Plasma levels of monocyte chemotactic protein-1(MCP-1), a proangiogenic protein, are elevated during first month after minimally invasive colorectal resection for benign indications.

Hmc Shantha Kumara, PhD, Sonali A C Herath, BS, Myers A Elizabeth, MD, Hiromichi Miyagaki, MD, Joon J Jang, MD, Yan Xiaohong, PhD, Linda Njoh, MS, Vesna Cekic, RN, Richard L Whelan, MD

Division of Colon and Rectal Surgery, Department of Surgery, St Luke-Roosevelt Hospital Center, Suite 7B, 425 West, 59th Street, New York, NY 10019, USA

Introduction: Plasma from the 2nd and 3rd weeks after minimally invasive colorectal resection (MICR) for both benign disease and cancer stimulates in vitro endothelial cell (EC) proliferation, migration, and invasion which are critical for new blood vessel formation. These persistent changes are unique and may have negative implications for cancer patients. After MICR for colorectal cancer (CRC) persistent elevations (3-4 weeks long) in the plasma levels of a number of pro-angiogenic proteins including MCP-1 have been noted. The present study’s purpose is to determine if similar MCP-1 plasma changes occur during the first month after MICR for benign indications. Our hypothesis is that the elevated MCP-1 levels are due to the procedure and not the indication. MCP-1, a direct mediator of angiogenesis, induces in-vitro EC migration and sprouting. MCP-1 is produced by EC’s, fibroblasts and monocytes and its expression has been confirmed in numerous malignancies. MCP-1 receptor CCR2 is expressed as a surface protein on EC’s and is upregulated by inflammatory cytokines. The binding of MCP-1/CCR2 on EC facilitates endothelial regeneration and vascular remodeling during wound repair. MCP-1’s proangiogenic effects are mediated via ANG-1 and VEGF.

Method: Patients enrolled in an IRB approved data/plasma bank who underwent elective MICR for benign colorectal pathology for whom adequate plasma samples were available were included in this study. The prospectively gathered clinical, demographic, pathologic and short term outcome data were reviewed. Blood samples were collected preoperatively (PreOp) and at a variety of post operative (PostOp) time points. Plasma was isolated and stored at -80°C. Late samples were bundled into 7 day blocks and considered as single time points. MCP-1 levels (pg/ml) were determined in duplicate via ELISA and results reported as mean± SD. The paired t-test was used for statistical analysis (significance set at p<0.0008 after Bonferroni correction).

Results: Plasma samples from 86 MICR patients were assessed (mean age: 59.3±13.3 years; 42 male, 44 female). The indications for surgery were diverticulitis (n=30) and benign neoplasm (n=56). The mean incision length was 5.2±1.9cm, length of stay, 4.7±2.0 days, and operative time, 230.5±98.2 minutes. The mean PreOp MCP-1 level was 239.5± 98.5 pg/ml (n=86). When compared to PreOp levels significantly elevated MCP-1 levels (pg/ml) were noted on POD1 (481.9± 254.7,n=86), POD3 (429.5± 184.9, n=63), POD7-13 (385.5± 152.2;n=39), POD14-20 (442.1± 209.3; n=33), POD 21-27 (354.2± 116.2;p=0.0004; n=21) and on POD28-34 (365.2± 102.2;n=21) (P<0.0001 for all comparisons except for POD 21-27 time point).

Conclusion: Plasma MCP-1 levels are significantly elevated for over a month after MICR for benign indications. The etiology of this persistent change may be related to both the acute inflammatory response (early Postop) and wound healing (weeks 2-5). These results are similar to those noted in CRC patients who underwent MICR, thus, the plasma MCP-1 changes are likely related to surgical trauma and not the indication for surgery. Further studies are needed to determine the duration of this change as well as the clinical significance of the MCP-1 and other proangiogenic plasma protein changes noted after MICR.

Session: Poster Presentation

Program Number: P074