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Erschienen in: Annals of Surgical Oncology 3/2006

01.03.2006 | Original Article

Profile of Plasma Angiogenic Factors Before and After Hepatectomy for Colorectal Cancer Liver Metastases

verfasst von: Sam S. Yoon, MD, Sung H. Kim, MD, PhD, Mithat Gonen, PhD, Nancy M. Heffernan, RN, BSN, Kara Y. Detwiller, BS, William R. Jarnagin, MD, Michael D’Angelica, MD, Leslie H. Blumgart, MD, Kenneth K. Tanabe, MD, Ronald P. DeMatteo, MD

Erschienen in: Annals of Surgical Oncology | Ausgabe 3/2006

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Abstract

Background

Circulating angiogenic factors in patients with colorectal cancer liver metastases may promote tumor growth and contribute to liver regeneration after partial hepatectomy.

Methods

We analyzed blood samples from 26 patients with colorectal cancer liver metastases before and after liver resection and used samples from 20 healthy controls as a reference. Plasma levels of vascular endothelial growth factor (VEGF), basic fibroblast growth factor (bFGF), epidermal growth factor (EGF), and hepatocyte growth factor (HGF) were measured, and levels were correlated with recurrence.

Results

The median preoperative levels of all four factors were significantly higher and more variable in colorectal cancer liver metastasis patients than in controls. HGF and bFGF levels increased significantly 3 days and 1 month after hepatectomy, respectively, and returned to near preoperative levels at 3 months. Postoperative VEGF and EGF levels remained relatively stably increased over 3 months. After a median follow-up of 19 months, 10 patients (42%) experienced recurrence. Higher preoperative VEGF and HGF levels correlated with subsequent recurrence (P = .018 and .021, respectively), and a preoperative adjusted total value of all four factors accurately identified patients at low, moderate, and high risk of recurrence (P = .034). Patients who experienced disease recurrence also had relatively higher bFGF levels 3 months after operation (P = .035).

