Precancerous mucosal changes in the gallbladder of patients with occult pancreatobiliary reflux

BACKGROUND: Pancreatobiliary reflux can occur even if the pancreaticobiliary junction is normal (occult pancreatobiliary reflux), and it may be associated with gallbladder carcinoma. The aim of the present study was to examine precancerous mucosal changes in the gallbladder from patients with occult pancreatobiliary reflux. METHODS: The mucosa of the gallbladder from 13 patients who underwent cholecystectomy was examined histopathologically. These patients had an anatomically normal pancreatobiliary junction and a biliary amylase concentration greater than 10,000 IU/L. The gallbladder of patients without carcinoma was further examined by using immunohistochemical techniques to detect Ki-67, and the results were compared with those from control patients. RESULTS: Of the 13 patients, 5 (38%) had gallbladder carcinoma and 8 (62%) did not. Of the 8 patients without carcinoma, 4 (50%) had dysplasia accompanied by hyperplasia, and 2 (25%) had hyperplasia alone of the gallbladder mucosa. The Ki-67 labeling index was significantly higher in hyperplastic and dysplastic mucosa than in control gallbladder mucosa (p < 0.0004). CONCLUSIONS: Occult pancreatobiliary reflux could be associated with precancerous mucosal changes in the gallbladder, such as hyperplasia and dysplasia with increased cellular proliferation, and could be a possible risk factor for gallbladder carcinoma.