Report of the Asia-Pacific consensus on the management of gastroesophageal reflux disease

This report summarizes the conclusions and recommendations of a panel of gastroenterologists practising in the Asia-Pacific region. The group recognized that although gastroesophageal reflux disease (GERD) is less common and milder in endoscopic severity in Asia than in the West, there is nevertheless data to suggest an increasing frequency of the disease. During a 2-day workshop, the evidence for key issues in the diagnosis and clinical strategies for the management of the disease was evaluated, following which the recommendations were made and debated. The consensus report was presented at the Asia-Pacific Digestive Week 2003 in Singapore for ratification. Upper gastrointestinal (GI) endoscopy is the gold standard for the diagnosis of erosive GERD. There is no gold standard for the diagnosis of non-erosive GERD (NERD). Diagnosis therefore relies on symptoms, a positive 24-h pH study or a response to a course of proton pump inhibitor (PPI) treatment. The goals of treatment for GERD are to heal esophagitis, relieve symptoms, maintain the patient free of symptoms, improve quality of life and prevent complications. The PPI are the most effective medical treatment. Following initial treatment, on-demand therapy may be effective in some patients with NERD or mild (GI) erosive esophagitis. Anti-reflux surgery by a competent surgeon could achieve a similar outcome, although there is an operative mortality of 0.1-0.8%. The decision is dependent on the patient's preference and the availability of surgical expertise. Currently, endoscopic treatment should be performed only in the context of a clinical trial. Treatment of patients with typical GERD symptoms without alarm features in primary care could begin with PPI for 2 weeks followed by a further 4 weeks before going to on-demand therapy.     

胃食管反流病抑酸疗效预测因素研究进展

质子泵抑制剂(PPI)是胃食管反流病(GERD)治疗首选药物,但调查显示48%～63%的患者抑酸治疗后仍有症状[1],且长期使用会出现诸多副反应。因此,预测哪些患者抑酸治疗有效,对于指导临床治疗、节省花费及减少药物副反应是非常必要的。     

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.     

A novel endoscopic submucosal dissection technique for proton pump inhibitor-refractory gastroesophageal reflux disease

Abstract

Objectives: Although drug treatment is the usual first-line therapy for gastroesophageal reflux disease (GERD), not all patients receive satisfactory relief from drug therapy, alone. We developed an endoscopic fundoplication technique using endoscopic submucosal dissection (ESD); the technique is referred to as ESD for GERD (ESD-G). This study investigated the safety and efficacy of this novel technique in patients with drug-refractory GERD. Patients and methods: ESD-G narrows the hiatal opening through ESD of the esophagogastric junction (EGJ) mucosa. For safety reasons, the range of mucosal resection was limited to half (1/2 or 1/4 +1/4) of the circumference of the EGJ lumen. ESD-G was performed on 13 patients with proton pump inhibitor (PPI)-refractory GERD. GERD symptoms, PPI dose, and 24-h esophageal pH monitoring results were compared before and 6 months after the procedure. Results. In 12 cases, symptoms significantly improved after ESD-G. Five patients demonstrated improved esophagitis, three were able to discontinue PPI therapy, and three were able to reduce their PPI dosage following surgery. The esophageal pH <4 holding time ratio was also decreased after ESD-G. Conclusions. ESD-G may be useful for PPI-refractory GERD patients.     

Management strategies for gastroesophageal reflux disease

Abstract   In the treatment of gastroesophageal reflux disease (GERD), the most effective treatment option is the use of proton pump inhibitor (PPI), which minimizes the effect of gastric acid on the distal esophagus. Both the step-up and step-down treatment strategies have advantages and disadvantages. Most physicians would like to choose the step-down therapy rather than the step-up therapy. The 'No-step' PPI therapy (i.e. continuous PPI therapy) is another relevant option. After an initial remission, long-term PPI therapy is an appropriate form of maintenance therapy in many patients.
As a treatment plan for non-erosive reflux disease, a standard dose of PPI for 4–8 weeks followed by either the step-down strategy or the on-demand treatment strategy is acceptable. When treating erosive esophagitis, PPI is better than H₂ receptor blockers in healing mucosal breaks and relieving symptoms. Long-term maintenance PPI therapy is reported to be very effective in maintaining the remission of reflux esophagitis for up to 5 years. On-demand PPI is also another good option for a maintenance therapy in erosive esophagitis. In Barrett's esophagus, symptoms seem to be well-controlled with PPIs. Unfortunately, however, PPIs have no effect on the shortening of Barrett's esophagus or in preventing the progression to dysplasia and adenocarcinoma.
In summary, after reviewing existing guidelines a rather simple guideline on the management of GERD is suggested – PPI should be given for 4–8 weeks followed by either on-demand or maintenance PPI therapy according to the clinical severity.     

