The risk of oesophageal adenocarcinoma after gastrectomy for peptic ulcer disease

Abstract

Background

The influence of bile reflux in the development of oesophageal adenocarcinoma remains controversial. This was tested in a cohort of patients who had undergone gastrectomy, a procedure often entailed by substantial bile reflux.

Methods

A population-based cohort study of patients who had undergone gastrectomy for peptic ulcer disease in 1964–2008 in Sweden. Follow-up for cancer and censoring for death were achieved through linkages to nationwide registries of Cancer and Population, respectively. The number of observed cancer cases in the gastrectomy cohort was divided by the expected number, calculated from the incidence of the entire Swedish population of corresponding age, sex and calendar year. Relative risks were thus presented as standardised incidence ratios with 95% confidence intervals.

Results

After exclusion of all person-years the first year after surgery, the final gastrectomy cohort comprised of 19,767 patients. These patients were followed up for a median of 17 years, and contributed with a total of 348,231 person-years at risk. The observed number of patients with oesophageal adenocarcinoma (n = 7) was not higher than the expected (n = 11.6), providing a standardised incidence ratio of 0.6 (95% CI 0.2–1.2). There were no clear differences between sexes, age groups or latency intervals after gastrectomy.

Conclusions

Gastrectomy for peptic ulcer disease does not appear to increase the risk of oesophageal adenocarcinoma.

Introduction

Oesophageal adenocarcinoma is characterised by a poor prognosis and a rapidly increasing incidence during the last few decades,1, 2 patterns that stress the need for aetiological research. Gastro-oesophageal reflux, causing the premalignant epithelial metaplasia Barrett’s oesophagus, is the main risk factor for this tumour.³ Animal studies have indicated that duodeno-gastro-oesophageal reflux, with high contents of bile in the oesophagus, is an especially harmful component of reflux in the development of oesophageal adenocarcinoma,4, 5, 6, 7 and mechanisms explaining the carcinogenic effects of bile are being explored.7, 8, 9 The association between bile reflux and oesophageal adenocarcinoma in humans has, however, not been established. The slightly increased risk of oesophageal adenocarcinoma reported after cholecystectomy might be caused by an increased presence of bile in the oesophagus,¹⁰ but the average oesophageal bile exposure after cholecystectomy is low. The situation that occurs after partial or total gastrectomy mimics a human experimental model of bile reflux, since such surgery is often followed by a substantially increased risk of oesophageal exposure to bile.11, 12, 13, 14, 15, 16, 17, 18, 19 The anatomical rearrangement after gastrectomy means that duodenal contents easily flow back and reach the oesophagus. Data from a case series have suggested an increased risk of oesophageal adenocarcinoma after such surgery.²⁰ Problems with evaluating risk of oesophageal adenocarcinoma after gastrectomy include the limited number of patients currently treated with such surgery, the need for a long follow-up time to assess cancer risk, and the low incidence of oesophageal adenocarcinoma. In Sweden, there are excellent opportunities for research based on nationwide and complete health care registries with a long history. These sources were utilised to conduct a cohort study assessing the relation between gastrectomy for peptic ulcer disease and risk of developing oesophageal adenocarcinoma.