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.     

Pathogenesis of gastroesophageal reflux and Barrett esophagus

Barrett esophagus is a metaplastic condition that affects the lower esophagus and is a complication of gastroesophageal reflux disease (GERD). Under normal circumstances, the reflux of gastric contents into the esophagus is prevented by a complex barrier at the esophagogastric junction. Dysfunction of the lower esophageal sphincter and the presence of a hiatal hernia lead to failure of this barrier. Esophageal mucosal damage results from the chronic exposure of the esophageal mucosa to gastroduodenal contents and the lack of an effective mucosal defense. This article is an overview of the dysfunction of the esophagogastric junction that leads to GERD. The role of the contents of the reflux and that of Helicobacter pylori infection in the pathogenesis of Barrett esophagus are also summarized.     

胃食管反流病合并食管裂孔疝患者的临床特点分析

目的分析胃食管反流病(GERD)合并食管裂孔疝(HH)患者的临床特点及其危险因素。方法回顾性分析2018年1月-2019年3月在宁夏回族自治区人民医院消化内科诊断为GERD合并HH的40例患者并作为研究组,另外40例GERD未合并HH的患者为对照组,比较两组患者的基本临床资料、内镜分级、Barrett食管发生率。结果研究组患者的年龄、体重、吸烟史、糖尿病与对照组比较,差异均有统计学意义(P<0.05),两组性别、饮酒史和冠心病比较,差异均无统计学意义(P>0.05);研究组食管外症状较多见,内镜下分级仅有C级与对照组比较差异有统计学意义(P<0.05);A级、B级、D级两组差异无统计学意义(P>0.05);两组Barrett食管发生率比较,差异有统计学意义(P<0.05)。结论GERD合并HH与年龄、体重、吸烟史、糖尿病有关,且其会使Barrett食管发生率升高,积极防控可改变的因素对该类患者可能有一定的好处。     

Diagnosis and treatment of esophageal motility disorders

Apart from gastroesophageal reflux disease, achalasia, non-cardiac chest pain and functional dysphagia are the most important manifestations of disturbed esophageal motility. Achalasia is characterized by esophageal aperistalsis and impaired deglutitive relaxation of the lower esophageal sphincter. The morphological correlate is a degeneration of nitrergic neurons in the myenteric plexus. Diagnosis is based on barium esophagram or esophageal manometry with the latter setting the gold standard. Endoscopic exclusion of a tumor at the gastroesophageal junction is mandatory. Appropriate therapeutic interventions are pneumatic dilatation or (laparoscopic myotomy) of lower esophageal sphincter. In patients unfit for these procedures endoscopic injection of botulinum toxin into the lower esophageal sphincter is appropriate. Non-cardiac chest pain may be of esophageal origin. Gastroesophageal reflux, spastic motility disorders and visceral hypersensitivity are arguable underlying mechanisms. The most important diagnostic procedure is 24 h esophageal pH metry correlating symptoms and reflux episodes. Proton pump inhibitors and tricyclic antidepressants serving as visceral analgesics are appropriate therapeutic approaches. Functional dysphagia defines the sensation of impaired passage without mechanical obstruction or a neuromuscular disease with known pathology, e.g. scleroderma. Impaired transit is proven by esophageal scintigraphy or radiogram both using solid boluses. Manometry assesses the underlying mechanisms.     

Controversies in Barrett Esophagus

Barrett esophagus develops when metaplastic columnar epithelium predisposed to develop adenocarcinoma replaces esophageal squamous epithelium damaged by gastroesophageal reflux disease. Although several types of columnar metaplasia have been described in Barrett esophagus, intestinal metaplasia with goblet cells currently is required for a definitive diagnosis in the United States. Studies indicate that the risk of adenocarcinoma for patients with nondysplastic Barrett esophagus is only 0.12% to 0.38% per year, which is substantially lower than previous studies had suggested. Nevertheless, the incidence of esophageal adenocarcinoma continues to rise at an alarming rate. Regular endoscopic surveillance for dysplasia is the currently recommended cancer prevention strategy for Barrett esophagus, but a high-quality study has found no benefit of surveillance in preventing deaths from esophageal cancer. Medical societies currently recommend endoscopic screening for Barrett esophagus in patients with multiple risk factors for esophageal adenocarcinoma, including chronic gastroesophageal reflux disease, age of 50 years or older, male sex, white race, hiatal hernia, and intra-abdominal body fat distribution. However, because the goal of screening is to identify patients with Barrett esophagus who will benefit from endoscopic surveillance and because such surveillance may not be beneficial, the rationale for screening might be made on the basis of faulty assumptions. Endoscopic ablation of dysplastic Barrett metaplasia has been reported to prevent its progression to cancer, but the efficacy of endoscopic eradication of nondysplastic Barrett metaplasia as a cancer preventive procedure is highly questionable. This review discusses some of these controversies that affect the physicians and surgeons who treat patients with Barrett esophagus. Studies relevant to controversial issues in Barrett esophagus were identified using PubMed and relevant search terms, including Barrett esophagus, ablation, dysplasia, radiofrequency ablation, and endoscopic mucosal resection.     

