组织抵抗性异常在非糜烂性反流病烧心机制中的作用

烧心一直以来都被看作是一个酸介导的事件,并作为胃食管反流病的一个可靠指标而存在。但是近来该观点受到质疑。此文通过回顾内脏高敏感性、持续食管收缩和组织抵抗性异常这3个不同的机制, 提出可用组织抵抗性异常来统一解释烧心机制,从而再次证实非糜烂性反流病烧心症状是由酸介导并且以能被制酸剂缓解为特点。     

光学显微镜测量胃食管反流病患者食管下段细胞间隙的临床价值

目的 通过光学显微镜（光镜）对糜烂性食管炎（ERD）、非糜烂性食管炎（NERD）、Barrett食管（BE）患者及正常对照组食管下段鳞状上皮细胞间隙宽度的测量,探讨胃食管反流病（GERD）患者各亚型尤其是BE食管下段细胞间隙的光镜下改变及其对临床诊断的意义.方法 顺次收集具有GERD症状且内镜和24 h食管pH监测证实为ERD 21例、NERD 21例;胃镜诊断为BE,并在病变处活检且经病理证实BE 13例;对照组为内镜检查及24 h食管pH监测均为阴性者,共20例.ERD组、NERD组及对照组在食管齿状线上2 cm取活检,经常规方法制成HE切片,在油镜下（×1000）观察细胞间隙增宽情况,并采集图像采用图像分析系统对鳞状上皮层基底上层细胞间隙宽度进行定量测量.每例样本测量10个细胞,每个细胞连续测量10个细胞间隙,即每例患者测量100个细胞间隙,求其均值后进行统计学分析.结果 光镜下正常对照组、BE、ERD及NERD组平均细胞间隙分别为0.59、0.99、1.29及1. 06μm.GERD各亚型的细胞间隙均较正常对照组显著增宽,ERD组平均、最大及最小细胞间隙均较NERD组和BE组显著增宽,差异有显著性意义（P=0.000）;NERD组和BE组平均、最大及最小细胞间隙差异无显著性意义（P＞0.05）.光镜下细胞间隙增宽诊断GERD的截断（cut-off）值为0.85 μm,联合临床症状、内镜表现及细胞间隙增宽大于此cut-off值,则光镜下细胞间隙增宽诊断ERD、NERD、BE的敏感度为89.1%,特异度为100.0%.结论 GERD各亚型食管下段均可见细胞间隙增宽的改变,光镜测量GERD患者食管下段鳞状上皮细胞间隙可作为ERD、NERD及BE诊断的一项辅助检查.     

Differences in oesophageal bolus transit between patients with and without erosive reflux disease

BACKGROUND: We determined any difference in oesophageal function between reflux patients with and without erosive esophagitis by the application of concurrent manometry and impedance. METHODS: Twenty patients with erosive esophagitis, 20 patients with non-erosive reflux disease, and 15 controls were included in this study. All subjects underwent studies with a catheter containing four impedance-measuring segments and five solid-state pressure transducers. Each subject received 10 liquid and 10 viscous boluses to be swallowed. RESULTS: Healthy controls had greater distal oesophageal peristaltic amplitude than both patient groups (p < 0.05). Normal oesophageal peristalsis was found more frequently in healthy controls than either of the patient groups (p < 0.05). Patients with erosive esophagitis exhibited a lower percentage of complete bolus transit compared to healthy controls and non-erosive reflux disease patients (both p < 0.05). Patients with erosive esophagitis had a longer total bolus transit time compared to healthy controls and non-erosive reflux disease patients (both p < 0.05). CONCLUSIONS: Erosive esophagitis is characterized by longer oesophageal bolus transit and fewer complete bolus transit than non-erosive reflux disease. The noted differences in oesophageal bolus transit may reflect a continuum of dysfunction secondary to increasing oesophageal mucosal damage.     

