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By Kathryn Blair

ORLANDO, FL--Five per cent of people with Barrett's esophagus progress to adenocarcinoma. But who are they?

Although Barrett's esophagus can be diagnosed on endoscopy and biopsy, the challenge is to identify those individuals at risk of progression to esophageal adenocarcinoma, said Richard Sampliner, MD, at the annual meeting of the American College of Gastroenterology.

"High-grade dysplasia is currently the best indicator of risk of cancer," said the Professor of Medicine, University of Arizona, Tucson.

What that risk is, however, is controversial. Rates of progression vary widely by study. While a Veterans Affairs hospital study showed that 16 per cent of patients with high-grade dysplasia developed adenocarcinoma, a University of Washington study showed that 59 per cent did so. "Clearly there is a major risk of high-grade dysplasia going on to cancer, but it's not an instant process in many patients."

Furthermore, the absence of dysplasia does not necessarily guarantee that a patient will not develop high-grade dysplasia or esophageal carcinoma in the future, Dr. Sampliner said.

Ideally, high-grade dysplasia will be identified without endoscopy or biopsy. Newer optical modalities may make this possible, he predicted.

Meanwhile, risk of progression can be assessed when evaluating a patient with Barrett's esophagus (risk of progression is higher in older caucasian men, those living in Scotland, those with a history of reflux, and those with a family history of adenocarcinoma).

"There are remarkable differences in the frequency of adenocarcinoma, even in the same areas of the world. This surely provides us with some clues that we have yet to unravel." The incidence of adenocarcinoma in American caucasian men is 3.6 per 100,000; in American african american men, 0.8; and in American caucasian women, 0.3. National rates are much higher in England and Scotland (6.9 per 100,000, 16 per 100,000, respectively).

The longer the history of reflux, the greater the chance of progression. According to a Swedish study, people who have had reflux for more than 20 years are at 16 times the risk of people with no history of reflux.

About 20 per cent of the relatives of a person with Barrett's esophagus that progressed to adenocarcinoma will, themselves, have Barrett's esophagus or esophageal cancer (as compared to only five per cent of GERD controls).

There are predictors of unsuspected cancer at esophagectomy. Some studies have indicated that on endoscopy any esophageal nodularity or diffuse rather than focal high-grade dysplasia predicts cancer.

Surveillance
Surveillance alternatives include endoscopy and biopsy, and biomarkers. However there have been no randomized trials of surveillance methods.

Although endoscopy is invasive, costly, and cannot identify dysplasia, it is linked to a better chance of survival in people who develop cancer, presumably because the cancer is found at an earlier stage. In a California study, 73 per cent of the patients who had Barrett's esophagus and then presented with cancer while under surveillance survived, while none of the patients who had Barrett's esophagus and then presented with cancer while not under surveillance survived. Improved survival was linked to endoscopic surveillance in 700 patients from the SEER and Medicare database. "These series - that are more than surgical case studies - suggest that there is an advantage to endoscopy."

Biopsy techniques are neither standardized nor validated. Studies of surveillance intervals will likely not be done because of their expense. Proposed studies have been turned down in two countries because of funding.

The best-studied biomarkers are flow cytometry and 17p loss heterozygosity.

As there is currently no evidence for how surveillance might best be done, Dr. Sampliner suggested it should be tailored for each patient.

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