Elevated intraperitoneal matrix metalloproteinases-8 and -9 in patients who develop anastomotic leakage after rectal cancer surgery: a pilot study

Colorectal Dis. 2010 Jul;12(7 Online):e93-8. doi: 10.1111/j.1463-1318.2009.01908.x. Epub 2009 Apr 16.

Abstract

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.

Method: 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.

Conclusion: 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.

Publication types

  • Comparative Study
  • Research Support, Non-U.S. Gov't

MeSH terms

  • Adult
  • Aged
  • Aged, 80 and over
  • Anastomosis, Surgical / adverse effects
  • Ascitic Fluid / enzymology*
  • Biomarkers, Tumor / analysis
  • Colon / surgery*
  • Enzyme-Linked Immunosorbent Assay
  • Female
  • Flow Cytometry
  • Follow-Up Studies
  • Humans
  • Male
  • Matrix Metalloproteinase 8 / analysis*
  • Matrix Metalloproteinase 9 / analysis*
  • Middle Aged
  • Pilot Projects
  • Postoperative Complications / metabolism*
  • Prognosis
  • Rectal Neoplasms / metabolism
  • Rectal Neoplasms / surgery*
  • Retrospective Studies

Substances

  • Biomarkers, Tumor
  • Matrix Metalloproteinase 8
  • Matrix Metalloproteinase 9