Neil Osterweil

October 22, 2015

HONOLULU — In patients with Barrett's esophagus, low-grade dysplasia carries a substantial risk for progression to esophageal adenocarcinoma, investigators report.

The risk for progression in patients with low-grade dysplasia is eight times higher than in patients downstaged by independent expert pathologists to a diagnosis of no dysplasia, report Rajesh Krishnamoorthi, MD, from the Mayo Clinic in Rochester, Minnesota, and colleagues.

"Barrett's esophagus subjects with low-grade dysplasia diagnosis reconfirmed by expert GI pathologists may be candidates for endoscopic therapy," he said here at the American College of Gastroenterology 2015 Annual Meeting.

Endoscopic ablation is a recommended management strategy in these patients, according to guidelines issued by the American College of Gastroenterology and other professional societies, said Dr Krishnamoorthi.

His team evaluated whether independent confirmation of a low-grade dysplasia diagnosis is associated with progression risk. To do so, they took a retrospective look at data from a prospective registry of 1998 patients with long-segment Barrett's esophagus and 952 patients with esophageal adenocarcinoma.

Two gastrointestinal pathologists reviewed demographic data, endoscopic findings, histologic data, and biopsy samples from the index diagnosis of low-grade dysplasia. When they came to a consensus diagnosis, they grouped the patients into one of five categories: confirmed low-grade dysplasia, adenocarcinoma, high-grade dysplasia, indefinite dysplasia, or no-dysplasia Barrett's esophagus.

In the final sample there were 249 patients with an index diagnosis of low-grade dysplasia — 201 men and 48 women. Mean age was 64.3 years.

The independent pathologists identified low-grade dysplasia in 92 of the patients and indefinite dysplasia in 91, and downgraded 66 patients to no-dysplasia Barrett's esophagus.

They then identified the patients whose disease progressed — from low-grade dysplasia to high-grade dysplasia or adenocarcinoma — more than 12 months after the index diagnosis.

Progressed to High-Grade Dysplasia

Over a mean follow-up of 7.8 years, 15 patients progressed to high-grade dysplasia or adenocarcinoma, for an annual progression rate of 0.8%.

Time to progression was significantly shorter in the confirmed low-grade and indefinite dysplasia groups than in the no-dysplasia group (univariate hazard ratio [HR], 7.1; 95% confidence interval [CI], 1.41 - 128; P = .0227).

The risk for progression was higher in the confirmed low-grade and indefinite dysplasia groups than in the no-dysplasia group, after adjustment for age, sex, smoking status, Barrett's segment length, and other disease features (HR, 8.4; 95% CI, 1.6 - 153.0).

Dr Krishnamoorthi acknowledged that the study was limited because of its observational design, which precludes detailed information about potential confounders, and because of the small number of progressors in each group, leading to wide confidence intervals.

This was "a great presentation on a very confusing topic," said Nicholas Shaheen, MD, from the University of North Carolina at Chapel Hill.

He noted, however, there is substantial variability in reported rates of progression from low-grade dysplasia to esophageal adenocarcinoma. In a Dutch study, for example, rates were as high as 13.4% (Am J Gastroenterol. 2010;105:1523-1530).

Dr Shaheen asked Dr Krishnamoorthi if he could explain why the annual incidence rate in this study is so much lower.

Dr Krishnamoorthi said that in the Dutch study, expert pathologists reviewed diagnoses originally made by community-based pathologists. This resulted in about 85% of patients being downstaged to no dysplasia.

In contrast, Dr Krishnamoorthi explained, in their study, diagnoses were originally made by pathologists with expertise in gastrointestinal disease, and were then reviewed by two independent experts, so only 26.5% of patients were downstaged.

The funding source for this study was not disclosed. Dr Krishnamoorthi and Dr Shaheen report no relevant financial relationships.

American College of Gastroenterology (ACG) 2015 Annual Meeting: Abstract 6. Presented October 19, 2015.

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