2025 Volume 39 Issue 1 Pages 95-101
Pancreaticobiliary maljunction allows bile and pancreatic juice reflux, which causes abdominal pain and vomiting in children and biliary carcinomas in adults. The symptoms are caused by protein plugs that transiently obstruct a narrow segment or common channel. Trypsinogen and lithostathine (a protein) in the pancreatic juice are regurgitated into the biliary tract, in which activated trypsin cleaves soluble lithostathine into insoluble forms, which aggregate to form protein plugs. A mixture of bile and pancreatic juice produces hazardous substances that constantly irrigate the biliary epithelia, in which bile stagnates. Hazardous substances include activated pancreatic enzymes, especially phospholipase A2 and lysolecithin, and some mutagens. Chronic inflammation causes multiple molecular abnormalities, including KRAS point mutation activation and COX-2 overexpression, causing an increased cell cycle of biliary epithelia and hyperplasia in the early phase and subsequent TP53 inactivation, resulting in carcinogenesis known as the hyperplasia-dysplasia-carcinoma sequence.
