Gastroesophageal reflux disease: presentation and assessment of a common, challenging disorder

Although gastroesophageal reflux disease (GERD) is frequently referred to as a continuous spectrum, it is more useful to consider GERD as 2 discrete entities with several subsets that differ in pathophysiology, clinical presentation, natural history, and therapy. One entity is classic severe acid reflux with erosive esophagitis and its complications. Barrett's esophagus is an important subset of this group, with markedly increased acid exposure and an increased risk of adenocarcinoma. The second entity is nonerosive reflux disease (NERD) with minimal or no esophagitis. Patients with NERD do not develop local mucosa complications, like stricture or Barrett's esophagus, but their symptom severity can equal that of erosive esophagitis. Acid is involved in the symptoms of many but not all NERD patients. This acid dependence is evident either as an increase in esophageal acid reflux or a hypersensitivity to acid, and both generally respond well to proton pump inhibitor (PPI) therapy. NERD patients who are not acid-dependent have what is called functional heartburn; GERD-like symptoms are present, but there is no obvious involvement of refluxed acid. An important subset of GERD is refractory GERD, which consists of patients who fail aggressive PPI therapy. Parallel findings with other refractory syndromes can be anticipated; however, there are indications that psychosocial factors play a major role in refractory GERD, and these patients may benefit more from an integrated biopsychosocial approach. Diagnosis of GERD is usually made on clinical grounds, often supplemented by a therapeutic trial with antisecretory agents. Endoscopy is reserved for patients with alarm symptoms, such as dysphagia, anemia, or weight loss, or to detect Barrett's esophagus. Endoscopy is not useful to exclude the diagnosis of GERD because it will be negative in 70% of cases in primary care. Ambulatory 24-hour esophageal pH monitoring is necessary only when the diagnosis is in doubt, the patient fails medical management, or surgery is contemplated.     

Gastroesophageal reflux disease: natural history and long-term medical and surgical outcomes

Gastroesophageal reflux disease (GERD) is a chronic condition that affects a large proportion of the adult population. Persistent untreated GERD can lead to esophageal strictures, premalignant Barrett's esophagus, and an increased risk of adenocarcinoma of the esophagus. Currently, the most effective medical treatment targets gastric acid suppression, allowing healing of erosive/peptic lesions and controlling symptoms. Most patients take over-the-counter medication or are successfully treated by their primary care physician. Gastroenterologists and gastrointestinal surgeons see patients with complications, refractory symptoms despite acid-suppressive therapy, or atypical symptoms. For the medical management of GERD, proton pump inhibitors are potent acid suppressants with favorable side-effect profiles and long-term efficacy and safety. Medical therapy can heal 80% to 100% of patients with erosive esophagitis with 30% to 60% of patients reporting sustained resolution of heartburn. Surgery may be offered to patients with GERD as an alternative to long-term antireflux medication. Careful selection of appropriate surgical candidates is important, and the risk of developing new or recurrent symptoms requiring medication should be disclosed to patients contemplating the surgical alternative.     

Primary care for GEDR

Current approach for the treatment of gastroesopageal reflux disease (GERD) was reviewed. The most effective treatment of erosive esophagitis or symptomatic GERD is to reduce gastric acid secretion with either an H2 receptor antagonists (H2RA) or a proton pump inhibitor (PPI). The PPI lead to more rapid healing and symptom relief than H2RA. Despite treatment with PPI, some patients with GERD continue to have symptoms or endoscopic evidence of esophagitis. Nocturnal acid breakthrough may be one of the mechanisms responsible for the refractory GERD. There are two approaches to the initial medical treatment of gastroesophageal reflux disease ('step down' therapy or 'step up' approach). Although there are arguments in favour of both approaches, the former is considered to be preferable these days.     

