Optical Markers May Offer Test for Early Pancreatic Cancer

EVANSTON, Ill., Aug. 1 -- Early pancreatic cancer at a resectable stage may be revealed by the scattering of light in the intestinal mucosa, investigators here reported.

The potential test emerged from studies of optical technologies that detect subtle changes in the mucosa without the need for direct visualization of the pancreas, Randall E. Brand, M.D., of Evanston Northwest Healthcare and Northwestern, and colleagues, reported in the Aug. 1 issue of Clinical Cancer Research.

The light-scattering techniques identified neoplastic changes in normal-appearing biopsies with 95% sensitivity and 91% specificity, they said. The diagnostic accuracy was unaffected by confounding factors such as tumor location and stage.

"This approach can potentially revolutionize screening for pancreatic cancer by providing a highly accurate, minimally invasive means of risk assessment," asserted Dr. Brand.

Assessment of duodenal mucosa adjacent to the ampulla represents an attractive approach to screening for pancreatic cancer because of its accessibility and straightforwardness, the authors wrote. Such as strategy is based on the "field effect" proposition of pancreatic carcinogenesis: Given a similar genetic and environmental milieu, a neoplastic lesion in a particular tissue site should also be detectable outside the site.

Dr. Brand and colleagues have developed two complementary optical techniques that allow previously unattainable quantitative assessment of tissue nanoarchitecture-microarchitecture in situ. The techniques are four-dimensional elastic light-scattering spectroscopy (4D-ELF) and low-coherence enhanced backscattering spectroscopy (LEBS).

The two techniques permit analysis of tissue-specific light-scattering signal patterns or fingerprints, which can be used to examine depth-sensitive tissue organization on scales ranging from macromolecules to whole cells. Combined analysis with the two techniques enhances diagnostic accuracy. The investigators have already used the techniques to achieve "unprecedented sensitivity for the assessment of the genetic/epigenetic changes of the field effect of colon carcinogenesis."

In the current study, 4D-ELF and LEBS were used to analyze duodenal biopsy specimens obtained within 1 cm to 3 cm of the ampulla from normal-appearing mucosa in 19 patients, age 70 12.1 years, with diagnosed pancreatic cancer. The findings were compared with those involving similar specimens obtained from 32 control patients, age 50 15 years, undergoing routine endoscopic procedures.

To characterize epithelial tissue architecture, the investigators used 4D-ELF and LEBS-derived quantitative optical markers previously validated for diagnosis of colon cancer.

"These markers were selected because they were previously shown to be highly diagnostic for detecting colon carcinogenesis far earlier than any other existing techniques," the authors stated.

Analysis of the light-scattering signal patterns revealed multiple statistically significant differences between biopsy samples from patients with and without pancreatic cancer, they wrote.

In addition to distinguishing specimens from control and cancer patients, the optical signal analysis distinguished between control patients and pancreatic cancer patients with resectable disease. For that analysis the techniques yielded a sensitivity of 100% and specificity of 94%.

Analysis of performance characteristics by patient age and smoking status, two factors that affect the risk for pancreatic cancer, showed that neither variable affected the optical markers' ability to detect cancer.

"The compelling diagnostic performance suggests the potential of this technique for pancreatic cancer screening," the authors stated.

The authors noted "limitations of this initial study include the modest number of patients in this study. Despite no statistical evidence of an age effect on these markers, the large difference in age between controls and pancreatic cancer patients leaves open the possibility (albeit unlikely) of residual confounding. In future studies, we will also evaluate benign pancreatic and biliary diseases to further define the specificity of these markers."