胃食管反流病中非酸反流的比例及其与烧心的关系

目的 应用食管联合阻抗-pH监测技术探讨胃食管反流病中非酸反流的比例及其与烧心的相关程度.方法 选取消化专科门诊以烧心为主诉的连续病例,通过上消化道内镜将上述患者分为糜烂性食管炎(EE)组和非糜烂性反流病(NERD)组,并进一步通过24 h食管多通道腔内阻抗-pH监测及雷贝拉唑试验性治疗予以确诊.比较两组的联合阻抗-pH监测指标.结果 EE组36例,NERD组62例.两组患者酸反流次数、酸反流时间百分比差异有统计学意义(P值分别=0.001和0.002).EE组和NERD组中非酸反流次数的百分比分别为37.3%(663/1777)和44.3%(1220/2754),差异有统计学意义(x=21.723,P=0.000).EE组酸反流烧心症状指数阳性、非酸反流烧心症状指数阳性及总反流烧心症状指数阳性的百分比分别为36.1%(13/36)、19.4%(7/36)和55.6%(20/36),NERD组则为27.4%(17/62)、6.4%(4/62)和33.8%(21/62).结论 EE组和NERD组患者中非酸反流次数的比例分别为37.3%及44.3%,非酸反流与烧心关系密切.     

Non-erosive and uncomplicated erosive reflux diseases: Difference in physiopathological and symptom pattern

AIM:To investigate differences in the physiopathological findings(manometry and pH monitoring) and symptoms between cases of non-erosive reflux disease(NERD) and erosive reflux disease(ERD) found positive at 24 h pH monitoring. METHODS:For a total of 670 patients who underwent 24 h pH monitoring,esophageal manometry and upper endoscopy were retrospectively evaluated,assessing the reflux symptoms,manometric characteristics of the lower esophageal sphincter(LES) and esophageal body and the presence or absence of esophagitis and hiatal hernia. Typical and atypical symptoms were also evaluated. For inclusion in the study,patients had to have NERD or ERD and be found positive on pH monitoring(NERD+) . Patients with Gastroesophageal reflux disease(GERD) complicated by stenosis,ulcers or Barrett’s esophagus were ruled out. RESULTS:214 patients were involved in the study,i.e. 107 cases of NERD+ and 107 of ERD. There were no significant gender-or age-related differences between the two groups. The ERD group had more cases of hiatal hernia(P = 0.02) and more acid reflux,both in terms of number of reflux episodes(P = 0.01) and as a percentage of the total time with a pH < 4(P = 0.00) ,when upright(P = 0.007) and supine(P = 0.00) . The NERD+ cases had more reflux episodes while upright(P = 0.02) and the ERD cases while supine(P = 0.01) . The LES pressure was higher in cases of NERD+(P = 0.03) while the amplitude and duration of their esophageal peristaltic waves tended to be better than in the ERD group(P >0.05) . The NERD+ patients presented more often with atypical symptoms(P = 0.01) . CONCLUSION:The NERD+ patients’ fewer reflux episodes and the fact that they occurred mainly while in the upright position(unlike the cases of ERD) may be two factors that do not favor the onset of esophagitis. The frequently atypical symptoms seen in patients with NERD+ need to be accurately evaluated for therapeutic purposes because patients with GERD and atypical symptoms generally respond only partially to medical and surgical treatments.     

