Skip to main content

Advertisement

SpringerLink
Log in

Minimally invasive colorectal resection is associated with a rapid and sustained decrease in plasma levels of epidermal growth factor (EGF) in the colon cancer setting

  • Published:
Surgical Endoscopy Aims and scope Submit manuscript

Abstract

Background

Epidermal growth factor (EGF) stimulates tumor growth directly via tumor cell EGF receptors or indirectly via its proangiogenic effects. This study’s purpose was to determine the impact of minimally invasive colorectal resection (MICR) on postoperative (postop) plasma EGF levels in the colorectal cancer (CRC) and benign disease settings and to see if preoperative (PreOp) EGF levels are altered in cancer patients.

Methods

MICR patients with benign pathology (n = 40) and CRC (n = 48) had blood samples taken PreOp and on postoperative days (POD) 1 and 3. In some patients, late samples were taken between POD7 and POD60; these were bundled into 7-day blocks and considered as single time points. EGF levels were determined by enzyme-linked immunosorbent assay (ELISA) and results were reported as mean ± SD after logarithmic transformation. The Student t test was used (p < 0.008 after Bonferroni correction).

Results

The cancer and benign groups were comparable except for age. The mean PreOp CRC plasma EGF level (122.9 ± 75.9 pg/ml) was significantly higher than that of the benign group (85.3 ± 38.5 pg/ml) (p = 0.015). The cancer group’s EGF levels were significantly decreased on POD1 and POD3 and for the POD31-55 time point (mean EGF level = 63.1 ± 42.2 (n = 10). The benign group’s POD3 and POD7-14 EGF levels were significantly lower than the PreOp level; later levels returned toward baseline. Small late sample size limited analysis.

Conclusion

Plasma EGF levels are significantly higher in cancer patients. MICR is associated with a significant decrease in EGF levels early postop in both cancer and benign settings. Unlike the benign group, EGF blood levels in cancer patients remain low during the second postop month. A larger study with more late samples is needed to verify these results. EGF may have value as a tumor marker.

This is a preview of subscription content, log in via an institution to check access.

Access this article

Log in via an institution

Price excludes VAT (USA)
Tax calculation will be finalised during checkout.

Instant access to the full article PDF.

Institutional subscriptions

Fig. 1
Fig. 2

Similar content being viewed by others

References

  1. Allendorf JD, Bessler M, Horvath KD, Marvin MR, Laird DA, Whelan RL (1998) Increased tumor establishment and growth after open vs laparoscopic bowel resection in mice. Surg Endosc 12:1035–1038

    Article  CAS  PubMed  Google Scholar 

  2. 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 134:432–436

    Article  PubMed  Google Scholar 

  3. Weese JL, Ottery FD, Emoto SE (1986) Do operations facilitate tumour growth? An experimental model in rats. Surgery 100:273–277

    CAS  PubMed  Google Scholar 

  4. Lennard TW, Shenton BK, Borzotta A, Donnelly PK, White M, Gerrie LM, Proud G, Taylor RM (1985) The influence of surgical operations on components of the human immune system. Br J Surg 72:771–776

    Article  CAS  PubMed  Google Scholar 

  5. Eggermont AM, Steller EP, Sugerbaker PH (1987) Laparotomy enhances intraperitoneal tumor growth and abrogates the antitumor effects of interleukin-2 and lymphokine-activated killer cells. Surgery 102:71–78

    CAS  PubMed  Google Scholar 

  6. Allendorf JD, Bessler M, Horvath KD, Marvin MR, Laird DA, Whelan RL (1999) Increased tumor establishment and growth after open versus laparoscopic surgery in mice may be related to differences in postoperative T-cell function. Surg Endosc 13:233–235

    Article  CAS  PubMed  Google Scholar 

  7. 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 22:287–297

    Article  CAS  PubMed  Google Scholar 

  8. Shantha Kumara HMC, Feingold D, Kalady M, Dujovny N, Senagore A, Hyman N, Cekic V, Whelan RL (2009) Colorectal resection is associated with persistent proangiogenic plasma protein changes: postoperative plasma stimulates in vitro endothelial cell growth, migration, and invasion. Ann Surg 249:973–977