Long-term results of conservative management of reflux esophagitis

Reflux esophagitis is a frequent and chronic disease. Impairment of the quality of life by the reflux symptoms and the risk of complications are the most important indications for a long-term treatment. The base of the treatment of reflux esophagitis is the inhibition of the gastric acid secretion with proton pump inhibitors (PPI) or by H2-receptor antagonist. In general, PPI's are more efficient in the treatment of refluxesophagitis as compared to H2-receptor antagonists blockers regarding the relieve of symptoms and the healing of erosive esophageal lesions. The use of an antacids and procinetics in the long-term treatment is not indicated. The treatment strategy depends on the severity of the symptoms and the esophageal lesions. Patient with mild esophagitis can be treated either with H2-receptor antagonists or with PPI's on demand or continuous. In the case of severe esophagitis, a long-term treatment with PPI's is indicated to avoid complications. Recurrence of esophagitis during a long-term therapy should be treated by PPI's. After healing the long-term treatment should be adapted either by increasing the given dose of the medicament or by a switch to more effective medicaments in acid suppression.     

Lansoprazole-induced improvement of esophageal submucosal injury

The proton pumpvinhibitor, lansoprazole, is reported to have acid secretion inhibiting effect as well as anti-inflammatory effects such as inhibition of cytokine secretion from inflammatory cells. Clinically, excellent efficacy of lansoprazole is reported for not only gastric ulcer but also gastroesophageal reflux disease (GERD). Since GERD is categorized endoscopically into erosive esophagitis and non-erosive reflux disease, it is important to make accurate assessment of any improvement in the inflammatory process when using endoscopic ultrasonography (EUS) capable of visualizing the submucosal structure. We report here our experience in assessing the effect of treatment with lansoprazole on esophageal wall structure using EUS in patients with GERD. At baseline (before treatment), EUS showed abnormalities in the mucosa, submucosa and muscularis propria caused by inflammation, thickening of the entire esophageal wall and changes in the contractile properties of esophageal smooth muscles reflecting the effects of inflammation on the entire wall of the lower esophagus in reflux esophagitis regardless of whether it is erosive or endoscopically-negative. Treatment with lansoprazole resulted in normalization of esophageal wall structure and improvement of motility, suggesting that lansoprazole improves not only mucosal inflammation but also submucosal inflammation in GERD.     

Histopathological diagnosis in gastroesophageal reflux disease

We reviewed the histopathological features for the diagnosis of gastroesophageal reflux disease (GERD). The presence of infiltration inflammatory cells, thickened basal cell layer, increased papillary height was histopathologically evaluated in GERD patients. It is often difficult to diagnose GERD symptoms when there were few endoscopic findings, such as lack of hiatal hernia and erosive esophagitis. At that time, we might be able to diagnose GERD by the histopathological examination except the pH monitor was performed. We showed that the histopathological esophagitis correlated with reflux symptoms and laryngopharyngeal symptoms. These indicated that the histopathological esophagitis may be diagnosed as not only typical GERD but also atypical GERD.     

Management of gastroesophageal reflux disease

The primary treatment goals in patients with gastroesophageal reflux disease are relief of symptoms, prevention of symptom relapse, healing of erosive esophagitis, and prevention of complications of esophagitis. In patients with reflux esophagitis, treatment is directed at acid suppression through the use of lifestyle modifications (e.g., elevating the head of the bed, modifying the size and composition of meals) and pharmacologic agents (a histamine H2-receptor antagonist [H2RA] taken on demand or a proton pump inhibitor IPPI] taken 30 to 60 minutes before the first meal of the day). The preferred empiric approach is step-up therapy (treat initially with an H2RA for eight weeks; if symptoms do not improve, change to a PPI) or step-down therapy (treat initially with a PPI; then titrate to the lowest effective medication type and dosage). In patients with erosive esophagitis identified on endoscopy, a PPI is the initial treatment of choice. Diagnostic testing should be reserved for patients who exhibit warning signs (i.e., weight loss, dysphagia, gastrointestinal bleeding) and patients who are at risk for complications of esophagitis (i.e., esophageal stricture formation, Barrett's esophagus, adenocarcinoma). Antireflux surgery, including open and laparoscopic versions of Nissen fundoplication, is an alternative treatment in patients who have chronic reflux with recalcitrant symptoms. Newer endoscopic modalities, including the Stretta and endocinch procedures, are less invasive and have fewer complications than antireflux surgery, but response rates are lower.     

