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.     

Multimodality evaluation of patients with gastroesophageal reflux disease symptoms who have failed empiric proton pump inhibitor therapy

Patients with symptoms suggestive of gastroesophageal reflux disease (GERD), such as chest pain, heartburn, regurgitation, and dysphagia, are typically treated initially with a course of proton pump inhibitors (PPIs). The evaluation of patients who have either not responded at all or partially and inadequately responded to such therapy requires a more detailed history and may involve an endoscopy and esophageal biopsies, followed by esophageal manometry, ambulatory esophageal pH monitoring, and gastric emptying scanning. To assess the merits of a multimodality ‘structural’ and ‘functional’ assessment of the esophagus in patients who have inadequately controlled GERD symptoms despite using empiric PPI, a retrospective cohort study of patients without any response or with poor symptomatic control to empiric PPI (>2 months duration) who were referred to an Esophageal Studies Unit was conducted. Patients were studied using symptom questionnaires, endoscopy (+ or – for erosive disease, or Barrett's metaplasia) and multilevel esophageal biopsies (eosinophilia, metaplasia), esophageal motility (aperistalsis, dysmotility), 24‐hour ambulatory esophageal pH monitoring (+ if % total time pH < 4 > 5%), and gastric emptying scanning (+ if >10% retention at 4 hours and >70% at 2 hours). Over 3 years, 275 patients (147 men and 128 women) aged 16–89 years underwent complete multimodality testing. Forty percent (n= 109) had nonerosive reflux disease (esophagogastroduodenoscopy [EGD]–, biopsy–, pH+); 19.3% (n= 53) had erosive esophagitis (EGD+); 5.5% (n= 15) Barrett's esophagus (EGD+, metaplasia+); 5.5% (n= 15) eosinophilic esophagitis (biopsy+); 2.5% (n= 7) had achalasia and 5.8% (n= 16) other dysmotility (motility+, pH–); 16% (n= 44) had functional heartburn (EGD–, pH–), and 5.8% (n= 16) had gastroparesis (gastric scan+). Cumulative symptom scores for chest pain, heartburn, regurgitation, and dysphagia were similar among the groups (mean range 1.1–1.35 on a 0–3 scale). Multimodality evaluation changed the diagnosis of GERD in 34.5% of cases and led to or guided alternative therapies in 42%. Overlap diagnoses were frequent: 10/15 (67%) of patients with eosinophilic esophagitis, 12/16 (75%) of patients with gastroparesis, and 11/23 (48%) of patients with achalasia or dysmotility had concomitant pathologic acid reflux by pH studies. Patients with persistent GERD symptoms despite empiric PPI therapy benefit from multimodality evaluation that may change the diagnosis and guide therapy in more than one third of such cases. Because symptoms are not specific and overlap diagnoses are frequent and multifaceted, objective evidence‐driven therapies should be considered in such patients.     

Use of proton pump inhibitor as a diagnostic test in NCCP

Abstract:   Non-cardiac chest pain (NCCP) is the most common extra-esophageal manifestation of gastroesophageal reflux disease. The proton pump inhibitor empirical trial (PPI test) is a simple non-invasive, arcurate and cast-saving test for evaluating patients with GERD-related NCCP. The review will discuss the use of the PPI test as a diagnostic test for NCCP.     

Belching during gastroscopy and its association with gastroesophageal reflux disease

