Blood samples collected from the portal vein, which carries blood from organs in the gastrointestinal tract (including the pancreas), to the liver, can tell physicians far more about a patient’s pancreatic cancer than peripheral blood collected from a more easily accessed vein in the arm. These findings were published in Gastroenterology (doi:10.1053/j.gastro.2015.08.050).
Primary tumors shed cancerous cells, known as circulating tumor cells (CTCs), into the blood. These have been widely studied as prognostic biomarkers for various cancers. Because these cells are often larger, irregularly shaped and tend to cluster together, they get trapped in smaller vessels.
The authors hypothesized that most cells released from a gastrointestinal tumor would flow into the portal vein and then get sequestered by the narrow vessels in the liver. These cells would not reach the peripheral venous system. CTCs from GI tumors are rarely identified in the peripheral blood until the cancer is widely metastatic.
To test this theory, researchers from the University of Chicago, in Illinois, used an ultrasound-guided endoscope and a small needle to take blood from the portal vein during routine diagnostic endoscopies. They found CTCs in 100% of 18 patients with suspected tumors in the pancreas and bile ducts. Tests using peripheral blood samples, the standard method, detected tumors cells in only 4 of the 18 patients.
“We demonstrated that this method is potentially quite valuable as well as noninvasive, feasible and safe,” said study director Irving Waxman, MD, professor of medicine and surgery and director of the Center for Endoscopic Research and Therapeutics at the University. “We had no complications related to portal vein blood acquisition.”
The findings could offer doctors a method for diagnosing pancreatic cancer earlier in patients. Only 7% of patients with stage II disease are still alive 5 years after diagnosis, making it one of the most lethal forms of cancer. The American Cancer Society estimates that in 2015, nearly 49 000 people will develop pancreatic cancer and 40 560 people with this disease will die.
The portal vein samples contained far more tumor cells in all stages evaluated, including locally advanced as well as metastatic tumors, reported the researchers. Blood collected from the portal vein had a mean of more than 100 CTCs per 7.5 milliliters. Patients with less advanced disease, who could potentially benefit from surgery to remove the tumor, had fewer CTCs. Those patients averaged about 80 CTCs per 7.5 milliliters.
In contrast, when the researchers used peripheral blood to test the same patients, they found few, if any, circulating tumor cells. Those samples contained, on average, less than 1 CTC in 7.5 milliliters of blood, the equivalent of 1 cell in a billion.
“Access to circulating tumor cells may help us define the diagnosis and guide treatment,” Waxman said. “Having the ability to count them and to probe their molecular profiles can make a substantial difference in how we treat each patient’s tumor.”
These hidden cells in the portal venous system could help cancer specialists make better clinical decisions. Molecular characterization of CTCs at the time of diagnosis or after neoadjuvant therapy can provide clues about each patient’s prognosis. The frequent loss of protective tumor-suppressor genes, such as TP53, SMAD4 and p16/CDK2NA, which are often inactivated in pancreatic cancer, correlates with a worse outcome.