Biopsies May Overlook Esophagus Disease

The location and density of eosinophils, which regulate allergy mechanisms in the immune system suggest the disease eosinophilic esophagitis, or EoE, may be under- or misdiagnosed in patients using the current method, which is to take tissue samples as biopsies with an endoscope.

Medical scientists at the University of Utah (Salt Lake City, UT, USA) showed that even a patient with known EoE would require more than 31 random tissue samples, or biopsies, from an area in the esophagus with low eosinophil density to reliably diagnose EoE. Currently, if a patient is suspected of having EoE, five to 12 biopsies are collected along the esophagus using an endoscope. If more than 15 eosinophils turn up in any one of these samples, a diagnosis of EoE is made.

To generate a map of eosinophil distribution in the esophagus the lead investigator examined each of 17 tissue sections taken at intervals every 0.32-0.51 cm along the esophagus of a known adult EoE patient. A typical adult esophagus is 25.4 cm long. Tissue was imaged with an Olympus microscope (Olympus, Center Valley, PA, USA) at ×400 magnification. The eosinophil count for each site was performed manually, one high-powered field (hpf) at a time, around the entire luminal perimeter. The number of sites containing a diagnostic level of eosinophils, either 15 eosinophils/hpf or 20 eosinophils/hpf was determined for each of the 17 circumferential sections.

A statistical simulation technique was used to determine whether randomly sampling tissue would result in a positive diagnosis of EoE based on eosinophil density. Leonard F. Pease, PhD, a senior author of the study said, "Our analysis shows that with current diagnostic conventions, you are only going to catch the patients with medium-to-high eosinophil densities, which means we may be misdiagnosing patients as much as one out of every five times. Given this data, clearly endoscopy is not sufficient for a disease this patchy."

The team is investigating technologies for labeling and detecting proteins shed by eosinophils in the esophagus, which would help detect EoE at an earlier stage. They have also filed a patent to use radiolabeled antibodies to map eosinophils throughout the entire esophagus, a new technique that would be evaluated with a clinical trial. The study was published in the September 2012 issue of the Journal of Allergy and Clinical Immunology.

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