Belching may result from transient lower esophageal sphincter relaxation; therefore, it has been proposed that belching may be a manifestation of gastroesophageal reflux disease (GERD). This study was conducted to investigate the frequency of belching during esophagogastroduodenoscopy (EGD) and its association with GERD. A retrospective review was performed on prospectively collected clinical and endoscopic data from 404 subjects who underwent EGD without sedation from December 2012 to May 2013 in a training hospital in Korea. All detectable belching events during endoscopy were counted. Frequency and severity of belching events were compared between the group with and without GERD using an ordinal logistic regression model. There were 145 GERD patients (26 erosive reflux disease and 119 nonerosive reflux disease [NERD]). In the multivariable analysis, GERD was significantly associated with a higher frequency of belching events (odds ratio = 6.59, P < 0.001). Central obesity, female, and younger age were also risk factors for frequent belching during EGD. Subgroup analyses were performed in subjects without erosive reflux disease (n = 378) and NERD (n = 293). NERD was also a predictive factor for frequent belching during EGD (odds ratio = 6.61, P < 0.001), and the frequency of belching was significantly correlated with GERD severity according to the Los Angeles classification (P < 0.05). Frequent belching during EGD was associated with GERD, including NERD. Future research should focus on its adjuvant role in the diagnosis of GERD/NERD and the necessity for applying differentiated endoscopy strategies for GERD patients, leading to less discomfort during EGD in patients at risk for intolerability.     

Short-term treatment of gastroesophageal reflux disease

OBJECTIVE: To investigate the efficacy of acid suppressant drugs in the empirical treatment of gastroesophageal reflux disease (GERD) and in the treatment of endoscopy-negative reflux disease (ENRD). DESIGN: medline, embase, and the Cochrane Controlled Trials Register were searched. Bibliographies were reviewed. SETTING: Studies were eligible that compared the short-term use of proton pump inhibitors (PPIs) and histamine-2 receptor antagonists (H2RAs) with each other or with placebo in adults with GERD who were enrolled irrespective of endoscopic findings (empirical cases) or in whom endoscopy showed no signs of esophagitis (endoscopy-negative cases). MEASUREMENTS: Of 1,408 studies, only 13 could be included for meta-analysis. Data on 3,433 patients empirically treated for GERD and 2,520 patients treated for ENRD were extracted. The primary endpoint was relief of heartburn. MAIN RESULTS: In the empirical treatment of GERD, the summary relative risk (sRR) for symptom relief from H2RAs versus placebo was 0.77 (95% confidence interval [95% CI], 0.60 to 0.99). RR in the only placebo-controlled PPI trial was 0.35 (95% CI, 0.26 to 0.46). The sRR for standard dose PPIs versus H2RAs was 0.55 (95% CI, 0.44 to 0.68). In treatment of ENRD, both PPIs (sRR, 0.64; 95% CI, 0.52 to 0.79) and H2RAs (sRR, 0.78; 95% CI, 0.62 to 0.97) were superior to placebo, and PPIs were superior to H2RAs (sRR, 0.81; 95% CI, 0.70 to 0.95). CONCLUSIONS: Acid suppressant therapy (with a PPI or an H2RA) is more effective than placebo for short-term relief of heartburn in patients with persistent symptoms who are treated empirically for GERD and in those in whom esophagitis was excluded after endoscopy. The benefit of PPIs compared with H2RAs is more pronounced in patients treated empirically.     

Systematic review: questionnaires for assessment of gastroesophageal reflux disease

Numerous questionnaires with a wide variety of characteristics have been developed for the assessment of gastroesophageal reflux disease (GERD). Four well‐defined dimensions are noticeable in these GERD questionnaires, which are symptoms, response to treatment, diagnosis, and burden on the quality of life of GERD patients. The aim of this review is to develop a complete overview of all available questionnaires, categorized per dimension of the assessment of GERD. A systematic search of the literature up to January 2013 using the Pubmed database and the Embase database, and search of references and conference abstract books were conducted. A total number of 65 questionnaires were extracted and evaluated. Thirty‐nine questionnaires were found applicable for the assessment of GERD symptoms, three of which are generic gastrointestinal questionnaires. For the assessment of response to treatment, 14 questionnaires were considered applicable. Seven questionnaires with diagnostic purposes were found. In the assessment of quality of life in GERD patients, 18 questionnaires were found and evaluated. Twenty questionnaires were found to be used for more than one assessment dimension, and eight questionnaires were found for GERD assessment in infants and/or children. A wide variety of GERD questionnaires is available, of which the majority is used for assessment of GERD symptoms. Questionnaires differ in aspects such as design, validation and translations. Also, numerous multidimensional questionnaires are available, of which the Reflux Disease Questionnaire is widely applicable. We provided an overview of GERD questionnaires to aid investigators and clinicians in their search for the most appropriate questionnaire for their specific purposes.     

