High Bile VEGF Levels Suggest Pancreatic Cancer

A VEGF level greater than 0.5 ng/mL in bile aspirated from the pancreas was 93% effective at identifying pancreatic cancer in patients with biliary stricture, according to a pilot study reported at the American College of Gastroenterology 2013 Annual Scientific Meeting.

The bile required for testing was collected using endoscopic retrograde cholangiopancreatography (ERCP), a procedure commonly used to treat biliary stricture. While this procedure can adequately biopsy and treat certain conditions, available diagnostic tools are largely ineffective at determining whether the narrowing in the bile duct or resulting jaundice is due to a benign or malignant cause. This lack of an early diagnostic method for pancreatic cancer remains an area of unmet need, with nearly 60% of patients receiving an initial diagnosis of advanced disease.

“Differentiating pancreatic cancer from other problems which also cause jaundice is important as treatment approach is very different. Since bile is produced in the liver and passes through the bile duct and mixes with pancreatic secretions, measurement of markers in bile could identify cancer earlier than measuring some markers in blood. We can measure VEGF in bile fluid which is an inexpensive test and confirm the presence of cancer rather than other expensive investigations,” said the study's lead investigator Udayakumar Navaneethan, MD, in a statement.

In the study, 53 patients had bile aspirated from the common bile duct during ERCP. Bile VEGF levels were measured and tested for VEGF expression along with resected pancreatic cancer via immunohistochemistry. Additionally, a secondary independent validation was performed on a cohort of 18 patients: 10 with pancreatic cancer and 8 with a benign condition.

The study found that VEGF levels were significantly higher in patients with pancreatic cancer (n = 15) compared to those with primary sclerosing cholangitis (PSC; n = 18), cholangiocarcinoma (CCA; n = 9), and benign conditions (n = 11). The median bile VEGF level for patients with pancreatic cancer was 1.9 ng/mL (interquartile range [IQR] 0.7, 2.2) compared to 0.7 ng/mL, 0.4 ng/mL, and 0.3 ng/mL, for PSC, CCA, and benign conditions, respectively.

Researchers established that a VEGF level of greater than 0.5 ng/mL accurately identified pancreatic cancer from CCA with a sensitivity of 93.3% and a specificity of 88.9%. Moreover, this same cut-off value distinguished a benign condition from pancreatic cancer with a sensitivity of 93.3% and a specificity of 72.7%.

“In patients with indeterminate biliary strictures, we feel that measurements of markers in bile can help identify pancreatic malignancy and plan for earlier treatment. Also in patients where tissue diagnosis cannot be obtained in spite of multiple biopsies, measurement of markers in bile fluid to improve our diagnostic ability would be of immense interest,” explained Navaneethan, a clinical investigator at the Cleveland Clinic.

A variety of tests and procedures are generally used to detect pancreatic cancer, none of which are completely effective. If diagnosed early, pancreatic cancer can be excised, providing slightly better outcomes; however the 5-year survival rate for patients remains low at 14% for stage IA and as low as 1% for patients diagnosed with stage IV disease.

Research has shown that VEGF plays an important role in the biology of pancreatic cancer. However, studies examining VEGF inhibition as a treatment for patients with these tumors have not yielded promising results in phase III trials. However, this marker may still have promise as a diagnostic tool, particularly since an early detection method for pancreatic cancer is not currently available.