Diagnosis and treatment of gastroesophageal reflux disease

Gastroesophageal reflux disease(GERD) is a common disease with a prevalence as high as 10%-20% in the western world. The disease can manifest in various symptoms which can be grouped into typical,atypi-cal and extra-esophageal symptoms. Those with the highest specificity for GERD are acid regurgitation and heartburn. In the absence of alarm symptoms,these symptoms can allow one to make a presumptive diagnosis and initiate empiric therapy. In certain situations,further diagnostic testing is needed to confirm the diagnosis as well as to assess for complications or alternate causes for the symptoms. GERD complications include erosive esophagitis,peptic stricture,Barrett's esophagus,esophageal adenocarcinoma and pulmonary disease. Management of GERD may involve lifestyle modification,medical therapy and surgical therapy. Life-style modifications including weight loss and/or head of bed elevation have been shown to improve esophageal pH and/or GERD symptoms. Medical therapy involves acid suppression which can be achieved with antacids,histamine-receptor antagonists or proton-pump inhibitors. Whereas most patients can be effectively managed with medical therapy,others may go on to require anti-reflux surgery after undergoing a proper pre-operative evaluation. The purpose of this review is to discuss the current approach to the diagnosis and treatment of gas-troesophageal reflux disease.     

Diagnostic approach to gastro-oesophageal reflux disease

It is neither practical nor necessary to embark on a diagnostic evaluation of every patient with classic symptoms of gastroesophageal reflux disease (GERD). In most cases a well-taken history is usually sufficient to confirm the diagnosis of GERD and begin therapy. However, some patients may present with atypical symptoms; and many with classic symptoms are refractory to standard medical therapy. In these cases one must rely on diagnostic studies to confirm that abnormal acid reflux is present and potentially responsible for the symptoms in question. Modern technology has given us many different modalities to quantify esophageal acid exposure and determine whether symptoms are correlated to reflux events. Unfortunately, these studies are not perfect and the work-up of refractory patients typically requires more than one test. The goal of the following review will be to summarize the currently available techniques for diagnosis of GERD and also discuss the possible impact of new techniques, such as intraluminal impedance monitoring and wireless ambulatory pH monitoring.     

Supraesophageal manifestations of gastroesophageal reflux disease.

An increasing amount of evidence indicates that gastroesophageal reflux disease (GERD) is a contributing factor to hoarseness, throat clearing, throat discomfort, chronic cough, and shortness of breath. The association between GERD and these supraesophageal symptoms may be elusive. Heartburn and regurgitation are absent in more than 50% of patients. Acid reflux should be considered if signs of GERD are present, symptoms are unexplained, or symptoms are refractory to therapy. The diagnosis of GERD may be unclear, despite a careful history and initial evaluation. A high index of suspicion is required to make the diagnosis. An empiric trial of antireflux therapy is appropriate when GERD is suspected. Multiprobe ambulatory pH monitoring is currently the diagnostic test of choice, but the level of sensitivity and specificity for supraesophageal manifestations of GERD is uncertain. Response to antireflux therapy is less predictable than typical GERD. More intensive acid suppression and longer treatment duration are usually required.     

Strategies for the diagnosis of gastro-esophageal reflux disease

With patients referring symptoms of gastro-esophageal reflux disease (GERD), 2 initial approaches should be considered: an empiric therapy (treat and test strategy) or a strategy based on instrumental investigations (test and treat). In most cases a well-taken history is usually sufficient to confirm the diagnosis of GERD and initiate treatment. However, some patients may present with 'atypical' symptoms, classic symptoms refractory to standard medical therapy or 'alarm' symptoms. In these cases, one must rely on diagnostic studies to document the presence of mucosal damage related or not to GERD and/or quantify the degree of gastro-esophageal reflux. The most relevant test to diagnose esophageal injury and complications of GERD is represented by upper gastrointestinal endoscopy, while the most diffuse procedure to quantify the degree of acid reflux is pH monitoring. Further studies are required to delineate the appropriate use and the possible impact of new techniques, such as intraluminal impedance monitoring, Bilitec and, wireless ambulatory pH monitoring in the management of GERD.     

The initial diagnosis of GERD

The diagnosis of GERD in primary care settings can be enhanced by the use of structured questionnaires that suggest a high probability of GERD. Clinical outcomes can be improved and costs reduced by adopting this strategy. Using predominant symptoms to determine the path of treatment or the use of an empirical test of proton pump inhibitors has not been proven to be reliable and should be abandoned.     