Histamine-2 receptor antagonists at night improve gastroesophageal reflux disease symptoms for patients on proton pump inhibitor therapy

While night-time symptoms of gastroesophageal reflux disease (GERD) are common, considerable controversy exists regarding the use of histamine-2 receptor antagonists (H2Ras) for night-time reflux control. Some studies have suggested possible tolerance to H2RA while others have suggested that long-term efficacy of gastric acid control can be maintained with night-time H2RA use. The aim of this study was to identify if GERD patients have sustained symptom improvement with long-term use of night-time H2RA. Records of 56 consecutive GERD patients on twice daily proton pump inhibitor (PPI) and night-time H2RA therapy were reviewed. During a phone interview patients were asked a 5-item questionnaire, which included overall assessment of symptoms, night-time symptoms, sleep disturbance, duration and frequency of therapy. Of the 56 patients, 39 (31 women, mean age 56) completed the questionnaire (15 were not reached and 2 did not recall enough information). All respondents had taken night-time H2RA for at least 1 month (28/39 patients with > 6 months duration) with 33/39 patients taking H2RAs every night. The addition of H2RA led to an improvement in overall symptoms in 28/39 (72%) patients, improvement in night-time reflux symptoms in 25/34 (74%) patients and improvement of GERD-associated sleep disturbance in 18/27 (67%) patients. Five (13%) patients had stopped the H2RA on their own, stating that its efficacy waned after 1 month. Our results suggest that the majority of patients report persistent improvement in GERD symptoms from night-time H2RA use and that possible clinically important tolerance to H2RAs occurs in a small number of patients. Further prospective, placebo-controlled studies may help confirm that there is a role for night-time H2RAs in GERD symptom control.     

Mortality associated with gastroesophageal reflux disease and its non-malignant complications: a systematic review

Objective. The mortality associated with malignant complications of gastroesophageal reflux disease (GERD) is well recognized. The aim of this systematic review was to assess the less well-examined mortality associated with GERD and its non-malignant complications, including esophageal erosions, ulcers, bleeding, perforation and strictures. Material and methods. Studies reporting mortality in GERD and its non-malignant complications were identified via systematic PubMed searches, and previously unpublished population mortality statistics from public access databases. Results. Three countries were examined (USA, UK, Finland). Cohort studies (n=3) in the UK showed a 1.16- to 1.6-fold increase in risk of death in individuals with GERD compared with the general population, the majority of deaths being due to cardiac disease. Population data indicate that GERD and its likely esophageal complications were the cause of death in 685 and 521 cases, respectively, in the USA (year: 2003) (age-adjusted mortality: 2.3/million and 1.8/million, respectively), and in 36 and 349 cases, respectively, in England and Wales (2004) (0.6/million and 5.4/million, respectively). In Finland (2000), GERD-related mortality was 4.6/million. Mortality from GERD and its likely esophageal complications increased with age, and was between 1.2-fold and 1.8-fold higher in men than in women. Cohort studies in the USA are inconsistent on mortality risk associated with surgical therapy. Time-trend data suggest that mortality from GERD and its non-malignant complications has been increasing. Conclusions. Data from Europe and the USA show that GERD and its non-malignant complications can on rare occasions cause death.     

