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Risk of esophageal adenocarcinoma after antireflux surgery in patients with gastroesophageal reflux disease in the Nordic countries

(2018) JAMA ONCOLOGY. 4(11). p.1576-1582
Author
Organization
Abstract
IMPORTANCE: Gastroesophageal reflux disease (GERD) is associated with a strong and severity-dependent increased risk of esophageal adenocarcinoma. Whether antireflux surgery prevents esophageal adenocarcinoma is a matter of uncertainty. OBJECTIVES: To examine whether antireflux surgery is associated with reduced risk of esophageal adenocarcinoma and whether the risk is different between surgically and medically treated patients. DESIGN, SETTING, AND PARTICIPANTS: In this multinational, population-based retrospective cohort study from Denmark, Finland, Iceland, Norway, and Sweden, patients undergoing surgery were followed up for a median of 12.7 years. and a comparison group of patients receiving medication only were followed up for a median of 4.8 years. All patients with a registered diagnosis of GERD (or an associated disorder), including 48 414 individuals undergoing surgery and 894492 receiving medication only, were included in the study. The study periods varied in the different countries depending on the year of initiation of registration and the date of data retrieval, from January 1, 1964, to December 21, 2014. EXPOSURES: Antireflux surgery for GERD. MAIN OUTCOMES AND MEASURES: The risk of esophageal adenocarcinoma over time after surgery was compared with that in a corresponding background population using standardized incidence ratios (SIRs) with 95% Os and with patients with GERD who received medication using multivariable Cox proportional hazards regression, providing hazard ratios (HRs) with 95% Os adjusted for confounders. RESULTS: In this study of 942 906 patients with GERD, 48 414 underwent antireflux surgery (median [interquartile range] age, 66.0 [58.0-73.0] years; 27 161male [56.1%]) and 894 492 received medication only (median [interquartile range] age, 71.0 [62.0-78.0] years; 434 035 male [48.6%]), Among patients undergoing surgery, 177 developed esophageal adenocarcinoma. Esophageal adenocarcinoma risk decreased in a time-dependent manner after surgery compared with the background population (5 to <10 years after surgery: SIR, 7.63; 95% CI, 5.42-10.43; 15 years after surgery: SIR, 1.34; 95%CI, 0.984.80). Among patients with more severe and objectively determined GERD, the SIRs were 10.08 (95% CI, 6.98-14.09) at 5 to less than 10 years after surgery and 1.67 (95% CI, 1.15-2.35) at 15 years or more after surgery. The risk of esophageal adenocarcinoma did not change over time in surgical patients compared with patients who received medication only (5 to <10 years after surgery: HR, 2.02; 95% CI, 144-2.84; 715 years: HR, 1.80; 95%CI,1.28-2.54). The risk remained stable over time in analyses restricted to severe reflux disease (5 to <10 years after surgery: HR, 1.81; 95% CI, 1.24-2.63; =15 years after surgery: HR, 1.69; 95% CI, 1.14-2.51). CONCLUSIONS AND RELEVANCE: Medical and surgical treatment of GERD were associated with a similar reduced esophageal adenocarcinoma risk, with the risk decreasing to the same level as that in the background population over time, supporting the hypothesis that effective treatment of GERD might prevent esophageal adenocarcinoma.
Keywords
CANCER REGISTRY, DATA QUALITY, BILE REFLUX, LAPAROSCOPIC ANTERIOR, BARRETTS-ESOPHAGUS, FUNDOPLICATION, METAANALYSIS, POSTERIOR, COHORT, ACID