The end of diagnosis: when to stop testing

Defining the end of diagnosis and deciding when to stop further testing represent crucial features of many medical pursuits. The aim of this article is to analyze the principles that govern the decision to discontinue a chain of consecutive diagnostic tests. Using Bayes formula and threshold analysis, four common "stop rules" of medical diagnostics can be derived. The first rule relates to a lack of therapeutic consequence associated with continued testing. The second rule concerns empirical therapy, that is, the use of a benign, effective, and specific type of therapy to cap a diagnostic chain and use therapeutic success as confirmation for a diagnostic suspicion. The third rule states that the benefit of a suspected diagnosis should stay higher than the costs of a test invested in confirming its presence. Lastly, as the fourth rule, the cumulative test costs should not exceed the expected risks of a missed diagnosis. Although in clinical practice the ambiguities and variations among patients may compromise the calculation of exact stop values for each rule, knowledge of these underlying general principles may be sufficiently helpful in managing the individual patient.     

A cost-effectiveness analysis of prescribing strategies in the management of gastroesophageal reflux disease

OBJECTIVE: Patients who have uncomplicated gastroesophageal-reflux disease (GERD) typically present with heartburn and acid regurgitation. We sought to determine the cost-effectiveness of H2-receptor antagonists (H2RAs) and proton-pump inhibitors (PPIs) as first-line empiric therapy for patients with typical symptoms of GERD. METHODS: Decision analysis comparing costs and benefits of empirical treatment with H2RAs and PPIs for patients presenting with typical GERD was employed. The six treatment arms in the model were: 1) Lifestyle therapy, including antacids; 2) H2RA therapy, with endoscopy performed if no response to H2RAs; 3) Step up (H2RA-PPI) Arm: H2RA followed by PPI therapy in the case of symptomatic failure; 4) Step down arm: PPI therapy followed by H2RA if symptomatic response to PPI, and antacid therapy if response to H2RA therapy; 5) PPI-on-demand therapy: 8 wk of treatment for symptomatic recurrence, with no more than three courses per year; and 6) PPI-continuous therapy. Measurements were lifetime costs, quality-adjusted life years (QALYs) gained, and incremental cost effectiveness. RESULTS: Initial therapy with PPIs followed by on-demand therapy was the most cost-effective approach, with a cost-effectiveness ratio of $20,934 per QALY gained for patients with moderate to severe GERD symptoms, and $37,923 for patients with mild GERD symptoms. This therapy was also associated with the greatest gain in discounted QALYs. The PPI-on-demand strategy was more effective and less costly than the H2RA followed by PPI strategy or the other treatment arms. The results were not highly sensitive to cost of therapy, QALY adjustment from GERD symptoms, or the success rate of the lifestyle arm. However, when the success rate of the PPI-on-demand arm was < or =59%, the H2RA-PPI arm was the preferred strategy. CONCLUSION: For patients with moderate to severe symptoms of GERD, initial treatment with PPIs followed by on-demand therapy is a cost-effective approach.     

Empirical trials in treatment of gastroesophageal reflux disease

The assortment of diagnostic tests that are currently available for detecting gastroesophageal reflux disease (GERD) are invasive, costly and not readily available to community-based physicians. In contrast, a short course of high-dose proton pump inhibitor (PPI) as an empirical trial is an attractive alternative. This simple diagnostic test has been demonstrated to be accurate and cost-effective in patients with symptoms suggestive of GERD and those with noncardiac chest pain. Early studies in patients with extraesophageal manifestations of GERD have yielded promising results. Cost assessment of the PPI empirical trial revealed significant cost savings, mainly due to a marked decrease in utilization of invasive diagnostic tests. Thus the PPI empirical trial should be considered as the initial diagnostic step in patients with the disease spectrum of GERD.     

The proton pump inhibitor test and the diagnosis of gastroesophageal reflux disease

