Esophageal cell proliferation in gastroesophageal reflux disease： Clinical-morphological data before and after pantoprazole

AIM： To evaluate esophageal mucosal defense mechanisms at an epithelial level to establish if pantoprazole treatment can induce ultrastructural healing and improvement in the proliferation activity of the esophageal epithelium in gastroesophageal reflux disease （GERD）. METHODS： This was a single-blinded study for pH- monitoring, and histological, ultrastructural and MIB1 immunostaining evaluation. Fifty eight patients with GERD were enrolled and underwent 24 h pH-monitoring and endoscopy. Patients were treated for 12 and 24 mo with pantoprazole. Esophageal specimens were taken for histological and ultrastructural evaluation, before and after the treatment. RESULTS： With transmission electron microscopy, all patients with GERD showed ultrastructural signs of damage with dilation of intercellular spaces （DIS）. After 3 mo of therapy the mean DIS values showed a significant reduction and the mean MIB1-LI values of GERD showed an increase in cell proliferation. A further 3 mo of therapy significantly increased cell proliferation only in the erosive esophagitis （ERD） group. CONCLUSION： Three months of pantoprazole therapy induced ultrastructural healing of mucosal damage in 89% and 93% of ERD and non-erosion patients, respectively. Moreover, long-term pantoprazole treatment may be helpful in increasing the capability for esophageal cell proliferation in GERD, particularly in ERD patients.     

Is the severity of obstructive sleep apnea or the magnitude of respiratory effort associated with gastroesophageal reflux？

TO THE EDITOR In a recent issue of World Journal of Gastroenterology, Demeter et al, reported that in patients having both gastro-esophageal reflux disease (GERD) and obstructive sleep apnea (OSA), there was a positive correlation between     

Is ineffective esophageal motility gastropharyngeal reflux disease？

AIM： TO evaluate the association between IEM and gastropharyngeal reflux disease （GPRD） in patients who underwent ambulatory 24-h dual-probe pH monitoring for the evaluation of supraesophageal symptoms.
METHODS： A total of 632 patients who underwent endoscopy, esophageal manometry and ambulatory 24-h dual-pH monitoring due to supraesophageal symptoms （e.g. globus, hoarseness, or cough） were enrolled. Of them, we selected the patients who had normal esophageal motility and IEM. The endoscopy and ambulatory pH monitoring findings were compared between the two groups.
RESULTS;： A total of 264 patients with normal esophageal motility and 195 patients with the diagnosis of IEM were included in this study. There was no difference in the frequency of reflux esophagitis and hiatal hernia between the two groups. All the variables showing gastroesophageal reflux and gastropharyngeal reflux were not different between the two groups. The frequency of GERD and GPRD, as defined by ambulatory pH monitoring, was not different between the two groups.
CONCLUSION： There was no association between IEM and GPRD as well as between IEM and GERD. IEM alone cannot be considered as a definitive marker for reflux disease.     

Effect of itopride, a new prokinetic, in patients with mild GERD： A pilot study

AIM: Itopride is a newly developed prokinetic agent, which enhances gastric motility through both antidopaminergic and anti-acetylcholinesterasic actions. The importance of esophageal motor dysfunction in the pathogenesis of gastro-esophageal reflux disease (GERD) makes it interesting to examine the effect of itopride on esophageal acid exposure. METHODS: The effect of itopride on esophageal acid reflux variables for 24 h was studied in 26 patients with GERD symptoms, pre-entry total acid exposure time (pH<4) of more than 5% and mild esophagitis (Savary-Miller grades I, II) proven by endoscopy. Ambulatory 24-h pH-metry and symptom assessment were performed after treatments with 150 or 300 mg itopride thrice a day (t.i. d.) for 30 d in random order, using an open label method. For evaluating the safety of itopride, blood biochemical laboratory test was performed and the serum prolactin level was also examined before and after treatment. RESULTS: Total symptom score was significantly decreased after treatment in 150- or 300-mg group. Itopride 300 mg was significantly effective than 150 mg on decreasing the total per cent time with pH<4, total time with pH<4 and DeMeester score. No serious adverse effects were observed with administration of itopride in both groups. CONCLUSION: Itopride 100 mg t.i.d. is effective on decreasing pathologic reflux in patient with GERD and therefore it has the potential to be effective in the treatment of this disease.     

