Antireflux surgery in the prevention of supra-esophageal cancer and mortality

Gastroesophageal reflux disease (GERD), mainly characterized by heartburn or regurgitation, is a common condition in the Western world with an increasing prevalence. GERD is associated with an increased risk of adenocarcinoma of the esophagus, and possibly of supraesophageal cancers of the larynx, pharynx and lung. GERD is typically treated with antireflux medication, mainly proton pump inhibitors, but an alternative is antireflux surgery with fundoplication. The present thesis aimed to assess outcomes of antireflux surgery with regards to supra-esophageal cancer risk and mortality by conducting multinational population-based cohort studies using the Nordic antireflux surgery cohort (NordASCo), which includes all adult individuals with a documented diagnosis of GERD or antireflux surgery procedure in the national patient registries in any of the five Nordic countries from year 1980 to 2014. Study I and II investigated whether antireflux surgery decreases the risk of laryngeal and pharyngeal squamous cell carcinoma (Study I) and the risk of small cell carcinoma, squamous cell carcinoma and adenocarcinoma of the lung (Study II) in NordASCo. We calculated standardized incidence ratios (SIR) and hazard ratios (HR) with 95% confidence intervals (CI). The overall risk of laryngeal or pharyngeal squamous cell carcinoma were decreased (SIR 0.62 [95% CI 0.44-0.85] and HR 0.55 [95% CI 0.38-0.80]), and the point estimates decreased further >10 years after surgery. The SIRs and HRs of laryngeal squamous cell carcinoma showed a particular decrease >10 years after surgery (SIR 0.28 [95% CI 0.08-0.72] and HR 0.23 [95% CI 0.08-0.69]). Regarding lung cancer, the overall risk was below unity for small cell (SIR 0.57 [95% CI 0.41-0.77] and HR 0.63 [95% CI 0.44- 0.90]) and squamous cell carcinoma (SIR 0.75 [95% CI 0.60-0.92] and HR 0.80 [95% CI 0.62-1.03]), but not for adenocarcinoma (SIR 0.90 [95% CI 0.76-1.06] and HR 1.03 [95% CI 0.84-1.26]). Study III examined all-cause and disease