Epidemiology and etiology of eosinophilic esophagitis

Eosinophilic esophagitis (EE) is an inflammatory disease of the esophagus characterized by eosinophilic infiltration of the esophageal mucosa. Symptoms of EE are variable, and include gastroesophageal reflux symptoms, abdominal pain, growth failure, and dysphagia. Dysphagia is a more common presentation in adults and older children. Serious complications of EE consisting of esophageal food impactions necessitating urgent endoscopic removal of the food and esophageal strictures requiring endoscopic balloon dilatations are also seen. The potential severity of these symptoms points to the importance of proper recognition and management of the disease, especially given that EE has become more prevalent over the past decade. In this article, available evidence on the epidemiology and etiology of EE is discussed.     

L’œsophagite à éosinophiles

Eosinophilic esophagitis (EE) is a recent diagnosis of growing prevalence which must be considered in children and adult patients, more often in male. EE is a chronic, immune/antigen-mediated, and esophageal-limited disease characterized by eosinophil-predominant inflammation. EE should always be considered in any impaction or dysphagia, but the spectrum of clinical manifestations is broad including manifestations of gastro-esophageal reflux disease resistant to anti-secretory. The endoscopic appearance alone can be misleading and only histological examination can confirm the diagnosis by showing infiltration of the esophagus with eosinophils. In other cases, drug therapy is based on inhibiting the proton pump and topical steroids aimed at controlling inflammation to prevent progression to fibrosis and esophageal strictures.     

Esophageal dysmotility in patients who have eosinophilic esophagitis

The understanding of esophageal motility alterations in patients who have eosinophilic esophagitis (EE) is in its infancy despite the common presenting complaint of dysphagia. A diversity of motility disorders has been reported in patients who have EE including achalasia, diffuse esophageal spasm, nutcracker esophagus, and nonspecific motility alterations including high-amplitude esophageal body contractions, tertiary contractions, abnormalities in lower esophageal sphincter pressure, and other peristaltic problems. Some evidence suggests that treatment of EE will improve motility. Technological advances such as high-resolution manometry and combined manometry with impedance may provide new insight into more subtle motility abnormalities.     

Translational research on the pathogenesis of eosinophilic esophagitis

Eosinophilic esophagitis (EE) is an inflammatory disease of the esophagus characterized by eosinophilic infiltration of the esophageal epithelium. EE is a relatively new disease from clinical and research standpoints. A recent surge in basic and translational studies has emerged to understand its pathogenesis since its recognition as a separate entity from acid-induced gastroesophageal reflux disease in 1995. Our understanding of this disease is still limited, however. In this article, available evidence from translational studies on EE is discussed, focusing on the allergic nature of the disease and highlighting the role of various inflammatory cells found in the esophagus of patients who have EE. Esophageal remodeling in EE is also discussed.     

Esophageal cancer: an overview.

Esophageal cancer is the second most common solid intrathoracic malignancy behind lung cancer. Treatment of esophageal cancer is dependent upon the stage of presentation and the options include chemotherapy, radiation therapy, surgery, multimodality therapy, or palliative care. Early detection of this disease is the primary method to decrease its high morbidity and mortality.     

Basic pathogenesis of eosinophilic esophagitis

Eosinophilic esophagitis (EE) is a newly recognized disease, which has largely been called idiopathic EE, emphasizing the poor understanding of its pathogenesis. EE is a severe disease of the esophagus characterized by an accumulation of eosinophils in the esophageal mucosa, and is highly associated with atopic disease. Nevertheless, the nomenclature "eosinophilic esophagitis" describes only the tip of the iceberg of a complex disorder, as the pathogenesis of EE involves multiple tissues, cell types, and genes, and derives from complex genetic and environmental factors. This article defines the fundamental knowledge available to date that characterizes the mechanisms by which certain etiological factors cause EE, reviewing human studies, murine models, and recent knowledge regarding the involvement of environmental, cellular, molecular, and genetic factors in the development of EE.     