Reactive oxygen species and chemokines： Are they elevated in the esophageal mucosa of children with gastroesophageal reflux disease？

AIM： To determine the role of inflammatory cytokines and reactive oxygen species （ROS） in childhood reflux esophagitis. METHODS： A total of 59 subjects who had complaints suggesting GERD underwent esophagogastroduoden oscopy. Endoscopic and histopathologic diagnosis of reflux esophagitis was established by Savary-Miller and Vandenplas grading systems, respectively. Esophageal biopsy specimens were taken from the esophagus 20% proximal above the esophagogastric junction for conventional histopathological examination and the measurements of ROS and cytokine levels. ROS were measured by chemiluminescence, whereas IL-8 and MCP-1 levels were determined with quantitative immunometric ELISA on esophageal tissue. Esophageal tissue ROS, IL-8 and MCP-1 levels were compared among groups with and without endoscopic/histo- pathologic esophagitis. RESULTS： Of 59 patients 28 （47.5%） had normal esophagus whereas 31 （52.5%） had endoscopic esophagitis. In histopathological evaluation, almost 73% of the cases had mild and 6.8% had moderate degree of esophagitis. When ROS and chemokine levels were compared among groups with and without endoscopic esophagitis, statistical difference could not be found between patients with and without esophagitis. Although the levels of ROS, IL-8 and MCP-1 were found to be higher in the group with histopathological reflux esophagitis, this difference was not statistically significant. CONCLUSION： These results suggest that the grade of esophagitis is usually mild or moderate during childhood and factors apart from ROS, IL-8 and MCP-1 may be involved in the pathogenesis of reflux esophagitis in children.     

24-hour esophageal pH-monitoring in children suspected of gastroesophageal reflux disease： Analysis of intraesophageal pH monitoring values recorded in distal and proximal channel at diagnosis

AIM To assess values of 24-h esophageal pH-monitoring parameters with dual-channel probe (distal and proximal channel) in children suspected of gastroesophageal reflux disease (GERD).METHODS 264 children suspected of gastroesophageal reflux (GER) were enrolled in a study (mean age χ = 20.78 ± 17.23 mo). The outcomes of this study,immunoallerrgological tests and positive result of oral food challenge test with a potentially noxious nutrient,enabled to qualify children into particular study groups.RESULTS 32 (12.1%) infants (group 1) had physiological GER diagnosed. Pathological acid GER was confirmed in 138 (52.3%) children. Primary GER was diagnosed in 76 (28.8%) children (group 2) and GER secondary to allergy to cow milk protein and/or other food (CMA/FA) in 62 (23.5%) children (group 3). 32(12.1%) of them had CMA/FA (group 4-reference group),and in remaining 62 (23.5%) children neither GER nor CMA/FA was confirmed (group 5). Mean values of pH monitoring parameters measured in distal and proximal channel were analyzed in individual groups. This analysis showed statistically significant differentiation of mean values in the case of number of episodes of acid GER,episodes of acid GER lasting ＞ 5 min, duration of the longest episode of acid GER in both channels, acid GER index total and supine in proximal channel. Statistically significant differences of mean values among examined groups, especially between group 2 and 3 in the case of total acid GER index (only distal channel) were confirmed.CONCLUSION 24-h esophageal pH monitoring confirmed pathological acid GER in 52.3% of children with typical and atypical symptoms of GERD. The similar pH-monitoring values obtained in group 2 and 3 confirm the necessity of implementation of differential diagnosis for primary vs secondary cause of GER.     

Is there a changing trend in surgical management of gastroesophageal reflux disease in children？

Gastroesophageal reflux disease (GORD) is a pathological process in infants manifesting as poor weight gain, signs of esophagitis, persistent respiratory symptoms and changes in neurobehaviour. It is currently estimated that approximately one in every 350 children will experience severe symptomatic gastroesophageal reflux necessitating surgical treatment. Surgery for GORD is currently one of the common major operations performed in infants and children. Most of the studies found favour laparoscopic approach which has surpassed open antireflux surgery as the gold standard of surgical management for GORD.However, it must be interpreted with caution due to the limitation of the studies, especially the small number of subject included in these studies. This review reports the changing trends in the surgical treatment of GORD inchildren.     