食管远端鳞状上皮细胞间隙增宽对非糜烂性反流病诊断的价值

目的:研究非糜烂性反流病(NERD)食管远端鳞状上皮细胞间隙变化及与食管酸暴露、反流症状严重程度的关系,探讨细胞间隙增宽对NERD诊断的价值.方法:纳入NERD患者(66例)和正常对照者(38例).所有受试者行GerdQ调查、食管24hpH值监测、胃镜检查并在食管齿状线(Z线)和Z上2cm线位置取活检,透射电镜测量鳞状上皮细胞间隙;pH监测阴性NERD患者行质子泵抑制剂诊断试验确诊.结果:(1)NERD组Z线和Z线上2cm的平均细胞间隙分别为(0.90±0.11)μm、(0.92±0.16)μm,正常对照组分别为(0.65±0.08)μm、(0.67±0.08)μm,两组间差异有统计学意义(P<0.05),组内差异无统计学意义(P>0.05);(2)NERD患者Z线和Z线上2cm两部位pH(+)亚组与pH(-)亚组的细胞间隙比较,差异均无统计学意义(P>0.05);GerdQ(+)亚组与GerdQ(-)亚组的细胞间隙比较,差异也均无统计学意义(P>0.05);(3)Z线和Z线上2cm两部位的平均细胞间隙与DeMeester积分均呈正相关性,r分别为0.33(P=0.001)、0.35(P=0.001);与GerdQ评分也均呈正相关性,r分别为0.32(P=0.006)、0.45(P<0.001);(4)Z线平均细胞间隙的cut-off值为0.81μm时,约登指数最大(0.808),诊断的敏感度为80.8%,特异度为100.0%.Z线上2cm平均细胞间隙的cut-off值为0.81μm时,约登指数最大(0.731),诊断的敏感度为75.8%,特异度为97.4%.结论:NERD食管远端鳞状上皮细胞间隙明显增宽,细胞间隙与食管远端胃酸暴露和反流症状的严重程度呈正相关.细胞间隙增宽可作为NERD诊断的一种敏感客观结构指标.     

非糜烂性反流病食管黏膜超微结构研究

目的探讨非糜烂性反流病(NERD)病理性酸反流组及生理性酸反流组,其食管黏膜细胞间隙及桥粒数目等超微结构的变化情况。方法对10例健康志愿者(对照组)、39例NERD患者及10例反流性食管炎(RE)患者进行内镜检查并作食管黏膜活检,透射电镜观察标本。图像分析仪测量食管黏膜细胞间隙宽度,同时统计相应间隙中的桥粒数目。结果RE组及NERD组的细胞间隙宽度分别为(2.39±0.42)μm及(2.21±0.68)μm,两组间差异无统计学意义(P〉0.05)。对照组细胞间隙宽度为(0.63±0.21)μm,明显小于RE组及NERD组(P〈0.05)。NERD病理性酸反流组及生理性酸反流组的细胞间隙宽度分别为(2.45±0.67)μm及(1.91±0.67)μm,两组间差异有统计学意义(P〈0.05)。RE组及NERD组的桥粒数目均数分别为(0.124±0.044)个/μm2及(0.141±0.043)个/μm2,两组间差异无统计学意义(P〉0.05),但均少于对照组[(0.221±0.031)个/μm2],P〈0.05。NERD病理性酸反流组的桥粒数目[(0.110±0.032)个/μm2]明显少于生理性酸反流组[(0.171±0.028)个/μm2]。结论NERD组的细胞间隙明显宽于正常对照组,但与RE组无明显差别。NERD病理性酸反流组的细胞间隙明显宽于生理性酸反流组;细胞间隙间的桥粒数目也可能是酸诱导的细胞损伤标志。     

上皮细胞间隙增宽对非糜烂性反流病的诊断意义

目的探讨光学显微镜下观察食管远端黏膜上皮细胞间隙的增宽对非糜烂性反流病（NERD）和糜烂性食管炎（RE）患者的诊断价值。方法104例受试者分为正常对照组20例、NERD组30例和RE组54例;在齿状线上2—3cm取活检行光镜检查,观察黏膜上皮细胞间隙是否增宽并对其进行统计学分析。结果RE组和NERD组平均细胞间隙分别为（1．40±0．17）μm、（1．11±0．14）μm与正常对照组（0．66±0．18）μm比较,差异均有统计学意义（x^2=154．170,P=0．000）,而RE组和NERD组间差异无统计学意义（t=0．044,P=0．834）。光镜下平均细胞间隙的截断（cut-off）值为0．89μm,光镜下平均细胞间隙诊断GERD的敏感度为95．2％,特异度为95．0％。结论光镜下黏膜上皮细胞间隙增宽可作为NERD诊断的敏感、特异且较为客观的指标。     

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.     

