The Role Of N-butyl-2-cyanoacrylate On Gastric Variceal Bleeding: Animal Study And Clinical Effects

[Background and objective] Esophagogastric variceal bleeding(EGVB) is a serious and emergent disease of digestive system and how to control hemorrhage in order to decrease death rate is an important problem. Variceal bleeding results in considerable morbidity and mortality. Initial treatment is aimed at achiving hemostasis and preventing bleeding-related complications such as renal failure, infection, and hepatic decompensation. Although Endoscopic variceal sclerotherapy (EVS) is an effective solution for EV, while there is controversythe of the treatment for GV, which is one of the most important cause of death from hepatic cirrhosis and portal hypertension. Recently some studies reported that endoscopic injection of N-butyl-2-cyanoacrylate is an effective alternative for EGV therapy. In this study, we discussed the fact behavior of cyanoacrylate in vessels so as to find out the most vessel diameter and propriate time it blocked. In animal experiment we investigated the structure and pathological representation after injection. At the same time, the long-term efficacy and safety of the endoscopic injection of cyanoacrylate were evaluated to define its role as the initial treatment for bleeding gastric varices.[Methods and materials] 1. Basic study: we created a varix model. A volume of 0.5ml or 1.0ml of cyanoacrylate was injected into vinyl tubes of 0.4, 0.6 and 0.8cm in diameter, which were filled with still blood or flowing blood. We investigated the influence of the vesse diameter, the blood velocity and the match concentration of cyanoacrylate and lipiodol on the process of blood polymerization. 2. Animal experiment: The objections were 42 rabbits with 2~ 3kg. We injected 0.1~0.2ml mixtures of cyanoacrylate and lipiodol into cervical veins and femoral arteries of rabbits. And then, the animals were euthanized at various time intervals after injection. A lcm strip of tissue was resected forhistological evaluation. We divided into seven groups according to different time. There were six rabbits in each group. We compared the histological difference between arteries and veins. 3. Clinica study: 148 patients of liver cirrhosis with EGV at our hospital from June 2003 to December 2004 subjected to the injection. Cyanoacrylate was injected intravariceally as a 1:1 mixture with Lipiodal. In which 30 had isolate gastric varices, 38 had postoperative residual GV, 72 had dominant GV. 0.5~2.0ml of 1:1 mixture of cyanoacrylate and lipiodol was injected into each point. Each patient underwent scheduled or emergent endoscopic injection of cyanoacrylate and countercheck on the 7th day, lth month and 3th month after the first treatment respectively. The information of each patients' gender, age, complications, stage of gastric varices, number of trentment, dosage of cyanoacrylate agent, outcome of GV, diameter of main portal tract, liver function, blood routine tests were collected. No marked side effects and complication were found.We described data with mean ±standard deviation( X ±SD), median(Md). [Results] 1. N-butyl-2-cyanoacrylate was similarly polymerized in the vinyl tubes and the animal veins. A volume of 1.0ml of the mixtures of cyanoacrylate and lipiodol (1:1) could block completely the blood stream with 15cm/s in velocity and 0.4cm in diameter or with lOcm/s in velocity and 0.6cm in diameter, respectively. With the increase of diameter and velocity, it can block vessel incompletely and we need more dosage of mixture. When the match concentration was changed, the effect decreased. Some polymer masses were fragmented. 2. When injected intravascularly, cyanoacrylate promptly solidifies, producing a cast of the vessel. Subtotal occlusion is immediate, and total occlusion occurs within hours. The results of animal experiment showed that we observed the acute inflammatory reaction at 3 days after injection, and then gradually developed into chronic granulomatous foreign body reaction. The elastic fibrin in arterial wall proliferated distinctly after three weeks resulted into the smallness of cavity. But there were little change in venous wall at fifferent time. 3. According to Sarin's category of GV, GOV- I detected in 68 (45.9%), GOV-II in 49 (33.1%), IGV- I in 30 (20.3%) and IGV-II in 1 (0.67%). The common cause of GOV was liver cirrhosis and IGV was segmental portal...