Pancreaticobiliary maljunction: pathophysiological and clinical aspects and the impact on biliary carcinogenesis

Background: Pancreaticobiliary maljunction (PBM) is frequently associated with congenital choledochal cyst (CCBD), but differs in embryonic cause and clinical features. It is thought to develop as a misarrangement of the embryonic connections in the pancreaticobiliary ductal system, with the terminal bile duct joined to one of the ducts of the ventral pancreas. Clinical aspects are intermittent abdominal pain, relapsing acute pancreatitis, jaundice, cholangitis, and gallbladder cancer. In patients with PBM and CCBD, primary bile duct stones, acute cholangitis, and bile duct cancer are considered to result from cholestasis, regurgitation of pancreatic juice, and reciprocal reflux of bile and pancreatic juice. The mixture of bile and pancreatic juice due to recipocal reflex very likely plays an important role in biliary carcinogenesis. Patients and methods: We reviewed the pathophysiological and clinical aspects and biliary carcinogenesis in 250 PBM patients (169 with benign hepatobiliary and pancreatic disease, 81 with malignancy). Results: PBM patients show elevated cellular proliferation activity in the gallbladder epithelia. A number of oncogenes and tumor suppressor genes have been identified and implicated in carcinogenesis, particularly the K-ras oncogene and the p53 suppressor gene. Some K-ras mutations do not appear essential for hyperplasia but may be an early event in carcinogenesis. The p53 mutations are involved in carcinogenesis in the biliary epithelium in PBM patients.