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. 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.

Comparison of two dosing regimens of gabexate in the prophylaxis of post-ERCP pancreatitis.

OBJECTIVES: A continuous 13-h infusion of gabexate starting 30-90 min before endoscopic cholangiopancreatography (ERCP) can reduce postprocedural pancreatitis, the onset of which is generally observed within the first 6 h after ERCP. This study was designed to verify whether a 6.5-h infusion of gabexate was as effective as a 13-h infusion, at the same concentration, for reducing the incidence of post-ERCP pancreatitis (primary endpoint) and pancreatic hyperenzymemia and pain (secondary endpoints). METHODS: A total of 434 patients (201 male and 233 female; mean age 63.9 yr, range 18-96 yr) scheduled for ERCP were prospectively recruited in 25 Italian centers. Patients were randomized double-blind to two treatment groups. All subjects enrolled were first treated with a 500-mg continuous intravenous infusion of gabexate, starting 30 min before the endoscopic maneuvers and continuing up to 6.5 h after it. Over the next 6.5 h, 214 patients (group I) continued the infusion of gabexate (for a total of 1 g over 13 h) and 220 patients (group II) were given placebo (saline solution). RESULTS: The overall incidence of acute pancreatitis was 1.8% (eight patients), which included 1.4% in group I (three of 214 patients) and 2.2% in group II (five of 220 patients). Serum amylase and lipase values over time, peak levels of the two enzymes, pancreatic pain, and need for analgesics did not significantly differ in the two groups. CONCLUSIONS: These results suggest that a 6.5-h infusion of gabexate (for a total of 500 mg) is not less effective than a 13 h infusion, with evident savings.