Ravelli Alberto M, Villanacci Vincenzo, Ruzzenenti Nella, Grigolato Piergiovanni, Tobanelli Pamela, Klersy Catherine, Rindi Guido
Gastrointestinal Pathophysiology and Gastroenterology, University Department of Pediatrics, Children's Hospital, Brescia, Italy.
J Pediatr Gastroenterol Nutr. 2006 May;42(5):510-5. doi: 10.1097/01.mpg.0000215312.78664.b9.
Dilated intercellular spaces (DIS) in the esophageal epithelium have been identified by electron microscopy as marker of acid reflux damage in experimental animals and adults with gastroesophageal reflux disease (GERD). We aimed to identify and quantify DIS by light microscopy in pediatric GERD and esophagitis.
We prospectively took esophageal biopsies in 70 consecutive pediatric patients, 48 of whom had GERD symptoms. On hematoxylin and eosin-stained sections esophagitis was scored histologically, and DIS were graded as 0 (absent), + (small and focal), ++ (moderate) or +++ (large and diffuse). A computerized image analysis identified total, cellular and nuclear areas and DIS were quantified as percentage of total minus cellular area.
Forty of 48 GERD patients had histological esophagitis (33 G1, 4 G2, 3 G3, 1 of which with Barrett esophagus), and all 40 had DIS (33 +, 4 ++, 3 +++) with 100% interobserver agreement; 15 of 29 (55%) had abnormal pH study (reflux index, 5.7%-36%). In 30 patients the esophagus was histologically normal. DIS values were 2.21% +/- 2.60% (range, 0.11%-12%) in patients with esophagitis and 0.44% +/- 0.13% (0.2%-0.7%) in patients with normal histology (P < 0.00001), with 0.71% bearing 70% sensitivity and 100% specificity for GERD versus controls. Five other children with esophagitis unrelated to GERD (eosinophilic, Candida, food allergy) also had DIS + to +++, and median DIS area was 5% (1.3%-12%).
DIS can be detected and evaluated by light microscopy, and the image analysis used provides an objective quantification of DIS and supports the light microscopy evaluation. DIS are a morphological feature of GERD and esophagitis in infancy and childhood.
食管上皮细胞间隙增宽（DIS）在实验动物和患有胃食管反流病（GERD）的成人中已通过电子显微镜被确认为酸反流损伤的标志物。我们旨在通过光学显微镜识别和量化小儿GERD和食管炎中的DIS。
我们前瞻性地对70例连续的儿科患者进行了食管活检，其中48例有GERD症状。在苏木精和伊红染色切片上对食管炎进行组织学评分，DIS分为0级（无）、+级（小且局灶性）、++级（中度）或+++级（大且弥漫性）。计算机图像分析确定总面积、细胞面积和核面积，DIS量化为总面积减去细胞面积后的百分比。
48例GERD患者中有40例有组织学食管炎（33例G1级，4例G2级，3例G3级，其中1例有巴雷特食管），所有40例均有DIS（33例+级，4例++级，3例+++级），观察者间一致性为100%；29例中有15例（55%）pH研究异常（反流指数，5.7%-36%）。30例患者食管组织学正常。食管炎患者的DIS值为2.21%±2.60%（范围，0.11%-12%），组织学正常患者的DIS值为0.44%±0.13%（0.2%-0.7%）（P<0.00001），以0.71%为界，GERD与对照组相比的敏感性为70%，特异性为100%。另外5例与GERD无关的食管炎患儿（嗜酸性粒细胞性、念珠菌性、食物过敏）也有DIS +至+++级，DIS面积中位数为5%（1.3%-12%）。
DIS可通过光学显微镜检测和评估，所采用的图像分析提供了DIS的客观量化并支持光学显微镜评估。DIS是婴幼儿和儿童GERD和食管炎的一种形态学特征。
