Barrett’s esophagus – Finding it without endoscopy by sweeping the lower esophagus with a disposable balloon – Esophageal pap smear

In this post we talk about finding Barrett’s esophagus in people who don’t know that they have it (screening). The surveillance of known Barrett’s esophagus requires endoscopy.

Esophagus cancer is one of the fastest growing cancers with only 20% of patients surviving 5 years. The only known precursor is Barrett’s esophagus, a premalignant intestinal-type columnar metaplasia that replaces the normal squamous mucosa of the distal esophagus.

Risk factors for Barrett’s esophagus

Patients with several of the following risk factors may be candidates for Barrett’s screening by endoscopy: chronic GERD, hiatal hernia, age ≥50, male gender, white race, elevated body mass index, and intra-abdominal body fat distribution. However, unlike for colon cancer, mass screening with endoscopy for average risk persons is not recommended.

The current screening approach is unsatisfactory because it is not efficient, too expensive, of questionable benefit and unsystematic.

Sweeping the lower esophagus for abnormal cells

Several groups are developing swallow able devices that try to scrape cells from the distal esophagus for analysis. To make this work, there are two problems to solve 1) the optimal device (ease of use, recovery of cells from the intended location) and 2) the algorithm for evaluation of the cells to detect metaplasia or neoplasia (sensitivity, specificity and overall accuracy).

A balloon is constrained in a sheath, swallowed, opened, closed, and withdrawn.

Recently, a group at Case Western Reserve University has published a research paper in Science Translational Medicine which seems to herald major progress [i]:

The device is swallowed in a pill-sized capsule attached to a thin 2.16-mm silicone catheter. After delivery to the stomach, the balloon is inflated by injecting  air through the catheter and then gently withdrawn 3 to 6 cm back through the distal esophagus to sample the luminal epithelial surface. The balloon is then deflated and inverted back into the capsule , thus protecting the acquired biosample from further dilution or contamination in the proximal esophagus and the oropharynx. After retrieval of the capsule through the mouth, DNA is extracted from the balloon surface for molecular analysis.

The researchers used CCNA1 DNA methylation and VIM DNA methylation as biomarkers for Barrett’s esophagus and were able to detected Barrett’s metaplasia with 90.3% sensitivity and 91.7% specificity.

A national multi-center trial to demonstrate the effectiveness of the technology compared with endoscopy in a population of individuals with GERD who have never received screening for Barrett’s esophagus will commence later this year.

 

[i] Moinova HR, LaFramboise T, Lutterbaugh JD, Chandar AK, Dumot J, Faulx A, Brock W, De la Cruz Cabrera O, Guda K, Barnholtz-Sloan JS, Iyer PG. Identifying DNA methylation biomarkers for non-endoscopic detection of Barrett’s esophagus. Science translational medicine. 2018 Jan 17;10(424):eaao5848.

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