Barrett Esophagus

Barrett esophagus is a metaplastic change in the lining of the distal esophageal epithelium, characterized by replacement of the normal squamous epithelium by specialized intestinal metaplasia. The presence of Barrett esophagus increases the risk of esophageal adenocarcinoma several-fold. Esophageal adenocarcinoma is a malignancy with rapidly rising incidence and persistently poor outcomes when diagnosed after the onset of symptoms. Risk factors for Barrett esophagus include chronic gastroesophageal reflux, central obesity, white race, male gender, older age, smoking, and a family history of Barrett esophagus or esophageal adenocarcinoma. Screening for Barrett esophagus in those with several risk factors followed by endoscopic surveillance to detect dysplasia or adenocarcinoma is currently recommended by society guidelines. Minimally invasive nonendoscopic tools for the early detection of Barrett esophagus are currently being developed. Multimodality endoscopic therapy—using a combination of endoscopic resection and ablation techniques—for the treatment of dysplasia and early adenocarcinoma is successful in eliminating intestinal metaplasia and preventing progression to adenocarcinoma, with outcomes comparable to those after esophagectomy. Risk stratification of those diagnosed with Barrett esophagus is a challenge at present, with active research focused on identifying clinical and biomarker panels to identify those with low and high risk of progression. This narrative review highlights some of the challenges and recent progress in this field.     

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 occurring as a complication of scleroderma

Two patients had both scleroderma and a columnar epithelium-lined lower esophagus (Barrett esophagus). Features of Barrett's esophagus included high esophageal strictures in both patients and ulcer craters in the columnar area of one. Biopsy confirmed columnar epithelium in the lower esophagus of each patient. In these patients, the Barrett esophagus probably was a complication of scleroderma and resulted from long-standing gastroesophageal reflux.     

Esophageal chest pain

Recurrent chest pain frequently results in significant disability and anxiety, even after cardiac disease has been excluded. A stepwise approach is recommended for the diagnosis of pulmonary conditions, musculoskeletal disorders and structural problems of the upper gastrointestinal tract that can produce chest pain. If a search for these disorders proves negative, an esophageal source of chest pain should be strongly suspected. Although gastroesophageal reflux disease is the most common and easily treated cause of esophageal chest pain, esophageal motility disorders should also be considered. Motility disorders include achalasia, diffuse esophageal spasm, nutcracker esophagus, hypertensive lower esophageal sphincter and nonspecific motility disorders.     

Primary esophageal motility disorders

Esophageal motility disorders often manifest with chest pain and dysphagia. Achalasia is a disorder of the lower esophageal sphincter and the smooth musculature of the esophageal body. In achalasia the lower esophageal sphincter typically fails to relax with swallowing, and the esophageal body fails to undergo peristalsis. In contrast to spastic disorders of the esophagus, achalasia can be progressive and cause pronounced morbidity. Pseudoachalasia mimics achalasia in terms of symptoms but can be caused by infectious disorders or malignancy. Treatment for achalasia is nonstandardized and includes medical, endoscopic, and surgical options. Spastic disorders of the esophagus, such as diffuse esophageal spasm and nutcracker esophagus, and nonspecific esophageal motility disorder are benign and nonprogressive, with similar findings on esophageal manometry. Although the exact cause remains unknown, these disorders may represent a manifestation of gastroesophageal reflux disease. Treatment of spastic disorders includes medical and surgical approaches and is aimed at symptomatic relief.     

Common Problems of The Esophagus

A brief review of common neuromuscular abnormality of the esophagus is given, with particular attention to the incompetent gastroesophageal sphincter and disordered motor activity of the esophageal body. There are a few simple messages to be emphasized and remembered. 1. The esophagus does not cause vague symptoms; they are definite and well-defined. 2. Dysphagia is an organic symptom unless proved otherwise. 3. Gastroesophageal reflux is caused by a poorly functioning physiological gastroesophageal sphincter. Gastroesophageal reflux and hiatus hernia are not directly related. 4. Gastroesophageal reflux is common but rarely serious. 5. Antacid has a sound physiological basis for its effectiveness in treating gastroesophageal reflux. 6. Anticholinergic medication is bad for gastroesophageal reflux. 7. Disordered esophageal motor activity is a common occurrence and may cause symptoms.     

