Muhammad A Altaf1, Thomas Ciecierega, Sara Szabo, Adrian Miranda, Christina Gorges, Pippa Simpson, Manu R Sood. 1. *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.
Abstract
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.
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.