Randomized Trial of N-Butyl-2-Cyanoacrylate Compared with Injection of Hypertonic Saline-Epinephrine in the Endoscopic Treatment of Bleeding Peptic Ulcers

Background and Study Aims: Theoretically, the injection of cyanoacrylate may be effective for peptic ulcer bleeding, but randomized clinical trials are rare. The aim of this study was to compare the efficacy of N-butyl-2-cyanoacrylate (Histoacryl) and hypertonic saline-epinephrine (HSE) in the endoscopic treatment of major peptic ulcer hemorrhage.

Patients and Methods: A total of 126 patients with major peptic ulcer hemorrhage and active bleeding or a nonbleeding visible vessel were randomly allocated to endoscopic injection with HSE (63 patients; group 1) or to injection with Histoacryl (63 patients; group 2). The two groups were well matched for age, sex, initial hemoglobin values, ulcer size and location, and bleeding stigmata.

Results: Initial hemostasis was achieved in 58 cases (92.1 %) in group 1 and in 60 cases (95.2 %) in group 2 (P = 0.717). Rebleeding rates were 16 of 58 in group 1 and seven of 60 in group 2 (P = 0.051). There were no significant differences regarding the rates of permanent hemostasis (51 of 63 in group 1 vs. 57 of 63 in group 2, P = 0.203), emergency surgery (seven of 58 in group 1 vs. three of 60 in group 2, P = 0.200), or hospital mortality due to bleeding (0 in group 1 and 0 in group 2). With regard to the rebleeding rate, there was a significant difference between group 1 and group 2 in the subgroup with active arterial bleeding (11 of 26 in group 1 and four of 29 in group 2, P = 0.039) but not in the subgroup with a nonbleeding visible vessel (five of 32 in group 1 and three of 31 in group 2, P = 0.708). There were no statistically significant differences in hemostatic results between the two treatment groups in the subgroups with gastric ulcers or duodenal ulcers. Although no complications followed HSE therapy, arterial embolization with infarction occurred in two patients in the Histoacryl group, of whom one died.

Conclusions: Compared with HSE injection, Histoacryl injection showed no statistically significant differences in hemostatic results, except for decreasing the rebleeding rate in the patients with active arterial bleeding. However, the use of Histoacryl to control peptic ulcer bleeding should be reserved as a last resort before surgery, because of possible embolic complication.

