Novel practical approaches to Barrett’s screening

Esophageal adenocarcinoma (EAC) has been the most rapidly increasing solid cancer in the U. S. during the past three decades. The prognosis of this cancer remains dismal with only one in five patients overall and three in five patients with localized cancer surviving over five years. Our only hope in this disease is to prevent cancer by diagnosing its precursor Barrett’s esophagus (BE) and effectively eradicating dysplasia when BE progresses.

Although between 1 and 5 percent of the adult population in the U. S. may have BE, it is only diagnosed in the small proportion who undergo upper endoscopy. Since endoscopy requires sedation, is invasive and not in-expensive, in practice it is only performed in selected patients who have gastroesophageal reflux disease (GERD), dyspepsia or other less common indications for esophagogastroduodenoscopy (EGD). General medical societies do not recommend endoscopic screening for BE. Recognizing that there are no randomized trials demonstrating effectiveness and that endoscopic screening will only impact a proportion of patients who will eventually develop cancers, endoscopic screening is cautiously recommended by the three major GI societies in patients with chronic GERD who have multiple risk factors for BE such as white race, male gender, smoking, obesity and family history. Our current practice diagnoses BE in less than 10 percent of patients who develop EAC. It is therefore imperative to develop an acceptable, robust, safe alternative to EGD for implementation of mass screening for BE.

Since transnasal endoscopy (TNE) failed to be adopted widely, investigators have focused on non-endoscopic alternatives, which include an optical coherence tomography (OCT), capsule tethered to a string, a mass spectrophotometry based device that “smells” volatile organic compounds in exhaled air, blood tests for circulating BE specific biomarkers and distal esophageal sampling devices that detect BE either by immunocytology or by chemical assays of nucleic acid based biomarkers.

“Our current practice diagnoses BE in less than 10 percent of patients who develop EAC. It is therefore imperative to develop an acceptable, robust, safe alternative to EGD for implementation of mass screening for BE.”

Rebecca Fitzgerald and her group at Cambridge University, U.K., have been true pioneers in the field by developing the Cytosponge, a swallowable encapsulated abrasive sponge. The capsule tethered to a string dissolves in the stomach releasing the 3 cm sponge, which obtains a cytological sample from the esophagus. Trefoil factor 3 (TFF3), an immunohistochemistry marker is then used to identify a cells Barrett’s epithelium with a sensitivity of about 70 to 80 percent and a specificity of over 90 percent. This promising technology has been tested, primarily in the U.K., in case control studies, primary detection studies and has now been implemented in a mass screening trial across the U.K.

Our group has tried to advance this field further by developing the Joe, Amitabh, Sandy Swallowable Sampling (JASSS) device, which consists of a balloon retracted within a silicone capsule, tethered to a soft silicone catheter that can be used to inflate the balloon when the capsule reaches the stomach. The inflated surfaced balloon can be used to feel the lower esophageal sphincter pressure and then selectively sample the distal esophagus. The sample on the surface of the balloon is then vacuum inverted back into the protective capsule to avoid dilution and contamination of the sample during withdrawal. We have further identified a two-marker methylated DNA panel (methylated VIM and methylated CCNA1) that can be assayed on the biomaterial adherent to the balloon. This assay is attractive because it can be automated, and similar diagnostic assays are already approved in the U.S. by the FDA. In our pilot study, this Esocheck technology, which was recently licensed for commercialization, had a 90 percent sensitivity and a 92 percent specificity for detecting BE and EAC. Others have recently reported on combinations or sponge-based whole esophageal sampling with methylated markers and even miRNA markers. New investigations will undoubtedly compare our selective distal esophageal sampling approach to the whole esophageal abrasive sampling approach of sponge devices as well as identify the optimal marker panel for non-endoscopic sampling of the esophagus. One or more new non-endoscopic office-based tests will make it possible to consider mass screening for BE and prevention of EAC in the very foreseeable future.

Disclosures: Dr. Chak has equity and a patent on the JASSS device and the Esocheck technology that has been licensed to Lucid Diagnostics for detection of Barrett’s esophagus.

Join the discussion

Your email address will not be published. Required fields are marked *