Conclusions

Plasma angiogenic factors are increased in patients with colorectal cancer liver metastases and remain increased at least 3 months after partial hepatectomy. Measurement of certain factors before and after hepatic resection can predict recurrence. Targeted biological agents may counteract the tumor-promoting effects of these circulating factors on subclinical disease.
Literatur
1.
Zurück zum Zitat Jemal A, Murray T, Ward E, et al. Cancer statistics. 2005 CA Cancer J Clin 55:10–30PubMed Jemal A, Murray T, Ward E, et al. Cancer statistics. 2005 CA Cancer J Clin 55:10–30PubMed
2.
Zurück zum Zitat Weiss L, Grundmann E, Torhorst J, et al. Haematogenous metastatic patterns in colonic carcinoma: an analysis of 1541 necropsies. J Pathol 1986;150:195–203CrossRefPubMed Weiss L, Grundmann E, Torhorst J, et al. Haematogenous metastatic patterns in colonic carcinoma: an analysis of 1541 necropsies. J Pathol 1986;150:195–203CrossRefPubMed
3.
Zurück zum Zitat Ballantyne GH, Quin J. Surgical treatment of liver metastases in patients with colorectal cancer. Cancer 1993;71:4252–66PubMed Ballantyne GH, Quin J. Surgical treatment of liver metastases in patients with colorectal cancer. Cancer 1993;71:4252–66PubMed
4.
Zurück zum Zitat Folkman J. Tumor angiogenesis: therapeutic implications. N Engl J Med 1971;285:1182–6PubMed Folkman J. Tumor angiogenesis: therapeutic implications. N Engl J Med 1971;285:1182–6PubMed
5.
Zurück zum Zitat Hanahan D, Folkman J. Patterns, emerging mechanisms of the angiogenic switch during tumorigenesis. Cell 1996;86:353–64CrossRefPubMed Hanahan D, Folkman J. Patterns, emerging mechanisms of the angiogenic switch during tumorigenesis. Cell 1996;86:353–64CrossRefPubMed
6.
Zurück zum Zitat Cross MJ, Claesson-Welsh L. FGF, VEGF function in angiogenesis: signalling pathways, biological responses and therapeutic inhibition. Trends Pharmacol Sci 2001;22:201–7CrossRefPubMed Cross MJ, Claesson-Welsh L. FGF, VEGF function in angiogenesis: signalling pathways, biological responses and therapeutic inhibition. Trends Pharmacol Sci 2001;22:201–7CrossRefPubMed
7.
Zurück zum Zitat Dvorak HF. Vascular permeability factor/vascular endothelial growth factor: a critical cytokine in tumor angiogenesis, a potential target for diagnosis and therapy. J Clin Oncol 2002;20:4368–80CrossRefPubMed Dvorak HF. Vascular permeability factor/vascular endothelial growth factor: a critical cytokine in tumor angiogenesis, a potential target for diagnosis and therapy. J Clin Oncol 2002;20:4368–80CrossRefPubMed
8.
Zurück zum Zitat Shing Y, Folkman J, Sullivan R, Butterfield C, Murray J, Klagsbrun M. Heparin affinity: purification of a tumor-derived capillary endothelial cell growth factor. Science 1984;223:1296–9PubMed Shing Y, Folkman J, Sullivan R, Butterfield C, Murray J, Klagsbrun M. Heparin affinity: purification of a tumor-derived capillary endothelial cell growth factor. Science 1984;223:1296–9PubMed
9.
Zurück zum Zitat Poon RT, Fan ST, Wong J. Clinical implications of circulating angiogenic factors in cancer patients. J Clin Oncol 2001;19:1207–1225PubMed Poon RT, Fan ST, Wong J. Clinical implications of circulating angiogenic factors in cancer patients. J Clin Oncol 2001;19:1207–1225PubMed
10.
Zurück zum Zitat Yoon SS, Tanabe KK. Surgical treatment, other regional treatments for colorectal cancer liver metastases. Oncologist 1999;4:197–208PubMed Yoon SS, Tanabe KK. Surgical treatment, other regional treatments for colorectal cancer liver metastases. Oncologist 1999;4:197–208PubMed
11.
Zurück zum Zitat Choti MA, Sitzmann JV, Tiburi MF, et al. Trends in long-term survival following liver resection for hepatic colorectal metastases. Ann Surg 2002;235:759–66CrossRefPubMed Choti MA, Sitzmann JV, Tiburi MF, et al. Trends in long-term survival following liver resection for hepatic colorectal metastases. Ann Surg 2002;235:759–66CrossRefPubMed
12.
