Proton pump inhibitor for non-erosive reflux disease: A meta-analysis

AIM:To evaluate the efficacy,safety and influential factors of proton pump inhibitor(PPI)treatment for non-erosive reflux disease(NERD).METHODS:PubMed,MEDLINE,EMBASE and the Cochrane Library were searched up to April 2013 to identify eligible randomized controlled trials(RCTs)that probed into the efficacy,safety and influential factors of PPI treatment for NERD.The rates of symptomatic relief and adverse events were measured as the outcomes.After RCT selection,assessment and data collection,the pooled RRs and 95%CI were calculated.This meta-analysis was performed using the Stata 12.0 software(Stata Corporation,College Station,Texas,United States).The level of evidence was estimated by the Grading of Recommendations Assessment,Development and Evaluation system.RESULTS:Seventeen RCTs including 6072 patients met the inclusion criteria.The results of the metaanalysis showed that PPI treatment was significantly superior to H2receptor antagonists(H2RA)treatment(RR=1.629,95%CI:1.422-1.867,P=0.000)and placebo(RR=1.903,95%CI:1.573-2.302,P=0.000)for the symptomatic relief of NERD.However,there were no obvious differences between PPI and H2RA(RR=0.928,95%CI:0.776-1.110,P=0.414)or PPI and the placebo(RR=1.000,95%CI:0.896-1.116,P=0.997)regarding the rate of adverse events.The overall rate of symptomatic relief of PPI against NERD was 51.4%(95%CI:0.433-0.595,P=0.000),and relief was influenced by hiatal hernia(P=0.030).The adverse rate of PPI against NERD was 21.0%(95%CI:0.152-0.208,P=0.000),and was affected by hiatal hernia(P=0.081)and drinking(P=0.053).CONCLUSION:PPI overmatched H2RA on symptomatic relief rate but not on adverse rate for NERD.Its relief rate and adverse rate were influenced by hiatal hernia and drinking.     

Rebuilding trust in proton pump inhibitor therapy

Introduction of proton pump inhibitor (PPI) therapy into clinical practice has revolutionized treatment approach to acid-related diseases. With its clinical success came a widespread use of PPI therapy. Subsequently, several studies found that PPIs were oftentimes overprescribed in primary care and emergency setting, likely attributed to seemingly low side-effect profile and physicians having low threshold to initiate therapy. However, now there is a growing concern over PPI side-effect profile among both patients and providers. We would like to bring more awareness to the currently available guidelines on PPI use, discuss clinical indications for PPIs and the evidence behind the reported side-effects. We hope that increased awareness of proper PPI use will make the initiation or continuation of therapy a well informed and an evidence-based decision between patient and physician. We also hope that discussing evidence behind the reported side-effect profile will help clarify the growing concerns over PPI therapy.     

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.     

Combined multichannel intraluminal impedance and pH monitoring is helpful in managing children with suspected gastro-oesophageal reflux disease

BackgroundGastro-oesophageal reflux is very common in the paediatric age group. There is no single and reliable test to distinguish between physiologic and pathological gastro-oesophageal reflux, and this lack of clear distinction between disease and normal can have a negative impact on the management of children.AimsTo evaluate the usefulness of 24-h oesophageal pH-impedance study in infants and children with suspected gastro-oesophageal reflux disease.MethodsPatients were classified by age groups (A–C) and reflux-related symptoms (typical and atypical). All underwent pH-impedance study. If the latter suggested an abnormal reflux, patients received therapy in accordance with NASPGHAN/ESPGHAN recommendations, while those with normal study had an additional diagnostic work-up. The efficacy of therapy was evaluated with a specific standardized questionnaire for different ages.ResultsThe study was abnormal in 203/428 patients (47%) while normal in 225/428 (53%). Of those with abnormal study, 109 exhibited typical symptoms (54%), and 94 atypical (46%). The great majority of the patients with abnormal study were responsive to medical anti-reflux therapy.ConclusionsWe confirm the utility of prolonged oesophageal pH-impedance study in detecting gastro-oesophageal reflux disease in children and in guiding therapy. Performing oesophageal pH-impedance monitoring in children with suspected gastro-oesophageal reflux disease is helpful to establish the diagnosis and avoid unnecessary therapy.     

