJ). In this situation, the ability to radiographically identify the cyanoacrylate would be helpful to delineate the source of emboli. Currently, the use of undiluted 2-octyl cyanoacrylate prevents visualization fluoroscopically or radiographically. As mentioned previously, dilution of this agent with Lipiodol will alter polymerization time, potentially affecting hemostasis and increasing the risk of embolization. We are currently considering the use of other radiopaque agents, which would allow fluoroscopic visualization without affecting polymerization. At this time, the relative potency of 2-octyl cyanoacrylate compared with n-butyl 2 cyanoacrylate is unknown. In the initial animal study of Nguyen et al.,3.Nguyen A.J. Baron T.H. Burgart L.J. Leontovich O. Rajan E. Gostout C.J. 2-Octyl-cyanoacrylate (Dermabond), a new glue for variceal injection therapy: results of a preliminary animal study.Gastrointest Endosc. 2002; 55: 572-575Abstract Full Text Full Text PDF PubMed Scopus (32) Google Scholar vascular occlusion rates were compared by using the two compounds with more than twice as much 2-octyl cyanoacrylate per injection. Because 2-octyl cyanoacrylate is considered a medical device and not a drug, the exact concentration of active cyanoacrylate in the compound is not known, making a 1 to 1 comparison impossible. Balloon-occluded retrograde transvenous obliteration (B-RTO) has been used in Japan in patients with a gastrorenal shunt. In case series, this technique has been effective in the prevention of bleeding, as well as in the treatment of active gastric variceal hemorrhage. Although this procedure is an ingenious method of obliterating gastric varices, it has many practical limitations. B-RTO has only been performed outside of the United States in a limited number of centers.4.Ryan B.M. Stockbrugger R.W. Ryan J.M. A pathophysiologic, gastroenterologic, and radiologic approach to the management of gastric varices.Gastroenterology. 2004; 126: 1175-1189Abstract Full Text Full Text PDF PubMed Scopus (256) Google Scholar It is invasive, time consuming, and requires significant expertise. From a practical standpoint, cyanoacrylate injection, now available in the United States, has been proven to be cost effective,5.Greenwald B.D. Caldwell S.H. Hespenheide E.E. Patrie J.T. Williams J. Binmoeller K.F. et al.N-2-butyl-cyanoacrylate for bleeding gastric varices: a United States pilot study and cost analysis.Am J Gastroenterol. 2003; 98: 1982-1988Crossref PubMed Scopus (84) Google Scholar is minimally invasive, and is relatively easy to perform. Many of the issues raised by Dr. Matsumoto and colleges will not be clarified until randomized controlled trials are performed comparing the various modalities used to treat gastric varices. Is the cyanoacrylate analogue, 2-octyl cyanoacrylate, a promising treatment for gastric fundal varices?Gastrointestinal EndoscopyVol. 60Issue 6PreviewTo the Editor: Full-Text PDF