In a new study published in the issue of Science Translational Medicine, researchers have developed a simple, swallowable test (>90% sensitive) for early detection of Barrett's esophagus that offers promise for preventing deaths from esophageal adenocarcinoma.

Barrett's esophagus (BE) is the precursor lesion of esophageal adenocarcinoma (EAC). Lethal EAC can be prevented when patients are diagnosed at the precursor stage of Barrett's esophagus, and early foci of near cancerous changes (dysplasias) are ablated. However, detection of BE has traditionally necessitated endoscopy, an expensive and invasive test that requires sedation and is thus unsuitable as a method for wide BE screening.

However, the team has developed an easy, five-minute outpatient test detect individuals with BE. Patients simply swallow a vitamin pill-sized balloon that swabs the esophagus, and that, after retrieval through the mouth, is tested for DNA abnormalities that are diagnostic of BE. Using genome-wide sequencing approaches, the researchers identified two genes, VIM and CCNA1, that each gets chemically modified by DNA methylation in BE.

DNA methylation test was more than 90% accurate in detecting BE or in recognizing an esophagus. The team led a clinical trial in which 86 individuals were tested using the swallowable esophageal balloon device. DNA assay of these balloon samples was again >90% accurate, with 90.3% sensitivity for detecting individuals with BE and 91.7% specificity for correctly identifying individuals who were normal.

Symptoms of Barrett's esophagus, such as heartburn, can also be commonly seen in individuals who have acid reflux disease without BE. These symptoms can easily be treated by over the counter medications so people often don't get tested for BE, particularly by an invasive test such as endoscopy. The test could provide a practical way for screening and early detection of individuals with BE who can then be followed closely to prevent the development of EAC."

The balloon device that patients swallowed is a pill-sized capsule attached to a thin silicone catheter. After delivery to the stomach, the small balloon was inflated by injecting air through the catheter. The inflated balloon was maneuvered to swab the lower esophagus near the stomach, the region where BE begins, and obtain a sample of the lining cells. The balloon was then deflated through the catheter and inverted back into the capsule, thus protecting the esophagus sample from dilution or contamination.

After retrieval of the capsule through the mouth, DNA was extracted from the balloon surface for the DNA methylation test. In an earlier study, the team had previously identified that VIM DNA methylation is common in BE. The genomic technology employed in the new study discovered CCNA1 DNA methylation is equally common in Barrett's esophagus (BE).

Having two accurate biomarkers increases confidence to correctly diagnose Barrett's esophagus. Taken together, the study findings show that non-endoscopic balloon sampling paired with molecular tests for the methylated VIM and CCNA1 biomarkers is effective in addressing the need for simple, non-invasive, safe, and accurate Barrett's esophagus screening.