Is analysis of lower esophageal sphincter vector volumes of valuein diagnosing gastroesophageal reflux disease？

AIM: With successful surgical treatment of gastroesophageal reflux disease (GERD), there is interest in understanding the anti-reflux barrier and its mechanisms of failure. To date, the potential use of vector volumes to predict the DeMeester score has not been adequately explored. METHODS: 627 patients in the referral database received esophageal manometry and ambulatory 24-hour pH monitoring. Study data included LES resting pressure (LESP), overall LES length (OL) and abdominal length (AL), total vector volume (TVV) and intrabdominal vector volume (IVV). RESULTS: In cases where LESP, TVV or IVV were all below normal, there was an 81.4 % probability of a positive DeMeester score. In cases where all three were normal, there was an 86.9 % probability that the DeMeester score would be negative. Receiver-operating characteristics (ROC) for LESP, TVV and IVV were nearly identical and indicated no useful cut-off values. Logistic regression demonstrated that LESP and IVV had the strongest association with a positive DeMeester score; however, the regression formula was only 76.1 % accurate. CONCLUSION: While the indices based on TVV, IVV and LESP are more sensitive and specific, respectively, than any single measurement, the measurement of vector volumes does not add significantly to the diagnosis of GERD.     

Severity of gastroesophageal reflux disease influences daytime somnolence： A clinical study of 134 patients underwent upper panendoscopy

AIM: To asses the relationship between severity of gastroesophageal refluxe disease and Epworth sleepiness scale as an indicator of daytime somnolence. METHODS: One hundred and thirty-four patients underwent an upper panendoscopy as indicated by the typical reflux symptoms and were also investigated with regard to somnolence. Sleepiness was evaluated by Epworth Sleepiness Scale, which was compared to the severity of endoscopic findings (Savary-Miller/modified by Siewert). Patients with psychiatric disorders or being on sedato-hypnotics as well as shift workers were excluded from the study. The relationship between the severity of the reflux disease and daytime somnolence was analyzed with the help of multivariate regression analysis. RESULTS: A positive tendency was found between the severity of the reflux disease and the corresponding Epworth Sleepiness Scale. In the case of the more severe type-Savary-Miller Ⅲ- at least a mild hypersomnia was found. For this group daytime somnolence was significantly higher than in the case of the non-erosive type of Gastroesophageal Reflux Disease representing the mildest stage of reflux disease. CONCLUSION: The severity of Gastroesophageal Reflux Disease influences daytime somnolence.     

Esophageal epithelial surface in patients with gastroesophageal reflux disease： An electron microscopic study

A/M： To investigate the intercellular spaces between the most superficially located esophageal epithelial cells in patients with gastroesophageal reflux disease （GERD）.
METHODS： Eighteen patients with erosive esophagitis, 10 patients with non-erosive reflux disease （NERD）, and 18 normal asymptomatic volunteers were enrolled. Biopsy specimens were obtained from the lower esophageal mucosa without ulcer or erosion. Scanning electron microscopy was employed to investigate the tightness of the superficial cellular attachment.
RESULTS： The intercellular space between the most superficially located epithelial cells in patients with erosive esophagitis or NERD was not different from that in asymptomatic healthy individuals.
CONCLUSION： Widened luminal intercellular spaces of esophageal superficial epithelium are not responsible for the induction of reflux symptoms in patients with GERD.     

胃食管反流病患者食管下段鳞状上皮细胞间隙的改变

目的观察胃食管反流病患者食管下段鳞状上皮细胞间隙的改变。方法11例胃食管反流病患者(非糜烂性反流病6例和糜烂性食管炎5例)及5名健康对照者行胃镜、24h食管pH值监测检查。于齿状线上方2cm处取活检,透射电镜下观察。结果健康对照组、非糜烂性反流病组和糜烂性食管炎组食管下段鳞状上皮平均细胞间隙分别为(0．374±0．073)μm、(1．308±0．079)μm和(1．332±0．144)μm,健康对照组和非糜烂性反流病组及糜烂性食管炎组相比差异有统计学意义(P＜0．05),非糜烂性反流病组和糜烂性食管炎组相比差异无统计学意义(P＞0．05)。结论非糜烂性反流病及糜烂性食管炎患者透射电镜下均存在食管上皮细胞间隙的增宽。     