Frequency scale for symptoms of gastroesophageal reflux disease predicts the need for addition of prokinetics to proton pump inhibitor therapy

Background and Aim: Proton pump inhibitor (PPI) monotherapy cannot cure all cases of gastroesophageal reflux disease (GERD), and combination therapy with prokinetics and PPI achieves symptomatic improvement for some GERD patients. Few studies have been performed to predict the need for prokinetics. Methods: Subjects were 163 patients (64 male, mean age 53.1 ± 16.6 years) with GERD symptoms. They were evaluated using the frequency scale for the symptoms of GERD (FSSG), a GERD‐specific questionnaire developed in Japan 1 and endoscopy. They were administered with rabeprazole 10 mg daily. At 12 and 24 weeks of treatment, subjects were offered a choice of four treatment regimens according to their degree of satisfaction (1, no need for further treatment; 2, opt for continued PPI treatment; 3, step‐down to H2RA; 4, dissatisfied with present treatment, so opt for combination treatment with prokinetics, mosapride 5 mg tid). Results: The choice of treatment after 12 weeks of treatment placed 79.1% of subjects in the satisfied group (1, 21; 2, 98; 3, 10). After 24 weeks, 98.2% of subjects were in the satisfied group. Pretreatment FSSG scores were significantly higher in the dissatisfied group (4, 17.4 ± 1.4) than in the satisfied group (1, 12.3 ± 1.3; 2, 12.8 ± 0.8; 3, 10.2 ± 1.8) (P < 0.05). Conclusions: The satisfaction rate with these treatment regimens was 98.2% at 24 weeks, suggesting that combination therapy with prokinetics was effective for patients dissatisfied with PPI monotherapy. The FSSG is a useful predictor of the necessity for combination therapy.     

Characteristics of non-erosive gastroesophageal reflux disease refractory to proton pump inhibitor therapy

AIM:To investigate whether potent acid inhibition is effective in non-erosive reflux disease (NERD) refractory to standard rabeprazole (RPZ) treatment. METHODS:We treated 10 Japanese patients with NERD resistant to standard dosages of RPZ:10 mg or 20 mg od,20 mg bid,or 10 mg qid for 14 d. All patients completed a frequency scale for symptoms of gastroesophageal reflux disease questionnaire frequency scale for the symptoms of GERD (FSSG); and underwent 24 h pH monitoring on day 14. RESULTS:With increased dos...     

Gastroesophageal reflux disease is a progressive disease

It is controversial whether gastrooesophageal reflux disease represents a spectrum disease from a nonerosive to a complicated one, or whether it is a categorial disease, i.e. it can be divided into three categories, such as nonerosive gastrooesophageal reflux disease, erosive gastrooesophageal reflux disease and Barrett's esophagus (BE) with little or no transition from one category to the other. This controversy might be of general interest, because it has some implications in the management of the patient. However, literature data concerning the natural history of gastrooesophageal reflux disease are very limited, and in particular very few papers have dealt with the issue of describing the natural history of patients with nonerosive gastrooesophageal reflux disease. Aim of the present review is to reassess these scanty data, and to try to demonstrate that progression from milder to more severe forms of gastrooesophageal reflux disease is possible and documented.     

Voluntary and controlled weight loss can reduce symptoms and proton pump inhibitor use and dosage in patients with gastroesophageal reflux disease: a comparative study