非糜烂性反流病患者食管感觉特征分析

目的研究非糜烂性反流病(NERD)患者对食管气囊扩张的机械性刺激和食管滴酸化学性刺激的感觉反应,以明确内脏高敏感在 NERD 中的作用。方法 10例健康对照者、31例经反流性疾病诊断问卷(RDQ)和内镜诊断为 NERD 的患者参与试验。采用 Synectics 内脏刺激器/电子气压泵行食管气囊扩张,测定其机械性感觉阈值,以气囊充气容积表示;行食管酸灌注试验测定其化学性感觉阈值,以触发症状时间和酸相关症状积分表示。结果 NERD 患者食管对气囊扩张刺激的初始感知阈值、疼痛阈值分别为(9.6±4.8)ml 和(12.3±3.2)mI,对照组为(1 3.2±7.5)ml 和(21.6±5.7)ml(P<0.01),70.9%的 NERD 患者酸灌注试验阳性(P<0.01),平均症状诱发时间为(4.8±2.1)min,对酸和(或)机械性刺激过敏的 NERD 患者总计占74.2%;对照组仅1例酸灌注试验阳性。结论 NERD 患者对食管机械扩张刺激、酸刺激的感觉阈值均降低,内脏高敏感性在 NERD 的发生机制中起重要作用。     

Reflux rising! An essay on witnessing a disease in evolution

BACKGROUND AND AIM: The prevalence of gastro-oesophageal reflux disease is thought to be rising but supporting evidence is sparse. We assessed trends from data prospectively collected over 25 years at our centre which serves Rotherham's 250000 population. PATIENTS AND METHODS: Detailed computerised records have been kept of all patients investigated for upper gastrointestinal symptoms. Definition: Erosive oesophagitis=endoscopy-verified erosive changes. Non-erosive reflux=heartburn+/-regurgitation but normal endoscopy. Gastro-oesophageal reflux disease=erosive oesophagitis+non-erosive reflux, i.e. total. RESULTS: The data, presented in 5-year time periods spanning 1977-2001, showed four major changing trends. (1) The numbers with newly diagnosed gastro-oesophageal reflux disease rose markedly, affecting both erosive oesophagitis and non-erosive reflux. Gastro-oesophageal reflux disease: n=714; 1587; 2381; 3812; 3880. (2) The proportion of women affected rose from 0.36 to 0.82. (3) Gastro-oesophageal reflux disease patients were older than the general population; the mean age at presentation rose from 48.0 to 53.5 years. (4) Presentation with haemorrhage (percentage of erosive oesophagitis) rose from 5.2% to 10.9% but, as with stricture (around 4%), remained uncommon. Throughout, few (4.4%) changed from non-erosive reflux to erosive oesophagitis. CONCLUSION: The marked increase in gastro-oesophageal reflux disease cannot be accounted for by greater awareness alone for the demographic profile has changed, or by misclassification as erosive oesophagitis was diagnosed on endoscopic appearances. The dramatic five-fold increase in gastro-oesophageal reflux disease is a new phenomenon, perhaps an example of a disease in evolution.     

Diagnostic value of dilated intercellular space and histopathologic scores in gastroesophageal reflux disease