难治性胃食管反流病的诊疗策略

胃食管反流病（GERD）是临床常见疾病,约30%~50%的患者症状在质子泵抑制剂（PPI）治疗后不能得到完全缓 解,其中难治性GERD占较大比例。pH阻抗监测、高分辨率食管测压、内镜及活检等有助于分析导致难治性GERD 发生的原因。其中,pH阻抗对分析导致难治性GERD成因非常重要。反流后吞咽诱发蠕动波指数（PSPWI）和夜间平 均基线阻抗（MNBI）这两个新指标有助于提高诊断率。难治性GERD的治疗手段包括更换PPI种类、加用H2受体阻 滞剂、辅以促动力药物、外科手术、内镜下治疗等。个体化治疗策略的制定有赖于难治性GERD的具体成因。     

Comparison of efficacy of pantoprazole alone versus pantoprazole plus mosapride in therapy of gastroesophageal reflux disease: a randomized trial

The present study aimed to compare the efficacy for the therapy of GERD of pantoprazole alone with a combination of pantoprazole and mosapride. The study was a prospective, randomized trial involving 68 patients suffering heartburn and/or regurgitation at least twice a week for 6 weeks. Sixty-one patients consented to be randomized to receive either pantoprazole 40 mg b.i.d. (n = 33, group A) or pantoprazole 40 mg b.i.d. plus mosapride 5 mg t.d.s. (n = 28, group B) for 8 weeks. Twenty-four-hour esophageal pH-metry and endoscopy were conducted at recruitment and endoscopy was repeated at 8 weeks in all the patients studied. There were no differences in symptomatic responses to therapy between the groups (69.7% vs 89.2%; P = 0.11). The mean symptom score after 8 weeks was significantly lower in group B (3.78 +/- 3.62 vs 1.67 +/- 2.09; P = 0.009). Nonerosive esophagitis was present in 29 patients. In patients with nonerosive GERD there was no significant difference in symptomatic response to either regimen (17/20 in group A and 7/9 in group B responded; P = 0.63). In erosive esophagitis, symptomatic responses occurred more frequently in group B, 18/19 (94.7%), than in group A, 6/13 (46.2%; P = 0.003). However endoscopic healing of esophagitis occurred equally with either regimen (6/11, 54.5% in group A; 12/17, 70.5% in group B; P = 0.44). In nonerosive GERD, the addition of mosapride offers no benefit over pantoprazole alone. A combination of pantoprazole and mosapride is more effective than pantoprazole alone in providing symptomatic relief to patients with erosive GERD.     

Stratification and symptom characteristics of non-erosive reflux disease based on acid and duodenogastroesophageal reflux

Background and Aim: The subgroups and symptom characteristics of non‐erosive reflux disease (NERD) based on acid and duodenogastroesophageal reflux may be different in Chinese patients to Western patients. This study aimed to explore the stratification and symptom characteristics of patients with NERD. Methods: Patients with typical heartburn and/or acid regurgitation symptoms were enrolled. Each patient filled out a questionnaire. An upper gastrointestingal endoscopy was performed for each patient followed by simultaneous ambulatory 24‐h esophageal pH and Bilitec (bilirubin) monitoring. A symptom index (SI) of ≥50% was considered to be positive. Results: Eighty‐two consecutive NERD patients were evaluated. Abnormal (NERD pH+) and normal (NERD pH–) 24‐h pH tests were found in 24 (29.3%) and 58 (70.7%) patients, respectively. Among 42 NERD pH– patients who reported heartburn symptoms during monitoring, SI was positive in 19 (45.2%) patients (NE‐SI+) and negative in 23 (54.8%) patients (NE‐SI–). Pathological duodenogastroesophageal reflux (DGER) was found in 43 (52.4%) patients. No significant differences were noted regarding the prevalence of other upper gastrointestinal symptoms, except for acid regurgitation in NERD pH+ and NERD pH– groups. Additionally, no significant differences were seen in the prevalence of other symptoms, except for chest pain, in groups with pathological and normal DGER. Conclusion: The proportion of NERD patients with pathological acid reflux was somewhat lower than that reported in Western countries. The role of DGER in NERD may be important. It is difficult to differentiate whether NERD patients have pathological acid or bile reflux according to symptoms.     

