Skip to main content
Top
Published in: Surgical Endoscopy 4/2009

01-04-2009

Minimally invasive colon resection is associated with a transient increase in plasma sVEGFR1 levels and a decrease in sVEGFR2 levels during the early postoperative period

Authors: H. M. C. Shantha Kumara, J. C. Cabot, A. Hoffman, M. Luchtefeld, M. F. Kalady, N. Hyman, D. Feingold, R. Baxter, R. Larry Whelan

Published in: Surgical Endoscopy | Issue 4/2009

Login to get access

Abstract

Introduction

Plasma vascular endothelial growth factor (VEGF) levels are elevated for 2–4 weeks after minimally invasive colorectal resection (MICR). VEGF induces wound and tumor angiogenesis by binding to endothelial cell (EC)-bound VEGF-receptor 1 (VEGFR1) and VEGFR2. Soluble receptors (sVEGFR1, sVEGFR2) sequester VEGF in the blood and decrease VEGF’s proangiogenic effect. The importance of the MICR-related VEGF changes depends on the effect of surgical procedures on sVEGFR1 and sVEGFR2; this study assessed levels of these proteins after MICR for benign indications.

Methods

Blood samples were taken (n = 39) preoperatively (preop) and on postoperative days (POD) 1 and 3; in most cases a fourth sample was drawn between POD 7 and 30. sVEGFR1 and sVEGFR2 levels were measured via enzyme-linked immunosorbent assay (ELISA), which detects free and VEGF bound soluble receptor. Late samples were bundled into POD 7–13 and POD 14–30 time points. Results are reported as mean and standard deviation. The data was assessed with paired-samples t-test.

Results

Preop, mean plasma sVEGFR2 level (9,203.7 ± 1,934.3 pg/ml) was significantly higher than the sVEGFR1 value (132.5 ± 126.2 pg/ml). sVEGFR2 levels were significantly lower on POD 1 (6,957.8 ± 1,947.7 pg/ml,) and POD 3 (7,085.6 ± 2,000.2 pg/ml), whereas sVEGFR1 levels were significantly higher on POD 1 (220.0 ± 132.8 pg/ml) and POD 3 (182.7 ± 102.1 pg/ml) versus preop results. No differences were found on POD 7–13 or 14–30.

