Sugar Test May Identify Barrett's

HOLLYWOOD, FLA. — A simple screening test—drinking a glass of sugar water—may identify patients with gastroesophageal reflux disease who probably have Barrett's esophagus and need further workup by endoscopy.

The idea is that in patients with Barrett's esophagus (BE), the sucrose in the drink would leak through the compromised mucosal barrier of the esophagus, enter the bloodstream, and eventually reach the urine, James M. Mullin, Ph.D., said while presenting a poster at a symposium on gastrointestinal cancers sponsored by the American Society of Clinical Oncology.

The increased levels of sucrose in the urine would flag the patient as needing endoscopy to diagnose possible BE.

“There are serious economic and logistic considerations of administering upper endoscopy to a large patient population”—that is, all patients with gastroesophageal reflux disease (GERD), said Dr. Mullin, a cell physiologist at the Lankenau Institute for Medical Research in Wynnewood, Pa. Many patients with GERD are currently treated with a proton pump inhibitor but are never assessed by endoscopy, even though about 10% of GERD patients have BE.

The diagnosis and monitoring of patients with BE is important because of their relatively high risk for esophageal adenocarcinoma.

A simple and inexpensive screening test for BE may help determine which of the millions of Americans with GERD should undergo endoscopy, he said.

To begin testing this idea, Dr. Mullin and his associates conducted a study that included 20 healthy volunteers, 9 patients with GERD, 13 patients known to have BE, and 6 patients with esophagitis. All participants underwent endoscopy to confirm these diagnoses, except for 15 of the healthy controls.

Two weeks after endoscopy, the 48 participants each drank 200 mL of water that contained 100g of dissolved sucrose. Because mammalian cells lack a disaccharide receptor, the only ways for sucrose to enter the blood are through a damaged epithelial barrier or via leaky tight junctions between epithelial cells. Dr. Mullin hypothesized that the tight-junction barrier is damaged in patients with BE, creating a sucrose leak.

Urine was collected from each participant overnight and subsequently passed through ion-exchange chromatography columns. The sucrose content was then measured using high-performance liquid chromatography.

The mean urinary sucrose concentrations in the patients with BE or esophagitis were significantly higher than the mean levels in their other groups tested.

Specifically, the five controls who underwent endoscopy had a mean urinary sucrose level of 60 mg, with a range of 17-80 mg. The 15 controls who did not have endoscopy had a mean level of 66 mg, with a range of 41-86 mg. The nine participants with GERD but no BE or esophagitis had a mean level of 62 mg of sucrose in their urine, with a range of 21-118 mg. Six patients had esophagitis but no BE, and their mean level was 153 mg, with a range of 122-265 mg. The 13 patients with BE had a mean urinary sucrose level of 184 mg, with a range of 95-428 mg.

These findings show that leakage of sucrose across the upper gastrointestinal epithelium occurs at a substantially greater rate in patients with BE and esophagitis, compared with healthy controls and compared with patients with GERD but no BE, said Dr. Mullin at the symposium, also sponsored by the American Gastroenterological Association, the American Society for Therapeutic Radiation and Oncology, and the Society of Surgical Oncology.

The next step is to undertake a similar study with a much larger number of participants and calculate the false-positive and false-negative rates for sucrose-leak screening, Dr. Mullin told this newspaper.

Another idea for future research is to place patients with GERD, esophagitis, or BE on treatment with a proton pump inhibitor a few weeks before the sucrose-leak test is done.

Treatment with a proton pump inhibitor should heal the esophagitis and therefore reduce or eliminate sucrose leak in these patients, but it should have no effect on sucrose leak in patients with BE, Dr. Mullin said.