Minimally invasive colon resection for malignant colonic conditions is associated with a transient early increase in plasma sVEGFR1 and a decrease in sVEGFR2 levels after surgery
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Plasma VEGF levels increase after minimally invasive colorectal resection (MICR) and remain elevated for 2–4 weeks. VEGF induces physiologic and pathologic angiogenesis by binding to endothelial cell (EC) bound VEGF-Receptor-1 (VEGFR1) and VEGFR2. Soluble forms of these receptors sequester plasma VEGF, decreasing the amount available to bind to EC-bound receptors. Ramifications of surgery-related plasma VEGF changes partially depend on plasma levels of sVEGFR1 and sVEGFR2. This study assessed perioperative sVEGFR1 and sVEGFR2 levels after MICR in patients with colorectal cancer.
Forty-five patients were studied; blood samples were taken from all patients preoperatively (preop) and on postoperative days (POD) 1 and 3; in most a fourth sample was drawn between POD 7–30. Late samples were bundled into two time points: POD 7–13 and POD 14–30. sVEGFR1 and sVEGFR2 levels were measured via ELISA. sVEGFR2 data are reported as mean ± SD and were assessed with the paired samples t test. sVEGFR1 data were not normally distributed. They are reported as median and 95% confidence interval (CI) and were assessed with the Wilcoxon signed-Rank test (p < 0.05).
Preoperatively, the mean plasma sVEGFR2 level (7583.9 pg/ml) was greater than the sVEGFR1 result (98.3 pg/ml). Compared with preop levels, sVEGFR2 levels were significantly lower on POD 1 (6068.2 pg/ml, ±2034.5) and POD 3 (6227.6 pg/ml, ±2007.0), whereas sVEGFR1 levels were significantly greater on POD 1 (237.5 pg/ml; 95% CI, 89.6–103.5), POD 3 (200.2 pg/ml; 95% CI, 159–253), and POD 7−13 (102.9 pg/ml; 95% CI, 189.7–253). No differences were found on POD 7–13 for sVEGFR2 or POD 14–30 for either protein.
sVEGFR2 values decreased and sVEGFR1 levels increased early after MICR; sVEGFR2 changes dominate due to their much larger magnitude. The net result is less plasma VEGF bound by soluble receptors and more plasma VEGF available to bind to ECs early after surgery.
KeywordssVEGFR1 sVEGFR2 Colon cancer Colorectal resection Surgery-related plasma alterations
- 1.Kirman I, Belizon A, Balik E, Feingold D, Arnell T, Horst P, Kumara S, Cekic V, Jain S, Nasar A, Whelan RL (2007) Perioperative sargramostim (recombinant human GM-CSF) induces an increase in the level of soluble VEGFR1 in colon cancer patients undergoing minimally invasive surgery. Eur J Surg Oncol 33:1169–1176PubMedGoogle Scholar
- 2.Mels AK, Statius Muller MG, van Leeuwen PA, von Blomberg BM, Scheper RJ, Cuesta MA, Beelen RH, Meijer S (2001) Immune-stimulating effects of low-dose perioperative recombinant granulocyte-macrophage colony-stimulating factor in patients operated on for primary colorectal carcinoma. Br J Surg 88:539–544CrossRefPubMedGoogle Scholar
- 5.Carter JJ, Feingold DL, Kirman I, Oh A, Wildbrett P, Asi Z, Fowler R, Huang E, Whelan RL (2003) Laparoscopic-assisted cecectomy is associated with decreased formation of postoperative pulmonary metastases compared with open cecectomy in a murine model. Surgery 134:432–436CrossRefPubMedGoogle Scholar