Significance of PPI-test in the diagnosis of GERD

Gastroesophageal reflux disease (GERD) is defined as 'Chronic symptoms or mucosal damage produced by the abnormal reflux of gastric contents into the esophagus'. Reflux esophagitis refers to a subgroup of GERD patients with histopathologically demonstrated characteristic changes in the esophageal mucosa. Besides, GERD includes symptoms without endoscopic findings (endoscopic negative GERD) and extra-esophageal symptoms. Therefore, GERD cannot be diagnosed only by endoscopy. Three methods are indispensable in the diagnosis of GERD; endoscopy, evaluation of patient symptoms and acid reflux. Since 'Symptom relief is well correlated with the degree or suppression of gastric acid secretion in GERD', symptom in relation to acid reflux can be evaluated by PPI-test. Characteristics of PPI-test including extra-esophageal GERD diagnosis are discussed in this review.     

Prevalence, pathophysiology, and treatment of patients with asthma and gastroesophageal reflux disease

About one third of the US adult population experiences symptoms of gastroesophageal reflux on a monthly basis. Asthma is present in about 5% of the same population. This article reviews and summarizes the literature in the following areas: (1) prevalence of gastroesophageal reflux disease (GERD) in asthmatic patients based on clinical symptoms, endoscopic esophagitis, and 24-hour ambulatory esophageal pH recordings; (2) proposed pathophysiologic mechanisms linking the 2 diseases; and (3) medical and surgical treatment trial results of antireflux therapy for asthmatic patients. Asthmatic patients appear to have an increased prevalence of GERD symptoms and 24-hour esophageal acid exposure. The clinical management of these patients remains controversial. Common management approaches to GERD in asthmatic patients include medical therapy with a proton pump inhibitor and/or antireflux surgery, which improve asthma symptoms in many patients but minimally affect pulmonary function.     

Pathogenesis of gastro-esophageal reflux disease

Gastro-esophageal reflux disease (GERD) refers a condition that develops when the reflux of stomach contents causes troublesome symptoms and/or complications. The disease was subclassified into esophageal and extraesophageal syndromes in the new Montreal Definition. Hiatal hernia, decreased lower esophageal sphincter, transient lower esophageal sphincter relaxation, esophageal acid clearance, and delayed gastric emptying might be implicated as the pathogenesis of esophageal syndrome. Although non-erosive reflux disease (NERD) is included in the esophageal syndrome, it might be different from reflux esophagitis because of the lower response rates to acid suppression with proton pump inhibitors. Esophageal visceral hypersensitivity, sustained esophageal contractions, and abnormal tissue resistance are thought to be the mechanisms of NERD. Further investigations for the pathogenesis of each classification are expected.     

从心身角度认识胃食管反流病

胃食管反流病(GERD)为一组疾病症候群,包括典型症状如反酸和烧心,以及不典型症状如胸痛、嗳气,还有食管外症状如咳嗽、哮喘等。其定义不断进行更新,最新定义为胃内容物反流入食管或口腔、咽喉、肺部引起的症状和并发症。GERD发病机制包括滑动性食管裂孔疝、一过性食管下括约肌松弛、酸囊、食管清除能力下降、胃排空延迟、十二指肠胃食管反流等。焦虑、抑郁等心理因素可导致食管的敏感性增高,而后者可产生GERD相关症状。心理应激对食管敏感性的影响主要通过外周及中枢机制,即外周致敏和中枢致敏,而后者起主要作用。对GERD患者的治疗中应根据每位患者的具体情况采取个体化原则,应重视心理因素。     

Barrett's esophagus

Gastroesophageal reflux disease (GERD) is a condition commonly managed in the primary care setting. Patients with GERD may develop reflux esophagitis as the esophagus repeatedly is exposed to acidic gastric contents. Over time, untreated reflux esophagitis may lead to chronic complications such as esophageal stricture or the development of Barrett's esophagus. Barrett's esophagus is a premalignant metaplastic process that typically involves the distal esophagus. Its presence is suspected by endoscopic evaluation of the esophagus, but the diagnosis is confirmed by histologic analysis of endoscopically biopsied tissue. Risk factors for Barrett's esophagus include GERD, white or Hispanic race, male sex, advancing age, smoking, and obesity. Although Barrett's esophagus rarely progresses to adenocarcinoma, optimal management is a matter of debate. Current treatment guidelines include relieving GERD symptoms with medical or surgical measures (similar to the treatment of GERD that is not associated with Barrett's esophagus) and surveillance endoscopy. Guidelines for surveillance endoscopy have been published; however, no studies have verified that any specific treatment or management strategy has decreased the rate of mortality from adenocarcinoma.     

