Enhanced expression of interleukin-8 and activation of nuclear factor kappa-B in endoscopy-negative gastroesophageal reflux disease

OBJECTIVE: Interleukin-8 (IL-8) mediates neutrophil trafficking via its receptors. Recent studies have shown that IL-8 is likely involved in the development and progression of erosive reflux esophagitis (RE), yet little is known about its implication in endoscopy-negative gastroesophageal reflux disease (GERD). The purpose of this study was to determine IL-8 messenger ribonucleic acid (mRNA) expression levels in endoscopy-negative GERD, along with assessment of nuclear factor kappaB (NF-kappaB) activation, which upregulates IL-8 expression. METHODS: We studied 31 patients with endoscopy-negative GERD, 15 patients with erosive RE, and 15 asymptomatic controls. Paired biopsy samples were taken from the esophagus 3 cm above the gastroesophageal junction; one biopsy was snap-frozen for measurement of IL-8 mRNA levels by real-time quantitative polymerase chain reaction, and another was formalin-fixed for histopathological evaluation. In nine endoscopy-negative GERD patients, the IL-8 mRNA expression levels were measured before and 8 wk after treatment with lansoprazole. We also sampled additional specimens for NF-kappaB-DNA binding assay and immunohistochemical analyses of NF-kappaB p65 and p50 subunits, IL-8 and specific IL-8 receptor, CXCR-1. RESULTS: The relative IL-8 mRNA expression levels were significantly higher in esophageal mucosa of patients with endoscopy-negative GERD than those of the controls. The presence of basal zone hyperplasia and intraepithelial neutrophils, histopathological hallmarks of GERD, were associated with higher levels of IL-8 mRNA. Lansoprazole treatment significantly reduced the IL-8 mRNA expression levels. The esophageal epithelium of patients with GERD showed intense immunoreactivity for IL-8, and expressed CXCR-1 antigen. We found NF-kappaB activation in esophageal mucosa in GERD patients and the NF-kappaB subunits were localized predominantly in the nuclei of IL-8-expressing cells. CONCLUSIONS: Our results demonstrate enhanced mucosal expression of IL-8 in incipient GERD even without mucosal breaks. NF-kappaB activation may be implicated in the pathogenesis in GERD.     

Interleukin-8 expression in the esophageal mucosa of patients with gastroesophageal reflux disease

BACKGROUND: It has been reported that inflammatory cell infiltration can be detected in patients with endoscopically negative gastroesophageal reflux disease (GERD) as well as those with erosive reflux esophagitis. In this study, we examined the expression of mRNA for interleukin (IL)-8, a potent chemokine for neutrophils, in the esophageal mucosa of patients with GERD and compared the results with their endoscopic findings and symptoms. METHODS: Biopsy samples were obtained from 80 patients. Endoscopic diagnosis was performed according to the Los Angeles classification. Patients with typical symptoms such as heartburn despite normal endoscopic findings were classified as the non-erosive GERD group. Total cellular RNA was extracted from the biopsy samples and IL-8 mRNA was quantified by real-time polymerase chain reaction (PCR). Localization of IL-8 protein in the esophageal mucosa was done by immunostaining. RESULTS: Expression of IL-8 mRNA was correlated with the endoscopic grade of esophagitis or with inflammatory cell infiltration, but not with the symptoms of the patients. Expression of IL-8 mRNA was also detected in all patients with non-erosive GERD. The level of IL-8 expression in non-erosive GERD was low compared with that in erosive GERD, but was higher than that in normal controls. IL-8 immunostaining was found in the basal layers of the esophageal mucosa. Administration of lansoprazole, a proton-pump inhibitor, decreased both IL-8 mRNA and protein levels in the esophageal mucosa. CONCLUSION: These results suggest that IL-8 in the esophageal mucosa may be involved in the pathogenesis of esophageal inflammation, including non-erosive GERD.     

