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Original Article |
1 Department of Surgery, Division of Surgical Oncology, Massachusetts General Hospital, Harvard Medical School, Yawkey 7B-7926, 55 Fruit Street, Boston, Massachusetts 02114
2 Department of Epidemiology and Biostatistics, Memorial Sloan-Kettering Cancer Center, 1275 York Avenue, New York, New York 10021
3 Department of Surgery, Hepatobiliary Service, Memorial Sloan-Kettering Cancer Center, 1275 York Avenue, New York, New York 10021
Correspondence: Address correspondence and reprint requests to: Sam S. Yoon, MD; E-mail: syoon{at}partners.org
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.
Key Words: Colorectal cancer • Liver metastases • Angiogenesis • Vascular endothelial growth factor • Basic fibroblast growth factor • Hepatocyte growth factor
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