A hamster model of bile duct carcinoma in anomalous junction of the pancreaticobiliary duct

众所周知，胰胆管系统异常交汇是导致胆管扩张和癌变的高发原因。一些哺乳动物如山羊、大鼠和仓鼠有一个非常长的共同胰胆管通道。然而，从未确定这些动物中不会发生胆管扩张和癌。我们曾报道过山羊的蛋白水解酶活性明显低于人，而人胰液注入山羊胆囊可引起幼山羊胆管扩张。本研究比较了人和仓鼠的胰液成分。仓鼠接受N-亚硝基双胺（BOP）给药3周。此外，通过胆囊造口术将人胰液注入仓鼠胆囊内10周，以观察胰液反流在胆管癌发生中的作用。我们的生化分析表明，仓鼠胰液中的蛋白水解酶水平明显低于人胰液。将人胰液注射到仓鼠胆囊中并给予BOP，与注射生理盐水并给予BOP相比，胆道腺瘤和癌的发生率明显较高。因此，人胰液可明显诱发仓鼠胆管癌，单纯将人胰液注入胆囊BOP不诱发胆管癌，单纯或联合应用胰酶注射代替人胰液，其胆管癌发生率无明显差异，但可产生肝外胆管腺瘤或增生导管的发病率明显较高。

It has been well known that an anomalous junction of pancreaticobiliary ductal system arise both dilatation and cancerous change of the bile duct in the high incidence. Some mammals such as goats, rats, and hamsters have a remarkably long common pancreaticobiliary channel. However, it has never been determined bile duct dilatation and carcinoma do not occur in these animals. We reported previously that the activity of proteolytic enzyme in goats was significantly lower compared with that in humans, and that the bile duct dilatation could be induced in young goats by infusion of human pancreatic juice into the gallbladder of goats. In this study the composition of pancreatic juice was compared in human and hamsters. Hamsters received administration of N-nitrosobis amine (BOP) for 3 weeks. In addition, humanpancreatic juice was injected into the gallbladder of hamsters via cholecystostomy for 10 weeks to examine the role of pancreatic juice reflux in the bile duct carcinogenesis. Our biochemical analysis demonstrated significantly lower levels of proteolytic enzymes in hamster pancreatic juice compared with human juice.Injection of human pancreatic juice into gallbladders of hamsters with administration of BOP produced adenoma and carcinoma of the biliary tract in significantly higher incidence compared with those of injection of salinewith administration of BOP.Thus, bileduct carcinoma was apparently induced in hamsters by human pancreatic juice.Injection of only human pancreatic juice into gallbladdeis BOP did not produce bile duct carcinoma, but hyperplasia in the extrahepatic bile duct occurred in high in cidence.Injection of single or combined pancreatic enzymes instead of human pancreatic juice Showed no difference in the incidence of bile duct carcinoma but produced adenoma or Hyperplasia of extrahepatic bile duct in significatly higher incidence.