A Negative Upper Endoscopy in Patients With GERD Reduces Incidence and Mortality From Upper GI Cancers

A Negative Upper Endoscopy in Patients With GERD Reduces Incidence and Mortality From Upper GI Cancers

Prateek Sharma, MD, FASGE, reviewing Holmberg D, et al. Gastroenterology 2021 Oct 7.

Gastroesophageal reflux disease (GERD) is the most common reason for referral for upper endoscopy. This study sought to determine whether there is a relationship between a negative endoscopy and the incidence of and mortality from upper GI (UGI) malignancies. 

This population-based cohort study included more than 1.06 million participants (median age, 58; 48% male) with GERD, newly diagnosed from 1979 through 2018 in Nordic countries. Exposure was defined as negative endoscopy (no diagnosis of premalignant conditions or GI cancer within 6 months of endoscopy). 

During 3.04 million unexposed person-years of follow-up (time when no endoscopies were performed), 3601 people (0.34%) developed UGI cancer. Of 736,759 patients with a negative endoscopy (4.43 million exposed person-years), 1723 patients (0.23%) developed UGI cancer, and 1609 (0.22%) died due to their malignancy. The incidence of UGI cancer during unexposed person-time in patients with GERD was 119 per 100,000 person-years (95% confidence interval [CI], 115-123). The rate after a negative endoscopy was 38 per 100,000 person-years (95% CI, 37-40), and the adjusted hazard ratio (HR) was 0.45 (95% CI, 0.43-0.48), amounting to a 55% decreased risk of UGI cancers in patients with a negative upper endoscopy. This risk reduction was similar when stratified for esophageal cancer (52% reduction: HR, 0.48; 95% CI, 0.44-0.51) and gastric cancer (59% reduction: HR, 0.41; 95% CI, 0.38-0.45). The decreased risk was greatest after the first year of follow-up and lasted 5 years. 

Patients with GERD who had negative upper endoscopy had a 61% decreased risk of mortality from UGI cancer compared with those without an upper endoscopy (HR, 0.39; 95% CI, 0.37-0.42). Similarly, the adjusted HRs were greatest during the first year of follow-up, but overall risk was improved for 10 years. 

In a subgroup analysis, the risk of developing esophageal adenocarcinoma was cut in half (HR, 0.50; 95% CI, 0.45-0.55), and the risk of dying from the same was reduced by 67% (adjusted HR, 0.33; 95% CI, 0.30-0.37). Finally, there was a larger risk reduction noted after 2007 compared with the earlier group, which was thought to be due to the improvement in endoscopy technology during the study period.

Prateek Sharma, MD, FASGE


This large cohort study shows that negative upper endoscopy for patients with GERD can greatly reduce the incidence and mortality from UGI cancers. Patients with GERD will benefit from endoscopic screening of the upper GI tract with careful inspection of the mucosa for neoplastic changes.

Note to readers: At the time we reviewed this paper, its publisher noted that it was not in final form and that subsequent changes might be made.


Holmberg D, Santoni G, von Euler-Chelpin MC, et al. Incidence and mortality in upper gastrointestinal cancer after negative endoscopy for gastroesophageal reflux disease. Gastroenterology 2021 Oct 7. (Epub ahead of print) (https://doi.org/10.1053/j.gastro.2021.10.003)

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