非糜烂性反流病患者食管内脏高敏感性与食管下括约肌局部降钙素基因相关肽阳性神经纤维的关系

背景：食管内脏高敏感性是非糜烂性反流病（NERD）最重要的病理生理特征之一，但引起食管内脏感觉过敏的确切机制仍不甚清楚。目的：通过测定NERD患者食管对机械扩张刺激和对酸刺激的敏感性变化和降钙素基因相关肽（CGRP）在食管下括约肌（LES）局部组织中的表达，探讨食管感知阈值与LES局部黏膜CGRP表达之间的关系。方法：采用Synectics内脏刺激器／电子气压泵行食管气囊扩张术以检测食管对机械扩张刺激的敏感性；采用食管酸灌注试验（betastein test）检测食管对酸的敏感性；采用免疫组化法和罔像分析技术观察LES局部组织中CGRP的表达。结果：根据对酸刺激和（或）机械扩张刺激的感知过敏，NERD患者可分为感知过敏组（21例）和感知正常组（10例）。感知过敏组患者食管对气囊扩张刺激的初始感知闽值和最大耐受疼痛阈值较感知正常组和正常对照组显著降低（P〈0．05）。感觉过敏组LES黏膜中CGRP阳性纤维数和平均吸光度（A）值较感知正常组和正常对照组显著增高（P〈0．05）。LES局部组织中CGRP阳性产物A值与食管初始感知阈值和最大耐受疼痛阈值呈直线负相关（r分别为-0．68和-0．79．P〈0．03）。结论：多数NERD患者存在对食管机械扩张刺激和（或）对食管酸刺激感知过敏；感知过敏的NERD患者其LES局部黏膜中CGRP表达增加，提示LES肽能神经的改变可能与食管内脏高敏感性有关。     

Interleukin‐8 expression in the esophageal mucosa of patients with gastroesophageal reflux disease

Background: It has been reported that inflammatory cell infiltration can be detected in patients with endoscopically negative gastroesophageal reflux disease (GERD) as well as those with erosive reflux esophagitis. In this study, we examined the expression of mRNA for interleukin (IL)‐8, a potent chemokine for neutrophils, in the esophageal mucosa of patients with GERD and compared the results with their endoscopic findings and symptoms. Methods: Biopsy samples were obtained from 80 patients. Endoscopic diagnosis was performed according to the Los Angeles classification. Patients with typical symptoms such as heartburn despite normal endoscopic findings were classified as the non‐erosive GERD group. Total cellular RNA was extracted from the biopsy samples and IL‐8 mRNA was quantified by real‐time polymerase chain reaction (PCR). Localization of IL‐8 protein in the esophageal mucosa was done by immunostaining. Results: Expression of IL‐8 mRNA was correlated with the endoscopic grade of esophagitis or with inflammatory cell infiltration, but not with the symptoms of the patients. Expression of IL‐8 mRNA was also detected in all patients with non‐erosive GERD. The level of IL‐8 expression in non‐erosive GERD was low compared with that in erosive GERD, but was higher than that in normal controls. IL‐8 immunostaining was found in the basal layers of the esophageal mucosa. Administration of lansoprazole, a proton‐pump inhibitor, decreased both IL‐8 mRNA and protein levels in the esophageal mucosa. Conclusion: These results suggest that IL‐8 in the esophageal mucosa may be involved in the pathogenesis of esophageal inflammation, including non‐erosive GERD.     

