Histology of esophageal mucosa from patients with achalasia

When achalasia becomes far advanced and leads to esophageal resection, inflammation of the esophageal mucosa is almost universal. The histology of the esophageal mucosa in less advanced cases of achalasia has not been firmly established. We have studied endoscopic biopsies obtained during evaluation of patients with achalasia. Two to four endoscopic biopsies from the lower esophagus of 26 patients with manometrically verified achalasia were mounted on mesh, serially sectioned, stained, coded and interpreted by two independent observers using recognized criteria. The histological findings were correlated with clinical data. Ten of 26 patients had at least one abnormal biopsy. Five of these 10 patients had a previous Heller myotomy; another patient had several pneumatic dilatations, and two other patients had endoscopically proven candida infections. Of the 16 patients with normal histology, four had prolonged stasis, five had heartburn and one patient had both heartburn and stasis. Unless the patient with achalasia has had a Heller myotomy, balloon dilatation, or a candida infection, the esophageal mucosa on biopsy appears to be within normal limits, even in patients with years of esophageal stasis or complaints of heartburn.     

Reflux injury of esophageal mucosa: experimental studies in animal models of esophagitis, Barrett''s esophagus and esophageal adenocarcinoma

Barrett's esophagus (BE), a gastroesophageal reflux associated complication, is defined as the replacement of normal esophageal squamous mucosa by specialized intestinal columnar mucosa with the appearance of goblet cells. The presence of BE is associated with an increased risk of developing esophageal adenocarcinoma (EAC). Although the exposure of gastroduodenal contents to the esophageal mucosa is considered to be an important risk factor for the development of esophagitis, BE and EAC, the mechanisms of reflux esophageal injury are not fully understood. Animal models are now being used extensively to identify the mechanisms of damage and to devise protective and mitigating strategies. Experimental studies on animal models by mimicking the processing of gastroesophageal reflux injury have bloomed during the past decades, however, there is controversy regarding which experimental model for reflux esophagitis, experimental BE and experimental EAC is best. In this review article we aim to clarify the basic understanding of gastroesophageal reflux injury and its complications of BE and EAC, as well as to present current understanding of the reflux experimental models. The animal models of experimental esophageal injury are summarized with focus on the surgical procedures to guide the investigator in choosing or developing a correct animal model in future studies. In addition, our own experimental studies of the animal models are also briefly discussed.     

Bioelectric Impedance Analysis in the Diagnosis of Vesicoureteral Reflux

Background:

Vesicoureteral reflux (VUR) is a common abnormality of the urinary tract in childhood.

Objectives:

As urine enters the ureters and renal pelvis during voiding in vesicoureteral reflux (VUR), we hypothesized that change in body water composition before and after voiding may be less different in children with VUR.

Patients and Methods:

Patients were grouped as those with VUR (Group 1) and without VUR (Group 2). Bioelectric impedance analysis was performed before and after voiding, and third space fluid (TSF) (L), percent of total body fluid (TBF%), extracellular fluid (ECF%), and intracellular fluid (ICF%) were recorded. After change of TSF, TBF, ECF, ICF (ΔTSF, ΔTBF%, ΔECF%, ΔICF%), urine volume (mL), and urine volume/body weight (mL/kg) were calculated. Groups 1 and 2 were compared for these parameters. In addition, pre- and post-voiding body fluid values were compared in each group.

Results:

TBF%, ECF%, ICF%, and TSF in both pre- and post-voiding states and ΔTBF%, ΔECF%, ΔICF%, and ΔTSF after voiding were not different between groups. However, while post-voiding TBF%, ECF% was significantly decreased in Group 1 (64.5 ± 8.1 vs 63.7 ± 7.2, P = 0.013 for TBF%), there was not post-voiding change in TSF in the same group. On the other hand, there was also a significant TSF decrease in Group 2.

Conclusions:

Bladder and ureter can be considered as the third space. Thus, we think that BIA has been useful in discriminating children with VUR as there was no decreased in patients with VUR, although there was decreased TSF in patients without VUR. However, further studies are needed to increase the accuracy of this hypothesis.     

