Esophagus to Small Intestine

BMJ. 2023;382:e076017

Holmberg D, Santoni G, von Euler-Chelpin M, Färkkilä M, Kauppila JH, Maret-Ouda J, Ness-Jensen E, Lagergren J

Non-erosive gastroesophageal reflux disease and incidence of esophageal adenocarcinoma in 3 Nordic countries: Population-based cohort study

Objective: To assess the incidence rate of esophageal adenocarcinoma among patients with non-erosive gastroesophageal reflux disease compared with the general population.
Design: Population-based cohort study.
Setting: All patients in hospital and specialized outpatient healthcare in Denmark, Finland, and Sweden from January 1, 1987, to December 31, 2019.
Participants: 486,556 adults (> 18 years) who underwent endoscopy were eligible for inclusion: 285,811 patients were included in the non-erosive gastroesophageal reflux disease cohort and 200,745 patients in the validation cohort with erosive gastroesophageal reflux disease.
Exposures: Non-erosive gastroesophageal reflux disease was defined by an absence of esophagitis and any other esophageal diagnosis at endoscopy. Erosive gastroesophageal reflux disease was examined for comparison reasons and was defined by the presence of esophagitis at endoscopy.
Main outcome measures: The incidence rate of esophageal adenocarcinoma was assessed for up to 31 years of follow-up. Standardized incidence ratios (SIRs) with 95% confidence intervals (CIs) were calculated by dividing the observed number of esophageal adenocarcinomas in each of the gastroesophageal reflux disease cohorts by the expected number, derived from the general populations in Denmark, Finland, and Sweden of the corresponding age, sex, and calendar period.
Results: Among 285,811 patients with non-erosive gastroesophageal reflux disease, 228 developed esophageal adenocarcinomas during 2,081,051 person-years of follow-up. The incidence rate of esophageal adenocarcinoma in patients with non-erosive gastroesophageal reflux disease was 11.0/100,000 person-years. The incidence was similar to that of the general population (SIR = 1.04 [95% CI: 0.91–1.18]), and did not increase with longer follow-up (SIR = 1.07 [95% CI: 0.65–1.65] for 15–31 years of follow-up). For validity reasons, the authors also analyzed people with erosive esophagitis at endoscopy (200,745 patients, 1,750,249 person-years, and 542 esophageal adenocarcinomas, corresponding to an incidence rate of 31.0/100,000 person-years) showing an increased overall SIR of esophageal adenocarcinoma (2.36 [95% CI: 2.17–2.57]), which became more pronounced with longer follow-up.

Conclusions: Patients with non-erosive gastroesophageal reflux disease seem to have a similar incidence of esophageal adenocarcinoma as the general population. This finding suggests that endoscopically confirmed non-erosive gastroesophageal reflux disease does not require additional endoscopic monitoring for esophageal adenocarcinoma.

Prof. Dr. J. Lagergren, Department of Molecular Medicine and Surgery, Karolinska Institute, Karolinska University Hospital, Stockholm, Sweden, E-Mail:

DOI: 10.1136/bmj-2023-076017

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