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Intercellular Space Distance Is Increased in Refractory heartburn Patients with GERD but Not Those with Functional heartburn (Fh)

a Study Using Impedance-pH and Electron Microscopy


Vela, Marcelo MD, MSCR*; Craft, Brandon MD; Sharma, Neeraj MD; Freeman, Janice RN; Hazen-Martin, Debra PhD

American Journal of Gastroenterology: September 2008 - Volume 103 - Issue - p S38
Supplement Abstracts Submitted for the 73rd Annual Scientific Meeting of the American College of Gastroenterology: ESOPHAGUS

GastPathology and Laboratory Medicine, Gastroenterology & Hepatology, Medical University of South Carolina, Charleston, SC.

Purpose: Patients with ongoing heartburn despite maximal acid suppression may have objective evidence of GERD on endoscopy or reflux monitoring; those with a negative evaluation are termed Functional Heartburn (FH). Multichannel Intraluminal Impedance and pH (MII-pH) increases the yield of reflux monitoring by assessing both acid and nonacid reflux in acid suppressed patients. Intercellular space distance (ISD) of esophageal epithelium masured by electron microscopy (EM) has recently emerged as a marker of ultrastructural damage. Our aim was to compare ISD in healthy controls and two groups of patients with refractory heartburn: those with evidence of GERD on endoscopy and/or 24-hour MII-pH, and those with Functional Heartburn.

Methods: Adult patients with ongoing heartburn despite BID PPI underwent MII-pH on therapy and endoscopy with biopsies for ISD measurement by EM. Patients were categorized as GERD if esophagitis was present on endoscopy or if 24-h MII-pH was abnormal by increased esophageal acid exposure or a positive symptom index (>50% heartburn events associated with a reflux episode). Patients with normal endoscopy and MII-pH were categorized as FH. Healthy controls (no past/present history GERD symptoms, normal 24-h pH monitoring) underwent endoscopy with esophageal biopsies for ISD measurement. ISD in μm determined in all subjects by transmission EM of esophageal biopsies at 5,000× magnification using computer-assisted morphometry (Image J software). 10 measurements of ISD taken in each of 10 fields; mean ISD for each subject was the average of the 100 measurements.

Results: 8 healthy controls, 7 FH, and 9 GERD patients studied so far. Two GERD subjects had esophagitis on endoscopy, all other study subjects had normal endoscopy. Results shown in the table. Mean ISD was significantly higher in GERD compared to controls (P= 0.043). Although ISD was numerically higher for GERD compared to FH as well as FH compared to controls, these differences were not statistically significant (type II error is possible).

Conclusion: In our preliminary data, GERD but not FH patients with refractory heartburn have increased ISD, even though most GERD patients had normal endoscopy. ISD may be a helpful tool to separate GERD from FH and may help direct therapy in patients not responding to acid suppression, with GERD patients requiring improved reflux control, while FH patients could benefit from non-GERD treatment (e.g. visceral analgesia).



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