Serum and biliary insulin-like growth factor I and vascular endothelial growth factor in determining the cause of obstructive cholestasis

Domenico Alvaro, Gianpiero Macarri, Maria Grazia Mancino, Marco Marzioni, Mariaconsiglia Bragazzi, Paolo Onori, Stefano Ginanni Corradini, Pietro Invernizzi, Antonio Franchitto, Adolfo F. Attili, Eugenio Gaudio, Antonio Benedetti

Research output: Contribution to journalArticlepeer-review


Background: Cholangiocarcinoma cells express and secrete insulin-like growth factor I (IGF-I) and vascular endothelial growth factor (VEGF). Objective: To measure IGF-I and VEGF in bile and serum of patients with extrahepatic cholangiocarcinoma and to evaluate their performance as diagnostic markers. Design: Cross-sectional study. Setting: Inpatients at the Division of Gastroenterology, University Hospital, Ancona, Italy. Patients: 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). Measurements: 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. Results: 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]). Limitations: Data were obtained in a small sample, the study was performed in a single center, and few patients had a tissue diagnosis. Conclusions: Biliary IGF-I levels in patients undergoing ERCP for biliary obstruction may differentiate extrahepatic cholangiocarcinoma from either pancreatic cancer or benign biliary abnormalities.

Original languageEnglish
Pages (from-to)451-459
Number of pages9
JournalAnnals of Internal Medicine
Issue number7
Publication statusPublished - Oct 2 2007

ASJC Scopus subject areas

  • Medicine(all)


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