Untersuchungen zum Kollagenstoffwechsel bei Patienten mit kolorektalen Resektionen

Introduction: Despite improved surgical techniques and optimized perioperative regimes, anastomotic leakage is still a serious complication in colorectal surgery, resulting in increased morbidity and mortality. This prospective study was initiated to test a hypothesis, that preexisting disorders in the metabolism of collagen in the extracellular matrix (ECM) may be one of the factors promoting the onset of anastomotic wound healing complications. Moreover clinical variables were registered.Material and Methods: In this prospective study 119 patients were included, on whom anastomoses were performed with participation of the colon or rectum. On the one hand 30 clinical parameters with possible influence on anastomotic complications were evaluated on the other hand samples of macroscopically intact colonic tissue were obtained at the index operation. With theses samples we performed crosspolarisation microscopy for the analysis of collagen type I/III ratio and immunohistochemical studies to determine the expression of matrix matalloproteinases 1, 2, 9 and 13. A semiquantative score was used, with whom the two layers mucosa and submucosa were analysed separately. The patients with uncomplicated postoperative healing were compared to those developing anastomotic leakage in the further course. First of all a univariate analysis was performed as well for the clinical parameters as for the histological facts. In addition we performed a multivariat analysis for each of the histological parameters.Results: Patients with impaired anastomotic healing showed a significantly lowered collagen type I/III ratio compared to the controls. Moreover a significant higher expression of MMP-1 and MMP-2 in the mucosal and of MMP-2 and MMP-9 in the submucosal layers was found in the normal bowel wall of the leakage group. These findings were statistically independent from the clinical parameters, which was shown in a logistic regression. Discussion: On the one hand this study confirms in many points the results of other studies as to clinical risk factors anastomotic healing. In this study perioperativ blood transfusions are linked to a higher rate of anastomotic leakages. Besides a significant higher rate of anastomotic leakages is found in patients who had already undergone operations of the intestine. On the other hand the present study confirms the tested hypothesis, that disturbances of the metabolism of collagen in the ECM play a role in the pathogenesis of anastomotic leakage after large bowel surgery. A clinical use of these results could be a peroperative classification, because of which one would chose an other procedure in the riskgroup, for example an operation with creation of an artificial anus