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

• Type of Material: Article
• Authors: Takashi Muraki, Shinshu University Hospital, Nagano, Japan; Burcin Pehlivanoglu, Emory University; Bahar Memis, Emory University; Michelle D Reid, Emory University; Takeshi Uehara, Shinshu University Hospital, Nagano, JapanShinshu University Hospital, Nagano, Japan; Olca Basturk, Memorial Sloan Kettering Cancer Center, New York, New York;; Jennifer Golia Pernicka, Memorial Sloan Kettering Cancer Center, New York, New York;; David S Klimstra, Memorial Sloan Kettering Cancer Center, New York, New York;; William R Jarnagin, Memorial Sloan Kettering Cancer Center, New York, New York;; Tetsuya Ito, Shinshu University Hospital, Nagano, Japan;; Osamu Hasebe, Nagano Municipal Hospital, Nagano, Japan; Shinji Okaniwa, iida Municipal Hospital, iida, Japan; Naoto Horigome, iida Municipal Hospital, iida, Japan; Takeshi Hisa, Saku Center Hospital, Nagano, Japan;; Pardeep Mittal, Emory University; Juan M Sarmiento, Emory University; Shishir K Maithel, Emory University; Jill Koshiol, National Institute of Health, Maryland; Susan Tsai, Medical College of Wisconsin, Milwaukee, Wisconsin; Douglas Evans, Medical College of Wisconsin, Milwaukee, Wisconsin;; Mert Erkan, Koc University, Istanbul, Turkey; Volkan Adsay, Koç University, Istanbul, Turkey.
• Language: English
• Date: 2022-07-01
• Publisher: LIPPINCOTT WILLIAMS & WILKINS
• Publication Version: Author Accepted Manuscript (After Peer Review)
• Copyright Statement: © 2020 Wolters Kluwer Health
• Final Published Version (URL): http://dx.doi.org/10.1097/SLA.0000000000004482
• Title of Journal or Parent Work: ANNALS OF SURGERY
• Volume: 276
• Issue: 1
• Start Page: E32
• End Page: E39
• Keywords: hyperplasia; junction; Surgery; MULTICENTER; MR CHOLANGIOPANCREATOGRAPHY; bile duct; Science & Technology; CARCINOMA; Life Sciences & Biomedicine; SQUAMOUS-CELL; carcinogenesis; reflux; maljunction; BILIARY; CHOLEDOCHAL CYSTS; JUNCTION; carcinoma; DILATATION; anomalous; BILE-DUCT; gallbladder; union; anomaly; DIAGNOSTIC-CRITERIA
• Research Categories: Health Sciences, Radiology; Health Sciences, Oncology; Health Sciences, Medicine and Surgery; Health Sciences, Pathology; Health Sciences, Epidemiology

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.