The aim of this paper is to investigate the diagnostic value of histopathologic score and the dilated intercellular space (DIS) in patients with gastroesophageal reflux disease (GERD) and functional heartburn (FH). Participants with GERD symptoms including reflux esophagitis, non‐erosive reflux disease (NERD), Barrett's esophagus (BE), functional heartburn (FH), along with a control group with atypical GERD‐like symptom (Sym‐C), and asymptomatic healthy volunteers (H‐C) were administered GERD questionnaire, and subjected to endoscopy and biopsies, as well as 24‐hour pH‐impedance monitoring. Biopsies were evaluated using standards from the 2011 Esohisto Project after Hematoxylin‐Eosin staining. DIS was measured quantitatively under light microscopy. Among the total of 565 participants with qualified biopsy specimens, the mean DIS of the reflux esophagitis (RE) group was significantly wider compared with the other five groups. DIS in patients with GERD‐like symptoms was significantly wider compared with the H‐C. No significant differences were observed between NERD and FH. Results from 24‐hour pH‐impedance monitoring indicated that only the DIS of patients with acid reflux or the amount of acid reflux episodes in patients with DIS was significantly wider compared with patients with nonacid reflux or patients without DIS (P < 0.001). With DIS = 0.9 μm as the cutoff value, the sensitivity and specificity were 62.6% and 54.1%, respectively. Using the total histopathologic score > 3 as the diagnostic criterion, the sensitivity and specificity were 71.7% and 47.4%. DIS is closely associated with GERD and acid reflux. The diagnostic value of histological scores in lower esophagus in GERD is very similar to that of the quantitative measurement of DIS.     

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.     

Comparison of multichannel intraluminal impedance-p H monitoring and reflux scintigraphy in pediatric patients with suspected gastroesophageal reflux

AIM To evaluate the agreement of multichannel intraluminal impedance-p H monitoring(MII-p HM) and gastroesophageal reflux scintigraphy(GES) for the diagnosis of gastroesophageal reflux disease. METHODS Seventy-five consecutive patients with suspectedgastroesophageal reflux disease(GERD) underwent 24-h combined MII-p HM recording and one hour radionuclide scintigraphy during the course of the MIIpH M study. Catheters with 6 impedance channels and 1 p H sensor were placed transnasally. Impedance and p H data analysis were performed automatically and manually. For impedance monitoring, reflux was defined as a retrograde 50% drop in impedance, starting distally and propagating retrogradely to at least the next two more proximal measuring channels. Reflux index(RI, percentage of the entire record that esophageal p H is 4.0) greater than 4.2% for p HM and number of refluxes more than 50 for 24 h for MII were accepted as positive test results. At scintigraphy, 240 frames of 15 seconds duration were acquired in the supine position. Gastroesophageal reflux was defined as at least one reflux episode in the esophagus. After scintigraphic evaluation, impedance-pH recordings and scintigraphic images were evaluated together and agreement between tests were evaluated with Cohen's kappa.RESULTS Sufficient data was obtained from 60(80%) patients(34 male, 56.7%) with a mean age of 8.7 ± 3.7 years(range: 2.5-17.3 years; median: 8.5 years). Chronic cough, nausea, regurgitation and vomiting were the most frequent symptoms. The mean time for recording of MII-pH M was 22.8 ± 2.4 h(range: 16-30 h; median: 22.7 h). At least one test was positive in 57(95%) patients. According to diagnostic criteria, GERD was diagnosed in 34(57.7%), 44(73.3%), 47(78.3%) and 51(85%) patients by means of p HM, MII, GES and MII-p HM, respectively. The observed percentage agreements/κ values for GES and p HM, GES and MII, GES and MII-p HM, and MII and p HM are 48.3%/-0.118; 61.7%/-0.042; 73.3%/0.116 and 60%/0.147, respectively. There was no or slight agreement between GES and p HM alone, MII alone or MII-p HM. p H monitoring alone missed 17 patients compared to combined MII-p HM. The addition of MII to pH monitoring increased the diagnosis rate by 50%.CONCLUSION No or slight agreement was found among p H monitoring, MII monitoring, MII-pH monitoring and GES for the diagnosis of gastroesophageal reflux disease.     