Conclusions

sVEGFR2 values decreased and sVEGFR1 levels increased early after MICR; due to its much higher baseline, the sVEGFR2 changes dominate. The net result is less VEGF bound to soluble receptor and more free plasma VEGF.
Literature
1.
go back to reference 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(5):792–798PubMedCrossRef 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(5):792–798PubMedCrossRef
2.
go back to reference 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(2):287–297PubMedCrossRef 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(2):287–297PubMedCrossRef
3.
go back to reference Hicklin DJ, Ellis LM (2005) Role of the vascular endothelial growth factor pathway in tumor growth and angiogenesis. J Clin Oncol 23(5):1011–1027CrossRef Hicklin DJ, Ellis LM (2005) Role of the vascular endothelial growth factor pathway in tumor growth and angiogenesis. J Clin Oncol 23(5):1011–1027CrossRef
4.
go back to reference Ferrara N, Davis-Smyth T (1997) The biology of vascular endothelial growth factor [Review]. Endocr Rev 18:4–25PubMedCrossRef Ferrara N, Davis-Smyth T (1997) The biology of vascular endothelial growth factor [Review]. Endocr Rev 18:4–25PubMedCrossRef
5.
go back to reference Hanahan D, Folkman J (1996) Patterns and emerging mechanisms of the angiogenic switch during tumorigenesis [Review]. Cell 86:353–364 Hanahan D, Folkman J (1996) Patterns and emerging mechanisms of the angiogenic switch during tumorigenesis [Review]. Cell 86:353–364
6.
go back to reference Jelkmann W (2001) Pitfalls in the measurement of circulating vascular endothelial growth factor. Clin Chem 47(4):617–623PubMed Jelkmann W (2001) Pitfalls in the measurement of circulating vascular endothelial growth factor. Clin Chem 47(4):617–623PubMed
7.
go back to reference Neufeld G, Cohen T, Gengrinovitch S, Poltorak Z (1999) Vascular endothelial growth factor (VEGF) and its receptors [Review]. FASEB J 13:9–22PubMed Neufeld G, Cohen T, Gengrinovitch S, Poltorak Z (1999) Vascular endothelial growth factor (VEGF) and its receptors [Review]. FASEB J 13:9–22PubMed
8.
go back to reference Grad S, Ertel W, Keel M, Infanger M, Vonderschmitt DJ, Maly FE (1998) Strongly enhanced serum levels of vascular endothelial growth factor (VEGF) after polytrauma and burn. Clin Chem Lab Med 36(6):379–383PubMedCrossRef Grad S, Ertel W, Keel M, Infanger M, Vonderschmitt DJ, Maly FE (1998) Strongly enhanced serum levels of vascular endothelial growth factor (VEGF) after polytrauma and burn. Clin Chem Lab Med 36(6):379–383PubMedCrossRef
9.
go back to reference Bottomley MJ, Webb NJ, Watson CJ, Holt L, Bukhari M, Denton J, Freemont AJ, Brenchley PE (2000) Placenta growth factor (PlGF) induces vascular endothelial growth factor (VEGF) secretion from mononuclear cells and is co-expressed with VEGF in synovial fluid. Clin Exp Immunol 119(1):182–188PubMedCrossRef Bottomley MJ, Webb NJ, Watson CJ, Holt L, Bukhari M, Denton J, Freemont AJ, Brenchley PE (2000) Placenta growth factor (PlGF) induces vascular endothelial growth factor (VEGF) secretion from mononuclear cells and is co-expressed with VEGF in synovial fluid. Clin Exp Immunol 119(1):182–188PubMedCrossRef
10.
go back to reference Seko Y, Imai Y, Suzuki S, Kamijukkoku S, Hayasaki K, Sakomura Y, Tobe K, Kadowaki T, Maekawa H, Takahashi N, Yazaki Y (1997) Serum levels of vascular endothelial growth factor in patients with acute myocardial infarction undergoing reperfusion therapy. Clin Sci (Lond) 92(5):453–454 Seko Y, Imai Y, Suzuki S, Kamijukkoku S, Hayasaki K, Sakomura Y, Tobe K, Kadowaki T, Maekawa H, Takahashi N, Yazaki Y (1997) Serum levels of vascular endothelial growth factor in patients with acute myocardial infarction undergoing reperfusion therapy. Clin Sci (Lond) 92(5):453–454
