Alternative approaches to Barrett's screening prove safe and effective
Barrett's esophagus (BE) is the precursor and strongest risk factor for esophageal adenocarcinoma. Though rare, the malignancy is rapidly increasing in western nations and has a poor prognosis when diagnosed after the onset of symptoms. Five-year survival is less than 20 percent in advanced cases. In spite of this, the benefits and cost-effectiveness of screening for BE remain controversial.
Prasad G. Iyer, M.D., of Mayo Clinic in Minnesota, notes that several factors make population-based testing for BE challenging, including the invasiveness, expense and risks of endoscopy and lack of a paradigm for determining the population that would benefit most. Gastroesophageal reflux is not an accurate predictor of risk; more than 80 percent of reflux patients don't have BE, whereas an increasingly well-documented subgroup of asymptomatic people do.
What are needed, he explains, are minimally or noninvasive tools for BE screening as well as optimally sensitive and specific markers that would effectively discriminate BE from normal esophagogastric mucosa.
To further those ends, Dr. Iyer and colleagues recently investigated the feasibility of unsedated screening endoscopies in outpatient settings as well as use of molecular markers for distinguishing BE from normal esophageal tissue. Results will be presented at Digestive Disease Week 2014.
Molecular markers study
Building on earlier studies at Mayo Clinic and elsewhere, the investigators identified a panel of abnormally methylated genes as candidate markers for BE and assessed their ability to identify BE tissue using endoscopic biopsies and brushings. A total of 100 participants — 50 with histologically confirmed intestinal metaplasia and 50 with no evidence of BE — were included in two study phases.
In phase I, endoscopic biopsies were obtained from 40 patients and 40 controls. In patients with Barrett's esophagus, biopsy samples were taken from Barrett's mucosa; the gastric cardia (1 centimeter below the gastroesophageal junction); and the squamous epithelium (2 centimeters above BE). Control biopsies were obtained from the gastric cardia and squamous epithelium (5 centimeters above the Z line).
With the exception of the tumor suppressor gene adenomatous polyposis coli (APC), median levels of methylated markers were 200 to 1,100 times higher in BE than in adjacent or normal tissue. Levels were also higher in the gastric cardia adjacent to BE than in similar tissue in controls. Methylated APC was higher in BE, but did not distinguish it from the gastric cardia. Marker levels increased with BE length for NDRG4, SFRP1, BMP3 and HPP1 and were not affected by age, sex, inflammation or dysplasia.
Phase II compared methylation markers in 10 BE patients with 10 controls using brushed specimens. In this case, NDRG4 and BMP3 — the most discriminant markers in Phase I — were able to differentiate between BE and normal tissue with 100 and 99 percent accuracy, respectively, making them especially promising for nonendoscopic screening.
Another large, randomized trial — the first of its kind — assessed the effectiveness, safety and tolerability of novel approaches for community BE screening. Participants included 209 adults age 50 and older with no history of endoscopic evaluation. Of these, 115 had reflux symptoms.
Patients were randomized to undergo sedated endoscopy or transnasal endoscopy in an outpatient endoscopy suite or mobile research van. Transnasal endoscopy was performed using an ultrathin, flexible esophagoscope with a single-use disposable sheath. The benefit of the device is that it doesn't require conscious sedation and can be used successfully in most people in outpatient settings.
Findings showed that although sedated endoscopy was better tolerated than mobile or clinic exams — mean score 0.4 versus 1.9 and 2.2, respectively — the majority of patients were willing to undergo the unsedated procedure again.
"There was also no statistical difference in yield, showing that unsedated transnasal endoscopy is accurate, feasible and practical in screening for Barrett's," Dr. Iyer says. "In addition, diagnostic biopsies, if needed, are just as accurate with the small endoscope. And the cost is dramatically different. Transnasal endoscopy is less expensive than conventional sedated endoscopy. There is no sedation or facility fee, and patients can go back to work immediately, without needing someone to drive them. So there are savings in both direct and indirect costs."
He adds, "We're launching the next phase of studies by looking at the accuracy, safety and tolerability of other diagnostic tools, such as the disposable E.G. II Scan, a tethered capsule endoscope."