Validity of endoscopic classification of nonerosive reflux disease

BACKGROUND: Minimal changes, such as erythema without sharp demarcation or whitish turbidity of the lower esophageal mucosa, have recently been used for endoscopic classification of nonerosive reflux disease (NERD) in Japan. This study examined the usefulness of such changes in characterizing the pathophysiology of NERD. METHODS: Physicians specializing in esophageal endoscopy performed endoscopy on 115 patients with NERD. Based on the presence or absence of minimal changes, patients were categorized as displaying NERD with minimal changes (grade M, n = 49) or with no minimal changes or mucosal breaks (grade N, n = 66). Clinical features, quality of life (QOL) scores, and ambulatory 24-h esophageal pH values were compared between groups. Ambulatory 24-h esophageal pH values were monitored in 31 patients (14 grade M and 17 grade N patients) who gave consent out of 115 patients. RESULTS: In ambulatory 24-h esophageal pH monitoring, 57.1% (8/14) of grade M patients had pH < 4 more than 4% of the time (abnormal acid reflux) compared with 11.8% (2/17) in the grade N group, a significant difference (P = 0.018). QOL scores did not differ significantly between grades and were significantly lower in both groups compared with the general Japanese population. No significant differences were observed in patient background between the grade M and grade N groups. CONCLUSIONS: Frequency of abnormal acid reflux with NERD is higher in patients with minimal changes than in patients without such changes. Minimal changes are most likely attributable to gastric acid reflux.     

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目的探讨非糜烂性胃食管反流病不同于反流性食管炎的发病机制。方法选择1996～2004年北京大学人民医院因反酸、胃灼热感等反流症状确诊为胃食管反流病患者57例,按照内镜下食管黏膜有无破损分为非糜烂性胃食管反流病组和反流性食管炎组,比较两组的一般情况、反流症状、是否合并H.pylori(Hp)感染,以及食管动力测定和食管胃24hpH监测结果。结果两组患者年龄、性别、烟酒嗜好等一般情况及合并Hp感染情况比较差异无显著性。非糜烂性胃食管反流病组不典型反流症状(胸骨后痛)的发生率明显高于反流性食管炎组。两组患者都存在病理性酸反流,但两组患者之间酸和(或)碱反流比较无差异。非糜烂性胃食管反流病患者的食管体部各段蠕动波峰值明显高于反流性食管炎患者。非糜烂性胃食管反流病患者卧位胃酸分泌高于反流性食管炎患者。结论非糜烂性胃食管反流病的不典型反流症状发生率更高。在两组发病机制异同上,反流的强弱并非主要因素,重要的是食管防御机制的差别。     

Role of Nociceptors/Neuropeptides in the Pathogenesis of Visceral Hypersensitivity of Nonerosive Reflux Disease

Background and Aims

Esophageal visceral hypersensitivity has been proposed to be a pathogenesis of heartburn in nonerosive reflux disease (NERD), but its further mechanisms are unclear. Recently, it has been suggested that nociceptors and neuropeptides control sensory and pain mechanisms. Therefore, the objective of the present study was to estimate expression of acid-sensitive nociceptors such as transient receptor potential vanilloid 1 (TRPV1) and acid-sensing ion channel 3, protease-activated receptor 2 (PAR2), neuropeptides such as substance P and calcitonin-gene-related peptide, and their receptors such as neurokinin 1 receptor (NK1R) and receptor activity-modifying protein 1 in the esophageal mucosa of NERD patients.

Methods

Biopsy samples were taken from NERD patients and healthy control subjects without heartburn. The expression level of nociceptors, neuropeptides, and their receptors were assessed by real-time RT-PCR and enzyme immunoassay. Localization of substance P and CGRP in the esophageal mucosa was determined by immunohistochemical staining.

Results

Expression of mRNA for TRPV1 and PAR2 was significantly elevated in the esophageal mucosa of NERD patients. Substance P protein level and its receptor NK1R mRNA also increased in NERD patients. A positive correlation between the substance P protein level and reflux symptoms was observed. Immunohistochemical study revealed the presence of substance P-positive nerves in the lamina propria of the esophagus.

Conclusions

These findings suggest that visceral hypersensitivity in NERD patients is involved in neurogenic inflammation showing the increase in both substance P release and NK1R expression, which may be associated with the activation of TRPV1 and PAR2.     

