H M C Shantha Kumara, PhD, Carl S Winkler, MD, Erica Pettke, MD, Sandhu K Jaspreet, MD, Simon Tian, BS, Abhinit Shah, MBBS, Xiaohong Yan, PhD, Cekic Vesna, RN, Nipa D Gandhi, MD, Richard L Whelan, MD. Mout Sinai West, New York USA
Introduction: Serpin E1, also known as Plasminogen activator inhibitor-1 (PAI-1) is an inhibitor of urokinase type plasminogen activator (uPA) and tissue-type plasminogen activators (tPA ) . PAI-1 plays a role in the regulation of angiogenesis, wound healing, and tumor cell invasion; over expression has been noted in breast, esophageal, and colorectal cancer (CRC). PAI-1 is also a potent regulator of endothelial cell (EC) proliferation and migration in vitro and of angiogenesis and tumor growth in vivo. The plasminogen/plasmin system plays a key role in cancer progression by mediating extracellular matrix degradation and tumor cell migration. Surgery’s impact on plasma PAI-1 levels is unknown. This study’s purpose was to measure plasma PAI-1 levels before and during the first month after minimally invasive colorectal resection (MICR) for CRC.
Method: CRC patients who had MICR who were enrolled in an IRB approved data/plasma bank for whom adequate plasma samples were available were eligible. Clinical and pathologic data were reviewed. Only patients for whom preoperative (PreOp), postoperative day (POD) 1, POD 3 and at least 1 late postop plasma sample (POD 7-34) were available were studied. Late samples were bundled into 7 day time blocks and considered as single time points. Plasma was isolated and stored at -80°C. PAI-1 levels were determined in duplicate via ELISA and the results reported as mean ±SD. The Wilcoxon paired t-test was used for analysis (significance, p<0.05).
Results: 91 MICR CRC patients (colon 73%; rectal 27%; 45 male /46 female, mean age 67.3± 13.6 years) were studied. The mean incision length was 8.0±3.9 cm and mean length of stay was 6.8± 4.3days. The final cancer stage breakdown follows; I (n=30), II (n=30), III (n=36) and IV (n=4). %. When compared to mean Preop levels (18.5±8.3 ng/ml), significantly elevated mean levels (ng/ml) were noted on POD 1 (32.2± 22.4; n=91,p<0.001), POD 3 (22.9±13.1,n=86,p=0.003), POD7-13 (30.2±17.5, n=65,p<0.001), and POD14-20 (28.5±16.4,n=26,p=0.001) , POD 21-27(28.2±15.8, n=19,p<0.001) and There was no significant difference noted between the POD 27-34 and PreOp results.
Conclusion: Plasma PIA-1 levels are significantly elevated vs. Preop levels for 1 month after MICR for CRC. The early increase after MICR may be related to the acute inflammatory response via macrophage activation. The elevation noted during weeks 2-4, however, may be related to PAI-1 associated VEGF induced angiogenesis occurring in the healing wounds; these plasma changes may also promote angiogenesis in residual tumor deposits. Further studies are warranted.
Presented at the SAGES 2017 Annual Meeting in Houston, TX.
Abstract ID: 85098
Program Number: P214
Presentation Session: iPoster Session (Non CME)
Presentation Type: Poster
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