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MLA
Maret-Ouda, John et al. “Risk of Esophageal Adenocarcinoma After Antireflux Surgery in Patients with Gastroesophageal Reflux Disease in the Nordic Countries.” JAMA ONCOLOGY 4.11 (2018): 1576–1582. Print.
APA
Maret-Ouda, J., Wahlin, K., Artama, M., Brusselaers, N., Farkkila, M., Lynge, E., Mattsson, F., et al. (2018). Risk of esophageal adenocarcinoma after antireflux surgery in patients with gastroesophageal reflux disease in the Nordic countries. JAMA ONCOLOGY, 4(11), 1576–1582.
Chicago author-date
Maret-Ouda, John, Karl Wahlin, Miia Artama, Nele Brusselaers, Martti Farkkila, Elsebeth Lynge, Fredrik Mattsson, et al. 2018. “Risk of Esophageal Adenocarcinoma After Antireflux Surgery in Patients with Gastroesophageal Reflux Disease in the Nordic Countries.” Jama Oncology 4 (11): 1576–1582.
Chicago author-date (all authors)
Maret-Ouda, John, Karl Wahlin, Miia Artama, Nele Brusselaers, Martti Farkkila, Elsebeth Lynge, Fredrik Mattsson, Eero Pukkala, Pal Romundstad, Laufey Tryggvadottir, My von Euler-Chelpin, and Jesper Lagergren. 2018. “Risk of Esophageal Adenocarcinoma After Antireflux Surgery in Patients with Gastroesophageal Reflux Disease in the Nordic Countries.” Jama Oncology 4 (11): 1576–1582.
Vancouver
1.
Maret-Ouda J, Wahlin K, Artama M, Brusselaers N, Farkkila M, Lynge E, et al. Risk of esophageal adenocarcinoma after antireflux surgery in patients with gastroesophageal reflux disease in the Nordic countries. JAMA ONCOLOGY. 2018;4(11):1576–82.
IEEE
[1]
J. Maret-Ouda et al., “Risk of esophageal adenocarcinoma after antireflux surgery in patients with gastroesophageal reflux disease in the Nordic countries,” JAMA ONCOLOGY, vol. 4, no. 11, pp. 1576–1582, 2018.
@article{8622093,
  abstract     = {IMPORTANCE: Gastroesophageal reflux disease (GERD) is associated with a strong and severity-dependent increased risk of esophageal adenocarcinoma. Whether antireflux surgery prevents esophageal adenocarcinoma is a matter of uncertainty. 
OBJECTIVES: To examine whether antireflux surgery is associated with reduced risk of esophageal adenocarcinoma and whether the risk is different between surgically and medically treated patients. 
DESIGN, SETTING, AND PARTICIPANTS: In this multinational, population-based retrospective cohort study from Denmark, Finland, Iceland, Norway, and Sweden, patients undergoing surgery were followed up for a median of 12.7 years. and a comparison group of patients receiving medication only were followed up for a median of 4.8 years. All patients with a registered diagnosis of GERD (or an associated disorder), including 48 414 individuals undergoing surgery and 894492 receiving medication only, were included in the study. The study periods varied in the different countries depending on the year of initiation of registration and the date of data retrieval, from January 1, 1964, to December 21, 2014. 
EXPOSURES: Antireflux surgery for GERD. 
MAIN OUTCOMES AND MEASURES: The risk of esophageal adenocarcinoma over time after surgery was compared with that in a corresponding background population using standardized incidence ratios (SIRs) with 95% Os and with patients with GERD who received medication using multivariable Cox proportional hazards regression, providing hazard ratios (HRs) with 95% Os adjusted for confounders. 
RESULTS: In this study of 942 906 patients with GERD, 48 414 underwent antireflux surgery (median [interquartile range] age, 66.0 [58.0-73.0] years; 27 161male [56.1%]) and 894 492 received medication only (median [interquartile range] age, 71.0 [62.0-78.0] years; 434 035 male [48.6%]), Among patients undergoing surgery, 177 developed esophageal adenocarcinoma. Esophageal adenocarcinoma risk decreased in a time-dependent manner after surgery compared with the background population (5 to <10 years after surgery: SIR, 7.63; 95% CI, 5.42-10.43; 15 years after surgery: SIR, 1.34; 95%CI, 0.984.80). Among patients with more severe and objectively determined GERD, the SIRs were 10.08 (95% CI, 6.98-14.09) at 5 to less than 10 years after surgery and 1.67 (95% CI, 1.15-2.35) at 15 years or more after surgery. The risk of esophageal adenocarcinoma did not change over time in surgical patients compared with patients who received medication only (5 to <10 years after surgery: HR, 2.02; 95% CI, 144-2.84; 715 years: HR, 1.80; 95%CI,1.28-2.54). The risk remained stable over time in analyses restricted to severe reflux disease (5 to <10 years after surgery: HR, 1.81; 95% CI, 1.24-2.63; =15 years after surgery: HR, 1.69; 95% CI, 1.14-2.51). 
CONCLUSIONS AND RELEVANCE: Medical and surgical treatment of GERD were associated with a similar reduced esophageal adenocarcinoma risk, with the risk decreasing to the same level as that in the background population over time, supporting the hypothesis that effective treatment of GERD might prevent esophageal adenocarcinoma.},
  author       = {Maret-Ouda, John and Wahlin, Karl and Artama, Miia and Brusselaers, Nele and Farkkila, Martti and Lynge, Elsebeth and Mattsson, Fredrik and Pukkala, Eero and Romundstad, Pal and Tryggvadottir, Laufey and von Euler-Chelpin, My and Lagergren, Jesper},
  issn         = {2374-2437},
  journal      = {JAMA ONCOLOGY},
  keywords     = {CANCER REGISTRY,DATA QUALITY,BILE REFLUX,LAPAROSCOPIC ANTERIOR,BARRETTS-ESOPHAGUS,FUNDOPLICATION,METAANALYSIS,POSTERIOR,COHORT,ACID},
  language     = {eng},
  number       = {11},
  pages        = {1576--1582},
  title        = {Risk of esophageal adenocarcinoma after antireflux surgery in patients with gastroesophageal reflux disease in the Nordic countries},
  url          = {http://dx.doi.org/10.1001/jamaoncol.2018.3054},
  volume       = {4},
  year         = {2018},
}

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