Variant anatomy of the biliary system as a cause of pancreatic and peri-ampullary cancers

HPB (Oxford). 2020 Dec;22(12):1675-1685. doi: 10.1016/j.hpb.2020.03.014. Epub 2020 Apr 24.


Background: The cause of most pancreatic and periampullary cancers (PAC) is unknown. Recently, anatomic variations such as pancreatobiliary maljunction have been recognized as risk factors, similar to Barrett-related gastro-esophageal cancers.

Methods: Pre-operative MRI from 860 pancreatic/biliary resections, including 322 PACs, were evaluated for low-union (cystic duct joining the common hepatic duct inside of the pancreas or within 5 mm of the pancreatic border) RESULTS: Low-union, seen <10% of the population, was present in 44% of PACs (73% distal bile duct/cholangiocarcinoma, 42% pancreatic head, and 34% ampullary). It was significantly lower(11%) in conditions without connection to the ductal system (thus not exposed to the ductal/biliary tract contents), namely mucinous cystic neoplasms and intrahepatic cholangiocarcinomas(p < 0.0001). Intra-pancreatic type low-union was seen in 16% of PACs versus 2% of controls(p < 0.0001).

Discussion: This study establishes an association between low-union and PACs, and points to an anatomy-induced chemical/bilious carcinogenesis. This may explain why most pancreas cancers are in the head. It is possible that the same chemical milieu, caused by conditions other than low-union/insertion, may also play a role in the remaining half of PACs. This opens various treatment opportunities including milieu modifications (chemoprevention), focused screening of at-risk patients, and early detection with possible corrective actions.

MeSH terms

  • Ampulla of Vater*
  • Bile Duct Neoplasms* / diagnostic imaging
  • Bile Duct Neoplasms* / surgery
  • Bile Ducts, Intrahepatic
  • Common Bile Duct Neoplasms*
  • Duodenal Neoplasms*
  • Humans
  • Pancreatic Neoplasms* / diagnostic imaging
  • Pancreatic Neoplasms* / surgery