Biliary carcinogenesis in pancreaticobiliary maljunction

J Gastroenterol. 2017 Feb;52(2):158-163. doi: 10.1007/s00535-016-1268-z. Epub 2016 Oct 4.

Abstract

Pancreaticobiliary maljunction (PBM) is a congenital malformation in which the pancreatic and bile ducts join anatomically outside the duodenal wall. Because of the excessive length of the common channel in PBM, sphincter action does not directly affect the pancreaticobiliary junction, which allows pancreatic juice to reflux into the biliary tract. According to the results of a nationwide survey, bile duct and gallbladder cancers were found in 6.9 and 13.4 % of adult patients with congenital biliary dilatation, respectively, and in 3.1 and 37.4 % of those with PBM without biliary dilatation, respectively. Biliary tract cancers develop about 15-20 years earlier in patients with PBM than in individuals without PBM; they sometimes develop as double cancers. Carcinogenesis is strongly associated with stasis of bile intermingled with refluxed pancreatic juice. Epithelial cells in the biliary tract of PBM patients are under constant attack from activated pancreatic enzymes, increased secondary bile acids, or other mutagens. This can result in hyperplastic change with increased cell proliferation activity, and in turn, oncogene and/or tumor suppressor gene mutations in the epithelia, leading to the biliary tract carcinogenesis. The carcinogenesis of biliary tract cancer accompanying PBM is considered to involve a hyperplasia-dysplasia-carcinoma sequence induced by chronic inflammation caused by the reflux of pancreatic juice into the biliary tract, which differs from the adenoma-carcinoma sequence or the de novo carcinogenesis associated with biliary tract cancers in the population without PBM. Patients with a relatively long common channel have a similar, albeit slightly lower, risk for gallbladder cancer compared with PBM patients.

Keywords: Bile duct cancer; Congenital biliary dilatation; Gallbladder cancer; Pancreaticobiliary maljunction; Pancreatobiliary reflux.

Publication types

  • Review

MeSH terms

  • Adult
  • Animals
  • Bile Duct Neoplasms / epidemiology
  • Bile Duct Neoplasms / pathology*
  • Bile Ducts / abnormalities*
  • Bile Ducts / pathology
  • Biliary Tract Neoplasms / epidemiology
  • Biliary Tract Neoplasms / pathology
  • Cell Proliferation
  • Common Bile Duct / abnormalities
  • Common Bile Duct / pathology
  • Gallbladder Neoplasms / epidemiology
  • Gallbladder Neoplasms / pathology*
  • Humans
  • Inflammation / pathology
  • Pancreatic Ducts / abnormalities*
  • Pancreatic Ducts / pathology
  • Pancreatic Juice / metabolism
  • Risk Factors