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Updated: May 14, 2026

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Published on: August 22, 2025
Risk factors for esophageal adenocarcinoma after antireflux surgery
Hedvig E Löfdahl1, Yunxia Lu, Pernilla Lagergren
1Unite of Upper Gastrointestinal Research, Department of Molecular Medicine and Surgery, Karolinska Institutet, Stockholm, Sweden. hedvig.lofdahl@ki.se
Objectives:
Gastroesophageal reflux is the main risk factor for esophageal adenocarcinoma, but there is no strong support for any cancer-protective effect after antireflux surgery. We hypothesized that recurrent reflux or high exposure to other established risk factors, that is, obesity and tobacco smoking, are overrepresented among patients who despite antireflux surgery develop esophageal adenocarcinoma.
Design:
A population-based case-control study was nested within an antireflux surgery cohort from the Swedish Patient Register between 1965 and 2006. Cases were patients who developed esophageal adenocarcinoma more than 5 years after antireflux surgery, whereas randomly selected controls were matched to the cases regarding age, sex, and calendar year of the antireflux surgery. Study exposures among cases and controls were collected through review of medical records. Data on cancer were assessed through the Swedish Cancer Register. Odds ratios (ORs) with 95% confidence intervals (CIs) were calculated using multivariable conditional logistic regression, adjusted for recurrent reflux, body mass index (BMI), tobacco smoking, and type of antireflux surgery.
Results:
From 14,102 patients in the total antireflux surgery cohort, 55 cases and 240 controls were included. Patients who developed esophageal adenocarcinoma were 3 times more likely to have recurrent reflux after their antireflux surgery, compared with those who had not (OR: 3.1, 95% CI: 1.5-6.3). There were no statistically significant differences in risk when comparing BMI of 30 kg/m or more with BMI of less than 25 kg/m (OR: 1.6, CI: 0.8-3.5), ever smokers with never smokers (OR: 1.4, 95% CI: 0.7-2.8), or total fundoplication with partial fundoplication (OR: 0.6, 95% CI: 0.3-1.3).
Conclusions:
Recurrence of reflux might explain the lack of protective effect of antireflux surgery regarding risk of developing esophageal adenocarcinoma.
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