Elevated intraperitoneal matrix metalloproteinases-8 and -9 in patients who develop anastomotic leakage after rectal cancer surgery: a pilot study.
OBJECTIVE
Experimental studies suggest that matrix metalloproteinase (MMP) enzymes mediate the early tissue breakdown that leads to a decrease in intestinal anastomotic strength. Patients with upregulation of MMPs in intestinal biopsies have an increased rate of anastomotic leakage. We measured MMPs and their inhibitors [tissue inhibitors of metalloproteinases (TIMPs)] in postoperative intraperitoneal fluid after rectal cancer surgery, and hypothesized that they would be elevated in patients who later would develop anastomotic leakage.


METHODS
Twenty-nine patients with rectal carcinoma underwent low anterior resection of the rectum for cancer. Intraperitoneal fluid was collected via a pelvic drain at a median of 4 h postoperatively. MMP-1, -2, -3, -7, -8, -9 and -13 were determined using particle-based multiplex flow-cytometry. TIMP-1 and -2 were measured by enzyme-linked immunosorbent assays. MMP-9 was considered the main outcome variable. RESULTS; Ten patients developed anastomotic leakage. These patients had increased intraperitoneal MMP-9 [median difference (m.d.) 29%; P = 0.03] and MMP-8 (m.d. 58%; P = 0.02), compared with patients who did not develop leakage. There were no differences between the groups for other MMPs and TIMPs.


CONCLUSIONS
Matrix metalloproteinase-8 and -9 appear to have an important role in the development of anastomotic leakage and may be promising pharmacological targets to protect anastomotic integrity. We suggest further investigation of MMPs as markers for anastomotic leakage.
Pasternak
B
B
Department of Clinical and Experimental Medicine, Linköping University, Linköping, Sweden.
Matthiessen
P
P
Jansson
K
K
Andersson
M
M
Aspenberg
P
P
D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D000714:Anastomosis, Surgical / Q000009:adverse effects; D001202:Ascitic Fluid / Q000201:enzymology*; D014408:Biomarkers, Tumor / Q000032:analysis; D003106:Colon / Q000601:surgery*; D004797:Enzyme-Linked Immunosorbent Assay; D005260:Female; D005434:Flow Cytometry; D005500:Follow-Up Studies; D006801:Humans; D008297:Male; D020784:Matrix Metalloproteinase 8 / Q000032:analysis*; D020780:Matrix Metalloproteinase 9 / Q000032:analysis*; D008875:Middle Aged; D010865:Pilot Projects; D011183:Postoperative Complications / Q000378:metabolism*; D011379:Prognosis; D012004:Rectal Neoplasms / Q000378:metabolism / Q000601:surgery*; D012189:Retrospective Studies
D014408:Biomarkers, Tumor; D020784:Matrix Metalloproteinase 8; D020780:Matrix Metalloproteinase 9