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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

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Abstract

Introduction

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).

Conclusion

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.

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Acknowledgments

This study was made possible by a generous donation from Mr. Wade Thompson and family to the Divisions of Colon and Rectal surgery, Department of Surgery, St Luke’s Roosevelt Hospital, New York.

Disclosures

All authors (HMC Shantha Kumara PhD, David J Gaita BS, Hiromichi Miyagaki MD, PhD, Xiaohong Yan PhD, Sonali AC Herath BS, Vesna Cekic RN, and Richard L Whelan MD) have no conflicts of interest or financial ties to disclose.

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Authors and Affiliations

  1. 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

    H. M. C. Shantha Kumara, David J. Gaita, Hiromichi Miyagaki, Xiaohong Yan, Sonali A. C. Herath, Vesna Cekic & Richard L. Whelan

  2. Department of Gastroenterological Surgery, Osaka University, 2-2, Yamadaoka, Suita, Osaka, 565-0871, Japan

    Hiromichi Miyagaki

  3. Icahn School of Medicine at Mount Sinai, New York, NY, 10029, USA

    Richard L. Whelan

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  1. H. M. C. Shantha Kumara
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Correspondence to Richard L. Whelan.

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Shantha Kumara, H.M.C., Gaita, D.J., Miyagaki, H. et al. 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. Surg Endosc 28, 3322–3328 (2014). https://doi.org/10.1007/s00464-014-3612-9

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