Low levels of adherence with proton pump inhibitor therapy contribute to therapeutic failure in gastroesophageal reflux disease

To assess adherence to proton pump inhibitor (PPI) treatment and associated variables in patients with gastroesophageal reflux disease (GERD). Cross‐sectional and prospective comprising 240 consecutive adult patients, diagnosed with GERD for whom continuous use of standard or double dose of omeprazole had been prescribed. Patients were ranked as ne‐GERD (162: 67.5%) or e‐GERD classified according to the Los Angeles classification as A (48:20.0%), B (21:8.6%), C (1:0.5%), D (1:0.5%), and Barrett's esophagus (7:2.9%). The Morisky questionnaire was applied to assess adherence to therapy and a GERD questionnaire to assess symptoms and their impact. Adherence was correlated with demographics, cotherapies, comorbidities, treatment duration, symptoms scores, endoscopic findings, and patient awareness of their disease. 126 patients (52.5%) exhibited high level of adherence and 114 (47.5%) low level. Youngers (P= 0.002) or married (O.R. 2.41, P= 0.03 vs. widowers) patients had lower levels of adherence; symptomatic patients exhibited lower adherence (P= 0.02). All other variables studied had no influence on adherence. Patients with GERD attending a tertiary referral hospital in São Paulo exhibited a high rate of low adherence to the prescribed PPI therapy that may play a role in the therapy failure. Age <60 years, marital status and being symptomatic were risk factors for low adherence.     

Meta-analysis used to identify factors associated with the effectiveness of proton pump inhibitors against non-erosive reflux disease

Background:  A lack of published data remains on factors associated with the treatment response to proton pump inhibitors (PPI) in patients with non-erosive reflux disease (NERD).
Methods:  Studies on effectiveness of PPI in patients with NERD were identified using the MEDLINE database and manual searches of the available literature. Twenty publications that comprised a total of 22 study arms were eligible, and meta-analyses of these 22 study arms were carried out.
Results:  Overall improvement rate in patients with PPI was 68%. Univariate meta-regression analysis was used to explore the source of heterogeneity, P -value for males was 0.192, and in the presence of Helicobacter pylori ( H. pylori ) infection was 0.186, indicating that these factors are associated with treatment effectiveness. Thus, as the frequency of male and H. pylori -infected patients increased, the effectiveness of PPI against NERD improved. By multivariate meta-regression analysis, the P -value for male and H. pylori infection decreased further ( P  = 0.002 and P  = 0.003, respectively), indicating little interaction between male sex and H. pylori infection.
Conclusion:  These results suggest that H. pylori infection and patient sex may be associated with the effectiveness of PPI against patients with NERD. The reasons are still unclear, and further examinations are needed to clarify them.     

Plasma concentration of rabeprazole after 8-week administration in gastroesophageal reflux disease patients and intragastric pH elevation

Background and Aim: The plasma concentration of rabeprazole in patients treated for gastroesophageal reflux disease (GERD) has not been reported, although the concentration in healthy volunteers has been reported previously. Here, CYP2C19 genotype effects of rabeprazole on the area under the plasma concentration‐time curve (AUC) and the pH elevation were studied in GERD patients. Methods: Rabeprazole 10 mg/day was administrated for 8 weeks. AUC of rabeprazole in 18 Helicobacter pylori‐negative GERD subjects (five CYP2C19 homozygous extensive metabolizers [homEM], eight heterozygous extensive metabolizers [hetEM] and five poor metabolizers [PM]) were determined after the final medication. Intragastric pH was recorded for 24 h at baseline and after the final medication. Results: The AUC in the PM group (957 ng·h/mL) was significantly higher than those of homEM (375 ng·h/mL) and hetEM (542 ng·h/mL) groups. Median 24‐h pH curves, median 24‐h pH values and 24‐h and nocturnal pH > 4 and pH > 3 holding times did not significantly differ among these groups. Disappearance of erosive lesions was observed after the treatment in all subjects with grade A, B or C at baseline irrespective of CYP2C19 genotypes. Conclusion: The AUC of rabeprazole depended on the CYP2C19 genotypes in Japanese GERD patients; however, the intragastric pH elevation was independent of CYP2C19 genotypes, which is consistent with the CYP2C19 genotype‐independent healing efficacy of erosive lesions by rabeprazole. The present low AUC values indicated that abnormal accumulative effects on AUC did not occur during the period of the 8‐week administration of rabeprazole.     

