University of Oulu

Holmberg, D., Santoni, G., von Euler-Chelpin, M. C., Färkkilä, M., Kauppila, J. H., Maret-Ouda, J., Ness-Jensen, E., & Lagergren, J. (2022). Incidence and mortality in upper gastrointestinal cancer after negative endoscopy for gastroesophageal reflux disease. Gastroenterology, 162(2), 431-438.e4.

Incidence and mortality in upper gastrointestinal cancer after negative endoscopy for gastroesophageal reflux disease

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Author: Holmberg, Dag1; Santoni, Giola1; von Euler-Chelpin, My Catarina2;
Organizations: 1Department of Molecular Medicine and Surgery, Karolinska Institutet and Karolinska University Hospital, Stockholm, Sweden
2Department of Public Health, University of Copenhagen, Copenhagen, Denmark
3Clinic of Gastroenterology, University of Helsinki and Helsinki University Hospital, Helsinki, Finland
4Department of Surgery, Oulu University Hospital and University of Oulu, Oulu, Finland
5Centre for Clinical Research Sörmland, Uppsala University, Eskilstuna, Sweden
6Department of Public Health and Nursing, Norwegian University of Science and Technology, Trondheim/Levanger, Norway
7Medical Department, Levanger Hospital, Nord-Trøndelag Hospital Trust, Levanger, Norway
8School of Cancer and Pharmacological Sciences, King’s College London, London, UK
Format: article
Version: published version
Access: open
Online Access: PDF Full Text (PDF, 0.7 MB)
Persistent link:
Language: English
Published: Elsevier, 2022
Publish Date: 2022-06-29


Background and Aims: Gastroesophageal reflux disease (GERD) is associated with an increased risk of cancer of the upper gastrointestinal tract. This study aimed to assess whether and to what extent a negative upper endoscopy in patients with GERD is associated with decreased incidence and mortality in upper gastrointestinal cancer (ie, esophageal, gastric, or duodenal cancer).

Methods: We conducted a population-based cohort study of all patients with newly diagnosed GERD between July 1, 1979 and December 31, 2018 in Denmark, Finland, Norway, and Sweden. The exposure, negative upper endoscopy, was examined as a time-varying exposure, where participants contributed unexposed person-time from GERD diagnosis until screened and exposed person-time from the negative upper endoscopy. The incidence and mortality in upper gastrointestinal cancer were assessed using parametric flexible models, providing adjusted hazard ratios (HRs) with 95% confidence intervals (CIs).

Results: Among 1,062,740 patients with GERD (median age 58 years; 52% were women) followed for a mean of 7.0 person-years, 5324 (0.5%) developed upper gastrointestinal cancer and 4465 (0.4%) died from such cancer. Patients who had a negative upper endoscopy had a 55% decreased risk of upper gastrointestinal cancer compared with those who did not undergo endoscopy (HR, 0.45; 95% CI, 0.43–0.48), a decrease that was more pronounced during more recent years (HR, 0.34; 95% CI, 0.30–0.38 from 2008 onward), and was otherwise stable across sex and age groups. The corresponding reduction in upper gastrointestinal mortality among patients with upper endoscopy was 61% (adjusted HR, 0.39; 95% CI, 0.37–0.42). The risk reduction after a negative upper endoscopy in incidence and mortality lasted for 5 and at least 10 years, respectively.

Conclusions: Negative upper endoscopy is associated with strong and long-lasting decreases in incidence and mortality in upper gastrointestinal cancer in patients with GERD.

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Series: Gastroenterology
ISSN: 0016-5085
ISSN-E: 1528-0012
ISSN-L: 0016-5085
Volume: 162
Issue: 2
Pages: 431 - 438.e4
DOI: 10.1053/j.gastro.2021.10.003
Type of Publication: A1 Journal article – refereed
Field of Science: 3126 Surgery, anesthesiology, intensive care, radiology
3122 Cancers
Funding: Supported by the Swedish Research Council (2019-00209) and Swedish Cancer Society (180684).
Copyright information: © 2022 by the AGA Institute. Published by Elsevier Inc. This is an open access article under the CC BY license (