Catheter-based pH monitoring: use in evaluation of gastroesophageal reflux disease symptoms (on and off therapy)

Tube-based ambulatory pH testing has rapidly evolved in the past 3 decades to become the standard by which other diagnostic approaches to gastroesophageal reflux disease are judged. Acid exposure 5 cm above the manometrically determined lower esophageal sphincter is the standard for documentation of pathologic acid exposure of the distal esophagus. Proximal esophageal or hypopharyngeal monitoring is an evolving technique that may shed light on patients with supraesophageal symptoms. The ability to simultaneously monitor esophageal and gastric acidity (usually in patients with persistent symptoms despite therapy) is another advantage of this technique. Whether the new system that allows simultaneous pH and impedance monitoring and the system that uses an implantable tubeless monitoring capsule will supplant this older but well-established technology remains to be determined.     

Pathogenesis,clinical manifestations,diagnosis, and treatment progress of achalasia of cardia

Achalasia cardia, type of esophageal dynamic disorder, is a relatively rare primary motor esophageal disease characterized by the functional loss of plexus ganglion cells in the distal esophagus and lower esophageal sphincter. Loss of function of the distal and lower esophageal sphincter ganglion cells is the main cause of achalasia cardia, and is more likely to occur in the elderly. Histological changes in the esophageal mucosa are considered pathogenic; however, studies have found that inflammation and genetic changes at the molecular level may also cause achalasia cardia, resulting in dysphagia, reflux, aspiration, retrosternal pain, and weight loss. Currently, the treatment options for achalasia focus on reducing the resting pressure of the lower esophageal sphincter, helping to empty the esophagus and relieve symptoms. Treatment measures include botulinum toxin injection, inflatable dilation, stent insertion, and surgical myotomy (open or laparoscopic). Surgical procedures are often subject to controversy owing to concerns about safety and effectiveness, particularly in older patients. Herein, we review clinical epidemiological and experimental data to determine the prevalence, pathogenesis, clinical presentation, diagnostic criteria, and treatment options for achalasia to support its clinical management.     

Esophageal manifestation in patients with scleroderma

The esophagus is the most commonly affected part of the gastrointestinal system in patients with systemic sclerosis (SSc). Esophageal involvement may lead to a significant reduction in patient quality of life. The exact pathophysiology is complex and not yet fully elucidated. Ultimately, esophageal smooth muscle becomes atrophied and replaced by fibrous tissue leading to severe motility disturbance of the distal esophagus. Symptoms are mainly attributed to gastroesophageal reflux disease and to esophageal dysmotility. Compelling evidence has correlated esophageal involvement to the severity of pulmonary disease. No formed guidelines exist about the diagnostic modalities used to assess esophageal disease in patients with SSc, though upper gastrointestinal endoscopy is the first and most important modality used as it can reveal alterations commonly observed in patients with SSc. Further exploration can be made by high resolution manometry and pH-impedance study. Proton pump inhibitors remain the mainstay of treatment, while prokinetic agents are commonly used as add-on therapy in patients with symptoms attributed to gastroesophageal reflux disease not responding to standard therapy as well as to motility disturbances. Gastroesophageal reflux disease symptoms in patients with SSc are frequently difficult to manage, and new therapeutic modalities are emerging. The role of surgical treatment is restricted and should only be preserved for resistant cases.     

Stretta procedure for the treatment of gastroesophageal reflux disease.

The Stretta procedure is a noninvasive alternative for individuals suffering from gastroesophageal reflux disease, the most common disorder of the digestive tract. Over 40% of the population reports symptoms of reflux. Primary treatment is medication therapy with proton pump inhibitors and lifestyle changes. For patients whose symptoms have not been adequately controlled by proton-pump inhibitors or those unwilling to take medication indefinitely, surgery has been the only option. Laparoscopic Nissen fundoplication is the most common surgery for reflux. Recently, noninvasive options have been studied. This article discusses the Stretta procedure, the application of radiofrequency energy to the lower esophageal sphincter. The Stretta procedure is performed in conjunction with an esophagogastroduodenoscopy under conscious sedation in the endoscopy lab.     

Schatzki环研究进展

Schatzki环(SR)是一种食管贲门交界处的黏膜环,可引起食管狭窄,是间歇性固体食物吞咽困难、食物嵌顿最常见原因之一。其病因尚不明确,可能与胃食管反流有关。SR可与食管裂孔疝、Barrett食管及嗜酸细胞性食管炎等一些食管疾病并存。其最主要的诊断方法是上消化道钡剂造影。有症状的SR可以使用抑酸药物治疗、内镜下治疗及外科手术。     

Esophageal complications of gastroesophageal reflux disease: presentation, diagnosis, management, and outcomes

The esophageal complications of gastroesophageal reflux disease include peptic esophageal erosion and ulceration, peptic esophageal strictures, and Barrett's esophagus. Endoscopy is the diagnostic procedure of choice for the initial evaluation of lesions. For most patients, symptoms can be controlled with proton pump inhibitor (PPI) therapy. PPIs are also highly effective for healing esophageal erosions and ulcerations and for preventing recurrence of peptic esophageal strictures. Because Barrett's esophagus predisposes individuals to esophageal adenocarcinoma, these patients are advised to have regular endoscopic surveillance to detect early, curable neoplasms.     

