Occult pancreaticobiliary reflux is a pathogenic factor of some benign biliary diseases and gallbladder cancer

Pancreaticobiliary maljunction (PBM) is a well-known high-risk factor for biliary malignant tumors because of constant pancreaticobiliary reflux (PBR). However, the impact of occult pancreaticobiliary reflux (OPR), which is characterized by high bile amylase levels in individuals with anatomically normal pancreaticobiliary junction, on biliary diseases remains unclear. The aim of this study was to assess the correlation between OPR and biliary diseases. We enrolled 94 consecutive patients with normal pancreaticobiliary junction and primary biliary diseases confirmed by magnetic resonance cholangiopancreatography. We prospectively collected patients’ bile samples and measured bile amylase levels. We investigated the incidence of OPR and the difference in bile amylase levels among these patients and assessed the correlation between high bile amylase levels (HBAL) and benign or malignant biliary diseases, as well as the OPR risk factors. The incidence of OPR was 36.6% in patients with benign biliary diseases, 26.7% in those with cholangiocarcinoma and 62.5% in those with gallbladder cancer. The median bile amylase level tended to be higher in patients with gallbladder cancer than in those with benign biliary diseases, but there was no significant difference (165.5 IU/L vs. 23.0 IU/L, P = 0.212). The prevalence of an HBAL with bile amylase levels of 1000-7500 IU/L was similar in patients with gallbladder cancer and benign biliary diseases. However, the incidence of HBAL with bile amylase levels greater than 7500 IU/L was significantly higher in patients with gallbladder cancer than in those with benign biliary diseases (37.5% vs. 4.2%, P = 0.012). Multivariate logistic regression analysis revealed that choledocholithiasis was an independent risk factor for OPR. OPR can occur in benign and malignant biliary diseases, and it may be a pathogenic factor for some benign biliary diseases and a high-risk factor for gallbladder cancer. There is a correlation between choledocholithiasis and OPR.