Impact of antisecretory treatment on respiratory symptoms of gastroesophageal reflux disease in children

The effect of antisecretory treatment on extraesophageal symptoms of gastroesophageal reflux disease was evaluated. Seventy‐eight children presenting with typical and extraesophageal symptoms of gastroesophageal reflux disease underwent a multichannel intraluminal impedance and pH monitoring (MII/pH). Children with a positive MII/pH were randomly treated with proton pump inhibitors (PPIs) or histamine H₂‐receptor antagonists (H₂RAs) during 3 months. At the end of the treatment period, all patients were recalled. A second treatment period of 3 months was given to those patients who were not symptom‐free after 3 months. Thirty‐five of the forty‐one (85.4%) children with a pathologic MII/pH presented with extraesophageal symptoms and were treated with PPIs (omeprazole; n:19) or H₂RAs (ranitidine; n:16) for 12 weeks. After 3 months, 11/19 (57.9%) PPI‐treated patients had a complete resolution of symptoms; 6/8 nonresponders were treated with PPI for another 3 months and became all symptom‐free. The other two underwent a Nissen fundoplication. Only 5/16 (31.2 %) patients treated with H₂RAs had a complete resolution of symptoms after 3 months; 1/11 was treated again with H₂RAs during 3 months, and 10/11 were changed to PPIs. In 3/10, a partial resolution of symptoms was achieved, while in 7/10, a complete remission was obtained (P < 0.05). Antisecretory reflux treatment improves extraesophageal reflux symptoms. The efficacy of PPIs is superior to that of H₂RAs in these children.     

Optimal management of severe symptomatic gastroesophageal reflux disease

Gastroesophageal reflux disease (GERD) is a common disorder, and empirical proton pump inhibitor (PPI) treatment is often the first step of management; however, up to 40% of patients remain symptomatic despite PPI treatment. Refractory reflux refers to continued symptoms despite an adequate trial of PPI, and management remains challenging. The differential diagnosis is important; other oesophageal (e.g. eosinophilic oesophagitis) and gastroduodenal disorders (e.g. functional dyspepsia) should be ruled out, as this changes management. A combination of clinical assessment, endoscopic evaluation and in selected cases oesophageal function testing can help characterize patients with refractory reflux symptoms into oesophageal phenotypes so appropriate therapy can be more optimally targeted. Medical options then may include adding a H2 receptor antagonist, alginates, baclofen or antidepressant therapy, and there is emerging evidence for bile acid sequestrants and diaphragmatic breathing. The demonstration of a temporal association of symptoms with reflux events on pH-impedance testing (reflux hypersensitivity) serves to focus the management on modulating oesophageal perception and reducing the reflux burden, or identifies those with no obvious pathophysiologic abnormalities (functional heartburn). Anti-reflux surgery based on randomized controlled trial evidence has a role in reflux hypersensitivity or continued pathological acid reflux despite PPI in carefully considered, fully worked up cases that have failed medical therapy; approximately two of three cases will respond but there is a small risk of complications. In patients with persistent volume reflux despite medical therapy, given the lack of alternatives, anti-reflux surgery is a consideration. Promising newer approaches include endoscopic techniques. This review aims to summarize current diagnostic approaches and critically evaluates the evidence for the efficacy of available treatments.     

Changing epidemiology of gastroesophageal reflux disease in the Asian–Pacific region: An overview

Abstract   Gastroesophageal reflux disease (GERD) is a common disease in the West, which now appears to be also increasing in prevalence in the Asian Pacific region. The reasons for this changing epidemiology are two-fold: an increased awareness among doctors and patients, and/or a true increase in the prevalence of the disease. Prevalence rates of reflux esophagitis (RE) of up to 16% and prevalence of GERD symptoms of up to 9% have been reported in the Asian population. However, the frequency of strictures and Barrett's esophagus remain very low. Non-erosive reflux disease (NERD) appears to be the most common form of GERD among Asian patients accounting for 50–70% of cases with GERD. Among Asian patients differences can also be discerned among different ethnic groups. For example, in Malaysia where a multiracial society exists, RE is significantly more common among Indians compared to Chinese and Malays whereas NERD is more frequently seen in the Indian and Malays compared to the Chinese. The reasons for these differences are not known but may indicate both genetic factors and environmental factors peculiar to the particular racial group. GERD has also been increasing in the region demonstrating a time-lag phenomenon compared to the West. Differing predisposition to GERD among different ethnic groups would mean that such an increase would be more prominent among certain racial groups.     

