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. 2022 Jul 1;276(1):e32-e39.
doi: 10.1097/SLA.0000000000004482. Epub 2020 Nov 12.

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  1 , Burcin Pehlivanoglu  2 , Bahar Memis  2 , Michelle D Reid  2 , Takeshi Uehara  3 , Olca Basturk  4 , Jennifer Golia Pernicka  5 , David S Klimstra  4 , William R Jarnagin  6 , Tetsuya Ito  1 , Osamu Hasebe  7 , Shinji Okaniwa  8 , Naoto Horigome  8 , Takeshi Hisa  9 , Pardeep Mittal  10 , Juan M Sarmiento  11 , Shishir K Maithel  11 , Jill Koshiol  12 , Susan Tsai  13 , Douglas Evans  13 , Mert Erkan  14 , Volkan Adsay  15
Affiliations

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 et al. Ann Surg. .

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.

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Conflict of interest statement

The authors report no conflicts of interest.

Figures

FIGURE 1.
FIGURE 1.
A schema of the junction between pancreatic and bile ducts. A: Normal junction. The junction between pancreatic and bile ducts is located in the duodenal wall. At the duodenal papilla, sphincter of Oddi surrounds the pancreaticobiliary junction, and regulates the flow of bile while preventing the reflux of pancreatic secretion into bile duct. B: Pancreatobiliary maljunction. The common channel is longer than normal, which abrogates the influence of the sphincter on the pancreatobiliary junction, allowing the reciprocal reflux of pancreatic secretion and bile. BD indicates bile duct;CH, common channel;PD, pancreatic duct; SO, sphincter of Oddi.
FIGURE 2.
FIGURE 2.
Two types of PBM in the US cohort. PBMs were classified into 2 distinct types based on imaging findings (10). A: “nondilated” (< 1.0 cm) type. B: “dilated” (2: 1.0 cm) type.
FIGURE 3.
FIGURE 3.
Ultrasonography and histopathological findings in the US cohort. A: Ultrasonography. The diffuse thickness of the inner layer of the gallbladder wall in pancreatobiliary maljunction-associated gallbladder carcinoma. (55 years, female, dilated type) B: Mucosal hyperplasia was seen in the background mucosa. (H&E stain, X20).
FIGURE 4.
FIGURE 4.
Kaplan-Meier overall survival curves. A: A comparison between of patients with pancreatobiliary maljunction (PBM)-associated (n = 39) and not associated (n = 73) GBCs. B: A comparison between of patients with PBM-associated GBCs in the US (n = 24) and Japan (n = 15) cohorts. C: Survival curve of PBM patients who underwent prophylactic cholecystectomy in Japan cohort (n = 40).
See this image and copyright information in PMC

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