title: Serum and biliary insulin-like growth factor I and vascular endothelial growth factor in determining the cause of obstructive cholestasis.
abstract: 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.
  
  
  METHODS
  Cross-sectional study.
  
  
  METHODS
  Inpatients at the Division of Gastroenterology, University Hospital, Ancona, Italy.
  
  
  METHODS
  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).
  
  
  METHODS
  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]).
  
  
  CONCLUSIONS
  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.
authors.affiliation: Division of Gastroenterology, Department of Clinical Medicine, University of Rome Sapienza, Rome, Italy. domenico.alvaro@uniroma1.it
authors.forename: Domenico
authors.initials: D
authors.lastname: Alvaro
authors.forename: Gianpiero
authors.initials: G
authors.lastname: Macarri
authors.forename: Maria Grazia
authors.initials: MG
authors.lastname: Mancino
authors.forename: Marco
authors.initials: M
authors.lastname: Marzioni
authors.forename: MariaConsiglia
authors.initials: M
authors.lastname: Bragazzi
authors.forename: Paolo
authors.initials: P
authors.lastname: Onori
authors.forename: Stefano Ginanni
authors.initials: SG
authors.lastname: Corradini
authors.forename: Pietro
authors.initials: P
authors.lastname: Invernizzi
authors.forename: Antonio
authors.initials: A
authors.lastname: Franchitto
authors.forename: Adolfo F
authors.initials: AF
authors.lastname: Attili
authors.forename: Eugenio
authors.initials: E
authors.lastname: Gaudio
authors.forename: Antonio
authors.initials: A
authors.lastname: Benedetti
mesh_terms: D000368:Aged; D000369:Aged, 80 and over; D001646:Bile / Q000737:chemistry*; D001650:Bile Duct Neoplasms / Q000150:complications / Q000175:diagnosis*; D001660:Biliary Tract Diseases / Q000150:complications / Q000175:diagnosis; D014408:Biomarkers, Tumor / Q000032:analysis*; D018281:Cholangiocarcinoma / Q000150:complications / Q000175:diagnosis*; D002779:Cholestasis / Q000209:etiology* / Q000378:metabolism; D003430:Cross-Sectional Studies; D003937:Diagnosis, Differential; D005260:Female; D005500:Follow-Up Studies; D006801:Humans; D007334:Insulin-Like Growth Factor I / Q000032:analysis*; D008297:Male; D008875:Middle Aged; D010190:Pancreatic Neoplasms / Q000150:complications / Q000175:diagnosis; D012372:ROC Curve; D042461:Vascular Endothelial Growth Factor A / Q000032:analysis* / Q000097:blood
chemical_list: D014408:Biomarkers, Tumor; D042461:Vascular Endothelial Growth Factor A; D007334:Insulin-Like Growth Factor I