放大内镜下胃食管反流病患者食管乳头内毛细血管环形态学观察

目的探讨胃食管反流病（GERD）患者食管乳头内毛细血管环（IPCL）形态学检查在GERD诊断中的临床价值及护理。方法对非糜烂性食管炎（NERD）患者20例、糜烂性食管炎（EE）患者20例和10例健康志愿者行24h食管pH监测,采用白光和放大内镜窄波成像（NBI）模式观察食管下段黏膜IPCL形态并进行分型,同时配合有效的护理措施。结果3组受检者顺利完成内镜检查。NERD组患者24h食管pH监测阳性率为55％,EE组为90％,健康对照组均为阴性,NERD组低于EE组;放大内镜NBI模式下健康对照组食管IPCL呈茶色规律排列的卷发状、小螺旋状;NERD组85％及EE组100％食管IPCL形态为Ⅱ型,但仍排列规律,与健康对照组比较差异均有统计学意义（P〈0．05）。结论食管ICPL形态特异性改变有助于GERD的内镜诊断;高质量的护理配合对顺利完成内镜检查起到了重要的作用。     

Barrett's esophagus

Esophageal cancer staging is a widely accepted indication for endoscopic ultrasonography (EUS). The evaluation of Barrett's esophagus (BE) with EUS is indicated only when there is high-grade dysplasia or a concern for malignancy in an endoscopic lesion. Because the options for the management of BE and early adenocarcinoma are diverse, proper selection of patients by accurate staging with EUS is critical, particularly when nonoperative management is considered. For example, patients with BE with high-grade dysplasia may be offered esophagectomy in some medical centers, but nonoperative therapies such as endoscopic ablative therapy or mucosal resection may be the preferred treatment options in other gastroenterology practices. This article discusses the scientific evidence for the use of EUS in BE or early esophageal adenocarcinoma.     

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.     

Expandable stents for malignant esophageal disease

Esophageal cancer is diagnosed in about 400,000 patients each year worldwide, and its incidence is increasing faster than that of any other malignancy. This makes it the ninth most common malignancy and sixth on the list of cancer mortality causes. Most patients with esophageal cancer present at a stage that is too advanced for curative therapy, and many die within a few months. Treatment of dysphagia is the main goal of palliative care in more than 50% of incurable cases. Although many different palliative options for malignant dysphagia are available, expandable stent placement is the most commonly performed treatment modality.     

Endoscopic palliation of malignant dysphagia.

Esophageal cancer is the primary cause of malignant dysphagia, a major cause of morbidity and mortality. In patients with esophageal cancer that is unresectable at the time of diagnosis, palliation is the major goal. Surgical treatment as well as radiation and chemoradiation therapy are traditional approaches for such patients. Endoscopic therapy is useful for patients with poor performance status, those in whom other treatments have failed, and those with tracheoesophageal fistulas. In recent years, self-expanding metal stents have become an important new endoscopic treatment modality for palliation of malignant dysphagia in a wide range of patients. Appropriate patient selection is paramount when a mode of palliation for malignant dysphagia is being selected. Although various treatment options exist for palliation of malignant dysphagia, comparative studies among these modalities are needed.     

Angiogenesis-related agents in esophageal cancer

Introduction: Esophageal cancer is an aggressive disease with poor prognosis. The majority of the patients are diagnosed at an advanced stage and many with early stage disease will develop recurrent disease. Areas covered: Angiogenesis is essential to the progress and aggressiveness of solid malignancies. Success of anti-angiogenic therapy in colorectal, lung and breast cancers is a proof of principle. Thus far, evidence for benefit from anti-angiogenic therapy in esophageal cancer is lacking. Several Phase II trials with different agents have provided mixed results and the only Phase III trial in the esophageal and gastric cancer failed to show that these agents improve overall survival (OS). However, lack of observed benefit could be due to the challenges specific to the management of esophageal cancers as well as issues with the design of clinical trials for anti-angiogenic therapy. Expert opinion: An understanding of the biology of the esophageal cancer and its management is essential to the development of anti-angiogenic therapy in this disease. This article reviews the management of esophageal cancer and elaborates on the challenges in the development of anti-angiogenic therapy in esophageal cancer. At the end, strategies are proposed for successful development of anti-angiogenic therapy in esophageal cancer.     

Angiogenesis in esophageal and gastric cancer: a paradigm shift in treatment

Introduction: Esophageal and stomach cancers are leading cause of cancer death worldwide, killing more than 1 million people each year. In unscreened population, patients’ symptoms will trigger diagnostic workup. Most patients are diagnosed with advanced stage and their disease is not amenable to surgical resection. The disease is aggressive in nature and mostly even those patients who have early stage disease will eventually succumb to recurrence after definitive therapy. Patients with advanced esophageal and stomach cancers have very limited options for target agents and conventional chemotherapy has remained the standard of care.

