Diagnostic Immunoassays Could Spare Patients High-Risk Pancreatic Resection

Researchers at Indiana University have confirmed the clinical utility of 2 laboratory tests that can distinguish benign pancreatic cancer lesions that mimic early signs of cancer and spare patients of unnecessary pancreatic cancer screenings or surgeries.

Pancreatic cancer is quite incurable, especially adenocarcinomas in the pancreas, which is the most common form of the disease, with a dismal 5-year survival rate of 12% to 14% if diagnosed early (stage IA to stage IB)—this falls back to 1% to 2% for patients with more advanced disease. However, a small fraction of patients harbor serous cystic neoplasms (SCNs), which are most often benign and may not need to be treated unless they grow or lead to symptoms.

However, patients with SCNs undergo routine imaging every 6 months to track changes within the SCN, or they may be operated on to remove a part of the pancreas. SCNs are hard to predict without surgery—more than 60% are not predicted preoperatively—and stand a chance of inaccurate diagnosis. In the study, the authors tested the hypothesis that combining the detection of vascular endothelial growth factor-A (VEGF-A; associated with angiogenesis, upregulated in tumors, and can be correlated with tumor stage) and the carcinoembryonic antigen (CEA; upregulated in certain cancers) in the cyst fluid of these patients can improve the diagnostic accuracy of VEGF-A.

The authors collected pancreatic cystic fluid from 149 consenting patients undergoing surgical cyst resection along with corresponding pathologic diagnoses, which included:

• Pseudocyst (14)
• SCN (26)
• Mucinous cystic neoplasm (40)
• Low-/moderate-grade intraductal papillary mucinous neoplasm (IPMN, 34)
• High-grade IPMN (20)
• Invasive IPMN (10)
• Solid pseudopapillary neoplasm (5)

The authors found that VEGF-A was significantly elevated in SCN cyst fluid compared with all other diagnoses. VEGF-A alone singled out SCN with a sensitivity of 100% and specificity of 83.7%, and CEA had a 95.5% sensitivity and 81.5% specificity. Together, however, the combination had a sensitivity of 95.5% and specificity of 100% for SCN, which the authors define as approaching “the gold standard for pathologic diagnosis, importantly avoiding false positives.” They concluded that the results of the VEGF-A/CEA test could have prevented 26 patients from having unnecessary surgery.

“Every day, surgeons follow patients who have pancreatic cysts that have no risk of cancer but are still worrisome,” C. Max Schmidt, MD, PhD, FACS, study author and professor of surgery and biochemical/molecular biology, Indiana University School of Medicine, said in a statement. "They perform surgery or conduct diagnostic tests just to make sure they’re not wrong. With VEGF-A and CEA, we believe we may have invented a test that can help that group of patients who don’t have a risk of cancer get off the testing cycle and avoid surgery which, in and of itself, has a risk of mortality or complications."

The study has been published in the Journal of the American College of Surgeons.