11.
go back to reference Shoab SS, Scurr JH, Coleridge-Smith PD (1998) Increased plasma vascular endothelial growth factor among patients with chronic venous disease. J Vasc Surg 28(3):535–540PubMedCrossRef Shoab SS, Scurr JH, Coleridge-Smith PD (1998) Increased plasma vascular endothelial growth factor among patients with chronic venous disease. J Vasc Surg 28(3):535–540PubMedCrossRef
12.
go back to reference Solovey A, Gui L, Ramakrishnan S, Steinberg MH, Hebbel RP (1999) Sickle cell anemia as a possible state of enhanced anti-apoptotic tone: survival effect of vascular endothelial growth factor on circulating and unanchored endothelial cells. Blood 93(11):3824–3830PubMed Solovey A, Gui L, Ramakrishnan S, Steinberg MH, Hebbel RP (1999) Sickle cell anemia as a possible state of enhanced anti-apoptotic tone: survival effect of vascular endothelial growth factor on circulating and unanchored endothelial cells. Blood 93(11):3824–3830PubMed
13.
go back to reference Terai M, Yasukawa K, Narumoto S, Tateno S, Oana S, Kohno Y (1999) Vascular endothelial growth factor in acute Kawasaki disease. Am J Cardiol 83(3):337–339PubMedCrossRef Terai M, Yasukawa K, Narumoto S, Tateno S, Oana S, Kohno Y (1999) Vascular endothelial growth factor in acute Kawasaki disease. Am J Cardiol 83(3):337–339PubMedCrossRef
14.
go back to reference Rak J, Mitsuhashi Y, Sheehan C, Tamir A, Viloria-Petit A, Filmus J, Mansour SJ, Ahn NG, Kerbel RS (2000) Oncogenes and tumor angiogenesis: differential modes of vascular endothelial growth factor up-regulation in ras-transformed epithelial cells and fibroblasts. Cancer Res 60:490–498PubMed Rak J, Mitsuhashi Y, Sheehan C, Tamir A, Viloria-Petit A, Filmus J, Mansour SJ, Ahn NG, Kerbel RS (2000) Oncogenes and tumor angiogenesis: differential modes of vascular endothelial growth factor up-regulation in ras-transformed epithelial cells and fibroblasts. Cancer Res 60:490–498PubMed
15.
go back to reference Rak J, Yu JL, Kerbel RS, Coomber BL (2002) What do oncogenic mutations have to do with angiogenesis/vascular dependence of tumors. Cancer Res 62:1931–1934PubMed Rak J, Yu JL, Kerbel RS, Coomber BL (2002) What do oncogenic mutations have to do with angiogenesis/vascular dependence of tumors. Cancer Res 62:1931–1934PubMed
16.
go back to reference Brown LF, Yeo KT, Berse B, Yeo TK, Senger DR, Dvorak HF, van de Water L (1992) Expression of vascular permeability factor (vascular endothelial growth factor) by epidermal keratinocytes during wound healing. J Exp Med 176(5):1375–1379PubMedCrossRef Brown LF, Yeo KT, Berse B, Yeo TK, Senger DR, Dvorak HF, van de Water L (1992) Expression of vascular permeability factor (vascular endothelial growth factor) by epidermal keratinocytes during wound healing. J Exp Med 176(5):1375–1379PubMedCrossRef
17.
go back to reference Detmar M, Yeo KT, Nagy JA, Van de Water L, Brown LF, Berse B, Elicker BM, Ledbetter S, Dvorak HF (1995) Keratinocyte-derived vascular permeability factor (vascular endothelial growth factor) is a potent mitogen for dermal microvascular endothelial cells. J Invest Dermatol 105(1):44–50PubMedCrossRef Detmar M, Yeo KT, Nagy JA, Van de Water L, Brown LF, Berse B, Elicker BM, Ledbetter S, Dvorak HF (1995) Keratinocyte-derived vascular permeability factor (vascular endothelial growth factor) is a potent mitogen for dermal microvascular endothelial cells. J Invest Dermatol 105(1):44–50PubMedCrossRef
18.
