VEGF LEVELS TO DISCRIMINATE PANCREATIC CANCER

SAN DIEGO — Vascular endothelial growth factor (VEGF)-1 levels distinguish between pancreatic cancer and other biliary diseases, and could be useful as a biomarker for diagnosing patients with indeterminate biliary stricture, new research suggests.

Biliary strictures are challenging to diagnose. Currently, physicians collect biliary tract brushings to test for signs of a tumor. However, this method only catches about half of all tumors, which leaves some patients without treatment until clear signs of cancer emerge. Ultrasound with biopsy is another useful diagnostic method, but some patients can't be biopsied.

Patients with a narrowing in the bile duct could have pancreatic cancer or a benign condition. "Differentiating these 2 is very difficult," said Uday Navaneethan, MD, an advanced endoscopy fellow at the Cleveland Clinic.

Dr. Navaneethan presented the research here at the American College of Gastroenterology 2013 Annual Scientific Meeting and Postgraduate Course.

VEGF-1 is involved in tumor angiogenesis, so the researchers hypothesized that higher levels would be diagnostic of cancer, but not other causes of biliary stricture.

They assessed 53 consecutive patients who underwent endoscopic retrograde cholangiography and collected bile during the procedure.

Ultimate diagnoses were 15 cases of pancreatic cancer, 18 cases of primary sclerosing cholangitis, 9 cases of cholangiocarcinoma, and 11 cases of benign biliary conditions, including sphincter of Oddi and choledocholihiasis.

Table 1. VEGF Levels in Biliary Conditions

Biliary Diagnosis	VEGF Level (ng/mL)	Interquartile Range	P Value
Pancreatic cancer	1.9	0.7–2.2	—
Benign biliary condition	0.3	0.2–0.6	<.001
Primary sclerosing cholangitis	0.7	0.5–0.9	.02
Cholangiocarcinoma	0.4	0.1–0.5	<.001

The researchers used a second cohort of 18 patients (10 with pancreatic cancer and 8 with benign conditions) to validate the diagnostic performance of their chosen VEGF-1 cutoff value of 0.5 ng/mL.

Table 2. VEGF-1 Performance in Distinguishing Pancreatic Cancer From Conditions

Condition	Sensitivity	Specificity	Area Under the Curve
Cholangiocarcinoma	93.3%	88.9%	0.93
Benign	93.3%	72.7%	0.89

"The specificity is still not great. We want numbers up to 85% to 90% to make it a great test. But I think it's a good test to differentiate cancer from other pancreatic conditions," said Dr. Navaneethan. He said he believes it could be combined with biliary tract brushings to improve accuracy.

Increasing the VEGF-1 cutoff point would improve specificity, but that would be at the cost of sensitivity. The research team is planning to repeat the study in a larger cohort of patients, and to compare results with brushings and serum levels of carbohydrate antigen 19-9.

"We hope to determine if a combination of any of these 3 will increase the sensitivity and specificity to close to 100%. I think VEGF will get it closer, but I don't think it will reach 100% by itself," said Dr. Navaneethan.

The biomarker approach has promise, according to session moderator Jonathan Leighton, MD, from the Mayo Clinic Arizona in Scottsdale. "Having better biomarkers for identifying pancreatic cancer is a huge issue because there are limitations to our current methods of diagnosis," he told Medscape Medical News.

It was surprising that the biomarker was negative in patients who were diagnosed with cholangiocarcinoma, Dr. Leighton noted, because they're both malignant processes. "I think we need clarification of that, but mainly we need to see prospective controlled trials," said Dr. Leighton.

Dr. Navaneethan and Dr. Leighton have disclosed no relevant financial relationships.

American College of Gastroenterology (ACG) 2013 Annual Scientific Meeting and Postgraduate Course: Abstract 4. October 14, 2013.