Serum and Biliary Insulin-like Growth Factor I and Vascular Endothelial Growth Factor in Determining the Cause of Obstructive Cholestasis

Abstract

Cholangiocarcinoma cells express and secrete insulin-like growth factor I (IGF-I) and vascular endothelial growth factor (VEGF). To measure IGF-I and VEGF in bile and serum of patients with extrahepatic cholangiocarcinoma and to evaluate their performance as diagnostic markers. Cross-sectional study. Inpatients at the Division of Gastroenterology, University Hospital, Ancona, Italy. 73 patients who consecutively had endoscopic retrograde cholangiopancreatography (ERCP), including patients with extrahepatic cholangiocarcinoma (n = 29), pancreatic cancer (n = 19), and benign biliary abnormalities (n = 25; bile duct stones, primary sclerosing cholangitis, and cholangitis). Diagnosis was based on conventional radiology, ERCP, and follow-up. Insulin-like growth factor I and VEGF were measured by using enzyme-linked immunosorbent assay. The biliary IGF-I concentration was 15- to 20-fold higher (P < 0.001) in extrahepatic cholangiocarcinoma (mean, 84.6 nmol/L [95% CI, 74.0 to 95.2 nmol/L]) than in pancreatic cancer (5.8 nmol/L [CI, 4.0 to 7.5 nmol/L]) or benign biliary abnormalities (4.1 nmol/L [CI, 3.1 to 5.2 nmol/L]). The area under the receiver-operating characteristic curve was 1 when biliary IGF-I values in the extrahepatic cholangiocarcinoma were compared with benign biliary abnormalities or pancreatic cancer. In contrast, biliary VEGF concentration was similar in the 3 groups. Serum IGF-I levels were similar among the groups, whereas serum VEGF levels were higher in the cholangiocarcinoma (0.97 ng/mL [CI, 0.59 to 1.35 ng/mL]; P = 0.0016) and pancreatic cancer groups (0.66 ng/mL [CI, 0.43 to 0.88 ng/mL]; P < 0.001) compared with patients with benign biliary abnormalities (0.28 ng/mL [CI, 0.17 to 0.37 ng/mL]). Data were obtained in a small sample, the study was performed in a single center, and few patients had a tissue diagnosis. Biliary IGF-I levels in patients undergoing ERCP for biliary obstruction may differentiate extrahepatic cholangiocarcinoma from either pancreatic cancer or benign biliary abnormalities.