Gastroesophageal reflux and bronchial asthma

Gastroesophageal reflux was established in 12 out of 38 patients with infectious allergic bronchial asthma out of exacerbation. According to intraesophageal pH-metry, it turned out appreciable in half of the cases. Prospective observations conducted for up to 8 years made it possible to recognize bronchial asthma in 9 out of 63 patients having initial reflux without any bronchopulmonary alterations. Diminution of the tone of the inferior sphincter of the esophagus proved by electromanometry should be regarded as the leading mechanism by which gastroesophageal reflux developed in bronchial asthma patients. In patients having gastroesophageal reflux without bronchopulmonary pathology, the tone of the upper sphincter of the esophagus was normal or elevated whereas in bronchial asthma patients with reflux, the tone of the superesophageal sphincter was naturally lowered, causing microaspiration into the bronchi of the gastric contents flown to the esophagus. It is desirable that metoclopramide (cerucal) which increases the initially reduced tone of the esophageal sphincters may be included into a complex of therapeutic measures elaborated for patients with associated bronchial asthma and gastroesophageal reflux.     

难治性胃食管反流病的反流危险因素调查

目的：收集胃食管反流病（gastroesophageaf reflux disease,GERD）患者的临床信息、胃镜表现以及24 h食管pH-阻抗监测结果,比较难治性GERD和非难治性GERD的反流特点,探讨难治性GERD的预测因素,为临床处理提供依据.方法：入选2008年10月-2012年12月因反酸、烧心、非心源性胸痛、咽痛等症状在复旦大学附属中山医院消化科疑诊为GERD的74例患者.记录患者的年龄、性别、身高、体质量、胃镜结果等.监测患者的食管下段pH和食管阻抗变化.难治性GERD诊断：符合GERD诊断标准,同时经过质子泵抑制剂（PPI）治疗4周（每天至少1次）无效或者deMeester评分下降少于50％;非难治性GERD诊断：符合GERD诊断标准,同时经过PPI治疗4周（每天至少1次）症状改善明显;非GERD诊断：内镜检查未见食管黏膜损害,且24 h食管pH-阻抗监测反流次数和deMeester评分不足以诊断GERD.计数资料正态分布者用r±s表示,菲正态分布者用中位数和百分位数（25th,75th）表示.采用SPSS 17.0软件进行统计学处理.按是否为GERD、是否为难治性GERD分组,比较患者的一般资料和反流特征性因素.结果：（1）难治性GERD患者与非难治性GERD患者的酸反流次数、总反流次数差异无统计学意义;难治性GERD患者的deMeester评分较非难活性GERD患者高,长酸反流次数较非难治GERD患者多（P=0.032,P=0.008）;（2）经Logistic多因素分析发现,难治性GERD与长酸反流次数、非糜烂性胃食管反流病（NERD）呈正相关（P值分别为0.01和0.045）.长酸反流次数增加1次,发生难治性GERD的危险增加36％;NERD患者发生难治性GERD的危险是反流性食管炎患者的4.54倍;（3）不同类型GERD的反流特征：NERD患者的近端反流次数大于反流性食管炎和Barrett食管患者,而近端反流百分比显著大于反流性食管炎患者和Barrett食管患者（P=0.006）.结论：（1）长酸反流次数多和NERD是难治性GERD的独立危险因素;（2）NERD患者比糜烂食管炎患者更容易发展为难治性GERD.NERD患者的近端反流百分比的升高可能与其对PPI的反应差有关.     

Behandlung der Achalasie

Achalasia is a condition of unknown etiology. It represents a motor disorder of the esophagus characterized by absent or incomplete relaxation of the lower esophageal sphincter upon swallowing and by non-propulsive swallow-induced contraction waves or amotility of the esophageal body. Dysphagia and regurgitation of ingesta are the most frequent symptoms. Medical treatment, i.e. by calcium-channel blockers and nitric oxide donors, may be tried in patients with mild dysphagia or in elderly patients but rarely yields adequate symptom relief. Mechanical dilatation of the achalasic sphincter may be performed as an initial treatment option. Intrasphincteric injections of botulinum toxin seemed to be a promising alternative, but it has become obvious that, in most cases, repeated applications of the toxin are required to maintain patients symptom-free. Myotomy of the achalasic sphincter with or without fundoplication to prevent gastroesophageal reflux, is employed mainly in patients in whom dilatations have failed, but since the introduction of minimally invasive surgery, myotomy has become the primary treatment at many centers. This article aims to provide an overview of the development of the conservative and surgical treatment of achalasia.