Forum for Science, Industry and Business

Sponsored by:     3M 
Search our Site:

 

Biopsies may overlook esophagus disease

07.09.2012
Study reveals limitations in detecting allergic disorder

University of Utah engineers mapped white blood cells called eonsinophils and showed an existing diagnostic method may overlook an elusive digestive disorder that causes swelling in the esophagus and painful swallowing.


These are microscope images of tissue from the esophagus of a patient with a disease named eosinophilic esophagitis, or EoE. The bar graphs around each image depict the number of white blood cells called eosinophils along the perimeter of each tissue sample. The cells eat away at the lining of the esophagus to cause the disorder. A University of Utah study suggests that the current method of diagnosing EoE by taking tissue samples with an endoscope may lead to under- or misdiagnosis of the disease.

Credit: Hedieh Saffari, University of Utah, for the Journal of Allergy and Clinical Immunology.

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

These findings are published as the cover article in the September 2012 issue of the Journal of Allergy and Clinical Immunology. Despite the limitations of current detection methods for EoE, the study authors say biopsies remain the current standard of care, but the engineers are working toward new diagnostic methods that could be available in five years.

In EoE, eosinophils typically found in the bloodstream invade the esophagus and start chewing away at its lining. Often triggered by food allergies, EoE symptoms overlap with other disorders such as acid reflux.

"The gold standard for understanding this disease is detecting the location and presence of eosinophils in the esophagus. Unfortunately, eosinophils are not uniformly distributed within the esophagus, which can lead to underdiagnosis," says study co-author Leonard Pease, assistant professor of chemical engineering at the University of Utah. He is also an adjunct professor of gastroenterology and pharmaceutics.

The University of Utah team 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.

"This is the first quantitative assessment of how eosinophils are distributed in the esophagus," says co-author Gerald Gleich, professor of dermatology at the University of Utah and specialist in eosinophil-related diseases. "Until now, someone would go in and snip around, but they wouldn't have this map to quantify the degree of infiltration of this disease in relationship to the actual anatomy. These findings impact how many biopsies a doctor should perform."

Since eonsinophils are scattered within the esophagus, EoE can go undetected until severe symptoms surface, ranging from painful swallowing to chest pains that mimic a heart attack.

"This is not the ideal way to diagnose EoE," says Pease. "If the distribution of eosinophils was 100 percent uniform, it wouldn't matter where you sample, but in fact it's patchy. Our mapping shows if you sample in one region, no diagnosis would be made, but if you took another region about an inch away, the same patient would appear to be severely diseased."

To generate a map of eosinophil distribution in the esophagus, lead author Hedieh Saffari examined each of 17 tissue sections taken at intervals every one-eighth to one-fifth of an inch along the esophagus of a known adult EoE patient. A typical adult esophagus is 10 inches long.

"For every cross section, I used microscopy to count the number of eosinophil cells along the entire perimeter of the tissue surface in each high-power field of view image," said Saffari, a chemical engineering graduate student. "There were somewhere between 40 and 120 of these images per cross section so it took a lot of time, but it was worth it to extract the information we were looking for. No one has done this type of mapping before."

Saffari's diligence paid off. With her painstakingly collected data, she and Pease used a statistical simulation technique to determine whether randomly sampling tissue would result in a positive diagnosis of EoE based on eonsinophil density.

"Our analysis shows that with current diagnostic conventions, you are only going to catch the patients with medium-to-high eonsinophil densities, which means we may be misdiagnosing patients as much as one out of every five times," says Pease. "Given this data, clearly endoscopy is not sufficient for a disease this patchy."

Gleich says their findings will inform future revisions of EoE diagnosis guidelines, but biopsies are "currently the standard of care and will not change in the near future."

Building on this study, Pease and Saffari are 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. "We're optimistic that such a diagnostic tool could be available in the next five years," Pease says.

Saffari adds this is part of the team's long-term goal to develop new strategies to enhance EoE diagnosis and understand what causes the disease.

Pease, Gleich and Saffari conducted the study with gastroenterologists Kathryn Peterson and John Fang and pathologist Carolin Teman at the University of Utah. This study was funded by the University of Utah, the Utah Governor's Office of Economic Development and the National Science Foundation.

