Cyclooxygenase-2 Is Essential for Colorectal Anastomotic Healing. Issue 3 (March 2017)

• Record Type: Journal Article
• Authors: Reisinger, Kostan W.; Schellekens, Dirk H. S. M.; Bosmans, Joanna W. A. M.; Boonen, Bas; Hulsewé, Karel W. E.; Sastrowijoto, Prapto; Derikx, Joep P. M.; Grootjans, Joep; Poeze, Martijn
• Is Part Of: Annals of surgery. Volume 265:Issue 3(2017:Mar.)
• Publication Date: 2017-03
• Subjects: anastomotic leakage -- colorectal surgery -- cyclooxygenase-2 -- diclofenac -- prostaglandin E2 -- ptgs2 -- PTGS2-765G>C; Surgery -- Periodicals; 617.005
• DOI: 10.1097/SLA.0000000000001744
• Languages: English
• ISSNs: 0003-4932

Abstract

Abstract : Objective: To study the effects of COX-2 on colonic surgical wound healing. Background: Cyclooxygenase-2 (COX-2) is a key enzyme in gastrointestinal homeostasis. COX-2 inhibitors have been associated with colonic anastomotic leakage. Methods: Wildtype, COX-2 knockout and COX-2 heterozygous mice were subjected to a model of colonic anastomotic leakage, and were treated with vehicle, diclofenac, or prostaglandin E2 (PGE2), the most important COX-2 product in the intestine. We assessed anastomotic leakage, mortality, angiogenesis, and inflammation. Furthermore, we investigated the association between anastomotic leakage and a human polymorphism of the COX-2 gene resulting in low COX-2 levels. Results: Diclofenac, a nonsteroidal anti-inflammatory drug inhibiting COX-2, increased anastomotic leakage compared to vehicle-treated mice (100% vs 25%, respectively). Similarly, 92% of COX-2-deficient mice developed anastomotic leakage ( P = 0.003) compared to WT. PGE2 partly rescued this severe phenotype because only 46% of PGE2-administered COX-2 knockout mice developed anastomotic leakage ( P = 0.02). This may be related to decreased neovascularization, because decreased CD31 staining, indicating less blood vessels, was observed in COX-2 −/− mice (2 vessels/mm 2 vs 6 vessels/mm 2 in controls ( P = 0.03)). This effect could partly be reversed by administration of PGE2 to COX-2 −/− mice. No significant differences in inflammation were found. PTGS2-765G>C polymorphism in humans, associated with reduced COX-2 expression, was associated with higher anastomotic leakage rates. Conclusions: COX-2-induced PGE2 production is essential for intestinal wound healing after colonic surgery, possibly via its effects on angiogenesis. These data emphasize that COX-2 inhibitors should be avoided after colonic surgery, and administration of PGE2 might be favorable for a selection of patients. Abstract : Supplemental Digital Content is available in the text