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 journalArticle

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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. 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 (US)
Pages (from-to)451-459
Number of pages9
JournalAnnals of Internal Medicine
Volume147
Issue number7
StatePublished - Oct 2 2007
Externally publishedYes

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Cholangiocarcinoma
Cholestasis
Insulin-Like Growth Factor I
Vascular Endothelial Growth Factor A
Pancreatic Neoplasms
Serum
Endoscopic Retrograde Cholangiopancreatography
Sclerosing Cholangitis
Cholangitis
Gastroenterology
Bile Ducts
Radiology
Bile
ROC Curve
Italy
Inpatients
Cross-Sectional Studies
Enzyme-Linked Immunosorbent Assay

ASJC Scopus subject areas

  • Medicine(all)

Cite this

Alvaro, D., Macarri, G., Mancino, M. G., Marzioni, M., Bragazzi, M., Onori, P., ... Benedetti, A. (2007). Serum and biliary insulin-like growth factor I and vascular endothelial growth factor in determining the cause of obstructive cholestasis. Annals of Internal Medicine, 147(7), 451-459.

Serum and biliary insulin-like growth factor I and vascular endothelial growth factor in determining the cause of obstructive cholestasis. / Alvaro, Domenico; Macarri, Gianpiero; Mancino, Maria Grazia; Marzioni, Marco; Bragazzi, Mariaconsiglia; Onori, Paolo; Corradini, Stefano Ginanni; Invernizzi, Pietro; Franchitto, Antonio; Attili, Adolfo F.; Gaudio, Eugenio; Benedetti, Antonio.

In: Annals of Internal Medicine, Vol. 147, No. 7, 02.10.2007, p. 451-459.

Research output: Contribution to journalArticle

Alvaro, D, Macarri, G, Mancino, MG, Marzioni, M, Bragazzi, M, Onori, P, Corradini, SG, Invernizzi, P, Franchitto, A, Attili, AF, Gaudio, E & Benedetti, A 2007, 'Serum and biliary insulin-like growth factor I and vascular endothelial growth factor in determining the cause of obstructive cholestasis', Annals of Internal Medicine, vol. 147, no. 7, pp. 451-459.
Alvaro, Domenico ; Macarri, Gianpiero ; Mancino, Maria Grazia ; Marzioni, Marco ; Bragazzi, Mariaconsiglia ; Onori, Paolo ; Corradini, Stefano Ginanni ; Invernizzi, Pietro ; Franchitto, Antonio ; Attili, Adolfo F. ; Gaudio, Eugenio ; Benedetti, Antonio. / Serum and biliary insulin-like growth factor I and vascular endothelial growth factor in determining the cause of obstructive cholestasis. In: Annals of Internal Medicine. 2007 ; Vol. 147, No. 7. pp. 451-459.
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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. 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.",
author = "Domenico Alvaro and Gianpiero Macarri and Mancino, {Maria Grazia} and Marco Marzioni and Mariaconsiglia Bragazzi and Paolo Onori and Corradini, {Stefano Ginanni} and Pietro Invernizzi and Antonio Franchitto and Attili, {Adolfo F.} and Eugenio Gaudio and Antonio Benedetti",
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T1 - Serum and biliary insulin-like growth factor I and vascular endothelial growth factor in determining the cause of obstructive cholestasis

AU - Alvaro, Domenico

AU - Macarri, Gianpiero

AU - Mancino, Maria Grazia

AU - Marzioni, Marco

AU - Bragazzi, Mariaconsiglia

AU - Onori, Paolo

AU - Corradini, Stefano Ginanni

AU - Invernizzi, Pietro

AU - Franchitto, Antonio

AU - Attili, Adolfo F.

AU - Gaudio, Eugenio

AU - Benedetti, Antonio

PY - 2007/10/2

Y1 - 2007/10/2

N2 - 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.

AB - 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.

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