不同亚型胃食管反流病食管黏膜下层炎症因子变化特点研究

目的分析3种亚型胃食管反流病患者与对照组食管黏膜的组织变化和局部IL-4、IL- 6表达,探讨Th2型炎症因子在胃食管反流病发生发展中的作用。 方法选取2016年12月至2017年12月新疆维吾尔自治区人民医院69例患者临床资料,根据Gerd Q评分和内镜结果将所有入选研究者分为Barrett食管（BE）、糜烂性食管炎（EE）、非糜烂性反流病（NERD）和对照4组,利用食管24 h pH监测法评价胃食管反流病（GERD）患者食管酸暴露及反流特点;通过食管组织HE染色进行组织病理学评分,使用免疫组化法和酶联免疫吸附剂测定法检测食管局部及血清中IL-4、IL-6表达情况。 结果食管24 h pH监测结果中,3亚组间DeMeester指数、弱酸反流次数、反流总事件数比较,差异均无统计学意义（P均>0.05）,NERD组酸反流次数较其余2组低,差异有统计学意义（P均<0.05）;4组样本食管黏膜组织病理学评分中发现,BE组、EE组与其余2组相比均明显升高,差异有统计学意义（P均<0.05）,BE组与EE组评分之间亦有显著差异（P<0.05）,NERD组与对照组间差异不明显;IL-4在4组食管标本中均有不同程度表达,但4组间IL-4阳性率的比较并无显著差异（P均>0.05）;IL-6在NERD组和对照组表达量较低甚至不表达,EE组IL-6阳性率明显高于对照组（P<0.05 ）,但与NERD组间无显著差异,BE组阳性率与对照组和NERD组之间均有明显差异（P均<0.05 ）。 结论GERD食管黏膜上皮组织学炎症等级随食管炎的恶化而升高,其中NERD的食管组织学已出现炎性化趋势,但尚不足以与正常食管区别;IL-4在不同亚型GERD食管黏膜组织中的表达差异不及IL-6显著。     

非糜烂性反流病放大内镜下微小变化的临床研究

研究显示胃食管反流病(GERD)大部分为非糜烂性反流病(NERD),目前NERD尚无内镜诊断标准.目的:应用放大内镜观察NERD的微小变化,探讨其特征性内镜表现.方法:58例GERD患者(NERD 47例,糜烂性食管炎11例)和6例健康志愿者行24 h食管pH监测和放大内镜检查,于食管、胃不同部位取活检行组织病理学检查.结果:内镜下,NERD组贲门口松弛,23.4%的患者食管黏膜水肿、血管网模糊;10.6%食管下段可见点状血管,27.2%可见隐性红斑;25.5%齿状线上有白色结节样变;29.8%齿状线模糊或部分模糊,形态与正常对照组相比有显著差异(P＜0.05);齿状线下黏膜不平程度亦显著高于正常对照组(P＜0.05).根据齿状线形态诊断NERD,锯齿型、三角型和半岛型的阳性率均为100%,宽大锯齿型为83.3%;根据齿状线下黏膜不平程度,斑块状凹凸不平和绒毛状不平阳性率均为100%,粗糙不平为91.7%.NERD组的食管上皮组织学表现与正常对照组相比无显著差异.结论:放大内镜下可以观察到NERD的齿状线形态和齿状线下黏膜不平程度,其特征性表现对完善NERD的诊断具有重要意义.     