There continues to be significant controversy related to diagnostic testing for gastroesophageal reflux disease (GERD). Symptoms of GERD may be associated with physiologic esophageal acid exposure measured by intraesophageal pH monitoring or pH-impedance monitoring, and a significant percentage of patients with abnormal esophageal acid (or weak acid) exposure have no or minimal clinical symptoms of reflux. On the other hand, endoscopic lesions are only present in a minority of GERD patients. In clinical practice, presumptive diagnosis of GERD is reasonably assumed by the substantial reduction or elimination of suspected reflux symptoms during the therapeutic trial of acid reduction therapy, the so-called proton pump inhibitor (PPI) test. We aimed to assess the optimal cutoff value and duration of this test in GERD patients with and without esophagitis. We conducted a prospective study of 544 patients, endoscopically investigated and treated for 2 weeks with PPIs at double dose, and for an additional 3 months at standard dose. The status of the patient at the end of the study was used as an independent diagnostic standard. We found esophagitis present in 55.8% and absent in 44.2% of patients (corresponding to a diagnosis of nonerosive reflux disease [NERD]). The test was positive in 89.7–97.8% of the patients according to the cutoff or duration of the test used. The sensitivity of the PPI test was excellent, ranging from 95.5 to 98.8%, whereas the specificity was poor, not exceeding 36.3%. Erosive esophagitis patients responded more favorably to the PPI test and subsequent PPI therapy compared with NERD patients. In conclusion, the PPI test is a sensitive but less specific test. Its optimal duration is 1 week, and the optimal cutoff value is a decrease of heartburn score of more than 75%. NERD patients respond less satisfactorily to PPIs, even when functional heartburn patients are excluded and only ‘true’ NERD patients are considered.     

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.     

Survey of primary care physicians' approach to gastroesophageal reflux disease in elderly patients

BACKGROUND: Although gastroesophageal reflux disease (GERD) is a common condition, little is known regarding physicians' approach to the diagnosis and management of GERD in elderly patients. METHODS: We surveyed by facsimile a random sample of 14,000 practicing primary care physicians throughout the United States. Physicians were questioned using a case-based format about the approach to a symptomatic patient with GERD including the use of empiric therapy, the role of diagnostic testing, and the drugs of choice to treat GERD. RESULTS: A total of 2241 surveys (16%) was returned and tabulated. Most respondents were either internists (37%) or family practice physicians (56%) in solo or group practice, and 74% had been in practice for 11 or more years. There were 1980 (90%) respondents who evaluated more than 6 patients per week with GERD. Empiric therapy was commonly recommended for the symptomatic patient, most often in a step-up approach beginning with H(2)-receptor blockers. Diagnostic testing, usually endoscopy, was recommended appropriately in patients with alarm symptoms. Proton-pump inhibitors were most often recommended for patients failing to respond to over-the-counter H(2)-receptor blockers and for those with endoscopic esophagitis; the use of cisapride in combination with H(2)-receptor blockers was also commonly recommended in these scenarios. CONCLUSIONS: The management of symptomatic GERD in elderly patients appears similar to the management of GERD in other patients. Empiric therapy was frequently recommended in a step-up approach, and diagnostic testing was appropriate. Combination therapy with cisapride and an acid-reducing agent was commonly recommended.     

Updates in the field of non-esophageal gastroesophageal reflux disorder

ABSTRACT

Introduction: Gastroesophageal reflux disease (GERD) is one of the most prevalent conditions in Western Countries, normally presenting with heartburn and regurgitation. Extra-esophageal (EE) GERD manifestations, such as asthma, laryngitis, chronic cough and dental erosion, represent the most challenging aspects from diagnostic and therapeutic points of view because of their multifactorial pathogenesis and low response to proton pump inhibitors (PPIs). In fact, in the case of EE, other causes must by preventively excluded, but instrumental methods, such as upper gastrointestinal endoscopy and laryngoscopy, have low specificity and sensitivity as diagnostic tools. In the absence of alarm signs and symptoms, empirical therapy with a double-dose of PPIs is recommended as a first diagnostic approach. Subsequently, impedance-pH monitoring could help to define whether the symptoms are GERD-related.

Areas covered: This article reviews the current literature regarding established and proposed EE-GERD, reporting on all available options for its correct diagnosis and therapeutic management.

Expert opinion: MII-pH could help to identify a hidden GERD that causes EE. Unfortunately, standard MII-pH analysis results are often unable to define this association. New parameters such as the mean nocturnal baseline impedance and post-reflux swallow-induced peristaltic wave index may have an improved diagnostic yield, but prospective studies using impedance-pH are needed.     

Extra-Esophageal Manifestations of Gerd: Who Responds to GERD Therapy?

Gastroesophageal reflux disease (GERD) is a common disease that is defined as a condition that develops when the reflux of stomach contents causes troublesome symptoms. In addition to the esophageal manifestations of heartburn and regurgitation, the role of GERD in causing extra-esophageal symptoms, such as laryngitis, asthma, cough, chest pain, and dental erosions, is increasingly recognized with renewed interest. Due to the poor sensitivity of endoscopy and pH monitoring, and the poor specificity of laryngoscopy, empiric therapy with proton pump inhibitors (PPI) is now considered the initial diagnostic step in patients suspected of having GERD-related symptoms. In those who are unresponsive to such therapy, other diagnostic testing such as impedance/pH monitoring may be reasonable in order to exclude continued acid or weakly acid reflux. Recent data suggest that patients with extra-esophageal symptoms who have concomitant typical symptoms, moderate-sized hiatal hernia and moderate reflux on pH testing may respond better to acid suppressive therapy. This group only accounts for 20?30 % of patients commonly referred for suspected GERD. PPI-unresponsive patients usually have causes other than GERD for their extra-esophageal signs and symptoms and continued PPI therapy in this group is not recommended.     

