New Strategy Detects High-Risk Barrett's Esophagus Patients

Roxanne Nelson

January 18, 2012

January 18, 2012 (San Francisco, California) — The use of optical biomarkers might improve the detection of esophageal cancer in patients with Barrett's esophagus, according to an upcoming presentation at the 2012 Gastrointestinal Cancers Symposium.

A unique method, known as spatial-domain low-coherence quantitative phase microscopy (SL-QPM), shows promise in differentiating dysplastic/neoplastic Barrett's epithelium from nondysplastic intestinal metaplasia in the esophagus, said study author Russell Brand, MD, professor of medicine at the University of Pittsburgh, Pennsylvania, at a press conference preceding the meeting.

Using a prediction model that combines 3 identified optical biomarkers, the researchers were able to distinguish Barrett's esophagus patients with occult high-grade dysplasia/esophageal adenocarcinoma from those with intestinal metaplasia only with a sensitivity of 89% and a specificity of 76% (accuracy, 0.87), explained Dr. Brand

"This test may be useful for the majority of Barrett's patients whose pathology examination shows nondysplastic intestinal metaplasia or is ambiguous for it," said Dr. Brand.

"We hope we will be able to detect patients who should be referred to a center that can do more high-resolution and endoscopic imaging to detect the dysplasia that wasn't appreciated with conventional endoscopy," he added.

Ultimately, the researchers are hoping that this technique provides a simpler and more accurate approach to biopsies. "Further, we think it may be useful in monitoring patients after ablative therapy or determining surveillance frequency," Dr. Brand said during his presentation.

Barrett's esophagus is defined as the presence of intestinal metaplasia in the esophagus, and requires surveillance because of a heightened risk for esophageal adenocarcinoma. Perhaps the most pressing challenge using current surveillance methodology is that tissue is randomly sampled; there is no way to identify patients with nondysplastic disease on surveillance who have occult high-grade dysplasia or who will ultimately progress to high-grade dysplasia or cancer, noted Dr. Brand.

Novel Strategy Uses Field Effect

Dr. Brand and colleagues proposed a strategy that is based on the concept of "field effect" to detect high-grade dysplasias or cancer by analyzing nondysplastic tissue. "The field effect means that there are genetic changes present in the site distant from the neoplastic lesion, or that cells near these cells are abnormal, but the changes weren't found with conventional microscopy," he explained.

This theoretically would identify Barrett's esophagus patients who are at high risk.

The group used SL-QPM to detect changes in nuclear structure as small as 0.9 nm, which is 1000 times smaller than what can be seen with conventional microscopy. Their hypothesis was that SL-QPM-derived optical biomarkers of nondysplastic intestinal metaplasia would be able to separate patients with high-grade or malignant lesions from those without neoplasia.

The researchers conducted a retrospective study in a cohort of 60 patients with Barrett's esophagus who had undergone biopsies according to the Seattle protocol (33 patients with intestinal metaplasia only, 21 with high-grade disease, and 6 with malignancy). From each case, 40 to 60 columnar cells were analyzed.

They identified 3 optical biomarkers — nuclear optical path length, intranuclear uniformity, and entropy — that were able to differentiate patients with nondysplastic disease from those with high-grade dysplasia or cancer with statistical significance (P < .01). Using these biomarkers, a prediction model was developed.

"Certainly, it is very exciting to have an additional test to identify patients who may harbor malignancy or a precancerous condition like high-grade dysplasia," said Morton Kahlenberg, MD, from Surgical Oncology Associates, San Antonio, Texas, who moderated the presscast.

"This is very noteworthy and has a real chance of modifying how this patient population is followed and treated," added Dr. Kahlenberg.

2012 Gastrointestinal Cancers Symposium (GICS). Abstract 14. To be presented January 19, 2012.

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