Clinical and oncopreventive outcomes of antireflux surgery

Gastro-oesophageal reflux disease (GORD), with heartburn and acid regurgitation as main symptoms, is a common disease with increasing prevalence. GORD is associated with oesophageal adenocarcinoma, a cancer with demanding treatment and yet poor prognosis. GORD is typically managed with pharmacological treatment, mainly using proton pump inhibitors, or through laparoscopic antireflux surgery. The aim of this thesis was to evaluate outcomes of antireflux surgery, i.e. safety, effectiveness and prevention of oesophageal adenocarcinoma.

Study I and II were nationwide Swedish cohort studies based on data from the Patient Registry, Causes of Death Registry, Registry of the Total Population (in study I only), and the Swedish Prescribed Drug Registry (in study II only). Study I assessed safety aspects with focus on the risk of mortality, reoperation and prolonged hospital stay among patients of working age who underwent primary laparoscopic antireflux surgery for GORD. In addition, it provided descriptive data regarding trends and comorbidities among patients who had undergone such surgery. The study found low risks of mortality (0.08%) and reoperation (0.4%) within 90 days of surgery. Patients of female sex, and older age and with more comorbidities had an increased risk of prolonged hospital stay. Generally, the number of patients who underwent antireflux surgery in Sweden decreased substantially during the period, while the proportion with severe comorbidities among the operated patients increased over time. Study II assessed the risk of recurrence of reflux symptoms following primary laparoscopic antireflux surgery for GORD, using reoperation or prescribed medications against reflux (exceeding six months of treatment) as the measures of this outcome. The reflux recurrence rate was 17.7% during the median follow-up of 5.6 years, and the majority of patients (83.6%) had medical treatment. Female sex, older age, and comorbidity were associated with an increased reflux recurrence, but hospital volume was not.

Study III was a systematic review and meta-analysis assessing if oesophageal adenocarcinoma can be prevented by antireflux surgery. No clear differences in risk were found when comparing surgery with medication, and the risk of oesophageal adenocarcinoma remained elevated following antireflux surgery compared to the general background population. Study IV was a Nordic cohort study, based on nationwide registries from Denmark, Finland, Iceland, Norway, and Sweden, including patients with GORD. The risk of oesophageal adenocarcinoma was initially high, but decreased over time both following antireflux surgery and presumed medical therapy to a risk in line with that of the general background population after 15 years. The risk of oesophageal adenocarcinoma was similar when directly comparing medical and surgical therapy.

In conclusion, laparoscopic antireflux surgery can be considered a safe and effective treatment option of GORD which is potentially underused in clinical practice, especially among young and otherwise healthy individuals who might otherwise need lifelong medical treatment. Effective treatment of GORD seems to reduce the risk of oesophageal adenocarcinoma.

List of scientific papers

I. Maret-Ouda J, Yanes M, Konings P, Brusselaers N, Lagergren J. Mortality from laparoscopic antireflux surgery in a nationwide cohort of the working-age population. British Journal of Surgery. 2016 Jun;103(7):863-70.
https://doi.org/10.1002/bjs.10141

II. Maret-Ouda J, Wahlin K, El-Serag HB, Lagergren J. Association between laparoscopic antireflux surgery and recurrence of gastroesophageal reflux. JAMA. 2017 Sep 12;318(10):939-946.
https://doi.org/10.1001/jama.2017.10981

III. Maret-Ouda J, Konings P, Lagergren J, Brusselaers N. Antireflux surgery and risk of esophageal adenocarcinoma: A systematic review and meta-analysis. Annals of Surgery. 2016 Feb;263(2):251-7.
https://doi.org/10.1097/SLA.0000000000001438

IV. Maret-Ouda J, Wahlin K, Artama M, Brusselaers N, Färkkilä M, Lynge E, Mattsson F, Pukkala E, Romundstad P, Tryggvadottir L, von EulerChelpin M, Lagergren J. The risk of esophageal adenocarcinoma following antireflux surgery in the five Nordic countries. [Submitted]