go back to reference Karayiannakis AJ, Zbar A, Polychronidis A, Simopoulos C (2003) Serum and drainage fluid vascular endothelial growth factor levels in early surgical wounds. Eur Surg Res 35(6):492–496PubMedCrossRef Karayiannakis AJ, Zbar A, Polychronidis A, Simopoulos C (2003) Serum and drainage fluid vascular endothelial growth factor levels in early surgical wounds. Eur Surg Res 35(6):492–496PubMedCrossRef
19.
go back to reference Hormbrey E, Han C, Roberts A et al (2003) The relationship of human wound vascular endothelial growth factor (VEGF) after breast cancer surgery to circulating VEGF and angiogenesis. Clin Cancer Res 9(12):4332–4339PubMed Hormbrey E, Han C, Roberts A et al (2003) The relationship of human wound vascular endothelial growth factor (VEGF) after breast cancer surgery to circulating VEGF and angiogenesis. Clin Cancer Res 9(12):4332–4339PubMed
20.
go back to reference Yamaguchi T, Bando H, Mori T, Takahashi K, Matsumoto H, Yasutome M, Weich H, Toi M (2007) Overexpression of soluble vascular endothelial growth factor receptor 1 in colorectal cancer: association with progression and prognosis. Cancer Sci 98(3):405–410PubMedCrossRef Yamaguchi T, Bando H, Mori T, Takahashi K, Matsumoto H, Yasutome M, Weich H, Toi M (2007) Overexpression of soluble vascular endothelial growth factor receptor 1 in colorectal cancer: association with progression and prognosis. Cancer Sci 98(3):405–410PubMedCrossRef
21.
go back to reference Matsumoto T, Claesson-Welsh L (2001) VEGF receptor signal transduction. Sci STKE 112:RE21 Matsumoto T, Claesson-Welsh L (2001) VEGF receptor signal transduction. Sci STKE 112:RE21
22.
23.
go back to reference Toi M, Bando H, Ogawa T, Muta M, Hornig C, Weich HA (2002) Significance of vascular endothelial growth factor (VEGF)/soluble VEGF receptor-1 relationship in breast cancer. Int J Cancer 98(1):14–18PubMedCrossRef Toi M, Bando H, Ogawa T, Muta M, Hornig C, Weich HA (2002) Significance of vascular endothelial growth factor (VEGF)/soluble VEGF receptor-1 relationship in breast cancer. Int J Cancer 98(1):14–18PubMedCrossRef
24.
go back to reference Yamaguchi T, Bando H, Mori T, Takahashi K, Matsumoto H, Yasutome M, Weich H, Toi M (2007) Overexpression of soluble vascular endothelial growth factor receptor 1 in colorectal cancer: Association with progression and prognosis. Cancer Sci 98(3):405–410PubMedCrossRef Yamaguchi T, Bando H, Mori T, Takahashi K, Matsumoto H, Yasutome M, Weich H, Toi M (2007) Overexpression of soluble vascular endothelial growth factor receptor 1 in colorectal cancer: Association with progression and prognosis. Cancer Sci 98(3):405–410PubMedCrossRef
25.
go back to reference 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(9):1884–1891PubMedCrossRef 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(9):1884–1891PubMedCrossRef
26.
go back to reference Gill M, Dias S, Hattori K, Rivera ML, Hicklin D, Witte L, Girardi L, Yurt R, Himel H, Rafii S (2001) Vascular trauma induces rapid but transient mobilization of VEGFR2(+)AC133(+) endothelial precursor cells. Circ Res 88(2):167–174PubMed Gill M, Dias S, Hattori K, Rivera ML, Hicklin D, Witte L, Girardi L, Yurt R, Himel H, Rafii S (2001) Vascular trauma induces rapid but transient mobilization of VEGFR2(+)AC133(+) endothelial precursor cells. Circ Res 88(2):167–174PubMed
27.
go back to reference Shantha Kumara HMC, Hoffman A, Kim IY, Feingold D, Dujovny N, Kallady M, Luchtefeld M, Whelan RL (2008) 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 [Epup ahead of print]. doi:10.1007/s00464-008-0132-5 Shantha Kumara HMC, Hoffman A, Kim IY, Feingold D, Dujovny N, Kallady M, Luchtefeld M, Whelan RL (2008) 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 [Epup ahead of print]. doi:10.​1007/​s00464-008-0132-5
28.