Management of gastroesophageal reflux disease in primary care: results of a survey in 2 areas in Germany.

BACKGROUND: The incidence of gastroesophageal reflux disease (GERD) is increasing. Although guidelines have been issued on the diagnosis and treatment of GERD, the way in which these should be applied in everyday practice is unclear. The aim of the present survey was to interview private-practice physicians on their personal opinions concerning the management of GERD. METHODS: A questionnaire based on the case of a typical patient with reflux was sent out to a total of 918 private-practice physicians. The questions concerned general measures for avoiding reflux symptoms (dietary and lifestyle modifications), the diagnosis of GERD, and the type and dosage of antireflux treatment. RESULTS: A total of 255 questionnaires were evaluated (28 %), which had been returned by 151 family doctors, 63 internal medicine specialists, and 41 gastroenterologists. 70 % of the respondents carry out specific diagnostic tests (endoscopy in 98 % of cases) prior to treatment. Altering specific dietary and lifestyle factors (such as sleeping position) was considered useful by the majority of respondents. 99 % of the physicians administer some form of GERD therapy, and 88 % of the internists/gastroenterologists and 74 % of family doctors (P = 0.006) do so using a "step-down" approach (with proton-pump inhibitors as the initial strategy). With the "step-up" procedure, the initial recommendation includes primarily antacids, with a change to more effective drugs only when symptomatic relief is not achieved. CONCLUSIONS: The current guidelines on the diagnosis and treatment of GERD are largely adhered to, particularly by specialists. In addition to the well-established drug treatment, empirical recommendations on dietary and lifestyle measures still form part of the management of GERD, despite the lack of scientific evidence to support them.     

Extra-esophageal gastroesophageal reflux disease and asthma: understanding this interplay

Gastroesophageal reflux disease (GERD) is a condition that develops when there is reflux of stomach contents, which typically manifests as heartburn and regurgitation. These esophageal symptoms are well recognized; however, there are extra-esophageal manifestations of GERD, which include asthma, chronic cough, laryngitis and sinusitis. With the rising incidence of asthma, there is increasing interest in identifying how GERD impacts asthma development and therapy. Due to the poor sensitivity of endoscopy and pH monitoring, empiric therapy with proton pump inhibitors (PPIs) is now considered the initial diagnostic step in patients suspected of having GERD-related symptoms. If unresponsive, diagnostic testing with pH monitoring off therapy and/or impedance/pH monitoring on therapy, may be reasonable in order to assess for baseline presence of reflux with the former and exclude continued acid or weakly acid reflux with the latter tests. PPI-unresponsive asthmatics, without overt regurgitation, usually have either no reflux or causes other than GERD. In this group, PPI therapy should be discontinued. In those with GERD as a contributing factor acid suppressive therapy should be continued as well as optimally treating other etiologies requiring concomitant treatment. Surgical fundoplication is rarely needed but in those with a large hiatal hernia, moderate-to-severe reflux by pH monitoring surgery might be helpful in eliminating the need for high-dose acid suppressive therapy.     

The relationship between ineffective esophageal motility and gastro-esophageal reflux disease]

BACKGROUND/AIMS: Ineffective esophageal motility (IEM) is a distinct manometric entity characterized by a hypocontractile esophagus. Recently, IEM replaced the nonspecific esophageal motility disorder (NEMD), and its associations with gastro-esophageal reflux disease (GERD) and respiratory symptoms are well known. We evaluated the relationship of IEM with GERD, and the diagnostic value of IEM for GERD. METHODS: We retrospectively analyzed recent 3-year (Jan. 1998-Sep. 2002) datas of esophageal manometry, acid perfusion test and simultaneous 24 hr-ambulatory pH-metry with manometry studies in 270 consecutive patients with esophageal and/or GERD symptoms. The prevalence of IEM in GERD group and non-GERD group, and the variables of pH-metry and manometry among esophageal motility disorders were compared. In addition, the sensitivity, specificity, positive predictive value, negative predictive value of IEM, esophageal symptom, and acid perfusion test for GERD were calculated. RESULTS: There was no significant difference in IEM prevalence rate between GERD group and non-GERD group. In addition, there was no significant difference in GERD prevalence rate and esophageal acid clearance in variety of motility disorder groups. Total percent time of pH <4 in IEM group did not show any difference when compared with other groups except in the achalasia group. In regard of diagnostic value to detect GERD, all positive results showed high specificity (97%) in IEM with esophageal symptom and positive acid perfusion test. CONCLUSIONS: The diagnosis of IEM using esophageal manometry in patients with various esophageal symptoms does not strongly suggest on association with GERD. However, IEM with concomitant esophageal symptoms and positive acid perfusion test has diagnostic values for GERD.     