    Article  PubMed  Google Scholar 

  9. Folkman J (1990) What is the evidence that tumors are angiogenesis dependent? J Natl Cancer Inst 82:4–6

    Article  CAS  PubMed  Google Scholar 

  10. Folkman J (1974) Tumor angiogenesis factor. Cancer Res 34:2109–2113

    CAS  PubMed  Google Scholar 

  11. Kissmeyer-Nielsen P, Vinter-Jensen L, Smerup M (1996) Effects of long-term epidermal growth factor treatment on the normal rat colon. Gut 38:582–586

    Article  CAS  PubMed  Google Scholar 

  12. Yokoi K, Thaker PH, Yazici S, Rebhun RR, Nam DH, He J, Kim SJ, Abbruzzese JL, Hamilton SR, Fidler IJ (2005) Dual inhibition of epidermal growth factor receptor and vascular endothelial growth factor receptor phosphorylation by AEE788 reduces growth and metastasis of human colon carcinoma in an orthotopic nude mouse model. Cancer Res 65:3716–3725

    Article  CAS  PubMed  Google Scholar 

  13. Yoon SS, Kim SH, Gonen M, Heffernan NM, Detwiller KY, Jarnagin WR, D’Angelica M, Blumgart LH, Tanabe KK, Dematteo RP (2006) Profile of plasma angiogenic factors before and after hepatectomy for colorectal cancer liver metastases. Ann Surg Oncol 13:353–362

    Article  PubMed  Google Scholar 

  14. Rikimaru K, Tadokoro K, Yamamoto T, Enomoto S, Tsuchida N (1992) Gene amplification and overexpression of epidermal growth factor receptor in squamous cell carcinoma of the head and neck. Head Neck 14:8–13

    Article  CAS  PubMed  Google Scholar 

  15. Reeves JR, Smith G, Keith WN, Ozanne BW, Cooke TG, Stanton PD (1996) Stanton quantitative estimation of epidermal growth factor receptor and c-erbB-2 in human breast cancer. Cancer Res 56:3823–3830

    PubMed  Google Scholar 

  16. Veale D, Kerr N, Gibson GJ, Kelly PJ, Harris AL (1993) The relationship of quantitative epidermal growth factor receptor expression in non-small cell lung cancer to long term survival. Br J Cancer 68:162–165

    CAS  PubMed  Google Scholar 

  17. Hollstein MC, Smits AM, Galiana C, Yamasaki H, Bos JL, Mandard A, Partensky C, Montesano R (1988) Amplification of epidermal growth factor receptor gene but no evidence of ras mutations in primary human esophageal cancers. Cancer Res 48:5119–5123

    CAS  PubMed  Google Scholar 

  18. Korc M, Chandrasekar B, Yamanaka Y, Friess H, Buchier M, Beger HG (1992) Overexpression of the epidermal growth factor receptor in human pancreatic cancer is associated with concomitant increases in the levels of epidermal growth factor and transforming growth factor alpha. J Clin Invest 90:1352–1360

    Article  CAS  PubMed  Google Scholar 

  19. Ishikawa J, Maeda S, Umezu K, Sugiyama T, Kamidono S (1990) Amplification and overexpression of the epidermal growth factor receptor gene in human renal-cell carcinoma. Int J Cancer 45:1018–1021

    Article  CAS  PubMed  Google Scholar 

  20. Kim JW, Kim YT, Kim DK, Song CH, Lee JW (1996) Expression of epidermal growth factor receptor in carcinoma of the cervix. Gynecol Oncol 60:283–287

    Article  CAS  PubMed  Google Scholar 

  21. Fischer-Colbrie J, Witt A, Heinzl H, Speiser P, Czerwenka K, Sevelda P, Zeillinger R (1997) EGFR and steroid receptors in ovarian carcinoma: comparison with prognostic parameters and outcome of patients. Anticancer Res 17:613–619