胆汁在胃食管反流病中的作用

随着24 h食管pH监测和胆汁监测技术的开展,胃、十二指肠液混合反流在胃食管反流病(GERD)的发生、发展中的作用已被逐步认识.胆汁反流在GERD发病过程中所扮演的角色,成为近年来人们研究的焦点之一.基础研究证明胆汁在不同酸碱环境、不同浓度对食管黏膜的损伤作用是不同的.不少临床试验对GERD进行研究发现,胆汁反流与症状和食管损伤严重度存在一定关系,但研究结果不尽一致,胆汁在GERD中的作用仍有争议.明确胆汁在GERD中的作用,有助于为预防此类疾病开辟新的道路.本文就有关胆汁反流在胃食管反流病中的作用的研究进展作一综述.     

Belching,regurgitation,chest tightness and dyspnea:Not gastroesophageal reflux disease but asthma

Belching is a common symptom of gastroesophageal reflux disease.If the symptoms are not relieved after anti-reflux treatment,another etiology should be considered.Here,we report a case of a 43-yearold man who presented with belching,regurgitation,chest tightness and dyspnea for 18 mo,which became gradually more severe.Gastroscopic examination suggested superficial gastritis.Twenty-four-houresophageal pH monitoring showed that the Demeester score was 11.4,in the normal range.High-resolution manometry showed that integrated relaxation pressure and intrabolus pressure were higher than normal(20 mm Hg and 22.4 mm Hg,respectively),indicating gastroesophageal junction outflow tract obstruction.Pulmonary function test showed severe obstructive ventilation dysfunction [forced expiratory volume in 1 second(FEV1)/forced vital capacity 32%,FEV1 was 1.21 L,occupying 35% predicted value after salbuterol inhalation],and positive bronchial dilation test(△FEV1 260 m L,△FEV1% 27%).Skin prick test showed Dermatophagoides farinae(++),house dust mite(++++),and shrimp protein(++).Fractional exhaled nitric oxide measurement was 76 ppb.All the symptoms were alleviated completely and pulmonary function increased after combination therapy with corticosteroids and long-acting β2-agonist.Bronchial asthma was eventually diagnosed by laboratory tests and the effect of anti-asthmatic treatment,therefore,physicians,especially the Gastrointestinal physicians,should pay attention to the belching symptoms of asthma.     

GERD患者的心理因素及综合治疗

目的: 探讨胃食管反流病GERD患者心理健康水平与治疗方法的选择.方法:随机选取符合胃食管反流病诊断患者80例, 采用诊断胃食管反流病GERD患者的问卷评分及MMPI问卷测评, 使用质子泵抑制剂, 胃黏膜保护剂, 胃动力剂, 抗抑郁药等药物联合应用及心理辅导治疗. 比较治疗前后的评分变化.结果: 治疗前GERD评分均大于12分, 治疗后小于10分, 治疗前GERD评分及MMPI评分各项均明显高于治疗后(P<0.01). 结论:治疗胃食管反流病的同时需对患者进行综合心理辅导治疗.     

光学显微镜食管下段细胞间隙的测量对胃食管反流病诊断的意义

目的 通过光学显微镜(光镜)对胃食管反流病(GERD)患者食管下段细胞间隙的测量,探讨光镜下细胞问隙的变化对GERD的诊断意义.方法 158例受试者行内镜检查,分为正常对照组(25例)、非糜烂件反流病(NERD)组(58例)和糜烂性食管炎(EE)组(75例),在齿状线以上2～3 cm取活榆行光镜检查,并随机选取43例(其中正常对照组4例,EE组28例,NERD组11例)在相同部位取活检同时进行电镜检查.光镜/电镜下观察切片并采集图像,采用图像分析系统对每例切片测量100个细胞问隙,并进行统计学分析.结果 正常对照组、NERD组及EE组光镜下测量的平均细胞问隙(LMIS)分别为(0.61±0.10)μm、(1.12±0.61)μm和(1.30±0.19)μm,3组两两相比差异均有统计学意义(P<0.05);EE组不同洛杉矶分级的各亚组间相比,细胞间隙增宽程度的差异无统计学意义(P>0.05);NERD患者食管24 h pH监测阳性者(40例)与阴性者(17例)LMIS的差异无统计学意义(P>0.05);光镜下LMIS的截断(cut-off)值为0.85 μm,如果以临床症状加内镜和食管24 h pH监测综合作为诊断GERD的金标准,LMIS诊断GERD的敏感性为95.5%,特异性为100.0%;同时做光镜和电镜测量的受试者共43例,经相火性分析和一致性检验,光镜测量和电镜测量的细胞间隙宽度显著相关(r=0.737,P=0.000),且一致性好.结论 GERD患者食管下段组织的细胞间隙可通过光镜进行定晕测量,其结果与电镜测量结果的一致性好.光镜下细胞间隙增宽可以作为GERD诊断的敏感、特异且较为客观的指标之一.     