Management of gastro-esophageal reflux disease: Practice-oriented answers to clinical questions

Gastro-esophageal reflux disease (GERD) is a condition which is frequently faced by primary care physicians and gastroenterologists. Improving management of GERD is crucial to maximise both patient care and resource utilization. In fact, the management of patients with GERD is complex and poses several questions to the clinician who faces them in clinical practice. For instance, many aspects should be considered, including the appropriateness of indication to endoscopy, the quality of the endoscopic examination, the use and interpretation of ambulatory reflux testing, and the choice and management of anti-reflux treatments, i.e., proton-pump inhibitors and surgery. Aim of the present review was to provide a comprehensive update on the clinical management of patients with GERD, through a literature review on the diagnosis and management of patients with GER symptoms. In details, we provide practice-oriented concise answers to clinical questions, with the aim of optimising patient management and healthcare resource use.     

腹腔镜胃底折叠术治疗胃食管反流性疾病

目的　探讨腹腔镜胃底折叠术治疗胃食管反流性疾病的可行性及安全性。方法　回顾性分析 2 0 0 1年 6月至 2 0 0 4年 3月对 4 2例行腹腔镜胃底折叠术的胃食管反流性疾病患者的临床资料。结果　 33例行腹腔镜Nissen胃底折叠术 ,9例行腹腔镜Toupet胃底折叠术。术后症状评分由11 5 6± 1 32降到 2 0 4± 1 36 ,食管下段压力由 (7 32± 1 34)mmHg提高到 (18 2 0± 3 4 3)mmHg ,2 4hpH值监测评分由 183 36± 96 76降低到 8 0 4± 2 12 ,均较手术前有明显改善 (P <0 0 1) ,并达到正常范围。无手术并发症 ,无中转开腹及死亡病例。结论　对于严重的胃食管反流性疾病 ,腹腔镜胃底折叠术是一种安全、有效的治疗方法     

质子泵抑制剂联合依托必利对胃食管反流病的疗效评价

目的 观察质子泵抑制剂（proton pump inhibitor,PPI）联合盐酸伊托必利（itopride hydrochloride,ITO）对胃食管反流病（gastroesophageal reflux disease,GERD）的疗效,并评价该治疗方案的安全性及耐受性.方法 经内镜、24 h食管pH测定或PPI试验确诊的GERD患者93例,按治疗方案随机分为PPI联合ITO治疗组及PPI单药治疗组,PPI联合ITO治疗组：糜烂性食管炎（EE）16例,非糜烂性反流病（NERD）21例,Barrett食管（BE）14例,共51例;PPI单药治疗组：EE 14例,NERD 16例,BE 12例,共42例.采用前瞻性、随访对照研究,于治疗前、治疗8周后、24周后进行GerdQ评分及内镜检查.结果 8周初始治疗后,两组内的3个亚型患者GerdQ评分均较治疗前明显降低,差异有统计学意义（P＜0.01）,24周后两组内EE及BE患者GerdQ评分较8周时进一步降低,差异有统计学意义（P＜0.05）;治疗8周及24周后两组EE患者食管黏膜愈合率分别为81.3％、71.4％（8周,P=0.00047）及93.8％、85.7％（24周,P=0.00036）,PPI联合ITO治疗组食管黏膜愈合率高于PPI单药治疗组,差异有统计学意义（P＜0.05）.结论 就改善反流相关症状及食管黏膜愈合率而言,PPI联合ITO维持治疗方案优于PPI单药治疗,具有良好的安全性和耐受性.     

