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Comparison of Light and Electron Microscopy in Measurement of Esophageal Intercellular Space in Children

Altaf, Muhammad A.*; Ciecierega, Thomas; Szabo, Sara; Miranda, Adrian§; Gorges, Christina§; Simpson, Pippa||; Sood, Manu R.§

Journal of Pediatric Gastroenterology & Nutrition: August 2014 - Volume 59 - Issue 2 - p 232–236
doi: 10.1097/MPG.0000000000000373
Original Articles: Gastroenterology

Objectives: A good objective marker of esophageal mucosal damage from gastroesophageal reflux disease (GERD) is lacking in children. Increased esophageal epithelial intercellular (EEIC) space measured using electron microscopy (EM) has been proposed as a surrogate of esophageal mucosal damage in adults with GERD. The aim of the present study was to compare EEIC space measured using EM and light microscopy (LM) in children with nonerosive reflux disease (NERD) with asymptomatic controls.

Methods: Distal esophageal mucosal biopsy was used to measure EEIC space using EM in 35 NERD subjects and 8 controls. In a subset of these patients we used phase contrast LM to measure EEIC space area (26 NERD subjects and 8 controls).

Results: The median (range) EEIC space measured using EM in the NERD group was 1.15 (0.74–1.64) μm compared with 0.93 (0.67–1.11) μm in the control group (P = 0.002). The median (range) EEIC space measured using LM was 14.4% (9.6%–26.3%) in the NERD group and 9.6% (8.5%–17.2%) in controls (P = 0.003). Using a cutoff value of 1.02 μm for normal EEIC space measured by EM, we obtained 73% sensitivity and 75% specificity to distinguish the NERD group from the control group, and using a cutoff value of 11.1% for EEIC space measured by LM, we obtained 96% sensitivity and 75% specificity.

Conclusions: EEIC space is increased in children with NERD compared with that in controls, suggesting that changes in EEIC space can be a useful marker of esophageal mucosal injury in children with NERD. Our results suggest that the accuracy of EM and LM to evaluate EEIC space changes in NERD is comparable, and LM may be a more cost-effective option.

*Division of Pediatric Gastroenterology and Nutrition, University of Oklahoma Health Sciences Center, Oklahoma City

Division of Pediatric Gastroenterology and Nutrition, New York Presbyterian–Weill Cornell Medical College, New York, NY

Division of Pediatric Pathology

§Division of Pediatric Gastroenterology and Nutrition

||Division of Quantitative Health Sciences, Medical College of Wisconsin, Milwaukee.

Address correspondence and reprint requests to Manu R. Sood, MD, Division of Pediatric Gastroenterology, Hepatology and Nutrition, Medical College of Wisconsin, Milwaukee, WI 53226 (e-mail: Msood@mcw.edu).

Received 23 August, 2013

Accepted 13 March, 2014

Drs Altaf and Ciecierega contributed equally to the article.

Funding support was provided by the Children Research Institute, Medical College of Wisconsin.

The authors report no conflicts of interest.

© 2014 by European Society for Pediatric Gastroenterology, Hepatology, and Nutrition and North American Society for Pediatric Gastroenterology,