A minimally invasive esophageal sampling device has excellent potential for the early diagnosis of Barrett’s esophagus (BE) and the earlier detection of esophageal cancer in high-risk patients, new research indicates. The device is in the form of a small sponge, which is swallowed and gently drawn back through the esophagus, picking up genetic material on its way.
“Early detection is the whole ballgame when it comes to esophageal cancer,” senior author Stephen Meltzer, MD, professor of medicine and oncology, Johns Hopkins University School of Medicine, Baltimore, Maryland, said in a statement.
However, a significant proportion of patients with BE either don’t have symptoms of reflux or tend to minimize and disregard them, he told Medscape Medical News.
This is partially because, for patients with BE, the lining of the esophagus becomes like the lining of the intestine — so called intestinal metaplasia. Like the intestine, it can be exposed to large amounts of corrosive acid on a daily basis without provoking any symptoms, Meltzer explained.
Without symptoms, patients are not eligible for endoscopy because, Meltzer stressed, “endoscopy is not a screening test — you only get endoscopy for symptoms,” he said.
Given these obstacles, it is clear that alternative methods of BE screening are needed.
Novel Device — EsophaCap
Enter the EsophaCap (developed by CapNostics, New Jersey), a swallowable device consisting of a small gelatin capsule attached to a long string.
Once swallowed, the gelatin coating on the capsule dissolves in about 3 minutes, leaving a 2-cm polyurethane sponge attached to the string.
The string is then gently pulled back through the mouth. As the sponge makes its way up, it collects genetic material along the length and breadth of the esophagus.
When the sponge reaches the top of the esophagus, practitioners give a final tug, and it pops out, laden with DNA material that is subsequently extracted using a new technique known as methylation on beads (MOB).
Meltzer explained that MOB is a way of maximizing the amount of DNA that can be harvest from the sponge through the use of magnetic beads.
These beads bind to the DNA, which can be easily collected and subsequently analyzed by a methylation biomarker panel.
In an earlier study, Meltzer and colleagues identified eight methylation biomarkers that appear to predict which patients with BE experience progression to neoplasia and which do not.
“So we compared methylation levels of these 8 genes in sponge sample-derived DNAs between BE cases and controls,” the investigators explain.
Results showed that the levels of some methylation biomarkers were significantly higher in sponge DNA collected from patients diagnosed with BE compared with samples from control patients.
This prompted the team to winnow down the methylation panel to four biomarkers. These four biomarkers, combined with age, make up what the investigators call the “lasso” model.
The researchers then assessed this lasso model in an independent cohort of 28 patients, of whom 14 were found to have BE on subsequent endoscopy and 14 were not.
They report that in the cohort of patients with BE, the diagnostic accuracy of this high-predictability model was 86.7% for the detection of BE.
The sensitivity of the model was 78.6%, and the specificity was 92.8%, the study authors report.
Not the First
Meltzer noted that investigators from the Mayo Clinic in Rochester, Minnesota, were the first to use the EsophaCap to identify methylated DNA markers characteristic of BE.
Unlike a previously reported swallowable device used for essentially the same purposes, the EsophaCap does not require swallowing a balloon that must be inflated once it reaches the stomach.
Nor does the EsophaCap have to be protected against contamination from DNA material as the device passes through normal esophageal tissue in smokers, Meltzer added.
Most importantly, this novel sponge device can be administered by anyone with minimal training, ideally in any physician’s office, where the procedure could be routinely performed in appropriately aged patients.
“This is cheaper and easier and safer than endoscopy, and while we don’t yet know how much this device is going to cost, you don’t need anesthesia, you don’t need an endoscopist, and endoscopy — need I say it again — is not approved for screening,” Meltzer said.
Meltzer and colleagues are currently in discussion with companies to bring the device to the market as soon as possible.
The authors have disclosed no relevant financial relationships.
Clin Cancer Res. Published online January 22, 2019. Abstract