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组织黏合剂治疗胃静脉曲张出血的基础和临床研究

The Role of N-butyl-2-cyanoacrylate on Gastric Variceal Bleeding: Animal Study and Clinical Effects

【作者】 王艳梅

【导师】 程留芳;

【作者基本信息】 中国人民解放军军医进修学院 , 消化内科学, 2005, 博士

【摘要】 研究目的:食管胃静脉曲张出血(esophagogastric variceal bleeding,EGVB)是消化科的重危急症,如何控制其出血并防止再发出血,降低死亡率,是救治肝硬化患者生命、提高生活质量的重要问题。内镜下硬化剂治疗对制止食管静脉曲张急性出血以及预防再出血是一种有效的方法,已广泛被接受并应用于临床,但对胃静脉曲张出血的治疗还有争论。近年来,国内外许多临床研究已证实,经内镜注射组织粘合剂N-丁基-2-氰丙烯酸盐方法是控制胃静脉曲张出血的有效治疗方法。本课题从血管基础病理和临床治疗效果两个方面入手,旨在通过基础研究来探讨组织粘合剂在血管中的实际行为,分析影响其聚合的主要因素,找到发挥作用的最佳条件;并且观察注射入成兔血管后的组织病理学改变,阐明其止血机制及作用过程,更好的指导临床应用;通过临床研究组织粘合剂的用量和排胶规律,评价内镜下注射组织黏合剂治疗胃静脉曲张出血的远期疗效和安全性,从而明确其作为GV出血治疗首选方法的地位。 材料和方法:1、血液流变学研究:我们利用聚四氟乙烯管建立血流模型,分别研究血管直径、血流速度以及组织黏合剂配比浓度这三个因素对组织黏合剂聚合过程的影响。2、组织病理学研究:本部分采用2~3kg成兔作为研究对象,分别在其颈外静脉和股动脉内注入组织黏合剂(用量为0.1~0.2ml,顺血流方向),然后分别在注射后3天、7天、2周、3周和4周、2月和3月将注射部位及邻近血管周围组织切取成1cm的组织条,进行组织病理学研究。以不同的时间阶段分为7组,每组为6只新西兰白兔。取对侧正常血管作为对照。3、临床研究:在1年半内148例活动性或近期胃静脉曲张出血的患者行内镜下组织黏合剂注射治疗直到曲张静脉闭塞。组织黏合剂与碘油按1:1的混合比例快速注入曲张静脉内。25例为活动性出血,123例为近期出血。最常注射部位是胃底和贲门。根据上腹部平片和CT血管成像观察排胶规律。患者平均随访时间为13.1个月。 结果:组织黏合剂与碘油1:1配比混合物1.0ml快速注射至聚四氟乙烯

【Abstract】 [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

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