A wide variety of pieces of evidence has suggested that obesity is associated with a significant increase in the risk for gastroesophageal reflux disease (GERD) symptoms and its complications. The aim of this study was to evaluate the effect of weight loss on reflux symptoms in overweight/obese patients with proven GERD. We enrolled overweight/obese patients with typical GERD symptoms and erosive esophagitis. At baseline, patients underwent detailed reflux symptoms evaluation and anthropometric assessment, and were divided into two treatment groups: group A received proton pump inhibitor (PPI) and a personalized hypocaloric diet and aerobic exercise; and group B received PPI and a ‘standard of care diet’. The dietetic treatment was considered effective if at least 10% of weight loss was achieved within 6 months. All patients were evaluated in terms of anthropometric data, GERD symptoms, and PPI use. In group A, mean body mass index (BMI) decreased from 30.3 ± 4.1 to 25.7 ± 3.1 (P < 0.05), and mean weight decreased from 82.1 ± 16.9 kg to 69.9 ± 14.4 kg (P < 0.05). In group B, there was no change in BMI and weight. Symptom perception decreased (P < 0.05) in both groups during PPI therapy, but a higher improvement was recorded in group A. In group A, PPI therapy was completely discontinued in 27/50 of the patients, and halved in 16/50. Only 7/50 continued the same PPI dosage. In group B, 22/51 halved the therapy and 29/51 maintained full dosage of therapy, but none was able to discontinue PPI due to a symptom recurrence. Overall, weight loss of at least 10% is recommended in all patients with GERD in order to boost the effect of PPI on reflux symptom relief and to reduce chronic medication use.     

Risk factors for functional dyspepsia,erosive and non-erosive gastroesophageal reflux disease: A cross-sectional study

BackgroundConflicting data exists regarding risk factors associated with Gastroesophageal Reflux Disease (GERD) and Functional Dyspepsia (FD). Few studies examine anxiety/depression in relation to GERD phenotypes (Esophagitis/EE, and Non-Erosive Reflux Disease/NERD), FD, and Rome-IV syndromes. Our aim was to evaluate the association between epidemiological factors and comorbidities with GERD phenotypes, FD, and Rome-IV syndromes, as well as their relationship with anxiety/depression.Methods338 subjects were selected from 357 patients referred to three tertiary-centers for endoscopic evaluation. Every subject was interviewed individually to administer three validated questionnaires: GERD-Q, Rome-IV and HADS.Results45/338 patients were controls, 198/58.6% classified as GERD, 81/24.0% EE (49/14.5% symptomatic, and 32/9.5% asymptomatic), 117/34.6% NERD, 176/52.1% FD (43/12.7% epigastric pain syndrome, 36/10.7% postprandial distress syndrome, and 97/28.7% overlapping syndrome). 81 patients were mixed GERD-FD. Multivariate analysis found significant independent associations: age in NERD and FD; sex in EE, asymptomatic EE and FD; body mass index in NERD and FD; alcohol in EE; anxiety/depression in FD; use of calcium channel antagonists in EE; and inhalers in FD. We compared controls vs different groups/subgroups finding significantly more anxiety in NERD, FD, all Rome-IV syndromes, and mixed GERD-FD; more depression in FD, overlapping syndrome, and mixed GERD-FD; and higher levels of anxiety+depression in NERD, FD, overlapping syndrome, and mixed GERD-FD.ConclusionsNERD and FD share demographic and psychopathological risk factors which suggests that they may form part of the same pathophysiological spectrum. Regarding NERD anxiety was predominant, and in FD anxiety + depression, suggesting that both processes may require complementary psychological therapy.     

消化内科门诊胃食管反流病诊断问卷诊断胃食管反流病的状况及症状特征分析

目的利用胃食管反流病诊断问卷（Reflux disease questionnaire,RDQ）分析消化专家门诊胃食管反流病（GERD）患病情况及患者症状特征。方法对就诊于我院消化专家门诊的1636例患者进行RDQ问卷调查,得分≥12分者诊断为GERD。根据RDQ内容对GERD患者症状特点进行分析。结果1636例消化专家门诊的患者中,GERD的发生率为10．8％。男女发病无差异（11．0％VS10．5％,P〉0．05）。60岁以上年龄组GERD的患病率最高（14．6％）,而15～30岁年龄组患病率最低（7．7％）。各年龄组内患病率性别间比较差异无显著性。GERD症状中,烧心与反酸为最常见的症状。症状频率积分比严重程度积分更重要（P〈0．05）。结论消化门诊就诊患者GERD患病率较高。GERD患病无性别差异。老年人的GERD患病率高于其他年龄组。烧心和反酸为GERD最常见的症状。症状发生频率比严重程度对GERD的诊断更有意义。     

Relevance of sleep disturbance to the integrity and characteristics of secondary peristalsis in patients with gastroesophageal reflux disease

Objective: Sleep disturbance is common in patients with gastroesophageal reflux disease (GERD). Secondary peristalsis is important for clearance of the refluxate from the esophagus. We aimed to test the hypothesis whether secondary peristalsis is impaired in GERD patients with sleep disturbance.

