Detecting Esophageal Cancer with Light

A tiny light source and sensors at the end of an endoscope may provide a more accurate way to identify pre-cancerous cells in the lining of the esophagus.

Developed by biomedical engineers at Duke University and successfully tested on patients during a clinical trial at the University of North Carolina at Chapel Hill, the device holds the promise of being a less invasive method for testing patients suspected of having Barrett’s esophagus, a change in the lining of the esophagus due to acid reflux. Acid reflux occurs when stomach acid splashes, or refluxes, up into the esophagus.

Long periods of acid reflux can change the cells that line the esophagus, making them appear more like intestinal cells than esophageal cells. These cellular changes can also be a precursor to cancer. As in most cancers, early identification of these pre-cancerous cells often leads to better outcomes for patients. Barrett’s esophagus afflicts more than one percent of the U.S. population, with most patients above the age of 50.

Using an endoscope to reach the esophagus via the nose, physicians shine short bursts of this light at locations of suspected disease and sensors capture and analyze the light as it is reflected back. In particular, they are trying to spot characteristic changes within the layer of cells known as the epithelium, which line cavities and surfaces throughout the body.

“By interpreting the way the light scatters after we shine it at a location on the tissue surface, we can the spot the tell-tales signs of cells that are changing from their healthy, normal state to those that may become cancerous,” said Neil Terry, a Ph.D. student working in the laboratory of Adam Wax, associate professor of biomedical engineering at Duke’s Pratt School of Engineering, who developed the device.

The team published their findings online in the January issue of the journal Gastroenterology.

“Specifically, the nuclei of pre-cancerous cells are larger than typical cell nuclei, and the light scatters back from them in a characteristic manner,” Terry continued. “When we compared the findings from our system with an actual review by pathologists, we found they correlated in 86 percent of the samples.”

UNC gastroenterologist Nicholas Shaheen, M.D., conducted the preliminary clinical trial of the device on 46 patients with Barrett’s esophagus.

“Currently, we take many random tissue samples from areas we where we think abnormal cells may be located,” Shaheen said. “This new system may make our biopsies smarter and more targeted. Early detection is crucial, because the cure rate for esophageal cancer that is caught early is quite high, while the cure rate for advanced disease is dismal, with a 15 percent survival rate after five years.”

The technology that Wax and his team developed for cancer detection is known as angle-resolved low coherence interferometry (a/LCI). The technique is able to separate the unique patterns of the nucleus from the other parts of the cell and provide representations of its changes in shape in real time.

“This optical approach of sampling allows us to cover more tissue sites in less time and has the potential to significantly improve our ability to spot and monitor these pre-cancerous cells,” Wax said. “This type of approach could be used to improve and perhaps one day supplant the physical biopsies currently being used.”

Wax pointed out that since approximately 85 percent of all cancers begin within the layers of the epithelium in various parts of the body, he believes that the new system could also work in such cancers as those of the colon, trachea, cervix or bladder.

The research was supported by the National Institutes of Health, the National Science Foundation and Oncoscope, Inc., a company Wax founded in 2006, based on the Duke technology. Wax has a financial interest in the company, and Terry is a consultant.

Oncoscope plans a clinical trial of the system for approval, and Wax said there could be a commercially available device as early as 2012.

By Richard Merritt

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Stool DNA Testing Could Play Expanded Role in Colon Cancer Prevention

(BUSINESS WIRE)--Research teams led by Mayo Clinic have demonstrated for the first time that two types of colorectal pre-cancers can be detected through noninvasive stool DNA testing. The two studies being presented demonstrate that stool DNA testing may be useful for detection of premalignant dysplasia in patients with inflammatory bowel disease (IBD) and of an important type of colorectal pre-cancer called serrated polyps. The findings were presented at Digestive Disease Week 2010, the annual meeting of the American Gastroenterological Association.

“This was significantly higher than the 7 percent rate with conventional fecal blood tests.”

David Ahlquist, M.D., a gastroenterologist with Mayo Clinic and the senior investigator, said that sensitive stool DNA test methods developed at Mayo Clinic can detect common forerunners of colorectal cancer. “Detection of precursor lesions during screening is essential if cancer prevention is the goal,” Dr. Ahlquist says.

Compared to widely used fecal blood tests, stool DNA testing has higher detection rates for curable stage colorectal cancer and for common precancerous polyps (called adenomas).

Detection of Colorectal Precancerous Lesions in Inflammatory Bowel Disease

The first study, presented on May 3 at Digestive Disease Week, involves identifying both cancer and a precancerous lesion, called dysplasia, in people who suffer from IBD. In a blinded study with 10 cases and 10 controls done in conjunction with Mount Sinai Medical Center and the University of Chicago, researchers found that stool DNA testing was positive in nine out of 10 cases (five of five with cancer, and four of five with dysplasia).

“This study shows that cancer and pre-cancer in IBD can be detected noninvasively,” says Dr. Ahlquist. “The 90 percent detection rate by stool DNA testing is remarkable. It’s important for people with IBD because they are at much higher risk for colorectal cancer than the general population. Given the limitations of colonoscopies in detecting these lesions, stool DNA testing could play a complementary role to improve the effectiveness of cancer surveillance.”

Detection of Serrated Colorectal Polyps

The second study, presented on May 4, involves detecting serrated colorectal polyps. Unlike common adenomas, which usually protrude from the colon lining and are easy to see, serrated polyps are typically flat and the same color as the colon lining. Dr. Ahlquist says serrated polyps have been ignored or excluded from most screening studies to date because it wasn’t clear they were associated with cancer. “Now they are regarded as the forerunner in roughly 30 percent of colon cancers,” says Dr. Ahlquist. “Most of these are located on the right side of the colon, where screening has had less impact historically.”

For this study, researchers first took tissue and identified two genetic markers that were present in serrated polyps but not in normal colon. The team assayed the markers (mutant BRAF and methylated vimentin genes) in stool samples from 14 cases and 19 control patients who had undergone screening colonoscopies. In blinded fashion, they compared results to fecal blood tests on the same specimens.

“We observed a 71 percent detection rate with stool DNA testing,” says Dr. Ahlquist. “This was significantly higher than the 7 percent rate with conventional fecal blood tests.”

“Detection of these important types of precancer by stool DNA testing offers promise in our efforts to more effectively and affordably prevent colorectal cancer,” says Dr. Ahlquist. “However, findings from both pilot studies need to be corroborated in larger studies.”

Collaboration

The studies were funded by the National Institutes of Health and the Charles Oswald Foundation. Mayo Clinic co-authors for the colorectal neoplasia and inflammatory bowel disease study include John Kisiel, M.D.; Tracy Yab; Fareeda Hussain, William Taylor; Jonathan Harrington; Mary Devens; Julie Simonson; Megan Garrity-Park; William Sandborn, M.D.; Edward Loftus, M.D; and Hongzhi Zou, M.D., PhD. Co-authors for the serrated colorectal polyps study include Hussain, Yab, Harrington, Taylor, Thomas Smyrk, M.D.; Douglas Mahoney; and Dr. Zou.

Disclosure

Drs. D. Ahlquist and D. Zou, Mses. T. Yab and F. Hussain; and Messrs. Taylor and Harrington and Mayo Clinic have a financial interest related to technology used with this research. This technology has been licensed to Exact Sciences. Mayo Clinic stands to receive royalties from the licensing of this technology and holds an equity position in Exact Sciences.

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