Laparoscopic surgery for gastro-esophageal acid reflux disease

Gastro-esophageal reflux disease is a troublesome disease for many patients, severely affecting their quality of life. Choice of treatment depends on a combination of patient characteristics and preferences, esophageal motility and damage of reflux, symptom severity and symptom correlation to acid reflux and physician preferences. Success of treatment depends on tailoring treatment modalities to the individual patient and adequate selection of treatment choice. PubMed, Embase, The Cochrane Database of Systematic Reviews, and the Cumulative Index to Nursing and Allied Health Literature (CINAHL) were searched for systematic reviews with an abstract, publication date within the last five years, in humans only, on key terms (laparosc* OR laparoscopy*) AND (fundoplication OR reflux* OR GORD OR GERD OR nissen OR toupet) NOT (achal* OR pediat*). Last search was performed on July 23nd and in total 54 articles were evaluated as relevant from this search. The laparoscopic Toupet fundoplication is the therapy of choice for normal-weight GERD patients qualifying for laparoscopic surgery. No better pharmaceutical, endoluminal or surgical alternatives are present to date. No firm conclusion can be stated on its cost-effectiveness. Results have to be awaited comparing the laparoscopic 180-degree anterior fundoplication with the Toupet fundoplication to be a possible better surgical alternative. Division of the short gastric vessels is not to be recommended, nor is the use of a bougie or a mesh in the vast majority of GERD patients undergoing surgery. The use of a robot is not recommended. Anti-reflux surgery is to be considered expert surgery, but there is no clear consensus what is to be called an ‘expert surgeon’. As for setting, ambulatory settings seem promising although high-level evidence is lacking.     

Management of the patient with incomplete response to PPI therapy

Proton pump inhibitors (PPIs) remove most of the acid from the gastroesophageal refluxate. However, PPIs do not eliminate reflux and the response of specific GERD symptoms to PPI therapy depends on the degree to which acid drives those symptoms. PPIs are progressively less effective for heartburn, regurgitation, chest pain and extra-oesophageal symptoms. Hence, with an incomplete PPI response, obtaining an accurate history, detailing which symptoms are ‘refractory’ and exactly what evidence exists linking these symptoms to GERD is paramount. Reflux can continue to cause symptoms despite PPI therapy because of persistent acid reflux or weakly acidic reflux. Given these possibilities, diagnostic testing (pH or pH-impedance monitoring) becomes essential. Antireflux surgery is an alternative in patients if a clear relationship is established between persistent symptoms, particularly regurgitation, and reflux. Treating visceral hypersensitivity may also benefit the subset of GERD patients whose symptoms are driven by this mechanism.     

Efficacy of endoluminal gastroplication in Japanese patients with proton pump inhibitor-resistant, non-erosive esophagitis