Areas covered: Since its discovery, antiangiogenesis continues to be the repeating theme of cancer therapy of the modern era. However, although successful in other tumor types, the data from highly anticipated antiangiogenic agents from both the small molecule tyrosine kinase inhibitors and monoclonal antibodies for esophageal and gastric cancers had been disappointing. Many attribute the lack of survival benefit noted in clinical trials to the failure in identifying target in this patient population.

Expert opinion: The most recent clinical studies support that specifically attacking vascular endothelial growth factor receptors remain effective in esophageal and gastric cancers. These pivotal trials may prove to shift the paradigm of current therapy and will likely gain approval for the drug of interest. At the same time, the results generate more questions to understand the disease biology as well as to identify those patients who will benefit the most from such therapy.     

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.     

Management of gastroesophageal reflux disease

Gastroesophageal reflux disease is the most common and expensive digestive disease with complex and multi-factorial pathophysiologic mechanisms. Transient inappropriate relaxation of the lower esophageal sphincter is the predominant mechanism in the majority of patients with mild to moderate disease. Hiatal hernias and a reduced lower esophageal sphincter pressure have a significant role in patients with moderate to severe disease. Typical manifestations of gastroesophageal reflux disease include heartburn, regurgitation, and dysphagia. Atypical symptoms, such as noncardiac chest pain, pulmonary manifestations of asthma, cough, aspiration pneumonia, or ENT manifestations of globus and laryngitis, can be seen in patients with or without typical symptoms of gastroesophageal reflux disease. Endoscopy and ambulatory pH tests are best to evaluate the anatomic and physiologic impact ofgastroesophageal reflux disease. Complications of chronic gastroesophageal reflux disease include peptic strictures and Barrett metaplasia. Barrett esophagus is a major risk factor for esophageal adenocarcinoma, and upper endoscopy with surveillance biopsies is recommended for patients with Barrett esophagus. Medical therapy with anti-secretory agents (H2 blockers and proton pump inhibitors) is effective for most patients with gastroesophageal reflux disease. Surgical fundoplications and endoscopic treatment modalities are mechanical treatment options for patients with gastroesophageal reflux disease.     

PET/CT在食管癌分期诊断中的价值

目的评价18F-FDG PET/CT在食管癌分期诊断中的价值。方法对86例病理已明确证实为食管癌的患者进行PET/CT检查,利用18F-FDG在肿瘤病灶及转移灶中的高代谢原理,分析全身各系统病灶放射性摄取的最大标准摄取值（SUVmax）,对患者进行准确的诊断分析。结果 PET/CT的分期准确率（88.4%）以及区域淋巴结转移检查的敏感性（63.3%）、特异性（83.8%）均较单纯CT高。结论 18F-FDG PET/CT检查对食道癌患者的临床分期和治疗选择具有重要的指导意义。     

Esophageal dysmotility in patients undergoing photodynamic therapy

OBJECTIVE: To study the esophageal motility of patients with esophageal adenocarcinoma or Barrett esophagus with high-grade dysplasia before and after photodynamic therapy. PATIENTS AND METHODS: In this prospective study conducted between January 1998 and October 1999, esophageal motility testing of the lower esophageal sphincter and esophageal body was performed with a water-perfused catheter, 2 days before and at least 3 weeks after patients underwent photodynamic therapy for esophageal adenocarcinoma or Barrett esophagus. Results were classified as normal motility, ineffective esophageal motility, or aperistalsis. RESULTS: Twenty-three patients were studied, 13 with carcinoma and 10 with Barrett esophagus. Overall, 11 patients (48%) had normal motility, 6 (26%) had ineffective esophageal motility, and 6 (26%) had aperistalsis. Five patients with aperistalsis had carcinoma. Follow-up tracings after photodynamic therapy found that 6 patients (26%) had normal motility, 7 (30%) had ineffective esophageal motility, and 10 (43%) had aperistalsis. CONCLUSIONS: Esophageal dysmotility is common in patients with esophageal adenocarcinoma or Barrett esophagus. Photodynamic therapy may worsen esophageal motility in some patients. Dysphagia after photodynamic therapy therefore may be related to underlying esophageal dysmotility and may not always be caused by stricture or underlying carcinoma.     

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.