P物质和降钙素基因相关肽及炎症因子在非糜烂性食管炎发生中的作用研究

ObjectiveTo explore the mechanism of substance P (SP), calcitonin gene-related peptide (CGRP) and inflammatory cytokines in the development of non erosive reflux disease. MethodsA total of 25 NERD patients and 10 normal controls were enrolled. All the subjects underwent GERDQ score, 24 h pH monitoring, high resolution esophageal manometry monitoring and endoscopic removal of the local mucosa at 3 cm of the esophageal dentate line as specimens. The expression of SP, CGRP and inflammatory cytokines (IL-1β, IL-6, IFN-γ, TNF-α) was detected by HE staining and RT-PCR. Results24 h esophageal pH monitoring showed that the number of weak acid reflux (4＜pH＜7), acid reflux (pH≤4), acid reflux (%) in proximal esophagus and DeMeester score in NERD group were significantly higher than in control group the t values were -2.365, -2.145, -2.782 and -2.776, and the P values were 0.025, 0.021, 0.021 and 0.017, respectively (P＜0.05). H&E staining showed that there were obvious neutrophil infiltration and pre-inflammatory reaction in esophageal mucosa of NERD group, and the score of inflammation injury was significantly higher than that of control group,the P value were 0.003 (P＜0.01). The relative expression of SP and CGRP in NERD group was significantly higher than that in control group, the P values were 0.0046,0.002, respectively (P＜0.01). In NERD group, the relative expressions of IL-1β, IL-6, IFN-γ and TNF-α in esophageal mucosa were significantly increased,P values were 0.0034, 0.0043, 0.004 and 0.0028, respectively (P＜0.01). Pearson correlation analysis showed that the acid reflux score (DeMeester) in NERD group was positively correlated with the expression of SP, CGRP and inflammatory factors (IL-1β, IL-6, IFN-γ, TNF-α) respectively. The P values 0.003, 0.000, 0.002, 0.005, 0.004 and 0.000, respectively (P＜0.01), the correlation coefficients were r=0.678, 0.686, 0.90, 0.482, 0.374 and 0.415, respectively. ConclusionThe expression of SP, CGRP and inflammatory cytokines in NERD patients increased significantly, which may be closely related to the increase of esophageal acid sensitivity caused by acid reflux and the occurrence of inflammation.     

Antireflux surgery normalizes cyclooxygenase-2 expression in squamous epithelium of the distal esophagus

BACKGROUND: In some patients GERD presents with heartburn and regurgitation symptoms but a relative paucity of endoscopic and clinical findings, while in others symptoms may be minor or absent yet there is significant mucosal damage on endoscopy including the presence of Barrett's esophagus. The initial injury of gastroesophageal reflux is to the squamous esophageal mucosa, but while substantial research has been devoted to determining which genes are involved in the progression of Barrett's to dysplasia and cancer, little is known about the gene expression alterations in the squamous mucosa of patients with reflux. We hypothesized that the expression of cyclooxygenase-2 (Cox-2) might be increased in the squamous esophageal mucosal of patients with reflux, and might be a molecular indicator of reflux injury. Further, we hypothesized that Cox-2 expression in the squamous mucosa would be reduced following the elimination of reflux with an antireflux operation. METHODS: Biopsies of the distal esophageal squamous mucosa were taken 3 cm above the squamocolumnar junction (SCJ) in 28 GERD patients before and after Nissen fundoplication. Following microdissection and RNA isolation, quantitative real-time PCR was used to measure Cox-2 gene expression in paraffin-embedded (N = 16) and fresh frozen (N = 12) tissue. Biopsies from patients (paraffin N = 15, frozen N = 14) with normal acid exposure and no evidence of mucosal injury were analyzed as controls. RESULTS: Median Cox-2 expression in the squamous epithelium from paraffin embedded biopsies in patients with reflux disease was significantly increased compared to controls (p = 0.04). The presence of esophagitis or Barrett's esophagus did not significantly alter the expression of Cox-2 compared to patients with nonerosive reflux disease (NERD). After antireflux surgery median Cox-2 expression values were significantly reduced (p = 0.0003) and were normalized to levels similar to controls without reflux (p = 0.74). Similar results were observed in the prospectively obtained fresh frozen tissue. CONCLUSIONS: Cox-2 gene expression is increased in the distal esophageal squamous mucosa of most patients with GERD, and the elevation was similar whether there was mucosal injury in the form of esophagitis or Barrett's or no visible mucosal injury. This suggests that increased Cox-2 expression may serve as a molecular marker of reflux disease. The increased Cox-2 expression in patients with reflux was usually normalized following antireflux surgery. These findings demonstrate for the first time that gene expression can be altered by surgical correction of reflux. Thus, in addition to symptom control and improvement in the quality of life, perhaps future studies assessing the efficacy of antireflux therapy should also focus on the impact of the therapy on gene expression in the esophageal squamous mucosa.     

