Effect of postoperative non-steroidal anti-inflammatory drugs on anastomotic leakage after pancreaticoduodenectomy

Background: Although the association between an increase in anastomotic leakage (AL) and non-steroidal anti-inflammatory drugs (NSAIDs) has been reported in gastrointesti-nal surgeries, this issue has rarely been addressed for pancreaticoduodenectomy (PD). We aimed to investigate the association between postoperative NSAIDs administration and clinically relevant AL (CR-AL) following PD. Metbods: We retrospectively evaluated 2,163 consecutive patients who underwent PD be-tween 2007 and 2019. The patients were divided into two groups; patients who received and did not receive NSAIDs by postoperative day (POD) 5. We conducted a propensity score analysis using inverse probability of treatment weighting (IPTW) to adjust the base-line differences between both groups. We compared the occurrence of CR-AL and other postoperative outcomes before and after IPTW. Further, we used the multivariable binary logistic regression method for a sensitivity analysis for CR-AL. Results: A total of 2,136 patients were included in the analysis. Of these, 222 (10.4%) re-ceived NSAIDs by POD 5. The overall occurrence rate of CR-AL was 14.9%. After IPTW, postoperative NSAIDs were significantly associated with CR-AL (odds ratio [OR]: 1.24, 95% CI [1.05, 1.47], P = 0.012), prolonged postoperative hospitalization (OR: 1.31, 95% CI [1.14, 1.50], P < 0.001), and unplanned readmission within 30 days postoperatively (OR 1.48: 95% CI [1.15, 1.91], P = 0.002). However, this association was not consistent in the sensitivity analysis. Conclusions: Postoperative NSAIDs use was significantly associated with an increase in CR-AL incidence following PD. However, sensitivity analysis failed to show its association, which precludes a firm conclusion of its detrimental effect.