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Original Investigation
November 2018

Risk of Esophageal Adenocarcinoma After Antireflux Surgery in Patients With Gastroesophageal Reflux Disease in the Nordic Countries

Author Affiliations
  • 1Upper Gastrointestinal Surgery, Department of Molecular Medicine and Surgery, Karolinska Institutet, Karolinska University Hospital, Stockholm, Sweden
  • 2Impact Assessment Unit, Department of Health Protection, National Institute for Health and Welfare, Tampere, Finland
  • 3Centre for Translational Microbiome Research, Department of Microbiology, Tumor, and Cell Biology, Karolinska Institutet, Stockholm, Sweden
  • 4Science For Life Laboratory (SciLifeLab), Karolinska Institutet, Stockholm, Sweden
  • 5Clinic of Gastroenterology, University of Helsinki, Helsinki University Hospital, Helsinki, Finland
  • 6Department of Public Health, University of Copenhagen, Copenhagen, Denmark
  • 7Finnish Cancer Registry, Institute for Statistical and Epidemiological Cancer Research, Helsinki, Finland
  • 8Faculty of Social Sciences, University of Tampere, Tampere, Finland
  • 9Department of Public Health and General Practice, Faculty of Medicine, Norwegian University of Science and Technology, Trondheim, Norway
  • 10Icelandic Cancer Registry, Icelandic Cancer Society, Reykjavik, Iceland
  • 11Faculty of Medicine, University of Iceland, Reykjavik, Iceland
  • 12School of Cancer Sciences, King’s College London, London, United Kingdom
JAMA Oncol. 2018;4(11):1576-1582. doi:10.1001/jamaoncol.2018.3054
Key Points

Questions  Is treatment of gastroesophageal reflux disease (GERD) associated with decreased risk of esophageal adenocarcinoma, and is there a difference in risk between patients treated with antireflux surgery and those receiving medication only?

Findings  This multinational, population-based cohort study included 48 414 individuals who underwent antireflux surgery and 894 492 individuals with GERD treated with medication only in any of the 5 Nordic countries. The risk of esophageal adenocarcinoma decreased over time after antireflux surgery to reach a similar level as that in the background population and was similar when comparing individuals who underwent surgery with those who did not.

Meaning  Both antireflux surgery and medication may be associated with decreased risk of esophageal adenocarcinoma in patients with GERD, decreasing to a similar level as that in the background population over time.


Importance  Gastroesophageal reflux disease (GERD) is associated with a strong and severity-dependent increased risk of esophageal adenocarcinoma. Whether antireflux surgery prevents esophageal adenocarcinoma is a matter of uncertainty.

Objectives  To examine whether antireflux surgery is associated with reduced risk of esophageal adenocarcinoma and whether the risk is different between surgically and medically treated patients.

Design, Setting, and Participants  In this multinational, population-based retrospective cohort study from Denmark, Finland, Iceland, Norway, and Sweden, patients undergoing surgery were followed up for a median of 12.7 years, and a comparison group of patients receiving medication only were followed up for a median of 4.8 years. All patients with a registered diagnosis of GERD (or an associated disorder), including 48 414 individuals undergoing surgery and 894 492 receiving medication only, were included in the study. The study periods varied in the different countries depending on the year of initiation of registration and the date of data retrieval, from January 1, 1964, to December 21, 2014.

Exposures  Antireflux surgery for GERD.

Main Outcomes and Measures  The risk of esophageal adenocarcinoma over time after surgery was compared with that in a corresponding background population using standardized incidence ratios (SIRs) with 95% CIs and with patients with GERD who received medication using multivariable Cox proportional hazards regression, providing hazard ratios (HRs) with 95% CIs adjusted for confounders.

Results  In this study of 942 906 patients with GERD, 48 414 underwent antireflux surgery (median [interquartile range] age, 66.0 [58.0-73.0] years; 27 161 male [56.1%]) and 894 492 received medication only (median [interquartile range] age, 71.0 [62.0-78.0] years; 434 035 male [48.6%]). Among patients undergoing surgery, 177 developed esophageal adenocarcinoma. Esophageal adenocarcinoma risk decreased in a time-dependent manner after surgery compared with the background population (5 to <10 years after surgery: SIR, 7.63; 95% CI, 5.42-10.43; ≥15 years after surgery: SIR, 1.34; 95% CI, 0.98-1.80). Among patients with more severe and objectively determined GERD, the SIRs were 10.08 (95% CI, 6.98-14.09) at 5 to less than 10 years after surgery and 1.67 (95% CI, 1.15-2.35) at 15 years or more after surgery. The risk of esophageal adenocarcinoma did not change over time in surgical patients compared with patients who received medication only (5 to <10 years after surgery: HR, 2.02; 95% CI, 1.44-2.84; ≥15 years: HR, 1.80; 95% CI, 1.28-2.54). The risk remained stable over time in analyses restricted to severe reflux disease (5 to <10 years after surgery: HR, 1.81; 95% CI, 1.24-2.63; ≥15 years after surgery: HR, 1.69; 95% CI, 1.14-2.51).

Conclusions and Relevance  Medical and surgical treatment of GERD were associated with a similar reduced esophageal adenocarcinoma risk, with the risk decreasing to the same level as that in the background population over time, supporting the hypothesis that effective treatment of GERD might prevent esophageal adenocarcinoma.