Serum and biliary insulin-like growth factor I and vascular endothelial growth factor in determining the cause of obstructive cholestasis.
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.
Alvaro
Domenico
D
Division of Gastroenterology, Department of Clinical Medicine, University of Rome Sapienza, Rome, Italy. domenico.alvaro@uniroma1.it
Macarri
Gianpiero
G
Mancino
Maria Grazia
MG
Marzioni
Marco
M
Bragazzi
MariaConsiglia
M
Onori
Paolo
P
Corradini
Stefano Ginanni
SG
Invernizzi
Pietro
P
Franchitto
Antonio
A
Attili
Adolfo F
AF
Gaudio
Eugenio
E
Benedetti
Antonio
A
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
D014408:Biomarkers, Tumor; D042461:Vascular Endothelial Growth Factor A; D007334:Insulin-Like Growth Factor I