- 6.Belizon A, Balik E, Horst P, Feingold D, Arnell T, Azarani T, Cekic V, Skitt R, Kumara S, Whelan RL (2008) Persistent elevation of plasma vascular endothelial growth factor levels during the first month after minimally invasive colorectal resection. Surg Endosc 22:287–297CrossRefPubMedGoogle Scholar
- 7.Shantha Kumara HMC, Hoffman A, Kim IY, Feingold D, Dujovny N, Kallady M, Luchtefeld M, Whelan RL (2009) Colorectal resection, both open and laparoscopic- assisted, in patients with benign indications is associated with proangiogenic changes in plasma angiopoietin 1 and 2 levels. Surg Endosc 23:409–415CrossRefPubMedGoogle Scholar
- 13.Decaussin M, Sartelet H, Robert C, Moro D, Claraz C, Brambilla C, Brambilla E (1999) Expression of vascular endothelial growth factor (VEGF) and its two receptors (VEGF-R1-Flt1 and VEGF-R2-Flk1/KDR) in non-small cell lung carcinomas (NSCLCs): correlation with angiogenesis and survival. J Pathol 188:369–377CrossRefPubMedGoogle Scholar
- 17.Price DJ, Miralem T, Jiang S, Steinberg R, Avraham H (2001) Role of vascular endothelial growth factor in the stimulation of cellular invasion and signaling of breast cancer cells. Cell Growth Differ 2:129–135Google Scholar
- 18.George DJ, Halabi S, Shepard TF, Vogelzang NJ, Hayes DF, Small EJ, Kantoff PW (2001) Prognostic significance of plasma vascular endothelial growth factor levels in patients with hormone-refractory prostate cancer treated on Cancer and Leukemia Group B 9480. Clin Cancer Res 7:1932–1936PubMedGoogle Scholar
- 23.De Vita F, Orditura M, Lieto E, Infusino S, Morgillo F, Martinelli E, Castellano P, Romano C, Ciardiello F, Catalano G, Pignatelli C, Galizia G (2004) Elevated perioperative serum vascular endothelial growth factor levels in patients with colon carcinoma. Cancer 100:270–278CrossRefPubMedGoogle Scholar
- 26.Belizon A, Balik E, Feingold DL, Bessler M, Arnell TD, Forde KA, Horst PK, Jain S, Cekic V, Kirman I, Whelan RL (2006) Major abdominal surgery increases plasma levels of vascular endothelial growth factor: open more so than minimally invasive methods. Ann Surg 244:792–798CrossRefPubMedGoogle Scholar
- 28.Matsumoto T, Claesson-Welsh L (2001) VEGF receptor signal transduction. Sci STKE 2001 112:RE21Google Scholar
- 31.Dias S, Hattori K, Heissig B, Zhu Z, Wu Y, Witte L, Hicklin DJ, Tateno M, Bohlen P, Moore MA, Rafii S (2001) Inhibition of both paracrine and autocrine VEGF/ VEGFR-2 signaling pathways is essential to induce long-term remission of xenotransplanted human leukemias. Proc Natl Acad Sci U S A 98:10857–10862CrossRefPubMedGoogle Scholar
- 41.Taoka T, Iwasaki S, Uchida H, Fukusumi A, Kichikawa K, Nakagawa H, Takayama K, Sakamoto M, Ohishi H (2000) Suppression of tumor angiogenesis and growth by gene transfer of a soluble form of vascular endothelial growth factor receptor into a remote organ. Cancer Res 60:2169–2177Google Scholar
- 42.Hu Q, Dey AL, Yang Y, Shen Y, Jilani IB, Estey EH, Kantarjian HM, Giles FJ, Albitar M (2004) Soluble vascular endothelial growth factor receptor 1, and not receptor 2, is an independent prognostic factor in acute myeloid leukemia and myelodysplastic syndromes. Cancer 100:1884–1891CrossRefPubMedGoogle Scholar
- 44.Shantha Kumara HMC, Cabot CJ, Hoffman A, Luchtefeld M, Kalady M, Hyman N, Feingold D, Baxter R, Whelan RL (2009) Minimally invasive colon resection is associated with a transient early increase in plasma sVEGFR1 and a decrease in sVEGFR2 levels after surgery. Surg Endosc [Epub ahead of print]Google Scholar