Aim: Non-steroidal anti-inflammatory drugs (NSAIDs) are commonly used to control postoperative pain; however, their postoperative use has been associated with anastomotic leakage after gastrointestinal surgery. This systematic review and metaanalysis aimed to determine the correlation between the use of NSAIDs and anastomotic leakage. Methods:We conducted a comprehensive electronic literature search up to August 2018 to identify studies comparing anastomotic leakage in patients with and without postoperative NSAID use following gastrointestinal surgery. We then carried out a meta-analysis using random-effects models to calculate odds ratios (OR) with 95% confidence intervals (CI). Results:Twenty-four studies were included in this meta-analysis, including a total of 31 877 patients. Meta-analysis showed a significant association between NSAID use and anastomotic leakage (OR 1.73; 95% CI = 1.31-2.29, P < .0001). Subgroup analyses showed that non-selective NSAIDs, but not selective cyclooxygenase-2 inhibitors, were significantly associated with anastomotic leakage. However there was no significant subgroup difference between selective and non-selective NSAIDs. Conclusion:Results of this meta-analysis indicate that postoperative NSAID use is associated with anastomotic leakage following gastrointestinal surgeries. Caution is warranted when using NSAIDs for postoperative analgesic control in patients with gastrointestinal anastomoses. K E Y W O R D Sanastomotic leakage, cyclooxygenase inhibitor, gastrointestinal surgery, meta-analysis, nonsteroidal anti-inflammatory drugs | 65 JAMJITTRONG eT Al.

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Background/Aim: Although weekly administration of cetuximab is the standard regimen in patients with metastatic colorectal cancer (mCRC), the efficacy and safety of a biweekly regimen is a pending issue. We conducted this meta-analysis to compare the efficacy and safety of a biweekly vs. a weekly regimen of cetuximab in the treatment of mCRC. Patients and Methods: We conducted a comprehensive electronic literature search up to January 2020 to identify studies directly comparing the efficacy and safety of biweekly cetuximab administration and conventional weekly administration in patients with mCRC. We then performed a meta-analysis using random-effects models to calculate risk ratios and mean differences with 95% confidence intervals. Results: Four studies with a total of 381 patients were included in this meta-analysis. The meta-analysis showed that biweekly administration conferred equivalent efficacy, including objective response rate, disease-control rate, progression-free survival, and overall survival, as well as safety, including skin toxicity, gastrointestinal toxicity, and hematologic toxicity, compared with weekly administration in patients with mCRC. Conclusion: Results from this meta-analysis support the administration of biweekly instead of weekly cetuximab, which is beneficial for both patients and health resources.Cetuximab, an IgG1 human/mouse chimera-type monoclonal antibody, binds to the extracellular domain of the epidermal growth factor receptor (EGFR), inhibiting ligand binding and downstream signaling (1). In preclinical models, cetuximab was found to promote apoptosis, angiogenesis, and metastasis, and inhibit tumor cell proliferation (2, 3). Furthermore, antitumor antibody-dependent cell-mediated cytotoxicity is also known to play a role in the mode of action of cetuximab (4).The clinical efficacy of weekly cetuximab in patients with metastatic colorectal cancer (mCRC) has been demonstrated in randomized phase II and III clinical trials, either as monotherapy, or in combination with oxaliplatin-and irinotecan-based chemotherapy regimens in first-and subsequent-line treatment (5-10). Cetuximab is approved in several countries for clinical use in patients with mCRC. National Comprehensive Cancer Network (NCCN) Guidelines ® version 2.2020 suggest that both weekly and biweekly (every 2 weeks) cetuximab are indicated in combination with oxaliplatin-and irinotecan-based therapy or monotherapy in KRAS/NRAS/BRAF wild-type patients. In contrast, only conventional weekly cetuximab has been approved in Japan for initial IV infusion of 400 mg/m 2 on day 1 infused over 120 min followed by weekly doses of 250 mg/m 2 infused over 60 min.A pharmacokinetic study by Tabernero et al. (11) demonstrated no significant differences between weekly cetuximab of 250 mg/m 2 (following an initial dose of 400 mg/m 2 ) and biweekly cetuximab of 500 mg/m 2 in combination with irinotecan. Considering that many commonly used chemotherapy agents for mCRC are administrated on a biweekly basis, the synchronization of the a...