Esophagus to Small Intestine
Gastroenterology. 2022;162(2):431–8.e4
Incidence and mortality in upper gastrointestinal cancer after negative endoscopy for gastroesophageal reflux disease
Background and aims: Gastroesophageal reflux disease (GERD) is associated with an increased risk of cancer of the upper gastrointestinal (GI) 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 GI cancer (i.e., esophageal, gastric, or duodenal cancer).
Methods: The authors 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 GI cancer were assessed using parametric flexible models, providing adjusted hazard ratios (aHRs) with 95% confidence intervals (CIs).
Results: Among 1,062,740 patients with GERD (median age, 58 years; 52% women) followed for a mean of 7.0 person-years, 5324 (0.5%) developed upper GI cancer and 4465 (0.4%) died from such cancer. Patients who had a negative upper endoscopy had a 55% decreased risk of upper GI cancer compared with those who did not undergo endoscopy (aHR = 0.45, 95% CI: 0.43–0.48), a decrease that was more pronounced during more recent years (aHR = 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 GI mortality among patients with upper endoscopy was 61% (aHR = 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 gastroesophageal reflux disease.