A standardized method for measuring intercellular spaces in esophageal biopsies in patients with suspected gastroesophageal reflux disease (the intercellular space ratio).
OBJECTIVE
Dilated intercellular space (DIS) in esophageal biopsies is regarded as a possible early sign of mucosal injury in gastroesophageal reflux disease (GERD). This study presents a standardized approach of intercellular space measurement.


METHODS
Distal and proximal esophageal biopsies were taken from 19 patients with suspected GERD, and examined with TEM. A grid containing 150 line-crossing points was applied upon each photomicrograph. The number of points falling on the intercellular space was divided by the total number of points of the grid, thereby creating a ratio called the intercellular space ratio (ISR). The ISR method was validated with regard to intra- and interobserver agreement, and was compared to a widely used method for measuring intercellular space diameter developed by Tobey et al. (Tobey NA, Carson JL, Alkiek RA, Orlando RC. Dilated intercellular spaces: a morphological feature of acid reflux-damaged human esophageal epithelium. Gastroenterology 1996;111(5):1200-1205). The ISR was also compared to other markers for GERD. Results. Pearson's correlation coefficients for intra- and interobserver agreement were 0.91 (p < 0.001) and 0.82 (p < 0.001), respectively. The Pearson's correlation coefficient between the ISR and the intercellular space diameter according to Tobey et al., measured in the same micrographs, was 0.32 (p < 0.001). The proximal ISR correlated significantly with the distal ISR (Spearman's rho = 0.57, p = 0.010), and with heartburn symptom score (Spearman's rho = 0.50, p = 0.028).


CONCLUSIONS
The ISR showed a high intraobserver and interobserver agreement. It also displayed good external validity when compared to other markers for gastroesophageal reflux. A rather poor correlation was however found between the ISR and the intercellular space diameter measured as described by Tobey et al.
Unit for Gastroenterology, Department of Cancer Research and Molecular Medicine, Norwegian University of Science and Technology , Trondheim , Norway.
Rune
R
Johannessen
Nan
N
Skogaker
Jostein
J
Halgunset
Hermod
H
Petersen
Per Martin
PM
Kleveland
D000328:Adult; D004724:Endoscopy; D004947:Esophagus / Q000473:pathology*; D005110:Extracellular Space; D005260:Female; D005764:Gastroesophageal Reflux / Q000473:pathology*; D006801:Humans; D008297:Male; D046529:Microscopy, Electron, Transmission; D008875:Middle Aged; D009092:Mucous Membrane / Q000473:pathology; D015588:Observer Variation; D015203:Reproducibility of Results; D055815:Young Adult