GERD and tight junction proteins of the esophageal mucosa

Recent advancement in the research of GERD has revealed that endoscopy negative GERD may not be a milder form of erosive GERD and may have different pathogenesis. We have previously proven that hypersensitivity to the acid of the esophageal mucosa plays an important role in its pathogenesis. Regarding the mechanisms for the esophageal hypersensitivity, we hypothesized that the tight junction proteins of the esophageal mucosa are fully or partially impaired in GERD patients. Accordingly, we immunohistologically studied the expression of various tight junction proteins using the rat reflux esophagitis model. The results demonstrated that the several kinds of tight junction proteins are expressed differently in the various parts of esophagus and their expression altered according to the development of reflux esophagitis.     

Definition and classification of GERD

Gastro-esophageal reflux disease(GERD) is a condition which develops when the reflux of stomach contents causes troublesome symptoms and/or complications. Traditionally, it was defined as a condition in which either or both of reflux esophagitis and reflux symptoms can be identified. The Montreal definition expanded the category of GERD to complications of esophagitis and extra-esophageal symptoms with or without established evidence on the correlation with GERD. Symptomatic patients those who lacks the evidence of mucosal breaks are called as NERD. Functional heartburn, defined in Rome III, is similar in symptoms but different in the responsiveness to PPIs. Increasing knowledge will clarify what the gastroesophageal reflux really causes health problems.     

Recent advances in the treatment of GERD in the elderly: focus on proton pump inhibitors

The prevalence of gastroesophageal reflux disease (GERD) increases with age, and older people are more likely to develop severe disease. Studies of elderly patients with GERD indicate differences in presentation and diagnosis, compared with GERD in younger adults. Indeed, an older patient with GERD may present with atypical symptoms such as dysphagia, vomiting, weight loss, anaemia and anorexia, and less frequently with typical symptoms such as heartburn or acid regurgitation. These findings are attributed to pathophysiological changes in esophageal function that occur with age. Therefore, GERD in elderly patients is more likely to be poorly diagnosed or undiagnosed. Although few studies have concentrated specifically on elderly patients, the proton pump inhibitors (PPIs) have been shown to be more effective than histamine receptor antagonists for healing reflux esophagitis and for preventing its recurrence when they are given as maintenance therapy. In addition, the PPIs seem to be safe both in short- and in long-term therapy of elderly patients with GERD.     

Investigation and outcome of 121 infants and children requiring Nissen fundoplication for the management of gastroesophageal reflux

In a 6.5 year period starting January 1982, 121 patients (74 male, 47 female; 1.6:1) with complicated gastroesophageal reflux referred to Alberta Children's Hospital, University of Calgary, required a Nissen fundoplication at a mean age of 35.5 months (range 3 weeks to 18 years). The median age of onset of symptoms was less than 1 month. Symptoms and indications for surgery included regurgitation (88%), failure to thrive (52%), reflux-associated pulmonary symptoms and aspiration (48%), biopsy evidence of esophagitis (35%) with heartburn (17%), dysphagia (18%), hematemesis (17%), anemia (13%), and hypoproteinemia (22%). Sixty-four percent of the patients had a syndrome or chromosomal abnormality, respiratory disease, or neuromuscular disorder. The barium contrast upper-gastrointestinal radiographic series, performed in all patients, identified structural [gastric outlet obstruction (2%), esophageal stricture (11%), erosive esophagitis (9%)], and functional abnormalities [gastroesophageal reflux (90%), barium aspiration (8%), esophageal hypoperistalsis (30%), delayed gastric emptying (4%)]. Barium contrast upper gastrointestinal radiographic series identified gastroesophageal reflux with a sensitivity of 90% (compared to history), was 50% sensitive and 92% specific for erosive esophagitis (compared to biopsy), was 59% sensitive and 74% specific for esophageal dysmotility (compared to esophageal manometry), and there was a significant (p less than 0.01) association between barium aspiration and prior evidence of aspiration pneumonitis. Esophageal manometry demonstrated a significantly (p less than 0.001) lower esophageal sphincter pressure in patients compared with controls, but no significant correlation with failure to thrive, aspiration pneumonia, biopsy evidence of esophagitis, or parameters of the 24-hour esophageal pH study. Twenty-four hour pH monitoring showed significantly (p less than 0.05) more reflux episodes than in asymptomatic controls and there was significant (p less than 0.05) correlation between the percentage of time pH was less than 4 and the presence of hypoalbuminemia, and biopsy-proven erosive esophagitis or Barrett's esophagus. Endoscopic appearance was 91% sensitive and 60% specific for esophagitis when compared to biopsy. Nissen fundoplication was completely effective at resolving gastroesophageal reflux in 83%, and associated with marked improvement in 15%. No patient died as a result of fundoplication. Major complications included: recurrence of symptoms requiring reoperation (2%), subsequent mechanical bowel obstruction (8%), wound infection or pneumonia (12%).     

