New markers shed light on pancreatic cancer

The past decade has seen significant improvements in the quality of imaging studies for pancreatic cancer and the development of disease-specific molecular markers. But these advances have not led to earlier detection for most patients, 80 percent of whom have a locally advanced or metastatic tumor that is considered unresectable at the time of diagnosis.

Survival rates have not measurably improved, either. For all stages of pancreatic cancer, the one- and five-year survival rates are 20 and 4 percent, respectively. Michael B. Wallace, M.D., a gastroenterologist at the Mayo Clinic Cancer Center in Florida, says a safe, sensitive and cost-effective strategy for pancreatic cancer screening and early detection is urgently needed and a research priority at his institution.

PGS technology

One area of investigation involves the use of polarization gating spectroscopy (PGS) technology to detect early pancreatic adenocarcinoma by measuring markers of increased blood supply, such as deoxyhemoglobin concentration and blood vessel radius, in the adjacent duodenal mucosa.

Dr. Wallace explains, "This is based on the theory that a neoplastic lesion may cause a larger field effect in normal-appearing tissue distant from the site of the tumor. Detecting these remote neoplastic changes may make it possible to diagnose cancer from a distance. We have been studying versions of this in other cancers for 20 years and in the pancreas for about the last two years."

PGS uses a small, fiber-optic endoscopic probe to measure the intensity of light scattering in superficial tissue. The technology uses a subset of normal white light, with no risk of radiation injury. And because the probe gently comes in contact with the tissue surface, it adds little risk to the endoscopy procedure. It also adds little additional time, taking the measurement in a split second.

To evaluate the feasibility, safety and efficacy of PGS measurements in the duodenum to determine markers of early increased blood supply, Mayo Clinic researchers, in partnership with biomedical engineers at Northwestern University, conducted a prospective pilot study comparing patients with pancreatic adenocarcinoma with healthy controls. Initial findings were published in the April 2012 Gastrointestinal Endoscopy.

Study design and results

Fourteen patients with diagnosed but untreated pancreatic adenocarcinoma and 15 controls with no known history of the disease were included in the study. All underwent esophagogastroduodenoscopy (EGD) with upper endoscopic ultrasound (EUS) performed by an experienced endoscopist.

During EGD, four spectroscopy measurements were obtained at each of five locations in the periampullary duodenal mucosa. The data was then transferred to the Northwestern University biomedical lab, which performed the final analysis of the measurements.

Results showed that deoxyhemoglobin concentration and blood vessel radius measured from the ampulla had the greatest ability to differentiate cancer patients from controls. Deoxyhemoglobin measurements alone achieved sensitivity of 92 percent and specificity of 86 percent in distinguishing between the two. Combined with blood vessel radius, deoxyhemoglobin achieved sensitivity of 92 percent and specificity of 71 percent. Typical confounding factors such as age, sex, race, and history of smoking or alcohol use did not have a statistically significant effect on the results.

Dr. Wallace says the effectiveness of PGS for early detection of pancreatic cancer will now be tested in a much larger international clinical trial led by Mayo Clinic Cancer Center researchers.

Molecular marker for adenocarcinoma

Investigators at Mayo Clinic in Florida led by Massimo Raimondo, M.D., in collaboration with researchers at Mayo Clinic in Minnesota, also have developed a promising method for distinguishing pancreatitis from pancreatic adenocarcinoma using a molecular marker derived from pancreatic secretions. "Many researchers have been working on such a diagnostic test for a long time — for me, it has been 20 years," Dr. Raimondo says.

As in the PGS trial, pancreatic juices were collected from patients undergoing routine endoscopy and analyzed for markers. A single altered genetic marker, CD1D, was detected in 75 percent of patients later diagnosed with pancreatic cancer but in just 9 percent of those with pancreatitis.

Dr. Raimondo notes,"CD1D performed much better than any other pancreatic secretion marker previously tested in identifying pancreatic cancer."

The research team is working to further improve diagnostic accuracy of the test, which can potentially be used to screen patients at high risk of pancreatic cancer. "Although we know more research is needed, including validation of our findings, we can't help but be excited by this advance," Dr. Raimondo says.

For more information

Patel, MK, et al. Polarization gating spectroscopy of apparently normal duodenal mucosa to detect pancreatic cancer.
Gastrointestinal Endoscopy. 2012;75:AB162.

Sukhwinder K, et al. Neutrophil gelatinase-associated lipocalin, macrophage inhibitory cytokine 1, and carbohydrate antigen 19-9 in pancreatic juice: Pathologic implications in diagnosing benign and malignant disease of the pancreas.  Pancreas. 2013;42:494.