Experimental Colonic Obstruction and Anastomotic Healing

Colorectal cancer is one of the most common malignant diseases world-wide. Most patients can be diagnosed, staged and treated by surgery in an elective setting. However, about one fifth of the patients will have an emergency presentation and in most cases due to malignant obstruction of the left colon. Immediate resection and anastomosis is feasible but carries a 3-fold higher risk of developing anastomotic leakage compared to elective surgery. Anastomotic healing in patients can be evaluated as clinical outcome and related to preoperative or peroperative patient factors. Experimental research renders it possible to study biochemical factors and cellular events during the course of healing. Previous research in the field of anastomotic healing has suggested a potential role for tissue-degrading enzymes on the loss of collagen in the proximity of an anastomosis leaving it vulnerable to dehiscence. The work presented in this thesis is mainly based on an established model of colonic obstruction in rat. It was found that already 24 hours after initiation of obstruction the collagen levels, analyzed as hydroxyproline, were substantially depressed proximal to the stenosis. On the other hand, the intestine had the capability to recover after relief of the obstruction since hydroxyproline levels were found to return to normal levels. The parallel in the clinical situation would be stenting of an obstruction as a bridge-to-surgery. The activity of matrix metalloproteinases is upregulated in obstructed rat colon and an anastomosis in this condition carries a high risk of leakage. The effect of a MMP inhibitor was investigated but was, contrary to expected, found to deteriorate the anastomoses. On the other hand, if an inhibitor could be delivered locally, improved healing could possibly be expected without unwanted effects, since breaking strength was increased with coated sutures in normal colon