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Objective: The aim of this study was to clarify whether antireflux surgery prevents laryngeal and pharyngeal squamous cell carcinoma. Summary Background Data: Gastroesophageal reflux disease (GERD) seems to increase the risk of laryngeal and pharyngeal squamous cell carcinoma. Methods: All-Nordic (Denmark, Finland, Iceland, Norway, and Sweden) population-based cohort study of adults with documented GERD in 1980 to 2014. First, cancer risk after antireflux surgery was compared to the expected risk in the corresponding background population by calculating standardized incidence ratios (SIRs) with 95% confidence intervals (CIs). Second, cancer risk among antireflux surgery patients was compared to nonoperated GERD patients using multivariable Cox regression, providing hazard ratios (HR) with 95% CIs, adjusted for sex, age, calendar period, and diagnoses related to tobacco smoking, obesity, and alcohol overconsumption. Results: Among 814,230 GERD patients, 47,016 (5.8%) underwent antireflux surgery. The overall SIRs and HRs of the combined outcome laryngeal or pharyngeal squamous cell carcinoma (n=39) were decreased after antireflux surgery [SIR=0.62 (95% CI 0.44-0.85) and HR=0.55 (95% CI 0.38-0.80)]. The point estimates were further decreased >10 years after antireflux surgery [SIR=0.48 (95% CI 0.26-0.80) and HR=0.47 (95% CI 0.26-0.85)]. The risk estimates of laryngeal squamous cell carcinoma were particularly decreased >10 years after antireflux surgery [SIR=0.28 (95% CI 0.08-0.72) and HR=0.23 (95% CI 0.08-0.69)], whereas no such decrease over time after surgery was found for pharyngeal squamous cell carcinoma. Analyses of patients with severe GERD (reflux esophagitis or Barrett esophagus) showed similar results. Conclusion: Antireflux surgery may decrease the risk of laryngeal squamous cell carcinoma and possibly also of pharyngeal squamous cell carcinoma.

BACKGROUND & AIMS: Absolute rates and risk factors of short-term outcomes after antireflux surgery remain largely unknown. We aimed to clarify absolute risks and risk factors for poor 90-day outcomes of primary laparoscopic and secondary antireflux surgery. METHODS: This population-based cohort study included patients who had primary laparoscopic or secondary antireflux surgery in the 5 Nordic countries in 2000-2018. In addition to absolute rates, we analyzed age, sex, comorbidity, hospital volume, and calendar period in relation to all-cause 90-day mortality (main outcome), 90-day reoperation, and prolonged hospital stay (≥2 days over median stay). Multivariable logistic regression provided odds ratios (ORs) with 95% confidence intervals (95% CI), adjusted for confounders. RESULTS: Among 26,193 patients who underwent primary laparoscopic antireflux surgery, postoperative 90-day mortality and 90-day reoperation rates were 0.13% (n = 35) and 3.0% (n = 750), respectively. The corresponding rates after secondary antireflux surgery (n = 1 618) were 0.19% (n = 3) and 6.2% (n = 94). Higher age (56-80 years vs 18-42 years: OR, 2.66; 95% CI 1.03-6.85) and comorbidity (Charlson Comorbidity Index ≥2 vs 0: OR, 6.25; 95% CI 2.42-16.14) increased risk of 90-day mortality after primary surgery, and higher hospital volume suggested a decreased risk (highest vs lowest tertile: OR, 0.58; 95% CI, 0.22-1.57). Comorbidity increased the risk of 90-day reoperation. Higher age and comorbidity increased risk of prolonged hospital stay after both primary and secondary surgery. Higher annual hospital volume decreased the risk of prolonged hospital stay after primary surgery (highest vs lowest tertile: OR, 0.74; 95% CI, 0.67-0.80). CONCLUSION: These findings suggest that laparoscopic antireflux surgery has an overall favorable safety profile in the treatment of gastroesophageal reflux disease, particularly in younger patients without severe comorbidity who undergo surgery at high-volume c

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

Introduction: Airway micro-aspiration might contribute to the proposed associations between gastroesophageal reflux disease (GERD) and some lung diseases, including lung cancer. This study aimed to examine the hypothesis that antireflux surgery decreases the risk of small cell carcinoma, squamous cell carcinoma and adenocarcinoma of the lung differently depending on their location in relation to micro-aspiration. Methods: Population-based cohort study including patients having undergone antireflux surgery during 1980–2014 in Denmark, Finland, Iceland, Norway or Sweden. Patients having undergone antireflux surgery were compared with two groups: 1) the corresponding background population, by calculating standardised incidence ratios (SIRs) with 95% confidence intervals (CIs) and 2) non-operated GERD-patients, by calculating hazard ratios (HRs) with 95% CIs using multivariable Cox regression with adjustment for sex, age, calendar period, country, chronic obstructive pulmonary disease and obesity diagnosis or type 2 diabetes. Results: Among all 812,617 GERD-patients, 46,996 (5.8%) had undergone antireflux surgery. The SIRs were statistically significantly decreased for small cell carcinoma (SIR = 0.57, 95% CI 0.41–0.77) and squamous cell carcinoma (SIR = 0.75, 95% CI 0.60–0.92), but not for adenocarcinoma of the lung (SIR = 0.90, 95% CI 0.76–1.06). The HRs were also below unity for small cell carcinoma (HR = 0.63, 95% CI 0.44–0.90) and squamous cell carcinoma (HR = 0.80, 95% CI 0.62–1.03), but not for adenocarcinoma of the lung (HR = 1.03, 95% CI 0.84–1.26). Analyses restricted to patients with objective GERD (reflux oesophagitis or Barrett's oesophagus) showed similar results. Conclusions: This all-Nordic study indicates that patients who undergo antireflux surgery are at decreased risk of small cell carcinoma and squamous cell carcinoma of the lung, but not of adenocarcinoma of the lung.

Background: Effective treatment of severe gastro-oesophageal reflux disease is available through medication or surgery. Postoperative risks have contributed to decreased use of antireflux surgery. We aimed to assess short-term mortality following primary laparoscopic fundoplication. Method: Population-based nationwide Swedish cohort study including all Swedish hospitals performing laparoscopic fundoplication, between 1997 and 2013. All patients aged 18-65 years with gastro-oesophageal reflux disease who underwent primary laparoscopic fundoplication during the study period were included. Main outcome was absolute all-cause and surgery-related 90-day and 30-day mortality. Secondary outcomes were reoperation and length of hospital stay. Logistic regression was used to calculate odds ratios with 95% confidence intervals of reoperation within 90 days and prolonged hospital stay (>4 days). Results: Of 8947 included patients, 5306 (59.3%) were men, and 551 (6.2%) had a significant comorbidity (Charlson comorbidity score >0). Median age at surgery was 48 years, and median hospital stay was 2 days. Annual rate of laparoscopic fundoplication decreased from 15.3 to 2.4 cases per 100 000 inhabitants during the study period, while the proportion of patients with comorbidity increased more than 2-fold. All-cause 90- and 30-day mortality were 0.08% (n=7) and 0.03% (n=3), respectively. Only 1 death (0.01%) was directly surgery-related. 90-day reoperation rate was 0.4% (n=39). Comorbidity and higher age entailed increased risk for prolonged hospital stay, but not for reoperation. Conclusion: This population-based study revealed a remarkably low 90-day mortality and reoperation rate following laparoscopic, results which might influence clinical decision-making in the treatment of severe gastro-oesophageal reflux disease.