Intraepithelial cells with irregular nuclear contours as a marker of esophagitis in children with gastroesophageal reflux disease

The diagnostic usefulness of intraepithelial cells with irregular nuclear contours (CINC) (squiggle cells) in esophageal endoscopic biopsies was investigated in 76 children (range age: 6 months-12 years) with gastroesophageal reflux disease. A further 20 subjects (range age: 10 months-11 years) served as controls. Based on the microscopic changes of the esophagus, according to traditional histological criteria, four groups of patients were identified: esophagitis was severe in 27, moderate in 20, mild in 21, and 8 patients had no clear-cut evidence of microscopic esophagitis. Data are given as mean±sd. Intraepithelial CINC had an immunohistochemical profile consistent with T lymphocytes. Patients with severe esophagitis had a CINC density (number per high-power field) (9.0±3.5) significantly higher than patients with mild esophagitis (7.0±3.0) and those without evidence of microscopic esophagitis (6.5±1.9) (P<0.05), but not different from those with moderate esophagitis (8.0±3.6); in all patient groups the CINC density was higher than in controls (2.2±0.3) (P<0.01). The percentage of reflux at 24-hr intraesophageal pH monitoring was higher in severe esophagitis patients (11.4±6.0) as compared to the other groups (moderate: 7.8±6.3; mild: 6.5±3.6; no microscopic esophagitis: 6.3±2.0;P<0.05). There was no correlation between CINC density and the amount of intraesophageal acid exposure in all patients. Furthermore, 27 of our patients had a normal intraesophageal acid exposure at the prolonged pH test (24-hr % of reflux 4.5): the CINC density was significantly higher in them than in the controls. We conclude that intraepithelial CINC in esophageal endoscopic biopsies from children with reflux disease represent a sensitive and early criterion of esophageal mucosa damage; they should be scanned in addition to the traditional histological parameters of acid-related esophageal inflammation.Presented in an abstract form at the 28th Annual Meeting of the European Society of Paediatric Gastroenterology and Nutrition, Jerusalem, May 28–June 1, 1995.     

奥瑞凝胶对反流性食管炎大鼠模型食管组织中相关基因表达及血清相关分子含量的影响

目的:研究奥瑞凝胶对反流性食管炎大鼠模型食管组织中相关基因表达以及血清中相关分子含量的影响.方法:选择成年雄性SD大鼠作为研究对象,随机分为正常组、模型组和治疗组,模型组和治疗组建立反流性食管炎模型,治疗组给予奥瑞凝胶治疗.处死大鼠后,检测血清炎症因子含量和食管组织炎症因子、多肽类神经递质、促增殖基因的表达.结果:(1)炎症因子:与模型组比较,食管组织和血清中白介素-23、17(IL-23、IL-17)的含量在治疗组中呈降低趋势;(2)多肽类神经递质:与模型组比较,食管组织中一氧化氮(NO)、NOS、血管活性肠肽(VIP)、VIP-R1、VIP-R2含量在治疗组中呈升高趋势,P物质(SP)含量治疗组中呈降低趋势;(3)促增殖基因:与模型组比较,食管组织中c-myb、增殖细胞核抗原(PCNA)和Ki-67的mRNA和蛋白含量在治疗组中呈降低趋势.结论:奥瑞凝胶治疗有助于缓解炎症反应,调节多肽类神经递质表达,抑制食管黏膜上皮过度增殖,对反流性食管炎模型大鼠具有治疗作用.     

伏诺拉生治疗重症反流性食管炎的疗效及其对胃泌素和炎症因子的影响

 目的 探讨伏诺拉生治疗重症反流性食管炎(RE)的疗效及其对胃泌素和炎症因子的影响。方法 选取2021-02至2022-02在武警安徽总队医院消化科门诊确诊为重症RE患者62例,随机分为伏诺拉生组(31例)和对照组(31例)。伏诺拉生组采用伏诺拉生和依托必利治疗,对照组采用雷贝拉唑和依托必利治疗。比较两组治疗后临床有效率,以及治疗前后内镜评分、胃泌素、TNF-α、IL-6。结果 伏诺拉生组的有效率为87.10%,显著高于对照组(64.52%),差异有统计学意义(χ²=4.309,P＜0.05);治疗后,两组内镜评分(0.30±0.13, 0.64±0.26)均明显低于治疗前(3.42±0.51,3.38±0.48),并且伏诺拉生组改善得更显著(t=-6.51,P＜0.01)。伏诺拉生组的胃泌素水平[(88.93±11.37) pg/ml]明显高于对照组[(60.78±7.98) pg/ml],而TNF-α[(5.95±0.68) pg/ml]、IL-6[(5.55±0.67) pg/ml]水平明显低于对照组[(7.88±0.99)pg/ml,(8.24±0.92)pg/ml],且差异均有统计学意义(P＜0.01)。两组均发生1例不良反应(3.23%)。结论 伏诺拉生治疗重症RE可明显提升有效率,可修复损伤的胃黏膜,同时可显著调整血清胃泌素及炎症因子水平而不增加不良反应。     

