PLASMA LEVELS OF MMP 8, A TUMOR ANGIOGENSIS PROMOTING PROTEIN, ARE PERSISTENTLY ELEVATED DURING THE FIRST MONTH AFTER MINIMALLY INVASIVE COLORECTAL CANCER RESECTION WHICH MAY PROMOTE RESIDUAL TUMOR METASTASIS
Hmc Shantha Kumara*, Neil Mitra, Yanni Hedjar, Xiaohong Yan, Vesna Cekic, Joseph Martz, Jennifer L. Agnew, Richard L. Whelan
Surgery, Lenox Hill Hospital, Northwell Health, New York, NY
Introduction: Matrix metalloproteinases 8 (MMP-8), is a zinc-dependent protease that plays a role in the breakdown of extracellular matrix (ECM). MMP-8 is expressed by numerous cells including lymphocytes, epithelial cells, macrophages and, polymorphonuclear neutrophils (PMN's) which have MMP-8 containing granules. IL-1, IL-8, TNF-?, and GM-CSF stimulate release of MMP-8 from PMN's during pathological inflammation. MMP-8 plays a role in the escape of tumors from immune surveillance during colorectal cancer (CRC) progression and also regulates angiogenesis related Endothelial cell activity. Elevated MMP8 serum levels have been noted in hepatocellular cancer patients (pts) and correlated with prognosis. This study's purpose was to measure plasma MMP-8 levels before and during the first month after minimally invasive colorectal resection (MICR) for CRC.
Method: Consenting CRC pts enrolled in an IRB approved data/plasma bank who underwent minimally invasive colorectal resection (MICR) for whom plasma samples were available were eligible. Clinical and pathologic data were reviewed. Blood samples were collected preoperatively (PreOp) and on Postop Day (POD) 1, POD 3 and at least 1 late postop plasma sample (POD7-34); samples were processed and plasma frozen until use. Late samples were bundled into 7 day blocks and considered as single time points. MMP-8 levels were determined in duplicate using ELISA. Wilcoxon paired t-test was used for analysis (significance, p<0.05).
Results: Preop, early postop, and 1 or more late postop plasma sample were available for 83 MICR CRC pts (colon 73%; rectal 27%; laparoscopic-assisted (lap), 69%, hand-assisted laparoscopic (HA), 31%; 43 male,40 female; mean age 63.5± 14.3 years). The mean incision length was 7.7±3.5 cm (lap 6.9±3.7 cm; HA 9.3±2.3 cm) and mean length of stay was 6.3±2.6days. The cancer stage breakdown was; I, 24%; II, 33%; III,37% and IV, 6%. Compared to the mean Preop MMP-8 plasma level (8.7±7.1,n=83;ng/ml), significantly elevated levels (p<0.001) were noted on postop day (POD) 1 (27.7± 22.6; n=83), POD 3 (24.4±28.5,n=74), POD7-13 (24.7±27.8, n=66), POD14-20 (20.2±18.1,n=26,p=0.002) and POD 21-27(15.7±14.8, n=17,p=0.003). No significant difference was found between Preop and the POD 27-41 results. As regards MIS technique, non-significant elevations of plasma MMP-8 levels were noted in the HA group during POD 7-27 period compared to Lap group.
Conclusion: Plasma MMP-8 levels are notably and significantly elevated (91% - 217% over preop levels) for a month after MICR for CRC. The early MMP8 elevations may be related to acute inflammatory response related activation of PMN's and macrophages via IL-1 and TNF. The later elevations may be associated with wound healing related angiogenesis. This long duration MMP8 increase might impact angiogenesis in residual tumor deposits. Further studies are warranted.
Back to 2022 Posters