Zurück zum Zitat Jarnagin WR, Gonen M, Fong Y, et al. Improvement in perioperative outcome after hepatic resection: analysis of 1,803 consecutive cases over the past decade. Ann Surg 2002;236:397–406CrossRefPubMed Jarnagin WR, Gonen M, Fong Y, et al. Improvement in perioperative outcome after hepatic resection: analysis of 1,803 consecutive cases over the past decade. Ann Surg 2002;236:397–406CrossRefPubMed
13.
Zurück zum Zitat Koniaris LG, McKillop IH, Schwartz SI, Zimmers TA. Liver regeneration. J Am Coll Surg 2003;197:634–59PubMed Koniaris LG, McKillop IH, Schwartz SI, Zimmers TA. Liver regeneration. J Am Coll Surg 2003;197:634–59PubMed
14.
Zurück zum Zitat Weglarz TC, Sandgren EP. Timing of hepatocyte entry into DNA synthesis after partial hepatectomy is cell autonomous. Proc Natl Acad Sci U S A 2000;97:12595–600CrossRefPubMed Weglarz TC, Sandgren EP. Timing of hepatocyte entry into DNA synthesis after partial hepatectomy is cell autonomous. Proc Natl Acad Sci U S A 2000;97:12595–600CrossRefPubMed
15.
Zurück zum Zitat Chen MF, Hwang TL, Hung CF. Human liver regeneration after major hepatectomy. A study of liver volume by computed tomography. Ann Surg 1991;213:227–9PubMed Chen MF, Hwang TL, Hung CF. Human liver regeneration after major hepatectomy. A study of liver volume by computed tomography. Ann Surg 1991;213:227–9PubMed
16.
Zurück zum Zitat Court FG, Wemyss-Holden SA, Dennison AR, Maddern GJ. The mystery of liver regeneration. Br J Surg 2002;89:1089–95CrossRefPubMed Court FG, Wemyss-Holden SA, Dennison AR, Maddern GJ. The mystery of liver regeneration. Br J Surg 2002;89:1089–95CrossRefPubMed
17.
Zurück zum Zitat Schmidt C, Bladt F, Goedecke S, et al. Scatter factor/hepatocyte growth factor is essential for liver development. Nature 1995;373:699–702CrossRefPubMed Schmidt C, Bladt F, Goedecke S, et al. Scatter factor/hepatocyte growth factor is essential for liver development. Nature 1995;373:699–702CrossRefPubMed
18.
Zurück zum Zitat Jones DE Jr, Tran-Patterson R, Cui DM, Davin D, Estell KP, Miller DM. Epidermal growth factor secreted from the salivary gland is necessary for liver regeneration. Am J Physiol 1995;268:G872–78PubMed Jones DE Jr, Tran-Patterson R, Cui DM, Davin D, Estell KP, Miller DM. Epidermal growth factor secreted from the salivary gland is necessary for liver regeneration. Am J Physiol 1995;268:G872–78PubMed
19.
Zurück zum Zitat Funakoshi H, Nakamura T. Hepatocyte growth factor: from diagnosis to clinical applications. Clin Chim Acta 2003;327:1–23CrossRefPubMed Funakoshi H, Nakamura T. Hepatocyte growth factor: from diagnosis to clinical applications. Clin Chim Acta 2003;327:1–23CrossRefPubMed
20.
Zurück zum Zitat Morishita R, Aoki M, Hashiya N, et al. Therapeutic angiogenesis using hepatocyte growth factor (HGF). Curr Gene Ther 2004;4:199–206PubMed Morishita R, Aoki M, Hashiya N, et al. Therapeutic angiogenesis using hepatocyte growth factor (HGF). Curr Gene Ther 2004;4:199–206PubMed
21.
Zurück zum Zitat Bruns CJ, Solorzano CC, Harbison MT, et al. Blockade of the epidermal growth factor receptor signaling by a novel tyrosine kinase inhibitor leads to apoptosis of endothelial cells and therapy of human pancreatic carcinoma. Cancer Res 2000;60:2926–35PubMed Bruns CJ, Solorzano CC, Harbison MT, et al. Blockade of the epidermal growth factor receptor signaling by a novel tyrosine kinase inhibitor leads to apoptosis of endothelial cells and therapy of human pancreatic carcinoma. Cancer Res 2000;60:2926–35PubMed
22.
Zurück zum Zitat Ross MA, Sander CM, Kleeb TB, Watkins SC, Stolz DB. Spatiotemporal expression of angiogenesis growth factor receptors during the revascularization of regenerating rat liver. Hepatology 2001;34:1135–48CrossRefPubMed Ross MA, Sander CM, Kleeb TB, Watkins SC, Stolz DB. Spatiotemporal expression of angiogenesis growth factor receptors during the revascularization of regenerating rat liver. Hepatology 2001;34:1135–48CrossRefPubMed
23.