非糜烂性反流病研究概况

非糜烂性反流病(NERD)是指有典型胃食管反流症状而无内镜下食管黏膜损害表现的疾病,约占胃食管反流病(GERD)的60%~70%,其发病机制复杂,既与GERD有相似之处,又有其特殊性,主要包括酸反流与非酸反流、内脏高敏感、应激和精神因素等多种原因。其发病机制的多样性和复杂性是导致患者对抑酸治疗总体效果不佳的主要原因,强力抑酸治疗改善症状的疗效明显低于伴食管炎患者。现就NERD研究概况进行综述。     

GERD患者内镜、病理改变与食管测压及pH动态监测之间关系的研究

目前，对GERD（GastoesophagealRefluxDisease，GERD）有不少研究报道，如GERD患者的24h食管pH动态监测、压力测定、内镜和病理等，但对它们之间关系的研究却无系列报道。据称，食管pH动态监测较其它任何临床诊断方法都有更高的敏感性和特异性，被认为是诊断GER的“金标准”。本研究即利用这一“金标准”对GERD患者进行食管PH动态监测及食管压力测定，同时研究其与内铺表现及病理改变之间的关系。1对象与布法1．1研究对象1．1．1正常对照组选择无胃肠肝胆疾病，无食管返流症状、无腹部手术史，心电图、血尿常规、内镇及病理检查…     

Treatment of gastroesophageal reflux disease

Therapeutic modalities for gastroesophageal reflux disease (GERD) continue to evolve despite the introduction of proton pump inhibitors (PPIs), the most successful antireflux class of drugs. On-demand modalities such as antacids and alginates as well as histamine type-2 receptor antagonists continue to be popular with GERD patients who seek temporary relief of symptoms. The PPIs have revolutionized the treatment of patients with severe erosive esophagitis, complications of GERD, and atypical or extraesophageal manifestations of GERD. Antireflux surgery, commonly performed via laparoscopy, remains popular among patients who do not wish to take medications long term. In addition, the recent introduction of various endoscopic techniques offers GERD patients a long-term solution with less morbidity and lower cost than antireflux surgery.     

Gastroesophageal reflux disease: current treatment approaches.

Gastroesophageal reflux disease is a common, usually lifelong, disorder resulting from chronic abnormal exposure of the lower esophagus to gastric contents. Motor dysfunction of the lower esophageal sphincter is the primary cause of this disease. At this writing, no medical therapies can completely resolve abnormal lower esophageal sphincter function; therefore, the treatment of gastroesophageal reflux disease centers on suppression of intragastric acid secretion. Available acid-suppressant medications include proton pump inhibitors, H2-receptor antagonists, and antacids. Of these, the proton pump inhibitors are recognized generally as the mainstays of both short-term and long-term therapy for gastroesophageal reflux disease. All have a low incidence of side effects and are well tolerated by most patients. Five proton pump inhibitors are available currently for patients with gastroesophageal reflux disease. Of these, esomeprazole has shown greater efficacy in controlling intragastric acidity than the others. For patients with erosive esophagitis, esomeprazole has demonstrated higher healing rates and more rapid sustained resolution of heartburn than omeprazole or lansoprazole after up to 8 weeks of once-daily treatment. Because new therapies for gastroesophageal reflux disease are highly effective, patients can be reassured that their disease will be well controlled and their symptoms resolved with a safe and appropriate treatment.