AIM:To evaluate the efficacy,safety,and long-term outcomes of endoluminal gastroplication(ELGP) in patients with proton pump inhibitor(PPI)-resistant,nonerosive reflux disease(NERD).METHODS:The subjects were NERD patients,diagnosed by upper endoscopy before PPI use,who had symptoms such as heartburn or reflux sensations two or more times a week even after 8 wk of full-dose PPI treatment.Prior to ELGP,while continuing full-dose PPI medication,patients' symptoms and quality of life(QOL) were assessed using the questionnaire for the diagnosis of reflux disease,the frequency scale for symptoms of gastro-esophageal reflux disease(FSSG),gastrointestinal symptoms rating scale,a 36-item short-form.In addition,24-h esophageal pH monitoring or 24-h intraesophageal pH/impedance(MII-pH) monitoring was performed.The Bard EndoCinch TM was used for ELGP,and 2 or 3 plications were made.After ELGP,all acid reducers were temporarily discontinued,and medication was resumed depending on the development and severity of symptoms.Three mo after ELGP,symptoms,QOL,pH or MII-pH monitoring,number of plications,and PPI medication were evaluated.Further,symptoms,number of plications,and PPI medication were evaluated 12 mo after ELGP to investigate long-term effects.RESULTS:The mean FSSG score decreased significantly from before ELGP to 3 and 12 mo after ELGP(19.1 ± 10.5 to 10.3 ± 7.4 and 9.3 ± 9.9,P 0.05,respectively).The total number of plications decreased gradually at 3 and 12 mo after ELGP(2.4 ± 0.8 to 1.2 ± 0.8 and 0.8 ± 1.0,P 0.05,respectively).The FSSG scores in cases with no remaining plications and in cases with one or more remaining plications were 4.4 and 2.7,respectively,after 3 mo,and 2.0 and 2.8,respectively,after 12 mo,showing no correlation to plication loss.On pH monitoring,there was no difference in the percent time pH 4 from before ELGP to 3 mo after.Impedance monitoring revealed no changes in the number of reflux episodes or the symptom index for reflux events from before ELGP to 3 mo after,but the symptom sensitivity index decreased significantly 3 mo after ELGP(16.1 ± 12.9 to 3.9 ± 8.3,P 0.01).At 3 mo after ELGP,6 patients(31.6%) had reduced their PPI medication by 50% or more,and 11 patients(57.9%) were able to discontinue PPI medication altogether.After 12 mo,3 patients(16.7%) were able to reduce the amount of PPI medication by 50% or more,and 12 patients(66.7%) were able to discontinue PPI medication altogether.A high percentage of cases with remaining plications had discontinued PPIs medication after 3 mo,but there was no difference after 12 mo.No serious complications were observed in this study.CONCLUSION:ELGP was safe,resulted in significant improvement in subjective symptoms,and allowed less medication to be used over the long term in patients with PPI-refractory NERD.     

黛力新联合质子泵抑制剂治疗胃食管反流病伴咽喉部症状

目的 观察黛力新联合质子泵抑制剂（PPI）治疗胃食管反流病（GERD）咽喉部症状的临床疗效,探讨可能的治疗机制.方法 选取2009年8月-2012年5月门诊确诊GERD,经PPI加促动力药治疗12周后仍有咽喉部症状的患者,用综合性医院焦虑抑郁量表（HADS）进行情绪评定,把其中HADS〉9分患者分为两组,有症状黛力新治疗组,以黛力新＋耐信＋莫沙比利治疗;有症状对照组,以耐信＋莫沙比利治疗;HADS〈9分为无症状黛力新治疗组,以黛力新＋耐信＋莫沙比利治疗.疗程均为4周.三组治疗前后分别作Zung抑郁自评量表和Zung焦虑自评量表评分及临床疗效评分,观察其疗效.结果 HADS≥9分者63例,黛力新治疗组32例,对照组31例;HADS〈9分者35例.有症状黛力新治疗组与无症状黛力新治疗组的疗效相比,差异无统计学意义（P〉0.05）,但高于有症状对照组,且差异有统计学意义（P〈0.05）,有症状黛力新治疗组治疗后SDS和SAS指数均明显下降（P〈0.05）.结论 黛力新联合PPI治疗伴有咽喉部症状的GERD能显著改善患者精神和躯体两方面的症状.     

Gender difference in gastro-esophageal reflux diseases

The incidence of esophageal adenocarcinoma(EAC) has risen sharply in western countries over the past 4 decades. This type of cancer is considered to follow a transitional process that goes from gastro-esophageal reflux disease(GERD) to Barrett's esophagus(BE,a metaplastic condition of the distal esophagus), a precursor lesion and ultimately adenocarcinoma. This spectrum of GERD is strongly predominant in males due to an unidentified mechanism. Several epidemiologic studies have des cribed that the prevalence of GERD, BE and EAC in women is closely related to reproductive status, which suggests a possible association with the estrogen level. Recently, we revealed in an in vivo study that the inactivation of mast cells by the anti-inflammatory function of estrogen may account for the gender difference in the GERD spectrum. Other studies have described the contribution of female steroid hormones to the gender difference in these diseases. Estrogen is reported to modulate the metabolism of fat, and obesity is a main risk factor of GERDs. Moreover, estrogen could confer esophageal epithelial resistance to causative refluxate. These functions of estrogen might explain the approximately 20-year delay in the incidence of BE and the subsequent development of EAC in women compared to men, and this effect may be responsible for the male predominance. However, some observational studies demonstrated that hormone replacement therapy exerts controversial effects in GERD patients. Nevertheless, the estrogen-related endocrine milieu may prevent disease progression toward carcinogenesis in GERD patients. The development of innovative alternatives to conventional acid suppressors may become possible by clarifying the mechanisms of estrogen.     