Zurück zum Zitat Kaplan E, Meier P. Nonparametric estimation from incomplete observations. J Am Stat Assoc 1958;53:457–481 Kaplan E, Meier P. Nonparametric estimation from incomplete observations. J Am Stat Assoc 1958;53:457–481
24.
Zurück zum Zitat Davies MM, Jonas SK, Kaur S, Allen-Mersh TG. Plasma vascular endothelial but not fibroblast growth factor levels correlate with colorectal liver metastasis vascularity, volume. Br J Cancer 2000;82:1004–8PubMed Davies MM, Jonas SK, Kaur S, Allen-Mersh TG. Plasma vascular endothelial but not fibroblast growth factor levels correlate with colorectal liver metastasis vascularity, volume. Br J Cancer 2000;82:1004–8PubMed
25.
Zurück zum Zitat Dirix LY, Vermeulen PB, Hubens G, et al. Serum basic fibroblast growth factor and vascular endothelial growth factor and tumour growth kinetics in advanced colorectal cancer. Ann Oncol 1996;7:843–848PubMed Dirix LY, Vermeulen PB, Hubens G, et al. Serum basic fibroblast growth factor and vascular endothelial growth factor and tumour growth kinetics in advanced colorectal cancer. Ann Oncol 1996;7:843–848PubMed
26.
Zurück zum Zitat Fujisaki K, Mitsuyama K, Toyonaga A, Matsuo K, Tanikawa K. Circulating vascular endothelial growth factor in patients with colorectal cancer. Am J Gastroenterol 1998;93:249–52CrossRefPubMed Fujisaki K, Mitsuyama K, Toyonaga A, Matsuo K, Tanikawa K. Circulating vascular endothelial growth factor in patients with colorectal cancer. Am J Gastroenterol 1998;93:249–52CrossRefPubMed
27.
Zurück zum Zitat Hyodo I, Doi T, Endo H, et al. Clinical significance of plasma vascular endothelial growth factor in gastrointestinal cancer. Eur J Cancer 1998;34:2041–2045CrossRefPubMed Hyodo I, Doi T, Endo H, et al. Clinical significance of plasma vascular endothelial growth factor in gastrointestinal cancer. Eur J Cancer 1998;34:2041–2045CrossRefPubMed
28.
Zurück zum Zitat Landriscina M, Cassano A, Ratto C, et al. Quantitative analysis of basic fibroblast growth factor and vascular endothelial growth factor in human colorectal cancer. Br J Cancer 1998;78:765–70PubMed Landriscina M, Cassano A, Ratto C, et al. Quantitative analysis of basic fibroblast growth factor and vascular endothelial growth factor in human colorectal cancer. Br J Cancer 1998;78:765–70PubMed
29.
Zurück zum Zitat Dirix LY, Vermeulen PB, Pawinski A, et al. Elevated levels of the angiogenic cytokines basic fibroblast growth factor and vascular endothelial growth factor in sera of cancer patients. Br J Cancer 1997;76:238–243PubMed Dirix LY, Vermeulen PB, Pawinski A, et al. Elevated levels of the angiogenic cytokines basic fibroblast growth factor and vascular endothelial growth factor in sera of cancer patients. Br J Cancer 1997;76:238–243PubMed
30.
Zurück zum Zitat Fukuura T, Miki C, Inoue T, Matsumoto K, Suzuki H. Serum hepatocyte growth factor as an index of disease status of patients with colorectal carcinoma. Br J Cancer 1998;78:454–459PubMed Fukuura T, Miki C, Inoue T, Matsumoto K, Suzuki H. Serum hepatocyte growth factor as an index of disease status of patients with colorectal carcinoma. Br J Cancer 1998;78:454–459PubMed
31.
Zurück zum Zitat Fong Y, Fortner J, Sun RL, Brennan MF, Blumgart LH. Clinical score for predicting recurrence after hepatic resection for metastatic colorectal cancer: analysis of 1001 consecutive cases. Ann Surg 1999;230:309–18CrossRefPubMed Fong Y, Fortner J, Sun RL, Brennan MF, Blumgart LH. Clinical score for predicting recurrence after hepatic resection for metastatic colorectal cancer: analysis of 1001 consecutive cases. Ann Surg 1999;230:309–18CrossRefPubMed
32.
Zurück zum Zitat Kaneko A, Hayashi N, Tanaka Y, et al. Changes in serum human hepatocyte growth factor levels after transcatheter arterial embolization and partial hepatectomy. Am J Gastroenterol 1992;87:1014–17PubMed Kaneko A, Hayashi N, Tanaka Y, et al. Changes in serum human hepatocyte growth factor levels after transcatheter arterial embolization and partial hepatectomy. Am J Gastroenterol 1992;87:1014–17PubMed