Methods: Secondary peristalsis was stimulated with slow and rapid air injections into mid-esophagus in 8 age-matched health controls and 41 patients with GERD. Sleep disturbance was assessed by the Pittsburg Sleep Quality Index (PSQI). Objective sleep measures were assessed by ambulatory actigraphy.

Results: The threshold volume for inducing secondary peristalsis during slow air injection was significantly higher in GERD patients with sleep disturbance than healthy controls (14.3?±?1.2 vs. 8.9?±?0.5?mL, p?<?.05). GERD patients with sleep disturbance had higher threshold volume of secondary peristalsis during rapid air injection than GERD patients without sleep disturbance (5.1?±?0.4 vs. 3.9?±?0.2?mL, p?<?.05) and healthy controls (5.1?±?0.4 vs. 3.6?±?0.2?mL, p?<?.05). There was a negative correlation between PSQI score and peristaltic frequency during rapid air injection (r?=??.39, p?=?.01). Secondary peristaltic amplitude during rapid air injection was negatively correlated with wake after sleep onset (r?=??.34, p?=?.04).

Conclusions: Sleep disturbance is associated with secondary peristaltic response to distension-induced esophageal stimulation in patients with GERD. Our study suggests that sleep disturbance per se may adversely influence the effectiveness of esophageal peristalsis and bolus clearance during sleep in patients with GERD.     

Endoscopic grading of gastroesophageal flap valve helps predict proton pump inhibitor response in patients with gastroesophageal reflux disease

Abstract

Objective. Limited information is available on predictors of the response to proton pump inhibitor (PPI) treatment in patients with gastroesophageal reflux disease (GERD). Endoscopic grading of gastroesophageal flap valve (GEFV) is simple and reproducible, and can provide useful information on patients with suspected reflux undergoing an endoscopy. The aim of this study was to prospectively identify predictors, including endoscopic findings such as GEFV, for PPI treatment outcomes in patients with GERD. Material and methods. One hundred and fifty consecutive patients with GERD were enrolled. All patients were treated with pantoprazole 40 mg daily for 8 weeks. Treatment response was defined as greater than 50% reduction in symptom scores between the two symptom assessments (i.e., over 4 or 8 weeks). Univariate and multivariate logistic regression analyses between responders and non-responders were performed to identify variables predicting response to pantoprazole treatment. Results. Of the 150 consecutive patients considered for this study, 31 were excluded based on exclusion criteria and/or refusal to participate, leaving 119 eligible patients. After 4-week pantoprazole treatment, 70 of 119 (58.8%) patients were classified as responders. Patients with obesity and Helicobacter pylori infection demonstrated a higher response rate to 4-week pantoprazole treatment (odds ratio (OR) 5.28, p = 0.008; OR 3.76, p = 0.023, respectively). Patients with abnormal GEFV showed a lower response rate to 4-week treatment (OR 0.17, p = 0.016). After 8-week treatment, 86 of 119 (72.3%) patients were classified as responders. Abnormal GEFV and aspirin intake were associated with a lower response rate to 8-week treatment (OR 0.17, p = 0.021; OR 0.11, p = 0.020, respectively). Conclusions. Abnormal GEFV was a significant independent factor predicting poor response to both 4-week and 8-week pantoprazole treatment. Endoscopic grading of GEFV provides useful information for predicting the response to PPI treatment in patients with GERD.