Takashi Muraki1, Burcin Pehlivanoglu2, Bahar Memis2, Michelle D Reid2, Takeshi Uehara3, Olca Basturk4, Jennifer Golia Pernicka5, David S Klimstra4, William R Jarnagin6, Tetsuya Ito1, Osamu Hasebe7, Shinji Okaniwa8, Naoto Horigome8, Takeshi Hisa9, Pardeep Mittal10, Juan M Sarmiento11, Shishir K Maithel11, Jill Koshiol12, Susan Tsai13, Douglas Evans13, Mert Erkan14, Volkan Adsay15. 1. Department of Gastroenterology, Shinshu University Hospital, Nagano, Japan. 2. Department of Pathology, Emory University Hospital, Atlanta, Georgia. 3. Department of Pathology, Shinsu University Hospital, Nagano, Japan. 4. Department of Pathology, Memorial Sloan Kettering Cancer Center, New York, New York. 5. Department of Radiology, Memorial Sloan Kettering Cancer Center, New York, New York. 6. Department of Surgery, Memorial Sloan Kettering Cancer Center, New York, New York. 7. Department of Gastroenterology, Nagano Municipal Hospital, Nagano, Japan. 8. Department of Digestive Surgery, iida Municipal Hospital, iida, Japan. 9. Department of Gastroenterology, Saku Center Hospital, Nagano, Japan. 10. Department of Radiology, Emory University Hospital, Atlanta, Georgia. 11. Department of Surgery, Emory University Hospital, Atlanta, Georgia. 12. Cancer Epidemiology and Genetics, National Institute of Health, Maryland. 13. Department of Surgery, Medical College of Wisconsin, Milwaukee, Wisconsin. 14. Department of Surgery, Koc University, Istanbul, Turkey. 15. Department of Pathology and Research Center for Translational Medicine (KUTTAM), Koç University, Istanbul, Turkey.
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.
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.