胃食管反流病药物治疗进展

我国胃食管反流病(GERD)发病率逐年升高.GERD可能引起反流性食管炎、慢性咳嗽、哮喘、Barrett’s食管和食管腺癌等并发症,并且严重影响人们的生活质量.质子泵抑制剂(PPIs)的应用,使多数患者症状得到了缓解.但近年来发现PPIs对部分GERD患者无效,且长期使用会出现间质性肾炎、骨折和小肠细菌增生过多等并发症...     

胃食管反流病的食管外表现及其临床进展

胃食管反流病(GERD)的食管外表现是指除反酸、烧心等典型症状外,同时伴有呼吸系统、耳鼻喉、口腔等部位的症状,如支气管哮喘、慢性咳嗽、阻塞型睡眠呼吸暂停综合征、特发性肺纤维化、咽炎、喉炎、牙侵蚀症等.因其表现特殊、临床容易误诊,本文特对其发病机制及临床表现作一综述.     

脂肪性肝病与胃食管反流病的相关性研究

目的评估脂肪性肝病(FLD)与胃食管反流病GERD之间的关系。方法选取2 000例受试者,采用较简便的胃食管反流病问卷(GerdQ)作为初筛GERD诊断标准,对入选者均进行腹部超声波等检查,分析FLD与GERD关系。结果对2 000例患者利用GerdQ评估GERD诊断情况,有176例(8.8%)诊断为GERD,女68人(38.64%),男108人(61.36%);脂肪肝患者760例,患病率38.0%,在脂肪肝组中,男女性GERD症状的GerdQ阳性率分别为13.77%和12.24%,两者无明显差异(P>0.05)。脂肪肝人群发生GERD症状的患病率与对照组存在统计学差异(P<0.05)。结论脂肪肝与GERD显著相关,控制脂肪肝发展可以降低GERD发病率。     

胃食管反流病问卷对胃食管反流病的诊断价值

目的 评价胃食管反流病问卷(GerdQ)在胃食管反流病(GERD)患者中的诊断价值,初步探讨中国GERD人群的症状特点.同时探索一种适合中国人群的质子泵抑制剂(PPI)试验的诊断标准.方法 在全国五家医院进行多中心研究.所有入组患者填写GerdQ问卷表.以胃镜检查、24 h食管pH监测和PPI试验其中任何一项阳性作为GERD的诊断标准,评价GerdQ的诊断价值.以拟定PPI试验诊断标准与胃镜和食管pH监测的诊断相比较,并优化PPI试验的诊断标准.结果 拟定PPI试验诊断的敏感度为0.6627,特异度为0.4872.经统计分析,以PPI治疗1周最后3 d烧心、反流症状总评分较治疗前相比下降3分为优化PPI试验诊断标准,诊断的敏感度为0.3787,特异度为0.8077,阳性预测值为0.8101,阴性预测值为0.3750,Youden指数最大为0.1864.经人群矫正,GerdQ取临界值为10分时,Youden指数达到最大0.1080,诊断的敏感度为0.6690,特异度为0.4390.50岁以上女性患者随着评分的增高,问卷诊断价值下降.结论 GerdQ具有肯定的诊断价值.但在临床工作中,对特殊人群中症状突出而PPI诊断性治疗反应不佳的患者,GERD的诊断应慎重.PPI试验的评分以治疗1周最后3 d为佳.