Treatment of uncomplicated reflux disease

Uncomplicated reflux disease comprises the non-erosive reflux disease (NERD) and erosive reflux disease (ERD). The objectives of treatment are the adequate control of symptoms with restoration of quality of life, healing of lesions and prevention of relapse. Treatment of NERD consists in the administration of proton pump inhibitors (PPI) for 2-4 wk, although patients with NERD show an overall poorer response to PPI treatment than patients with ERD owing to the fact that patients with NERD do not form a pathophysiologically homogenous group. For long-term management on-demand treatment with a PPI is probably the best option. In patients with ERD, therapy with a standard dose PPI for 4-8 wk is always recommended. Long-term treatment of ERD is applied either intermittently or as continuous maintenance treatment with an attempt to reduce the daily dosage of the PPI (step-down principle). In selected patients requiring long-term PPI treatment, antireflux surgery is an alternative option. In patients with troublesome reflux symptoms and without alarming features empirical PPI therapy is another option for initial management. Therapy should be withdrawn after initial success. In the case of relapse, the long-term care depends on a careful risk assessment and the response to PPI therapy.     

Outcome of nonerosive gastro-esophageal reflux disease patients with pathological acid exposure

AIM: To assess the management and outcome of nonerosive gastro-esophageal reflux disease (NERD) patients who were identified retrospectively, after a 5-year follow-up.METHODS: We included patients with gastro-esophageal reflux disease (GERD) symptoms who had a negative endoscopy result and pathological 24-h esophageal pH-monitoring while off therapy. We interviewed them after an average period of 5 years (range 3.5-7 years) by means of a structured questionnaire to assess presence of GERD symptoms, related therapy, updated endoscopic data and other features. We assessed predictors of esophagitis development by means of univariate and multivariate statistical analysis.RESULTS: 260 patients (137 women) were included. Predominant GERD symptoms were heartburn and regurgitation in 103/260 (40%). 70% received a maintenance treatment, which was proton pump inhibitor (PPI) in 55% of cases. An average number of 1.5 symptomatic relapses per patient/year of followup were observed. A progression to erosive gastroesophageal reflux disease (ERD) was found in 58/193 (30.0%) of patients undergoing repeat endoscopy;72% of these were Los Angeles grade A-B.CONCLUSION: This study shows that progression to ERD occurs in about 5% of NERD cases per year,despite therapy. Only two factors consistently and independently influence progression: smoking and absence of PPI therapy.     

Risk factors for proton pump inhibitor refractoriness in Chinese patients with non-erosive reflux disease

