Neoadjuvant Therapy and Biliary Decompression Lower Biliary and Pancreatic Juice Vascular Endothelial Growth Factor Levels in Patients with Periampullary Adenocarcinoma

Abstract

Increased expression of vascular endothelial growth factor (VEGF) by pancreatic cancer correlates with poor survival. The significance of VEGF in biliary and pancreatic secretions in periampullary cancers is unknown. Bile and pancreatic juice samples were collected from patients undergoing pancreaticoduodenectomy (PD). All samples were frozen at -70°C until subsequent analysis for VEGF concentration using enzyme-linked immunoabsorbent assay (ELISA). Plasma VEGF levels in pancreatic cancer patients were <10 pg/mL. The biliary VEGF concentration for patients with malignancy was significantly elevated compared to benign disease (P = 0.05). There was no difference in pancreatic VEGF concentrations between benign and malignant disease. Cancer patients undergoing preoperative chemoradiation (CRT) had lower biliary and pancreatic VEGF concentrations than those who did not. Preoperative biliary drainage (BD) was associated with decreased VEGF concentrations in bile (3500 pg/mL vs 7740 pg/mL, P = 0.027). Patients undergoing both CRT and BD had diminished biliary and pancreatic VEGF concentrations compared to those who had neither. This was statistically significant for pancreatic VEGF concentrations (917 pg/mL vs 4723 pg/mL, P = 0.044). VEGF is highly concentrated in bile and pancreatic juice compared to plasma. Preoperative CRT and BD significantly reduce these levels in patients with periampullary cancers. Antiangiogenic therapy aimed at interrupting the VEGF pathway appears to be a logical target in periampullary cancer.