Interleukin 8 and 1beta and RANTES levels in esophageal mucosa predict recurrence of endoscopy-negative gastroesophageal reflux disease

BACKGROUND/AIMS: Endoscopy-negative gastroesophageal reflux disease (ENRD), an incipient GERD phenotype without mucosal breaks, is a chronic relapsing condition with an impact on quality of life. Proinflammatory cytokines and chemokines play a role in the pathogenesis of various conditions including GERD. METHODOLOGY: This study investigated the relationship between interleukin 8 (IL-8), monocyte chemoattractant protein 1 (MCP-1), regulated on activation normal T-cell expressed and presumably secreted (RANTES) and IL-1beta levels in esophageal mucosa and recurrence of the reflux symptom in 22 patients with ENRD. RESULTS: Based on analysis using Cox's proportional hazard regression model, significantly positive association was observed between the mucosal levels of cytokines (IL-8 and -1beta and RANTES) and ENRD recurrence. Otherwise, parameters including age, gender, body mass index, smoking habits, alcohol intake, hiatal hernia and Helicobacter pylori status were not significantly related to relapse of the symptom. CONCLUSIONS: Enhanced production of such cytokines as IL-8 and -1beta and RANTES in esophageal mucosa can be potential predictors for ENRD recurrence.     

Nonerosive reflux disease: A pathophysiologic perspective

Nonerosive reflux disease (NERD) is the most common phenotype of gastroesophageal reflux disease. By definition, patients with NERD have typical reflux symptoms caused by the intraesophageal reflux of gastric contents but have no visible esophageal mucosal injury. This is in contrast to patients with reflux esophagitis, also known as erosive reflux disease, and Barrett’s esophagus, who have obvious esophageal mucosal injury on endoscopy. Only 50% of patients with NERD have pathologic esophageal acid contact time (ACT) as detected on 24-hour pH monitoring (ie, NERD-positive). NERD patients with physiologic esophageal ACT and good temporal correlation of symptoms with reflux events (symptom index > 50% or symptom-association probability > 95%) are considered to have esophageal hypersensitivity (ie, NERD-negative). Finally, patients with physiologic esophageal ACT but poor symptom-reflux correlation are now considered to have functional heartburn and not NERD. NERD-positive patients have motor dysfunction and acidic reflux abnormalities that are similar to patients with reflux esophagitis and Barrett’s esophagus, whereas NERD-negative patients have minimal abnormalities that are not much different than healthy controls. The histopathologic feature most indicative of NERD is the presence of dilated intercellular spaces within squamous epithelium, an ultrastructural abnormality readily identified on transmission electron microscopy and on light microscopy.     

Elevated levels of chemokines in esophageal mucosa of patients with reflux esophagitis