AIM:To analyze risk factors for refractoriness to proton pump inhibitors(PPIs) in patients with non-erosive reflux disease(NERD).METHODS:A total of 256 NERD patients treated with the PPI esomeprazole were enrolled.They were classified into symptom-free and residual symptoms groups according to Quality of Life in Reflux and Dyspepsia(QolRad) scale.All subjects completed questionnaires on psychological status(self-rating anxiety scale;selfrating depression scale) and quality of life scale(Short Form 36).Multivariate analysis was used to determine the predictive factors for PPI responses.RESULTS:According to QolRad,97 patients were confirmed to have residual reflux symptoms,and the remaining 159 patients were considered symptom free.There were no significant differences between the two groups in lifestyle factors(smoking and alcohol consumption),age,Helicobacter pylori infection,and hiatal hernia.There were significant differences between the two groups in relation to sex,psychological distress including anxiety and depression,body mass index(BMI),and irritable bowel syndrome(IBS)(P < 0.05).Logistic regression analysis found that BMI < 23,comorbid IBS,anxiety,and depression were major risk factors for PPI resistance.Symptomatic patients had a lower quality of life compared with symptom-free patients.CONCLUSION:Some NERD patients are refractory to PPIs and have lower quality of life.Residual symptoms are associated with psychological distress,intestinal disorders,and low BMI.     

间质性肺疾病与胃食管反流

胃食管反流可以引起慢性咳嗽和哮喘,除此之外胃食管反流和一些间质性肺疾病,如特发性肺纤维化、闭塞性细支气管炎伴机化性肺炎、结缔组织疾病中的系统性硬化相关性肺疾病等也存在比较明显的关系,胃食管反流在上述疾病中高发.虽然胃内容物造成的肺组织损伤在动物实验中已得到证实,但是胃食管反流与间质性肺疾病的明确关系还需要更深入的研究和实验来阐明.本文主要综述近年来关于胃食管反流与间质性肺疾病关系的研究进展.     

Washed microbiota transplantation reduces proton pump inhibitor dependency in nonerosive reflux disease

BACKGROUND The pathogenesis of gastroesophageal reflux disease(GERD)is closely associated with the intestinal bacteria composition and their metabolites.AIM To investigate whether washed microbiota transplantation(WMT)improves symptoms of nonerosive reflux disease(NERD)with proton pump inhibitor(PPI)dependency.METHODS Patients with recurrent NERD and PPI dependency at the First Affiliated Hospital of Guangdong Pharmaceutical University from 2017 to 2018 were included and divided into a WMT or PPI group treated with PPI with/without WMT.The endpoint was NERD symptom frequency evaluated 1 mo after WMT using reflux disease questionnaire(RDQ)and GERD questionnaire(GERDQ)scores,remission time,PPI dose,and the examination of intestinal mucosal barrier function.RESULTS In the WMT(n=15)and PPI(n=12)groups,the total remission rate at 1 mo after treatment was 93.3%vs 41.7%.Compared with the PPI group,the WMT group showed better results in GERDQ(P=0.004)and RDQ(P=0.003)and in remission months(8 vs 2,P=0.002).The PPI dose was reduced to some extent for 80%of patients in the WMT group and 33.3%in the PPI group.In 24 patients,intestinal mucosal barrier function was examined before treatment,and changes in the degree of damage were observed in 13 of these patients after treatment.Only one of the 15 patients had minor side effects,including a mushy stool two or three times a day,which resolved on their own after 1 wk.CONCLUSION This study is the first to demonstrate that WMT may be safe and effective for relieving NERD symptoms and reducing PPI dependency and recurrence.     

Comparative clinical trial of S-pantoprazole versus racemic pantoprazole in the treatment of gastro-esophageal reflux disease

INTRODUCTION The primary treatment goals in patients with gastroesophageal reflux disease (GERD) are relief of symptoms, prevention of symptom relapse, healing of erosive esophagitis, and prevention of complications of esophagitis[1]. Proton pump inhibito…     

Proton pump inhibitor step-down therapy for GERD: a multi-center study in Japan

AIM:To investigate the predictors of success in stepdown of proton pump inhibitor and to assess the quality of life(QOL).METHODS:Patients who had heartburn twice a week or more were treated with 20 mg omeprazole(OPZ) once daily for 8 wk as an initial therapy(study 1).Patients whose heartburn decreased to once a week or less at the end of the initial therapy were enrolled in study 2 and treated with 10 mg OPZ as maintenance therapy for an additional 6 mo(study 2).QOL was in-vestigated using the gastrointesti...