University of Utah College of Engineering
72 S. Central Campus Dr., Room 1650 WEB, Salt Lake City, UT 84112
(801) 581-6911 fax: (801) 581-8692

Aditi Risbud | EurekAlert!
Further information:
http://www.utah.edu
http://www.coe.utah.edu

More articles from Health and Medicine:

nachricht Usher syndrome: Gene therapy restores hearing and balance
25.09.2017 | Institut Pasteur

nachricht MRI contrast agent locates and distinguishes aggressive from slow-growing breast cancer
25.09.2017 | Case Western Reserve University

All articles from Health and Medicine >>>

The most recent press releases about innovation >>>

Die letzten 5 Focus-News des innovations-reports im Überblick:

Im Focus: The fastest light-driven current source

Controlling electronic current is essential to modern electronics, as data and signals are transferred by streams of electrons which are controlled at high speed. Demands on transmission speeds are also increasing as technology develops. Scientists from the Chair of Laser Physics and the Chair of Applied Physics at Friedrich-Alexander-Universität Erlangen-Nürnberg (FAU) have succeeded in switching on a current with a desired direction in graphene using a single laser pulse within a femtosecond ¬¬ – a femtosecond corresponds to the millionth part of a billionth of a second. This is more than a thousand times faster compared to the most efficient transistors today.

Graphene is up to the job

Im Focus: LaserTAB: More efficient and precise contacts thanks to human-robot collaboration

At the productronica trade fair in Munich this November, the Fraunhofer Institute for Laser Technology ILT will be presenting Laser-Based Tape-Automated Bonding, LaserTAB for short. The experts from Aachen will be demonstrating how new battery cells and power electronics can be micro-welded more efficiently and precisely than ever before thanks to new optics and robot support.

Fraunhofer ILT from Aachen relies on a clever combination of robotics and a laser scanner with new optics as well as process monitoring, which it has developed...

Im Focus: The pyrenoid is a carbon-fixing liquid droplet

Plants and algae use the enzyme Rubisco to fix carbon dioxide, removing it from the atmosphere and converting it into biomass. Algae have figured out a way to increase the efficiency of carbon fixation. They gather most of their Rubisco into a ball-shaped microcompartment called the pyrenoid, which they flood with a high local concentration of carbon dioxide. A team of scientists at Princeton University, the Carnegie Institution for Science, Stanford University and the Max Plank Institute of Biochemistry have unravelled the mysteries of how the pyrenoid is assembled. These insights can help to engineer crops that remove more carbon dioxide from the atmosphere while producing more food.

A warming planet

Im Focus: Highly precise wiring in the Cerebral Cortex

Our brains house extremely complex neuronal circuits, whose detailed structures are still largely unknown. This is especially true for the so-called cerebral cortex of mammals, where among other things vision, thoughts or spatial orientation are being computed. Here the rules by which nerve cells are connected to each other are only partly understood. A team of scientists around Moritz Helmstaedter at the Frankfiurt Max Planck Institute for Brain Research and Helene Schmidt (Humboldt University in Berlin) have now discovered a surprisingly precise nerve cell connectivity pattern in the part of the cerebral cortex that is responsible for orienting the individual animal or human in space.

The researchers report online in Nature (Schmidt et al., 2017. Axonal synapse sorting in medial entorhinal cortex, DOI: 10.1038/nature24005) that synapses in...

Im Focus: Tiny lasers from a gallery of whispers

New technique promises tunable laser devices

Whispering gallery mode (WGM) resonators are used to make tiny micro-lasers, sensors, switches, routers and other devices. These tiny structures rely on a...

All Focus news of the innovation-report >>>

Anzeige

Anzeige

Event News

“Lasers in Composites Symposium” in Aachen – from Science to Application

19.09.2017 | Event News

I-ESA 2018 – Call for Papers

12.09.2017 | Event News

EMBO at Basel Life, a new conference on current and emerging life science research

06.09.2017 | Event News

 
Latest News

Nerves control the body’s bacterial community

26.09.2017 | Life Sciences

Four elements make 2-D optical platform

26.09.2017 | Physics and Astronomy

Goodbye, login. Hello, heart scan

26.09.2017 | Information Technology

VideoLinks
B2B-VideoLinks
More VideoLinks >>>