AT DDW 2015

WASHINGTON (FRONTLINE MEDICAL NEWS) – A diagnosis of Barrett’s esophagus “indefinite for dysplasia” doesn’t mean that the patient is home free; it may, in fact, be an indicator of increased risk for progression to high-grade dysplasia or esophageal adenocarcinoma, investigators suggest.

Among 87 patients who had follow-up endoscopies and biopsies within a year of a diagnosis of Barrett’s indefinite for dysplasia (IND), 7 had progression of disease, including 5 who developed high-grade dysplasia or adenocarcinoma, and 2 who developed low-grade disease.

Of these seven patients, four had disease progression with 6 months of a diagnosis of Barrett’s IND, Dr, Michelle Ma reported at the annual Digestive Disease Week.

“Indefinite for dysplasia is an important diagnostic category that is associated with an increased risk for prevalent dysplasia, particularly within the first 6 months after diagnosis. After 12 months, the risk for progressing to advanced neoplasia is low, and similar to other studies,” said Dr. Ma of the University of Pennsylvania, Philadelphia.

Although there is fairly strong evidence to guide the management of patients with low-grade and high-grade dysplasia, it’s less clear whether Barrett’s IND is risk marker for progression. Dr. Ma said, citing a somewhat fuzzy definition of the term: “Epithelial abnormalities insufficient to diagnose dysplasia, or epithelial abnormalities unclear due to inflammation or sampling.”

Uncertainty about the natural history of IND is reflected in practice guidelines, which either don’t address it, call for repeat endoscopy in 6 months, or call for an expert gastrointestinal pathology review with repeat endoscopy to clarify dysplasia status if the evidence is of low quality, Dr. Ma said.

To determine the rate of, and risk factors for, neoplastic progression of IND, the authors took a retrospective look at patients in their center’s pathology database and Barrett’s esophagus register with a histopathologic diagnosis of IND from 2000 through 2014. They excluded patients with frank dysplasia or carcinoma on diagnosis, and those who did not have follow-up endoscopies.

The investigatoes factored demographic variables into their analysis, including age, gender, body-mass index, smoking history, use of proton-pump inhibitors (PPI), nonsteroidal anti-inflammatory drugs, and family history of Barrett’s or esophageal adenocarcinoma. They also considered endoscopic/pathologic characteristics such as hiatal hernia size, Barrett’s segment length, muscosal nodularity, and multifocal IND.

A total of 106 patients with IND were eligible for the analysis, 87 of whom had follow-up endoscopy and biopsy within a year of diagnosis. As noted before, 7 of these patients had prevalent disease, with prevalence rates of 2.3% for low-grade dysplasia, 4.6% for high-grade dysplasia, and 1.1% for esophageal adenocarcinoma.

To determine the incidence of dysplasia, the authors first excluded the 7 patients with prevealent dysplasia and 33 patients who did not have a surveillance endoscopy in the first year following a diagnosis of IND, leaving 66 patients for analysis. Of this group, 3 developed incident dysplasia or adenocarcinoma, yielding an incidence of 4.5% over a median of 32 months of follow-up.

An analysis of risk factors for prevalent dysplasia showed that none of the variables was significant, although Barrett’s segment length approached statistical significance. Looking at risk factors for incident dysplasia, both smoking status (P = .0207) and segment length (P = .0253) were significant predictors.

A pathologist who was not involved in the study pointed out that a diagnosis of IND can mean many things to many people.

“Indefinite for dysplasia is really not an entity, it’s about 5,000 things that we choose to put into that category. It’s a horribly non-reproducible diagnosis,” commented Dr. Henry D. Appelman , a professor of anatomic pathology at the University of Michigan in Ann Arbor, during a aquestion-and-answer period.

He questioned whether the diagnoses of IND were subject to review at her center.

Dr. Ma noted that Barrett’s specimens at her institution are routinely reviewed by pathologists specializing in Barrett’s, who will also review slides of patients referred to the center from other institutions.

The study was internally funded. The authors reported no conflicts of interest.