The risk of oesophageal adenocarcinoma after gastrectomy for peptic ulcer disease
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.
Section snippets
Study design
This was a Swedish population-based cohort study, addressing the risk of developing oesophageal adenocarcinoma after gastrectomy, using the entire Swedish population during the study period 1964 through 2008 as database. The study cohort consisted of all patients who had undergone gastrectomy for a peptic ulcer disease during the study period, as recorded in the Swedish Patient Registry. Since there has been no private in-hospital care for patients undergoing gastrectomy in Sweden and patients
Results
The gastrectomy cohort included 19,767 patients. Some characteristics of this cohort are presented in Table 1. The cohort members were followed up for a median of 17 years, and the total number of person-years at risk was 348,231. The study cohort consisted of more men (62.3%) than women. The vast majority of operations were partial gastrectomies (96.4%), while the remaining part was total gastrectomies.
The observed number of patients who developed oesophageal adenocarcinoma during follow-up was
Discussion
This study does not provide any evidence in support of the hypothesis that gastrectomy increases the risk of oesophageal adenocarcinoma.
Advantages of the study include the population-based cohort design, the complete assessment of both the exposure and the outcome, and the long follow-up period. The use of a gastrectomy cohort could be regarded as a human experiment model that allows assessment of effects of the exposure to bile reflux. A limitation is the low number of incident patients
Author contribution
Jesper Lagergren was responsible for the study concept and design, acquisition and interpretation of data, drafting of the manuscript. Anna Lindam was responsible for the statistical analysis, and provided critical revision of the manuscript.
Responsibility statement
The corresponding author had full access to all of the data and takes full responsibility for the veracity of the data and statistical analysis.
Conflict of interest statement
None declared.
Acknowledgements
The study was supported by project grants from the Swedish Research Council (SIMSAM) and the Swedish Cancer Society. These fund givers had no influence on the contents of the paper.
References (28)
- et al.
Emerging concepts of bile reflux in the constellation of gastroesophageal reflux disease
J Gastrointest Surg
(2010) - et al.
Association between cholecystectomy and adenocarcinoma of the esophagus
Gastroenterology
(2001) - et al.
Post-gastrectomy bile vomiting
Lancet
(1965) - et al.
Impact of esophageal bile exposure on the genesis of reflux esophagitis in the absence of gastric acid after total gastrectomy
Am J Gastroenterol
(2002) - et al.
Gastric surgery is not a risk for Barrett’s esophagus or esophageal adenocarcinoma
Gastroenterology
(2001) - et al.
Global cancer statistics, 2002
CA Cancer J Clin
(2005) - et al.
Incidence of adenocarcinoma of the esophagus among white Americans by sex, stage, and age
J Natl Cancer Inst
(2008) - et al.
Symptomatic gastroesophageal reflux as a risk factor for esophageal adenocarcinoma
N Engl J Med
(1999) - et al.
Impact of the biliary diversion procedure on carcinogenesis in Barrett’s esophagus surgically induced by duodenoesophageal reflux in rats
Ann Surg
(2004) - et al.
Reflux of duodenal or gastro-duodenal contents induces esophageal carcinoma in rats
Int J Cancer
(1996)
Carcinogenesis in reflux disease – in search for bile-specific effects
Microsurgery
Bile acid reflux contributes to development of esophageal adenocarcinoma via activation of phosphatidylinositol-specific phospholipase Cgamma2 and NADPH oxidase NOX5-S
Cancer Res
Acid, bile, and CDX: the ABCs of making Barrett’s metaplasia
Am J Physiol Gastrointest Liver Physiol
Surgical management of reflux gastritis
Ann Surg
Cited by (4)
A Tool to Predict Risk for Gastric Cancer in Patients With Peptic Ulcer Disease on the Basis of a Nationwide Cohort
2015, Clinical Gastroenterology and HepatologyCitation Excerpt :On the other hand, routine surveillance endoscopy without consideration of other risk factors is unjustified. Gastrectomy is also a risk factor of gastric cancer, and the risk might be increased decades after partial gastrectomy.29,30 The carcinogenesis could be different among patients who underwent gastrectomy, and the cancer risk should be evaluated separately.
Reply to Gagner’s Letter RE Features of MGB and OAGB
2019, Obesity SurgeryControversy surrounding 'mini' gastric bypass
2014, Obesity Surgery"mini" gastric bypass: Systematic review of a controversial procedure
2013, Obesity Surgery