Oesophageal and Proximal Gastric Adenocarcinomas Are Rare After Detection of Helicobacter pylori Infection

Shria Kumar; David C. Metz; Gregory G. Ginsberg; David E. Kaplan; David S. Goldberg


Aliment Pharmacol Ther. 2020;51(8):781-788. 

In This Article


This retrospective cohort study was conducted within the Veterans Health Administration Corporate Data Warehouse which includes data from the unified electronic medical record of all Veterans Health Administration facilities (i.e. hospitals and outpatient) since 01 October 1999.

Study Cohort

We identified patients with H pylori infection, and this cohort has been extensively described elsewhere.[19] Briefly, patients with H pylori infection were included based on: 1) endoscopic pathology by natural language processing, 2) positive stool antigen test or 3) positive urea breath test. For patients with multiple criteria, the criterion with the earliest date were used. (Unique identifiers assured no duplications.)

Study Outcomes

The outcomes included both oesophageal adenocarcinoma and proximal (cardia) gastric adenocarcinomas. Both were identified using the Veterans Affairs Central Cancer Registry and/or ICD 9/10 codes.[20] The Central Cancer Registry is a comprehensive, national database of cancers diagnosed and treated in the Veterans Health Administration since 1995. ICD9/10 codes were used and included for oesophageal: ICD 9 150.9, 150.2, 150.5 and ICD 10 C15.5, 15.8, and 15.9 and for cardia cancer: ICD 9 151.0 and ICD 10 C16.0. There is no administrative code delineating the histologic subtype of oesophageal cancers, but oesophageal adenocarcinomas are the most common subtype of oesophageal cancer, particularly distally.[21,22] The diagnosis of either cancer was minimum 30 days after H pylori diagnosis to ensure testing was for H pylori, not a malignancy workup. We filtered to include cardia adenocarcinomas and oesophageal adenocarcinomas.

Statistical Analysis

We performed a time to event analysis using competing risk models, with start time the date of H pylori diagnosis. Follow-up time ended at development of oesophageal and proximal gastric cancers, death prior to oesophageal and proximal gastric cancers, development of non-proximal gastric adenocarcinoma, or end of follow-up. Death was considered a competing risk to oesophageal and proximal gastric cancers as patients could die from another cause, precluding the development of oesophageal and proximal gastric cancers, and factors associated with mortality might also be associated with oesophageal and proximal gastric cancers. Similarly, if patients developed non-proximal gastric adenocarcinoma, any predisposing factors may also be associated with oesophageal and proximal gastric cancers. Among the entire H pylori cohort, we evaluated covariates shown to be associated with various subtypes of foregut cancer: age at H pylori diagnosis, gender, race, ethnicity, history of ever smoking (current or prior diagnostic code)[23] and zip code-level poverty at H pylori diagnosis. Zipcode-level poverty was based on 2010 census data, categorised based on percentage of people within a zipcode below the federal poverty line. We also included whether the patient received prescription for an eradication regimen for H pylori as a covariate. Receipt of H pylori treatment was defined as receiving a recommended antibiotic regimen after H pylori diagnosis at the Veterans Health Administration using prescription filling data at any inpatient or outpatient Veterans Health Administration facility.[19]

A secondary analysis sought to evaluate the association between eradication status and oesophageal and proximal gastric cancers, given varying rates of re-testing and successful H pylori treatment.[4,24] This analysis was restricted to those who received treatment for H pylori. Eradication was based on having either a negative stool antigen, urea breath test, and/or pathology (gastric biopsy on endoscopy) upon repeat testing. Failed eradication was defined as a positive stool antigen, urea breath test and/or pathology, or a positive H pylori test after a prior negative test given that true re-infection is exceedingly rare. Patients without any eradication testing were considered as "unknown" eradication status. H pylori status on pathology was determined by repeat natural language processing, which has been described elsewhere.[19] We excluded patients who had eradication testing via endoscopy within 90 days of eventual cancer diagnosis, as this was possibly performed for alarm symptoms, versus eradication testing alone.

Stata/IC 15.1 was used to perform backward selection, with inclusion of all clinically significant sub-hazard ratios (SHRs), where P < 0.10. The Institutional Review Boards of the Corporal Michael J. Crescenz VA Medical Center and the University of Pennsylvania approved this study.