Endoscopy of the esophagus in gastroesophageal reflux disease: are we losing sight of symptoms? Another perspective

Gastroesophageal reflux disease (GERD) is an extremely common chronic disorder associated with impaired quality of life and huge economic burden. Recently, an International Consensus Group developed a global definition of GERD (The Montreal Definition): a condition that develops when the reflux of stomach contents causes troublesome symptoms and/or complications. The traditional endoscopy-based classification of GERD patients into one of three groups – non-erosive reflux disease, erosive esophagitis, and Barrett's esophagus – is fraught with several limitations. Due to the lack of a gold standard, GERD is a symptom-based diagnosis, and hence symptom evaluation will remain the primary means by which treatment decisions are made for patients with suspected GERD. We propose that patients reporting the predominant GERD-like symptoms (GERS) in the primary care setting be classified based upon their response to an empiric trial of acid suppressive therapy: complete response to acid suppressive therapy, partial response to acid suppressive therapy, and no response to acid suppressive therapy. Given the limitations of objective medical testing, implementation of our proposed new symptom-based classification of patients with GERS would guide primary care physicians on when to refer patients to a gastroenterologist, which in turn could help in better resource utilization. Validation of this proposed classification by well-designed prospective multicenter studies is awaited.     

Laparoscopic fundoplication for gastroesophageal reflux disease

Gastroesophageal reflux disease(GERD) is a condition that develops when the reflux of gastric contents into the esophagus leads to troublesome symptoms and/or complications. Heartburn is the cardinal symptom, often associated with regurgitation. In patients with endoscopy-negative heartburn refractory to proton pump inhibitor(PPI) therapy and when the diagnosis of GERD is in question, direct reflux testing by impedance-pH monitoring is warranted. Laparoscopic fundoplication is the standard surgical treatment for GERD. It is highly effective in curing GERD with a 80% success rate at 20-year follow-up. The Nissen fundoplication, consisting of a total(360°) wrap, is the most commonly performed antireflux operation. To reduce postoperative dysphagia and gas bloating, partial fundoplications are also used, including the posterior(Toupet) fundoplication, and the anterior(Dor) fundoplication. Currently, there is consensus to advise laparoscopic fundoplication in PPI-responsive GERD only for those patients who develop untoward side-effects or complications from PPI therapy. PPI resistance is the real challenge in GERD. There is consensus that carefully selected GERD patients refractory to PPI therapy are eligible for laparoscopic fundoplication, provided that objective evidence of reflux as the cause of ongoing symptoms has been obtained. For this purpose, impedance-pH monitoring is regarded as the diagnostic gold standard.     

The relationship between gastroesophageal reflux disease and recurrent wheezing in children

Gastroesophageal reflux disease occurs when gastric contents flow back into the esophagus and produce symptoms. Recurrent wheezing affects the quality of life for the patient and family. The association of gastroesophageal reflux with recurrent wheezing is suggested by different studies. The purpose of this study was to explore this relationship and to evaluate the outcome after appropriate treatment.A retrospective study on 85 children with recurrent wheezing, admitted in a pediatric gastroenterology regional center in Romania was performed. 24-hour continuous esophageal pH monitoring was used to evaluate the presence of gastroesophageal reflux and the results were interpreted using the Boix Ochoa score. All patients with positive score received treatment with proton pump inhibitors and they were evaluated again after 2 months.Gastroesophageal reflux was present in 71 children (83.5%), while 14 (16.5%) had a negative score, with a statistic significance (χ² = 6.88, P = .0086, 95% confidence interval). After 2 months treatment with proton pump inhibitors, the Boix Ochoa score was still positive in 15 patients (21.13%).Recurrent wheezing is a solid reason for evaluating the presence of gastroesophageal reflux by 24-hour continuous esophageal pH-metry. Adequate treatment of gastroesophageal reflux solves also the recurrent wheezing in the majority of patients.