OBJECTIVE: Chemokines play a key role in the pathogenesis of various inflammatory conditions. However, there is little information on their profile in reflux esophagitis (RE). We sought to study esophageal mucosa levels of chemokines in RE. METHODS: A total of 32 outpatients with RE and 13 normal controls were studied. Endoscopic severity of RE was classified according to the Los Angeles grading system. Paired biopsy specimens were taken from the esophagus 3 cm above the gastroesophageal junction; one biopsy was snap frozen for measurement of mucosal levels of interleukin 8 (IL-8), monocyte chemoattractant protein 1 (MCP-1), regulated on activation normal T-cell expressed and presumably secreted (RANTES), and IL-1 beta by enzyme linked immunosorbent assays, while the other was formalin-fixed for histopathological evaluation. RESULTS: IL-8, MCP-1, and RANTES levels were significantly higher in esophageal mucosa of RE patients than those of the controls. IL-8 levels correlated significantly with the endoscopic severity of RE. Basal zone hyperplasia and papillary elongation, histopathological hallmarks of RE, were both associated with higher levels of IL-8 and MCP-1. The presence of intraepithelial neutrophils and eosinophils, which also indicate RE, was associated with high levels of IL-8 and RANTES, respectively. There were no significant differences in IL-1 beta levels between the RE and control groups, but IL-1 beta levels correlated significantly with the IL-8 production. Again, the IL-8 levels were significantly decreased after lansoprazole treatment. CONCLUSION: Our results indicate that chemokines produced locally in the esophageal mucosa may be involved in the development and progression of RE.     

Minimal change esophagitis: prospective comparison of endoscopic and histological markers between patients with non-erosive reflux disease and normal controls using magnifying endoscopy

INTRODUCTION: More than half the patients with gastroesophageal reflux disease (GERD) show no endoscopic abnormality or minimal change esophagitis (non-erosive reflux disease, NERD). We investigated the value of endoscopic and histological markers for the prediction of NERD before and after treatment with 20 mg esomeprazole. METHODS: Between July and October 2002, consecutive patients presenting for upper endoscopy were stratified into GERD and non-reflux patients (control group) with the help of a questionnaire. The endoscopist was blind to the presence of reflux symptoms. Using magnifying endoscopes minimal change esophagitis was defined by the presence of vascular injection or vascular spots above the Z-line, villous mucosal surface and islands of squamous cell epithelium below the Z-line. Targeted and random biopsies were taken below and above the Z-line. Patients with endoscopically visible classical signs of esophagitis (Los Angeles A-D) or histologically proven Barrett's esophagus were not further investigated in the study (drop out). The esophageal specimens were histologically evaluated for erosions, infiltration with leukocytes, hyperplasia of basal cells and length of papillae. Patients with NERD were treated with 20 mg esomeprazole/day for 4 weeks and reevaluated by endoscopy as described before. RESULTS: 39 patients with heartburn and 39 patients without reflux symptoms (controls) were finally included in the analysis (per protocol). Patients with NERD significantly (p = 0.005) more often showed endoscopic signs of minimal change esophagitis (27/39) than the control group (8/39). An increased length of papillae (14/39 versus 2/39; p = 0.005) and basal cell hyperplasia (17/39 versus 4/39; p = 0.009) were significantly more common in the heartburn group. After treatment with esomeprazole, no significant endoscopic or histological differences between the NERD and control group could be observed. CONCLUSIONS: Minimal change esophagitis can be seen with high resolution magnifying endoscopy. By combining endoscopic and histological markers NERD can be predicted with a sensitivity of 62% and a specificity of 74%. Treatment with esomeprazole for 4 weeks reverses the slight alterations to normal.     

Increased Taurine Content in Esophageal Mucosa of Children Affected by Gastroesophageal Reflux

We studied the possible involvement of mucosal amino acid metabolism in the pathogenesis of gastroesophageal reflux disease in children. Eighteen children with gastroesophageal reflux disease (8 with reflux esophagitis and 10 without) and 10 children with normal 24-h esophageal pH monitoring as a comparative group underwent esophagogastroduodenoscopy with biopsies. Plasma and esophageal mucosa amino acids were assayed by liquid chromatography. In children affected by gastroesophageal reflux disease we found an increase of mucosal taurine (P < 0.01) and a decrease of serine (P < 0.01). No differences were noted between patients with and without esophagitis. Significant positive correlations (P < 0.001; r = 0.626) were found between mucosal taurine content and reflux index. Plasma amino acid concentrations did not show any significant differences among groups. Our results indicate that biochemical alterations precede the histological findings of inflammation, likely reflecting the adaptive response of the esophageal mucosa to the gastric contents exposure.