References

• 1 Gilbert K A, Silverstein F E, Tedesco F J, et al. The national ASGE survey on upper gastrointestinal bleeding III: endoscopy in upper gastrointestinal bleeding.  Gastrointest Endosc. 1981;  94 94-102
• 2 Swain C P, Storey D W, Bown S G, et al. Nature of the bleeding vessel in recurrently bleeding gastric ulcers.  Gastroenterology. 1986;  90 595-608
• 3 Wara P. Endoscopic prediction of major rebleeding: a prospective study of stigmata of hemorrhage in bleeding ulcers.  Gastroenterology. 1985;  8 1209-1214
• 4 Storey D W, Brown S G, Swain C P, et al. Endoscopic prediction of recurrent bleeding in peptic ulcers.  N Engl J Med. 1981;  305 915-916
• 5 Hirao M, Kobayashi T, Masuda K, et al. Endoscopic local injection of hypertonic saline-epinephrine solution to arrest hemorrhage from upper gastrointestinal tract.  Gastrointest Endosc. 1985;  31 313-317
• 6 Sugawa C, Fujita Y, Ikeda T, Walt A G. Endoscopic hemostasis of bleeding of the upper gastrointestinal tract by local injection of ninety-eight percent dehydrated ethanol.  Surg Gynecol Obstet. 1986;  162 159-163
• 7 Soehendra N, Grimm H, Stenzel M. Injection of non-variceal bleeding lesion of the upper gastrointestinal tract.  Endoscopy. 1985;  17 129-132
• 8 Rutgeerts P, Vantrappen G, Broeckaert L, et al. Comparison of endoscopic polidocanol injection and YAG-laser therapy for bleeding peptic ulcers.  Lancet. 1989;  I 1164-1166
• 9 Sugawa C, Joseph A L. Endoscopic interventional management of bleeding duodenal and gastric ulcers.  Surg Clin N Am. 1992;  72 317-334
• 10 Soehendra N, Nam V C, Grimm H, Kempeneers I. Endoscopic obliteration of large esophagogastric varices with Bucrylate.  Endoscopy. 1986;  18 25-26
• 11 Feretis C, Tabakopoulos D, Benakis P, et al. Endoscopic hemostasis of esophageal and gastric variceal bleeding with Histoacryl.  Endoscopy. 1990;  22 282-284
• 12 Soehendra N, Grimm H, Maydeo A. Endoscopic sclerotherapy: personal experience.  Hepatogastroenterology. 1991;  38 220-223
• 13 Labenz J, Borsch G. Successful endoscopic hemostasis of duodenal variceal bleeding with Histoacryl (letter).  Endoscopy. 1993;  25 194
• 14 Thakeb F, Salama Z, Salama H, et al. The value of combined use of N-butyl-2-cyanoacrylate and ethanolamine oleate in the management of bleeding esophagogastric varices.  Endoscopy. 1995;  27 358-364
• 15 Feretis C, Dimopoulus C, Benakis P, et al. N-butyl-2-cyanoacrylate (Histoacryl) plus sclerotherapy versus sclerotherapy alone in the treatment of bleeding esopahgeal varices: a randomized prospective study.  Endoscopy. 1995;  27 355-357
• 16 Oho K, Iwao T, Sumino M, et al. Ethanolamine oleate versus butyl cyanoacrylate for bleeding gastric varices: a nonrandomized study.  Endoscopy. 1995;  27 349-354
• 17 Vallieres E, Jamieson C G, Haber G B, Mackenzie R L. Pancreaticoduodenal necrosis following endoscopy treatment of bleeding duodenal ulcer with Histoacryl.  Endoscopy. 1988;  20 26
• 18 Loperfido S. Endoscopic hemostasis of gastric bleeding from Dieulafoy's ulcer with Histoacryl.  Endoscopy. 1989;  21 199-200
• 19 Kok K YY, Kum C K, Goh P MY. Endoscopic hemostasis of upper gastrointestinal bleeding with Histoacryl: last resort before surgery.  Endoscopy. 1996;  28 256-258
• 20 Swain C P, Salmon P R, Kirkham J S, et al. Controlled trial of Nd : YAG laser photocoagulation in bleeding peptic ulcers.  Lancet. 1986;  I 1113-1116
• 21 Brearley S, Hawker P C, Dykes P W, Keighley M RB. Per-endoscopic bipolar diathermy coagulation of visible vessels using a 3.2-mm probe: a randomized clinical trial.  Endoscopy. 1987;  19 160-163
• 22 Chung S C, Leung J W, Sung J Y, et al. Injection or heat probe for bleeding ulcer.  Gastroenterology. 1991;  100 33-37
• 23 Randall G M, Jensen D M, Hirabayashi K, Machicado G A. Controlled study of different sclerosing agents for coagulation of canine gut arteries.  Gastroenterology. 1989;  96 1274-1281
• 24 Rutgeerts P, Geboes K, Ventrappen G. Experimental studies of injection therapy for severe nonvariceal bleeding in dogs.  Gastroenterology. 1989;  97 610-621
• 25 Rajgopal C, Lessels A, Palmer K R. Mechanism of action of injection therapy for bleeding peptic ulcer.  Br J Surg. 1992;  79 782-784
• 26 Siedentop K H. Tissue adhesive Histoacryl in experimental middle ear surgery.  Am J Otolaryngol. 1980;  2 77-86
• 27 See A, Florent C, Lamy P, et al. Cerebrovascular accident after endoscopic obliteration of esophageal varices with isobutyl-2-cyanoacrylate in 2 patients.  Gastroenterol Clin Biol. 1986;  10 604-607
• 28 Mostafa I, Omar M M, Nouh A. Endoscopic control of gastric variceal bleeding with butyl cyanoacrylate.  Endoscopy. 1993;  25 A11
• 29 Stoesslein F, Ditscherlein G, Romaniuk P A. Experimental studies on new liquid embolization mixtures (Histoacryl-Lipiodol, Histoacryl-Panthopaque).  Cardiovasc Intervent Radiol. 1982;  5 264-267
• 30 Benedetti G, Sablich R, Lacchin T, Masiero A. Endoscopic treatment of bleeding duodenal varices by bucrylate injection.  Endoscopy. 1993;  25 432-433
• 31 Obara K, Irisawa A, Kojima T, et al. Endoscopic injection sclerotherapy for isolated gastric varices - a newly developed technique using α-cyanoacrylate monomer and evaluation of its therapeutic effects (Japanese; English abstract).  Endosc Dig. 1995;  7 43-53
• 32 Shimakawa T. Basic and clinical studies on endoscopic injection sclerotherapy with Histoacryl for esohagogastric varices (Japanese; English abstract).  Gastroenterol Endosc. 1993;  35 1531-1542