Pancreatobiliary Maljunction-associated Gallbladder Cancer Is as Common in the West, Shows Distinct Clinicopathologic Characteristics and Offers an Invaluable Model for Anatomy-induced Reflux-associated Physio-chemical Carcinogenesis

Takashi Muraki, Burcin Pehlivanoglu, Bahar Memis, Michelle D. Reid, Takeshi Uehara, Olca Basturk, Jennifer Golia Pernicka, David S. Klimstra, William R. Jarnagin, Tetsuya Ito, Osamu Hasebe, Shinji Okaniwa, Naoto Horigome, Takeshi Hisa, Pardeep Mittal, Juan M. Sarmiento, Shishir K. Maithel, Jill Koshiol, Susan Tsai, Douglas EvansMert Erkan, Volkan Adsay

Research output: Contribution to journalArticlepeer-review

14 Scopus citations

Abstract

Objective:To determine the associations of pancreatobiliary maljunction (PBM) in the West.Background:PBM (anomalous union of common bile duct and pancreatic duct) is mostly regarded as an Asian-only disorder, with 200X risk of gallbladder cancer (GBc), attributed to reflux of pancreatic enzymes. Methods: Radiologic images of 840 patients in the US who underwent pancreatobiliary resections were reviewed for PBM and contrasted with 171 GBC cases from Japan.Results:Eight % of the US GBCs (24/300) had PBM (similar to Japan; 15/ 171, 8.8%), in addition to 1/42 bile duct carcinomas and 5/33 choledochal cysts. None of the 30 PBM cases from the US had been diagnosed as PBM in the original work-up. PBM was not found in other pancreatobiliary disorders. Clinicopathologic features of the 39 PBM-associated GBCs (US:24, Japan:15) were similar; however, comparison with non-PBM GBCs revealed that they occurred predominantly in females (F/M = 3); at younger (<50-year-old) age (21% vs 6.5% in non-PBM GBCs; P = 0.01); were uncommonly associated with gallstones (14% vs 58%; P < 0.001); had higher rate of tumor-infiltrating lymphocytes (69% vs 44%; P = 0.04); arose more often through adenoma-carcinoma sequence (31% vs 12%; P = 0.02); and had a higher proportion of nonconventional carcinomas (21% vs 7%; P = 0.03). Conclusions: PBM accounts for 8% of GBCs also in the West but is typically undiagnosed. PBM-GBCs tend to manifest in younger age and often through adenoma-carcinoma sequence, leading to unusual carcinoma types. If PBM is encountered, cholecystectomy and surveillance of bile ducts is warranted. PBM-associated GBCs offer an invaluable model for variant anatomy-induced chemical (reflux-related) carcinogenesis.

Original languageEnglish (US)
Pages (from-to)E32-E39
JournalAnnals of surgery
Volume276
Issue number1
DOIs
StatePublished - Jul 1 2022
Externally publishedYes

Keywords

  • anomalous
  • anomaly
  • bile duct
  • carcinogenesis
  • carcinoma
  • gallbladder
  • hyperplasia
  • junction
  • maljunction
  • reflux
  • union

ASJC Scopus subject areas

  • Surgery

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