33.
Zurück zum Zitat Shiota G, Okano J, Kawasaki H, Kawamoto T, Nakamura T. Serum hepatocyte growth factor levels in liver diseases: clinical implications. Hepatology 1995;21:106–112CrossRefPubMed Shiota G, Okano J, Kawasaki H, Kawamoto T, Nakamura T. Serum hepatocyte growth factor levels in liver diseases: clinical implications. Hepatology 1995;21:106–112CrossRefPubMed
34.
Zurück zum Zitat Curley SA, Izzo F, Abdalla E, Vauthey JN. Surgical treatment of colorectal cancer metastasis. Cancer Metastasis Rev 2004;23:165–82CrossRefPubMed Curley SA, Izzo F, Abdalla E, Vauthey JN. Surgical treatment of colorectal cancer metastasis. Cancer Metastasis Rev 2004;23:165–82CrossRefPubMed
35.
Zurück zum Zitat Ellis LM, Liu W, Ahmad SA, et al. Overview of angiogenesis: biologic implications for antiangiogenic therapy. Semin Oncol 2001;28:94–104CrossRefPubMed Ellis LM, Liu W, Ahmad SA, et al. Overview of angiogenesis: biologic implications for antiangiogenic therapy. Semin Oncol 2001;28:94–104CrossRefPubMed
36.
Zurück zum Zitat Hurwitz H, Fehrenbacher L, Novotny W, et al. Bevacizumab plus irinotecan, fluorouracil, and leucovorin for metastatic colorectal cancer. N Engl J Med 2004;350:2335–42CrossRefPubMed Hurwitz H, Fehrenbacher L, Novotny W, et al. Bevacizumab plus irinotecan, fluorouracil, and leucovorin for metastatic colorectal cancer. N Engl J Med 2004;350:2335–42CrossRefPubMed
37.
Zurück zum Zitat Kabbinavar F, Hurwitz HI, Fehrenbacher L, et al. Phase II, randomized trial comparing bevacizumab plus fluorouracil (FU)/leucovorin (LV) with FU/LV alone in patients with metastatic colorectal cancer. J Clin Oncol 2003;21:60–5PubMed Kabbinavar F, Hurwitz HI, Fehrenbacher L, et al. Phase II, randomized trial comparing bevacizumab plus fluorouracil (FU)/leucovorin (LV) with FU/LV alone in patients with metastatic colorectal cancer. J Clin Oncol 2003;21:60–5PubMed
38.
Zurück zum Zitat Saltz LB, Meropol NJ, Loehrer PJ Sr, Needle MN, Kopit J, Mayer RJ. Phase II trial of cetuximab in patients with refractory colorectal cancer that expresses the epidermal growth factor receptor. J Clin Oncol 2004;22:1201–8CrossRefPubMed Saltz LB, Meropol NJ, Loehrer PJ Sr, Needle MN, Kopit J, Mayer RJ. Phase II trial of cetuximab in patients with refractory colorectal cancer that expresses the epidermal growth factor receptor. J Clin Oncol 2004;22:1201–8CrossRefPubMed
39.
Zurück zum Zitat Cunningham D, Humblet Y, Siena S, et al. Cetuximab monotherapy and cetuximab plus irinotecan in irinotecan-refractory metastatic colorectal cancer. N Engl J Med 2004;351:337–45CrossRefPubMed Cunningham D, Humblet Y, Siena S, et al. Cetuximab monotherapy and cetuximab plus irinotecan in irinotecan-refractory metastatic colorectal cancer. N Engl J Med 2004;351:337–45CrossRefPubMed
40.
Zurück zum Zitat Saltz LB, Lenz H, Kindler H, et al. Interim report of randomized phase II trial of cetuximab/bevacizumab/irinotecan (CBI) versus cetuximab/bevacizumab (CB) in irinotecan-refractory colorectal cancer (abstract). ASCO Gastrointestinal Cancers Symposium. 2005 Saltz LB, Lenz H, Kindler H, et al. Interim report of randomized phase II trial of cetuximab/bevacizumab/irinotecan (CBI) versus cetuximab/bevacizumab (CB) in irinotecan-refractory colorectal cancer (abstract). ASCO Gastrointestinal Cancers Symposium. 2005
Metadaten
Titel
Profile of Plasma Angiogenic Factors Before and After Hepatectomy for Colorectal Cancer Liver Metastases
verfasst von
Sam S. Yoon, MD
Sung H. Kim, MD, PhD
Mithat Gonen, PhD
Nancy M. Heffernan, RN, BSN
Kara Y. Detwiller, BS
William R. Jarnagin, MD
Michael D’Angelica, MD
Leslie H. Blumgart, MD
Kenneth K. Tanabe, MD
Ronald P. DeMatteo, MD
Publikationsdatum
01.03.2006
Erschienen in
Annals of Surgical Oncology / Ausgabe 3/2006
Print ISSN: 1068-9265
Elektronische ISSN: 1534-4681
DOI
https://doi.org/10.1245/ASO.2006.03.060

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