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 diagnosis of gastroesophageal reflux disease

Gastroesophageal reflux disease (GERD) is known to cause erosive esophagitis, Barrett esophagus and has been linked to the development of adenocarcinoma of the esophagus. Currently, endoscopy is the main clinical tool for visualizing esophageal lesions, but the majority of GERD patients do not have endoscopic visible lesions and other methods are required. Ambulatory esophageal pH monitoring is the gold standard in diagnosing GERD, since it measures distal esophageal acid exposure and demonstrates the relationship between symptoms and acid reflux. The effectiveness of selective gastric acid suppressive therapy led to the introduction of short trials of proton pump inhibitors (PPIs) to diagnose GERD and they are often used as a first line diagnostic tool in clinical practice and, in particular, in the primary care setting, the current trend being that gastroenterologists are asked to evaluate mainly patients with persistent GERD symptoms while on PPI therapy. In these patients the question is whether the persistent symptoms are or not associated with reflux (acid or nonacid). Recently, either combined multichannel intraluminal impedance and pH monitoring or bilimetry allow to study the mechanisms underlying the persistent symptoms on acid suppressive therapy. Manometry is mandatory prior to any surgical approach and to verify motility disorders that could be associated to GERD.     

Diagnostic evaluation in gastroesophageal reflux disease

Gastroesophageal reflux disease (GERD) describes the clinical manifestations of reflux of gastric contents and the associated symptoms and patterns of tissue injury. Although its exact prevalence is difficult to determine, there is no doubt the GERD is the most common esophageal disease and probably among the most prevalent conditions seen in the primary care setting. GERD has a wide clinical spectrum, making the diagnostic evaluation challenging and complicated at times. Confirmatory test are rarely needed in patients with typical symptoms of heartburn or regurgitation who have a good clinical response to GERD therapy. This article describes the diagnostic tests necessary for some cases of GERD.     

Detection and treatment of gastroesophageal reflux disease

The diagnosis of GERD requires the thoughtful evaluation of a patient's symptoms and clinical course. In young patients with classical reflux symptoms in the absence of untoward complications such as structure, bleeding or pulmonary aspiration, antireflux treatment can be instituted without the need for diagnostic testing. A large number of patients will demonstrate a good clinical response to medical therapy. The diagnostic challenge arises when symptoms of reflux masquerade as cardiac and pulmonary disease or do not respond to simple medical treatment. The use of diagnostic testing to determine the presence and quantity of reflux is helpful in establishing the diagnosis in atypical settings. Prolonged pH monitoring offers the opportunity to monitor symptoms in a physiologic setting over a prolonged period and to provide a correlation of symptoms with the presence of reflux. Endoscopic evaluation is most important in evaluating patients with complications such as peptic strictures, hemorrhagic esophagitis, or Barrett's metaplasia. In these situations, important diagnostic and prognostic information as well as therapeutic intervention can be gained through endoscopy. In patients with peptic strictures, palliation can be achieved by endoscopic dilatation. The number of options available for the medical management of reflux disease has increased significantly in recent years. The introduction of effective agents to block acid secretion has provided a significant advance in the medical treatment of gastroesophageal reflux. Prokinetic agents offer an attractive alternative either alone or in combination with acid inhibition. Early results using parietal cell proton-pump blocking agents suggest that they may be effective in the treatment of severe esophagitis previously resistant to medical therapy. Despite significant advances in the medical treatment of GERD, a number of patients (5 to 10 per cent) may require antireflux surgery. The Nissen fundoplication has been shown to be an effective means of attaining mucosal healing usually accompanied by symptomatic relief. The use of a "loose wrap" performed over a large bore dilator avoids the postoperative problems of dysphagia or gas bloat. Despite improvements in our diagnostic and therapeutic armamentarium, a number of patients continue to pose a challenge for the clinician. There remains a clear need for more well-designed, well-controlled studies to assist in the effective treatment of this ubiquitous and often debilitating disease.