title: Is intercellular space different among layers in normal esophageal mucosa? An electron microscopic study.
abstract: BACKGROUND
  Dilatation of intercellular space (IS) of esophageal epithelial cells is described as a sensitive early marker for epithelial damage by refluxate. Esophageal epithelia are morphologically subdivided into three layers according to the shape of the cells and nuclei. Meanwhile, ten transmission electron microscopy (TEM) photographs and ten randomly selected measurements per photo from gastroesophageal reflux disease (GERD) patients have been widely accepted without any theoretical criticism. We assumed that the IS differs among each layer and thus studied IS according to subdivided layers of normal esophageal epithelium. We also evaluated an optimal number of IS measurements per photograph.
  
  
  METHODS
  Esophagogastroduodenoscopy was performed in 15 healthy adults without any symptom of GERD, taking biopsies from mucosa above 5 cm from the squamo-columnar junction. Tissues were handled and prepared for TEM, verifying three layers of esophageal mucosa, i.e., squamous cell layer, prickle cell layer, and basal layer. Ten digital photomicrographs were taken from each three layers by TEM, and ISs were measured with a computerized image analysis program. For the method of measuring IS, 5, 10, 20, 30, and 40 measurements per photomicrograph were respectively performed by four different examiners. Mean value and intraclass correlation coefficient (ICC) was also yielded.
  
  
  RESULTS
  Mean IS of lower esophagus irrelevant to three epithelial layers were 0.39 ± 0.30 μm. When subdivided into three layers, however, mean IS of squamous cell layer was 0.62 ± 0.23 μm, prickle cell layer 0.23 ± 0.19 μm, and basal layer 0.55 ± 0.36 μm, with their difference statistically significant (p < 0.05). On the other hand, ICC of 5, 10, 20, 30, and 40 measurements were 0.688, 0.917, 0.837, 0.790, and 0.765, respectively.
  
  
  CONCLUSIONS
  Mean IS values of each three layers of esophageal epithelium in normal subjects were significantly different, and reconsideration of the standard measurement method is needed. Ten measurements per photo had an adequate inter-observer agreement.
authors: Institute of Digestive Disease and Nutrition, Department of Internal Medicine, Korea University College of Medicine, Korea University Medical Center, Inchon-ro 73, Seongbuk-gu, Seoul 136-705, Korea.
authors: Sanghoon
authors: S
authors: Park
authors: Hoon Jai
authors: HJ
authors: Chun
authors: Jin Su
authors: JS
authors: Jang
authors: Bora
authors: B
authors: Keum
authors: Yeon Seok
authors: YS
authors: Seo
authors: Yong Sik
authors: YS
authors: Kim
authors: Yoon-Tae
authors: YT
authors: Jeen
authors: Hong Sik
authors: HS
authors: Lee
authors: Soon Ho
authors: SH
authors: Um
authors: Chang Duck
authors: CD
authors: Kim
authors: Ho Sang
authors: HS
authors: Ryu
authors: Chang-Sub
authors: CS
authors: Uhm
authors: Sung Joon
authors: SJ
authors: Lee
mesh_terms: D000328:Adult; D001706:Biopsy; D016099:Endoscopy, Gastrointestinal; D004947:Esophagus / Q000473:pathology*; D005260:Female; D005764:Gastroesophageal Reflux / Q000175:diagnosis*; D006801:Humans; D007413:Intestinal Mucosa / Q000648:ultrastructure*; D042541:Intracellular Space; D008297:Male; D046529:Microscopy, Electron, Transmission / Q000379:methods*; D008875:Middle Aged; D012372:ROC Curve; D015203:Reproducibility of Results