非糜烂性反流病的食管动力与胃动素相关性研究

目的从胃肠激素-胃动素与食管动力方面探讨非糜烂性反流病（NERD）的发病机制。方法健康对照14例、反流性食管炎（RE）和NERD各30例参与试验。RE、NERD经症状评估和内镜诊断、结合24h食管pH动态监测、质子泵抑制剂（PPI）试验诊断入组。采用四通道胃肠功能仪检测食管动力,以下食管括约肌压力（LESP）、食管蠕动波推进速度、食管体部蠕动压力、下食管括约肌的松弛状况来表示;用放射免疫方法检测血浆胃动素（motilin,MTL）水平。结果NERD组胃动素水平较正常对照组明显降低（P〈0.01）,与RE组比较无显著性差异（P〉0.05）;LESP在NERD组、RE组、正常对照组间无显著性差异（P〉0.05）;食管蠕动波推进速度、食管体部蠕动压力、下食管括约肌的松弛状况在各组间无显著性差异（P〉0.05）;NERD组、RE组、正常对照组分别分析胃动素与各项动力学指标相关性,P均大于0.05。结论NERD患者的食管动力学改变与RE、正常对照并无区别,食管动力学各项指标与胃动素水平也不存在相关性;NERD、RE组胃动素水平明显低于正常对照组,胃动素在NERD的发生机制中可能起一定的作用。     

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。     

非糜烂性胃食管反流病患者的反流事件研究

[目的]研究非糜烂性胃食管反流病(NERD)患者的胃食管反流事件,为进一步探讨NERD发病机制和有效治疗提供临床依据。[方法]68例NERD患者进行食管阻抗-pH监测,根据监测结果、症状指数,分为病理性酸反流(PAR)组、功能性烧心(FH)组、高敏性食管(HE)组,比较3组间反流事件的差异,研究反流与症状之间的相关性。[结果]PAR组总反流次数、酸反流次数、混合反流次数均高于FH组、HE组;HE组总反流次数、弱酸反流次数、混合反流次数、非酸反流次数均高于FH组;各组近段反流次数比较差异无统计学意义。68例中35例(51.5%)SI和(或)SAP呈阳性,其中50%的症状与弱酸反流相关,40%的症状与酸反流相关,少部分症状与非酸反流相关。[结论]PAR、FH、HE患者的食管阻抗-pH监测结果存在差异,可为临床鉴别诊断和治疗提供一定的依据。     

食管黏膜屏障功能及其检测方法研究进展

食管黏膜屏障包括上皮屏障、顶端连接复合体、化学屏障及上皮后屏障。食管黏膜屏障功能的研究对进一步明确胃食管反流病病理生理学机制具有重要意义。目前临床上对于食管黏膜屏障功能的检测尚未有效开展。本文对其功能及其检测方法的研究进展作一概述。     

Characteristics of symptomatic reflux episodes in Japanese proton pump inhibitor-refractory non-erosive reflux disease patients

AIM: To clarify the pathogenesis of gastroesophageal reflux disease symptoms in non-erosive reflux disease(NERD) patients.METHODS: Thirty-five NERD patients with persistent symptoms, despite taking rabeprazole 10 mg twice daily for at least 8 wk, were included in this study. All patients underwent 24 h combined impedance- p H on rabeprazole. The symptom index(SI) was considered to be positive if ≥ 50%, and proximal reflux episodes were determined when reflux reached 15 cm above the proximal margin of the lower esophageal sphincter.RESULTS: In 14(40%) SI-positive patients, with liquid weakly acid reflux, the occurrence rate of reflux symptoms was significantly more frequent in proximal reflux episodes(46.7%) than in distal ones(5.7%)(P 0.001). With liquid acid reflux, there were no significant differences in the occurrence rate of reflux symptoms between proximal reflux episodes(38.5%) and distal ones(20.5%)(NS). With mixed liquid-gas weakly acid reflux, the occurrence rate of reflux symptoms in proximal reflux episodes was significantly more frequent(31.0%) than in distal reflux ones(3.3%)(P 0.001). With mixed liquid-gas acid reflux, there were no significant differences in the occurrence rate of reflux symptoms between proximal reflux episodes(29.4%) and distal ones(14.3%)(NS).CONCLUSION: The proximal extent of weakly acidic liquid and mixed liquid-gas reflux is a major factor associated with reflux perception in SI-positive patients on proton pump inhibitor therapy.