胆汁反流、胃酸和幽门螺杆菌感染共同作用对胃黏膜损伤程度和分布的影响

背景:胆汁反流、胃酸和幽门螺杆菌（H.pylori）感染均是胃黏膜损伤的独立致病因素。然而,它们共同存在时有无协同致病作用尚不清楚。目的:探讨胆汁反流、胃酸和H.pylori感染共同作用对胃黏膜损伤程度和分布的影响。方法:37例胃镜检查疑有十二指肠胃反流者均经24h胃内胆汁监测证实,同时行胃内PH监测。胃体和胃窦黏膜有或无活动性炎症、萎缩、肠化和不典型增生分别记2分或1分。分别以胃体和胃窦黏膜的各项病理学改变为应变量,以胃内胆红素吸收值>0.14的时间百分比、pH<4的时间百分比和H.pylori感染状态指标为自变量进行多变量逐步Logistic回归分析。结果:37例患者胃内胆红素吸收值>0.14的时间百分比为34.49％±22.69％,pH<4的时问百分比为78.68％土 9.91％,H.pylori阳性率为29.73％。胆汁反流出现在以胃体和胃窦黏膜肠化以及胃体黏膜活动性炎症为应变量的Logistic回归模型中,H.pylori出现在以胃体黏膜活动性炎症为应变量的回归模型中。结论:胆汁反流是胃黏膜肠化的危险因素;胃内有胆汁反流存在时,H.pylori感染是导致胃体新膜炎症的重要病因。     

返流性食管炎的内镜探讨

本文报告近５年我院内镜检出返流性食管炎２３７例，临床症状主要为烧心、上腹痛、腹胀、呕血、黑便及吞咽困难。食管裂孔疝和十二指肠球部病变为主要的消化系统伴随疾病。内镜表现食管粘膜红斑者占９．７％。孤立性或非融合性糜烂者占２９．１％。环周性或融合性糜烂者占３４．２％、溃疡形成者占２７．０％，且有３．４％发生食管下端狭窄。资料提示本病我国并不少见，发病明显与贲门功能不全和十二指肠病变有关。     

Molecular basis and cellular mechanisms of eosinophilic esophagitis for the clinical practice

Introduction: Eosinophilic esophagitis (EoE) is a chronic, allergen-driven inflammatory esophageal disease characterized by predominantly eosinophilic inflammation leading to esophageal dysfunction. Recent efforts to understand EoE have increased our knowledge of the disease.

Areas covered: Multiple cells, molecules, and genes interplay with early life environmental factors in the pathophysiology of EoE to converge in the esophageal epithelium at the center of disease pathogenesis. Epithelial cells constitute a mayor cytokine source for TSLP and Calpain-14; an impaired epithelial barrier function allowing penetration of food and microbiota-derived antigens is involved in triggering and maintaining inflammation. Eosinophil and mast cell-derived products, including TGFβ, together with IL-1β and TNFα, promote epithelial mesenchymal transition in EoE, contributing to tissue remodeling by synthetizing and depositing extracellular matrix in subepithelial layers. This article aims to provide a state-of-the-art update on the pathophysiology of EoE applied to clinical practice, and latest research and developments with potential interest to improve the diagnosis and treatment of patients with EoE are revised.

Expert commentary: Preliminary approaches have provided promising results toward incorporating minimally invasive methods for patient diagnosis and monitoring in clinical practice. Early diagnosis and optimized therapies will allow for personalized medicine in EoE.