    CAS  PubMed  Google Scholar 

  22. Olapade-Olaopa EO, Moscatello DK, MacKay EH, Horsburgh T, Sandhu DP, Terry TR, Wong AJ, Habib FK (2000) Evidence for the differential expression of a variant EGF receptor protein in human prostate cancer. Br J Cancer 82:186–194

    Article  CAS  PubMed  Google Scholar 

  23. Chow NH, Liu HS, Lee EI, Chang CJ, Chan SH, Cheng HL, Tzai TS, Lin JS (1997) Significance of urinary epidermal growth factor and its receptor expression in human bladder cancer. Anticancer Res 17:1293–1296

    CAS  PubMed  Google Scholar 

  24. Goldman CK, Kim J, Wong WL, King V, Brock T, Gillespie GY (1993) Epidermal growth factor stimulates vascular endothelial growth factor production by human malignant glioma cells: a model of glioblastoma multiforme pathophysiology. Mol Biol Cell 4:121–133

    CAS  PubMed  Google Scholar 

  25. Petit AM, Rak J, Hung MC, Rockwell P, Goldstein N, Fendly B, Kerbel RS (1997) Neutralizing antibodies against epidermal growth factor and ErbB-2/neu receptor tyrosine kinases down-regulate vascular endothelial growth factor production by tumor cells in vitro and in vivo: angiogenic implications for signal transduction therapy of solid tumors. Am J Pathol 151:1523–1530

    CAS  PubMed  Google Scholar 

Download references

Disclosures

Michael J. Grieco, H. M. C. Shantha Kumara, Raymond Baxter, Nadav Dujovny, Matthew F. Kalady, Vesna Cekic, Martin Luchtefeld, and Richard L. Whelan have no conflicts of interest or financial ties to disclose.

Author information

Authors and Affiliations

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

    Michael J. Grieco, H. M. C. Shantha Kumara, Raymond Baxter, Vesna Cekic & Richard L. Whelan

  2. Division of Colon and Rectal Surgery, Ferguson Clinic, 4100 Lake Drive SE, Suite 205, Grand Rapids, MI, 49546, USA

    Nadav Dujovny & Martin Luchtefeld

  3. Department of Colorectal Surgery, Digestive Disease Institute, 9500 Euclid Avenue, A 30, Cleveland, OH, 44195, USA

    Matthew F. Kalady

  4. Section of Colon and Rectal Surgery, Department of Surgery, New York-Presbyterian Hospital, Columbia University, 177 Fort Washington Avenue, New York, NY, 10032, USA

    Richard L. Whelan

Authors
  1. Michael J. Grieco
    View author publications

    You can also search for this author in PubMed Google Scholar

  2. H. M. C. Shantha Kumara
    View author publications

    You can also search for this author in PubMed Google Scholar

  3. Raymond Baxter
    View author publications

    You can also search for this author in PubMed Google Scholar

  4. Nadav Dujovny
    View author publications

    You can also search for this author in PubMed Google Scholar

  5. Matthew F. Kalady
    View author publications

    You can also search for this author in PubMed Google Scholar

  6. Vesna Cekic
    View author publications

    You can also search for this author in PubMed Google Scholar

  7. Martin Luchtefeld
    View author publications

    You can also search for this author in PubMed Google Scholar

  8. Richard L. Whelan
    View author publications

    You can also search for this author in PubMed Google Scholar

Corresponding author

Correspondence to Richard L. Whelan.

Rights and permissions

Reprints and permissions

About this article

Cite this article

Grieco, M.J., Shantha Kumara, H.M.C., Baxter, R. et al. Minimally invasive colorectal resection is associated with a rapid and sustained decrease in plasma levels of epidermal growth factor (EGF) in the colon cancer setting. Surg Endosc 24, 2617–2622 (2010). https://doi.org/10.1007/s00464-010-1018-x

Download citation

  • Received:

  • Accepted:

  • Published:

  • Issue Date:

  • DOI: https://doi.org/10.1007/s00464-010-1018-x

Keywords

Search

Navigation