Introduction Background: Loss of the gallbladder reservoir function at cholecystectomy may critically alter the dynamics of bile storage and release. Consequent iatrogenic duodeno-gastro-esophageal reflux (DGER) may be associated with oesophago-gastric adenocarcinoma.

Aims To examine the histological and molecular effects of cholecystectomy-induced DGER on gastric and oesophageal mucosae.

Methods Patients and Methods: In a retrospective study we compared 26 gallstone-free controls with 25 patients pre-cholecystectomy and 29 patients post-cholecystectomy for one or more years. In a prospective study we compared 26 controls with 25 patients before and within 1 year of cholecystectomy. All underwent oesophago-gastro-duodenoscopy (EGD) with biopsies from the antrum, esophagogastric junction (EGJ) and 5 cm above the EGJ. A histochemical bile reflux index (BRI) was calculated and immunohistochemistry was performed for p53 and Ki67.

Results Results: In the retrospective study antral BRI positivity was 11% in controls vs 69% in cholecystectomy patients (p=0.001); at the EGJ BRI positivity was 19% in controls vs 41% in cholecystectomy patients (p=0.032). p53 was expressed at the antrum in 4% of controls vs 52% cholecystectomy patients(p=0.001) and in 19% vs 66% at the EGJ (p=0.001). Ki67 was expressed at the antrum in 23% vs 59% (p=0.001) and at the EGJ in 19% vs 62% (p=0.001). Prospectively, BRI positivity increased from 11% to 36% (p=0.04) at the antrum within 1 year of cholecystectomy. Ki67 expression increased from 19% to 48% (p=0.044) at EGJ in patients within 1 year of cholecystectomy while p53 remained unchanged.

Conclusion Changes attributable to DGER occur early in the gastric and LES mucosae of patients following cholecystectomy. Ki67 and p53 over-expression suggests that these changes may be precursors of malignant transformation. Such concerning changes suggest that options other than cholecystectomy be considered for patients with gallstones in a functioning gallbladder.

Competing interests None declared.