Johannessen Rune, Skogaker Nan, Halgunset Jostein, Petersen Hermod, Kleveland Per Martin
Unit for Gastroenterology, Department of Cancer Research and Molecular Medicine, Norwegian University of Science and Technology , Trondheim , Norway.
Scand J Gastroenterol. 2013 Nov;48(11):1235-41. doi: 10.3109/00365521.2013.838996. Epub 2013 Sep 30.
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.
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).
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.
食管活检中扩张的细胞间隙（DIS）被视为胃食管反流病（GERD）黏膜损伤的一种可能早期迹象。本研究提出了一种细胞间隙测量的标准化方法。
从19例疑似GERD患者获取食管远端和近端活检组织，并进行透射电镜检查。在每张显微照片上应用一个包含150个线交叉点的网格。落在细胞间隙上的点数除以网格的总点数，从而得出一个称为细胞间隙比率（ISR）的比值。ISR方法在观察者内和观察者间一致性方面进行了验证，并与Tobey等人开发的一种广泛使用的测量细胞间隙直径的方法进行了比较（Tobey NA，Carson JL，Alkiek RA，Orlando RC。扩张的细胞间隙：酸反流损伤的人食管上皮的形态学特征。胃肠病学1996；111(5)：1200 - 1205）。ISR还与GERD的其他标志物进行了比较。结果：观察者内和观察者间一致性的Pearson相关系数分别为0.91（p < 0.001）和0.82（p < 0.001）。在相同显微照片上，根据Tobey等人测量的ISR与细胞间隙直径之间的Pearson相关系数为0.32（p < 0.001）。近端ISR与远端ISR显著相关（Spearman秩相关系数 = 0.57，p = 0.010），并与烧心症状评分相关（Spearman秩相关系数 = 0.50，p = 0.028）。
ISR在观察者内和观察者间显示出高度一致性。与胃食管反流的其他标志物相比，它还显示出良好的外部有效性。然而，发现ISR与按照Tobey等人描述测量的细胞间隙直径之间的相关性相当差。
