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

Takashi Muraki, Michelle D. Reid, Burcin Pehlivanoglu, Raul S. Gonzalez, Aarti Sekhar, Bahar Memis, Yue Xue, Jeanette Cheng, Kee Taek Jang, Pardeep Mittal, Kenneth Cardona, David A. Kooby, Shishir Maithel, Juan M. Sarmiento, Bassel El-Rayes, Gwen Lomberk, Raul A. Urrutia, Kathleen Christians, Susan Tsai, Douglas B. EvansVolkan Adsay*

*Corresponding author for this work

Research output: Contribution to journalArticlepeer-review

10 Scopus citations


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.

Original languageEnglish (US)
Pages (from-to)1675-1685
Number of pages11
Issue number12
StatePublished - Dec 2020

ASJC Scopus subject areas

  • Gastroenterology
  • Hepatology


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