Pancreaticobiliary reflux in patients with a normal pancreaticobiliary junction: Pathologic implications

Knowledge on pancreaticobiliary reflux in normal pancreaticobiliary junction and its pathologic implications has experienced tremendous progress during the last few years. This editorial reviews the current knowledge on this condition and its pathological implications on gallbladder diseases. The following aspects were defined appropriate for discussion: (1) Evidence of carcinogenesis associated with pancreaticobiliary reflux; (2) Evidence of pancreaticobiliary reflux in normal pancreaticobiliary junction; and (3) Evidence of sphincter of Oddi (SO) dysfunction as a cause of pancreaticobiliary reflux in normal pancreaticobiliary junction. The articles reviewed were selected and classified according to five levels of evidence: Level I, meta-analysis double-blind randomized clinical trials, Level II, cohort non-blinded studies and non-randomized clinical trials, Level III, good quality case-control studies and non-randomized cohort studies, Level IV, case series and poor quality case-control studies, and Level V, case report articles and experts' opinion. Evidence levels II, III, IV and V were found to support biliary carcinogenesis associated with pancreaticobiliary reflux in normal and abnormal pancreaticobiliary junction. The same levels of evidence were found to support the common occurrence of pancreaticobiliary reflux in normal pancreaticobiliary junction, and SO dysfunction as the most plausible cause of this condition. Although an important body of research has been published regarding pancreaticobiliary reflux in normal pancreaticobiliary junction and its clinical significance, the current evidence does not fully support what has been suggested. Studies with evidence level I have not been undertaken. This is a fascinating subject of study, and if finally supported by evidence level I, the importance of this condition will constitute a major breakthrough in biliary pathology.