title: Minimally invasive colorectal resection is associated with significantly elevated levels of plasma matrix metalloproteinase 3 (MMP-3) during the first month after surgery which may promote the growth of residual metastases.
abstract: BACKGROUND
  MMP-3, a member of the matrix metalloproteinase (MMP) family, is involved in the breakdown of the extracellular matrix in tissue remodeling and may also play a role in cancer progression and metastasis. Minimally invasive colorectal resection (MICR) may increase plasma MMP-3 levels directly via surgical trauma or indirectly due to surgery-associated elevations in TNF-α and IL1 which are regulators of MMP-3. This study's purpose was to evaluate plasma MMP-3 levels during the first month after MICR for colorectal cancer.
  
  
  METHODS
  Patients enrolled in an IRB approved data/plasma bank who underwent elective MICR for CRC. Blood plasma samples had been collected preoperatively, on postoperative day (POD) 1, 3 and at varying postoperative time points and were stored at -80 °C. The late samples (POD 7-41) were bundled into 7 day time blocks and considered as single time points. MMP-3 levels were analyzed in duplicate via ELISA and the results reported as mean ± SD. The paired t test was used for analysis (significance, p < 0.008 after Bonferroni's correction).
  
  
  RESULTS
  A total of 73 CRC patients who underwent MICR met the inclusion criteria. The mean PreOp MMP-3 level was 14.9 ± 7.8 ng/ml (n = 73). Significantly elevated mean plasma levels were noted on POD 1 (21.4 ± 14.7 ng/ml, n = 73, p < 0.0001), POD 3 (37.9 ± 21.5 ng/ml, n = 72, p < 0.0001), POD 7-13 (22.0 ± 13.0 ng/ml, n = 56, p < 0.0001), POD 14-20 (21.9 ± 10.3 ng/ml, n = 20, p = 0.003), and on POD 21-27 (21.9 ± 11.43 ng/ml, n = 20, p = 0.002) when compared to PreOp levels. Plasma levels returned to the PreOp baseline at the POD 28-41 time point (n = 16, p = 0.07).
  
  
  CONCLUSIONS
  Plasma MMP-3 levels remained significantly elevated from baseline for 4 weeks after MICR for CRC. The early postoperative increase in MMP-3 levels may be due to the surgery-related acute inflammatory response; the elevation noted during weeks 2-3 may be related to wound healing. Increased MMP-3 levels may promote metastases or the growth of residual cancer.
authors.affiliation: Division of Colon and Rectal Surgery, Department of Surgery, St Luke's-Roosevelt Hospital Center, Suite 7B, 425 West, 59th Street, New York, NY, 10019, USA, hmsach_6@yahoo.com.
authors.forename: H M C
authors.initials: HM
authors.lastname: Shantha Kumara
authors.forename: David J
authors.initials: DJ
authors.lastname: Gaita
authors.forename: Hiromichi
authors.initials: H
authors.lastname: Miyagaki
authors.forename: Xiaohong
authors.initials: X
authors.lastname: Yan
authors.forename: Sonali A C
authors.initials: SA
authors.lastname: Herath
authors.forename: Vesna
authors.initials: V
authors.lastname: Cekic
authors.forename: Richard L
authors.initials: RL
authors.lastname: Whelan
mesh_terms: D000328:Adult; D000368:Aged; D014408:Biomarkers, Tumor / Q000097:blood*; D003082:Colectomy / Q000379:methods*; D015179:Colorectal Neoplasms / Q000097:blood / Q000473:pathology / Q000601:surgery*; D005260:Female; D005500:Follow-Up Studies; D006801:Humans; D010535:Laparoscopy; D008297:Male; D019278:Matrix Metalloproteinase 3 / Q000097:blood*; D008875:Middle Aged; D018365:Neoplasm, Residual / Q000473:pathology; D011184:Postoperative Period; D011446:Prospective Studies; D012007:Rectum / Q000601:surgery*; D016896:Treatment Outcome
chemical_list: D014408:Biomarkers, Tumor; D019278:Matrix Metalloproteinase 3