Minimally invasive colorectal resection is associated with persistently elevated levels of Interleukin-8(IL8) during the first month after surgery that may promote residual cancer growth and metastasis

Hmc Shantha Kumara, PhD, Hiromichi Miyagaki, MD, Xiaohong Yan, PhD, Myers A Elizabeth, MD, Sonali A C Herath, BS, Joon J Jang, MD, 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: Minimally invasive colorectal resection (MICR) for cancer results in persistently elevated levels of plasma VEGF, Angiopoietin 2, sVCAM-1, PlGF and other proangiogenic proteins. Plasma from 2nd and 3rd week after MICR stimulates in-vitro endothelial cell (EC) migration, invasion and EC tube formation. The proangiogenic plasma after MICR may stimulate residual cancer growth after surgery. Various cancers (colon, breast, prostate, etc) and endothelial cells (EC) have been shown to express IL8 (CXCR8) and its receptors CXCR1 and CXCR2. Tumor derived IL8, in an autocrine fashion, enhances tumor cell proliferation and survival and also promotes pathologic angiogenesis, tumor growth and metastasis. The proangiogenic effects of IL8 is independent of its chemotactic effect on neutrophils and its other pro-inflammatory effects. Furthermore, IL8 mediates angiogenesis independently of VEGF. Bioactive IL8 in wounds stimulates angiogenesis and enhances wound healing. The impact of MICR for colorectal cancer (CRC) on plasma levels of IL8 is unknown. This study’s purpose was to evaluate plasma IL8 levels during first month after MICR for CRC.

Methods: Patients enrolled in an IRB approved data/plasma bank who underwent elective MICR for CRC for whom adequate plasma samples were available were included in this study. Clinical, demographic and pathological data were prospectively collected. Blood samples had been obtained PreOp and at varying postoperative (Postop) time points and were stored at -80C. Only patients for whom PreOp, Postop day (POD) 1, 3 and at least 1late postop plasma sample (POD7-34) were available were included in this study. The late samples were bundled into 4 time periods (POD7-13, POD14-20, POD21-27, and POD 28-34) and considered as single time points. IL8 levels were analyzed in duplicate via ELISA and the results reported as mean and ±SD .The paired t-test was used for analysis. (Significance, p<0.008 after Bonferroni’s correction).

Results: A total of 73 MICR CRC patients (colon, 62%; rectal, 38%; 36 males/37 female, mean age 65.8± 12.8 years) met the entry criteria. Hand and laparoscopic-assisted methods were used. The mean incision length was 7.8± 3.5cm and the mean length of stay was 6.3±2.6 days. The cancer stage breakdown was as follows: stage I, 27%; stage II, 29%; stage III, 41%; and stage IV, 3%. The mean PreOp IL8 level was 20.4 ± 10.6 pg/ml(n=73). When compared to PreOp levels, significant elevations in the mean plasma IL8 levels (pg/ml) were noted on POD1 (43.1± 38.6;n=72, p<0.0001), POD 3 (33.0±30.1,n=71, p<0.0001), POD7-13 (29.9±21.9,n=50, p<0.0001), POD14-20 (33.1±18.3,n=24, P=0.002), and for the POD21-27 (24.0±9.2,n=16, p=0.002). There was no significant difference in plasma levels noted on POD27-34 (vs PreOp).

Conclusion: Plasma IL8 levels remained significantly elevated from baseline for 4 weeks after MICR for CRC. In addition to its proangiogenic properties, IL8 is best known for its pro-inflammatory effects on immune cells. Surgical trauma induced acute inflammation may account for the early Postop IL8 elevations, however, the cause(s) of the persistent increases noted during weeks 2-4 are unclear but may be related to wound healing. Increased IL8 levels may promote tumor angiogenesis and growth. Further studies are warranted.


Session: Poster Presentation

Program Number: P076

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