go back to reference Choi SH, Park EY, Jung HL, Shim JW, Kim DS, Park MS, Shim JY (2006) Serum vascular endothelial growth factor in pediatric patients with community-acquired pneumonia and pleural effusion. J Korean Med Sci 21(4):608–613PubMedCrossRef Choi SH, Park EY, Jung HL, Shim JW, Kim DS, Park MS, Shim JY (2006) Serum vascular endothelial growth factor in pediatric patients with community-acquired pneumonia and pleural effusion. J Korean Med Sci 21(4):608–613PubMedCrossRef
29.
go back to reference Lange M, Hamahata A, Enkhbaatar P, Esechie A, Connelly R, Nakano Y, Jonkam C, Cox RA, Traber LD, Herndon DN, Traber DL (2008) Assessment of vascular permeability in an ovine model of acute lung injury and pneumonia-induced Pseudomonas aeruginosa sepsis. Crit Care Med 36(4):1284–1289PubMedCrossRef Lange M, Hamahata A, Enkhbaatar P, Esechie A, Connelly R, Nakano Y, Jonkam C, Cox RA, Traber LD, Herndon DN, Traber DL (2008) Assessment of vascular permeability in an ovine model of acute lung injury and pneumonia-induced Pseudomonas aeruginosa sepsis. Crit Care Med 36(4):1284–1289PubMedCrossRef
30.
go back to reference Maitre B, Boussat S, Jean D, Gouge M, Brochard L, Housset B, Adnot S, Delclaux C (2001) Vascular endothelial growth factor synthesis in the acute phase of experimental and clinical lung injury. Eur Respir J 18(1):100–106PubMedCrossRef Maitre B, Boussat S, Jean D, Gouge M, Brochard L, Housset B, Adnot S, Delclaux C (2001) Vascular endothelial growth factor synthesis in the acute phase of experimental and clinical lung injury. Eur Respir J 18(1):100–106PubMedCrossRef
31.
go back to reference Shapiro NI, Yano K, Okada H, Fischer C, Howell M, Spokes KC, Ngo L, Angus DC, Aird WC (2008) A prospective, observational study of soluble FLT-1 and vascular endothelial growth factor in sepsis. Shock 29(4):452–457PubMedCrossRef Shapiro NI, Yano K, Okada H, Fischer C, Howell M, Spokes KC, Ngo L, Angus DC, Aird WC (2008) A prospective, observational study of soluble FLT-1 and vascular endothelial growth factor in sepsis. Shock 29(4):452–457PubMedCrossRef
32.
go back to reference Tsokos M, Pufe T, Paulsen F, Anders S, Mentlein R (2003) Pulmonary expression of vascular endothelial growth factor in sepsis. Arch Pathol Lab Med 127(3):331–335PubMed Tsokos M, Pufe T, Paulsen F, Anders S, Mentlein R (2003) Pulmonary expression of vascular endothelial growth factor in sepsis. Arch Pathol Lab Med 127(3):331–335PubMed
33.
go back to reference Shantha Kumara HMC, Kirman I, Feingold D, Cekic V, Nasar A, Arnell T, Balik E, Hoffman A, Baxter R, Conte S, Whelan RL (2008) Perioperative GMCSF limits the pro-angiogenic plasma protein changes associated with colorectal cancer resection. Eur J Surg Oncol [Epup ahead of print]. doi:10.1016/j.ejso.2008.07.012 Shantha Kumara HMC, Kirman I, Feingold D, Cekic V, Nasar A, Arnell T, Balik E, Hoffman A, Baxter R, Conte S, Whelan RL (2008) Perioperative GMCSF limits the pro-angiogenic plasma protein changes associated with colorectal cancer resection. Eur J Surg Oncol [Epup ahead of print]. doi:10.​1016/​j.​ejso.​2008.​07.​012
Metadata
Title
Minimally invasive colon resection is associated with a transient increase in plasma sVEGFR1 levels and a decrease in sVEGFR2 levels during the early postoperative period
Authors
H. M. C. Shantha Kumara
J. C. Cabot
A. Hoffman
M. Luchtefeld
M. F. Kalady
N. Hyman
D. Feingold
R. Baxter
R. Larry Whelan
Publication date
01-04-2009
Publisher
Springer-Verlag
Published in
Surgical Endoscopy / Issue 4/2009
Print ISSN: 0930-2794
Electronic ISSN: 1432-2218
DOI
https://doi.org/10.1007/s00464-008-0323-0

Other articles of this Issue 4/2009

Surgical Endoscopy 4/2009 Go to the issue