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

胰胆管系统异常连接处是胆管扩张和癌变的高发部位。一些哺乳动物，如山羊、老鼠和仓鼠，有一条非常长的共同胰胆通道。然而，从未确定这些动物不会发生胆管扩张和癌。我们以前报道过山羊的蛋白水解酶活性明显低于人，并且将人胰汁注入山羊胆囊可以诱导小山羊的胆管扩张。本研究比较了人和仓鼠胰液的组成。给仓鼠注射n -亚硝基叔胺（BOP） 3周。此外，通过胆囊造瘘将人胰液注入仓鼠胆囊，持续10周，观察胰液反流在胆管癌变中的作用。我们的生化分析表明，与人的胰液相比，仓鼠胰液中的蛋白水解酶水平明显降低。在给药的仓鼠胆囊内注射人胰液产生胆道腺瘤和胆道癌的发生率明显高于给药后注射盐水。因此，人胰液在仓鼠体内明显诱导胆管癌。仅将人胰液注入胆囊BOP未产生胆管癌，但肝外胆管增生发生率高。注射单一胰酶或联合胰酶代替人胰汁对胆管癌的发生率无差异，但产生肝外胆管腺瘤或增生的发生率明显增高。

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.