Journal of Gastrointestinal Surgery

, Volume 22, Issue 4, pp 587–594 | Cite as

Ketorolac and Other NSAIDs Increase the Risk of Anastomotic Leakage After Surgery for GEJ Cancers: a Cohort Study of 557 Patients

  • Kaare Terp Fjederholt
  • Cecilie Okholm
  • Lars Bo Svendsen
  • Michael Patrick Achiam
  • Jakob Kirkegård
  • Frank Viborg Mortensen
Original Article



The objective of this study is to investigate the impact of ketorolac and other nonsteroidal anti-inflammatory drugs on anastomotic leakage after surgery for gastro-esophageal-junction cancer.

Summary Background Data

Within the last two decades, the incidence of gastro-esophageal-junction cancer has increased in the western world and surgery is the curative treatment modality of choice. Anastomotic leakage is a feared complication of gastro-esophageal surgery, as it increases recurrence, morbidity, and mortality. Nonsteroidal anti-inflammatory drugs are widely used for postoperative pain relief. Nonsteroidal anti-inflammatory drugs have, however, in colorectal surgery, been shown to increase the risk of anastomotic leakage.


In a historical cohort study, we investigated the impact of nonsteroidal anti-inflammatory drugs on anastomotic leakage in 557 patients undergoing surgery for gastro-esophageal-junction cancer. Data were collected from a prospective maintained database, the Danish National Patient Registry, and patient medical records. Data were analyzed using univariate and multivariate statistical models and were stratified for theoretical confounders.


In univariate analysis, we did not observe any difference in age, gender, tobacco exposure, or comorbidity status between patients experiencing anastomotic leakage and those without. In multivariate analysis, gender, histology, and type of anastomosis proved to affect odds ratios for anastomotic leakage. After adjustment for possible confounders, we found an odds ratio of 6.05 (95% confidence interval 2.71; 13.5) for ketorolac use and of 5.24 (95% confidence interval 1.85; 14.8) for use of other nonsteroidal anti-inflammatory drugs for anastomotic leakage during the first seven postoperative days.


In the present study, we found a strong association between the postoperative use of ketorolac and other nonsteroidal anti-inflammatory drugs and the risk for anastomotic leakage after surgery for gastro-esophageal-junction cancers.


Anastomotic leak Epidemiology Esophageal neoplasms Anti-inflammatory agents,  Nonsteroidal 



We are grateful for the funding of this work provided by the Danish Cancer Society and Aage and Johanne Louis-Hansen’s Foundation.


Kaare Terp Fjederholt: Study design, manuscript draft, data analysis, and critical revision

Cecilie Okholm: Data collection and critical revision

Lars Bo Svendsen: Study design, data collection, and critical revision

Michael Patrick Achiam: Data collection and critical revision

Jakob Kirkegård: Critical revision

Frank Viborg Mortensen: Study design, manuscript draft, and critical revision

Source of Funding

The Danish Cancer Society and Aage and Johanne Louis-Hansen’s Foundation supported this work.

Compliance with Ethical Standards

Conflicts of Interest

No conflicts of interest declared.


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Copyright information

© The Society for Surgery of the Alimentary Tract 2017

Authors and Affiliations

  • Kaare Terp Fjederholt
    • 1
  • Cecilie Okholm
    • 2
  • Lars Bo Svendsen
    • 2
  • Michael Patrick Achiam
    • 2
  • Jakob Kirkegård
    • 1
  • Frank Viborg Mortensen
    • 1
  1. 1.Department of Surgery, Section for upper gastrointestinal and hepato-pancreato-biliary surgeryAarhus University HospitalAarhus CDenmark
  2. 2.Department of Surgical Gastroenterology and TransplantationRigshospitaletCopenhagenDenmark

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