Changes of the extracellular matrix as a risk factor for anastomotic leakage after large bowel surgery.
BACKGROUND
Despite improved surgical techniques, anastomotic leakage remains as a serious complication in colorectal surgery, producing increased morbidity and mortality. This prospective study was initiated to test the hypothesis that preexisting disorders in the extracellular matrix (ECM) may be a factor influencing the onset of anastomotic wound healing complications.


METHODS
In this prospective study of 119 patients with colorectal anastomoses, 30 clinical parameters with possible influence on anastomotic complications were evaluated. From all patients, samples of macroscopically intact colonic tissue were obtained at the index operation. Crosspolarization microscopy was performed to analyze the collagen type I/III ratio, and immunohistochemical studies were done to determine the expression of matrix metalloproteinase (MMP) 1, 2, 9, and 13. The patients with uncomplicated postoperative healing were compared with those developing anastomotic leakage.


RESULTS
Patients with impaired anastomotic healing exhibited a significantly lower collagen type I/III ratio compared with the controls. Significantly higher expression of MMP-1 and MMP-2 in the mucosal layers 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.


CONCLUSIONS
The present study confirms the hypothesis that disturbances of the ECM play a role in the pathogenesis of anastomotic leakage after large bowel surgery.
Stumpf
Michael
M
Department of Surgery, University Hospital, Medical Faculty of the Rhenish-Westphalian Technical University-Aachen, Pauwelsstrasse 30, 52074 Aachen, Germany. m.stumpf@chir.rwth-aachen.de
Klinge
Uwe
U
Wilms
Arnulf
A
Zabrocki
Robert
R
Rosch
Rafael
R
Junge
Karsten
K
Krones
Carsten
C
Schumpelick
Volker
V
D000714:Anastomosis, Surgical / Q000009:adverse effects*; D024042:Collagen Type I / Q000378:metabolism; D024061:Collagen Type III / Q000378:metabolism; D017364:Collagenases / Q000378:metabolism; D003106:Colon / Q000601:surgery; D005109:Extracellular Matrix / Q000378:metabolism*; D006801:Humans; D007420:Intestine, Large / Q000601:surgery*; D020781:Matrix Metalloproteinase 1 / Q000378:metabolism; D053509:Matrix Metalloproteinase 13; D020778:Matrix Metalloproteinase 2 / Q000378:metabolism; D020780:Matrix Metalloproteinase 9 / Q000378:metabolism; D011183:Postoperative Complications / Q000209:etiology* / Q000378:metabolism; D011446:Prospective Studies; D012007:Rectum / Q000601:surgery; D012307:Risk Factors
D024042:Collagen Type I; D024061:Collagen Type III; D017364:Collagenases; C507079:MMP13 protein, human; D053509:Matrix Metalloproteinase 13; D020778:Matrix Metalloproteinase 2; D020780:Matrix Metalloproteinase 9; D020781:Matrix Metalloproteinase 1