Matrix metalloproteinase-9 in relation to patients with complications after colorectal surgery: a systematic review

Purpose: Anastomotic leakage (AL) is the most severe complication following colorectal resection and is associated with increased mortality. The main group of enzymes responsible for collagen and protein degradation in the extracellular matrix is matrix metalloproteinases. The literature is conflicting regarding anastomotic leakage and the degradation of extracellular collagen by matrix metalloproteinase-9 (MMP-9). In this systematic review, the possible correlation between anastomotic leakage after colorectal surgery and MMP-9 activity is investigated. Methods: Embase, MEDLINE, Cochrane, and Web of Science databases were searched up to 3 February 2020. All published articles that reported on the relationship between MMP-9 and anastomotic leakage were selected. Both human and animal studies were found eligible. The correlation between MMP-9 expression and anastomotic leakage after colorectal surgery. Results: Seven human studies and five animal studies were included for analysis. The human studies were subdivided into those assessing MMP-9 in peritoneal drain fluid, intestinal biopsies, and blood samples. Five out of seven human studies reported elevated levels of MMP-9 in patients with anastomotic leakage on different postoperative moments. The animal studies demonstrated that MMP-9 activity was highest in the direct vicinity of an anastomosis. Moreover, MMP-9 activity was significantly reduced in areas further proximally and distally from the anastomosis and was nearly or completely absent in uninjured tissue. Conclusion: Current literature shows some relation between MMP-9 activity and colorectal AL, but the evidence is inconsistent. Innovative techniques should further investigate the value of MMP-9 as a clinical biomarker for early detection, prevention, or treatment of AL.