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.     

Short segment Barrett esophagus and specialized columnar mucosa at the gastroesophageal junction

The rising incidence of adenocarcinoma of the esophagus and the gastric cardia has generated interest in the finding of intestinal metaplasia or specialized columnar mucosa in this location. Short segment Barrett esophagus is defined by the presence of columnar-appearing mucosa in the distal esophagus (<3 cm in length) with intestinal metaplasia on biopsy. In contrast, intestinal metaplasia may also be present if biopsy specimens are obtained from a normal-appearing squamocolumnar junction or from the gastric cardia (ie, immediately below the gastroesophageal junction) in the absence of columnar lining of the distal esophagus. This has been termed cardia intestinal metaplasia, gastroesophageal junction intestinal metaplasia, or specialized columnar mucosa at the gastroesophageal junction. This article reviews the currently available data on these rapidly evolving entities of short segment Barrett esophagus and specialized columnar mucosa at the gastroesophageal junction.     

Barrett esophagus: update for radiologists

Barrett esophagus is a well-recognized entity in which there is progressive columnar metaplasia of the lower esophagus due to longstanding gastroesophageal reflux and reflux esophagitis [1]. This condition is important because it is associated with an increased risk of developing esophageal adenocarcinoma by a well-established sequence from dysplasia to carcinoma [2]. During the past decade, however, an explosion of new data has dramatically affected our understanding of Barrett esophagus. Not only have revised histopathologic criteria been developed for this condition, but it is currently believed that patients with Barrett esophagus should be classified as having short-segment or long-segment disease based on the extent of columnar metaplasia in the distal esophagus. This distinction has important implications for the risk of developing esophageal adenocarcinoma and subsequent need for endoscopic surveillance. The purpose of this article is to present these new concepts about Barrett esophagus and provide radiologists with a more current framework for diagnosing this condition.     

The history of Barrett esophagus

The term Barrett esophagus has become well established in the medical literature to indicate columnar metaplasia of the distal esophagus associated with chronic gastroesophageal reflux disease. However, the historical events that led to the use of this term have become obscured. Here, the historical aspects of Barrett esophagus are reviewed, providing insight not only to this condition but also to the evolution of medical thought in general.     

Barrett食管37例临床分析

目的探讨Barrett食管（BE）临床特点及相关致病因素。方法对经胃镜及病理检出的37例Barrett食管进行回顾性分析。结果37例BE病人中有烧心、胸骨后疼痛、反酸等反流性食管炎症状者各占73．0％、64．9％和51．4％，无症状者3例（8．1％）。胃镜下伴有反流性食管炎表现者占89．2％，伴有胆汁反流者7例（18.9％），胃动力减弱者6例（16．2％）。病理检查结果为37例食管下段复层鳞状上皮被柱状上皮取代。结论BE多见于老年人，其发病主要与胃食管反流有关；小部分无明显胃食管反流症状和反流性食管炎胃镜表现的病人，其病因还有待进一步研究。     

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.     

套扎辅助内镜下黏膜切除术治疗Barrett食管的前瞻性研究

目的 研究套扎辅助黏膜切除治疗Barrett食管的有效性、安全性。方法 采用前瞻性研究。套扎辅助黏膜切除治疗57例Barrett食管患者。单环或多环套扎器预先吸引病灶形成假息肉,后再通电切除。切除前不予黏膜下注射。术后1个月复查胃镜。结果 57例患者接受套扎辅助黏膜切除,46例为岛型,11例为舌型。舌型组中特殊肠化、异型增生发生率高于岛型组。活检准确率为94.74%。5例术中出血。无狭窄、穿孔发生。结论 套扎辅助黏膜切除用于Barrett食管诊断治疗安全有效。     

Rationale for surgical therapy of Barrett esophagus

Barrett esophagus has malignant potential and seems to be an acquired abnormality. It is associated with chronic gastroesophageal reflux disease and represents its severest form. The literature comparing medical treatment with antireflux surgery was reviewed. Questions regarding the advantages of surgery, who should undergo surgery, whether surgery can change the course of Barrett esophagus, the change in cancer risk, who needs surveillance, and cost-effectiveness were addressed. The incidence of developing Barrett cancer was 1 in 145 patient-years in reviewing 2032 patient-years of medical therapy compared with 1 in 294 patient-years in reviewing 4122 patient-years after surgery. Median follow-up time in the 2 groups was 2.7 years in the medically treated patients and 4.0 years in the surgically treated patients. Surveillance of Barrett esophagus is required irrespective of treatment. Laparoscopic antireflux surgery was found to be cost-effective after 7 years. Although these data do not prove that surgery is superior to medical treatment in the prevention of cancer related to Barrett esophagus, we found a tendency for surgery to be better than medical therapy to prevent the development and progression of Barrett carcinoma.     

The use of imaging and biomarkers in diagnosing Barrett’s esophagus and predicting the risk of neoplastic progression

Long-standing gastroesophageal reflux disease can result in transformation of the normal squamous lining of the esophagus into columnar epithelium (with goblet cells). This condition, Barrett’s esophagus (BE), is considered a risk factor for esophageal cancer (EAC) and may be the cause of the increased incidence of EAC over the last few decades. Currently, endoscopy with biopsies revealing dysplasia is the best predictor for neoplastic progression in patients with BE. However, the use of more sophisticated imaging techniques and biomarkers with or without histological assessment may be helpful in more accurate prediction of malignant transformation in these patients. New approaches to the evaluation of BE such as epigenetics, miRNA analysis, detection of DNA content abnormalities and loss of heterozygosity have great potential to shed light on the complex gastroesophageal reflux disease –BE–EAC sequence.     

The definition of Barrett's esophagus

Recently, according to increasing gastroesophageal reflux disease (GERD), the patients with Barrett's esophagus (BE) are increasing. Since Barrett have reported cases of esophageal ulcers surrounding by columnar epithelium, the various criteria of the BE have been proposed. In 1998, practice guidelines for BE were developed under the auspices of the American College of Gastroenterology. They proposed that BE was a chance in the esophageal epithelium of any length that can be recognized at endoscopy, and confirmed to have intestinal metaplasia by biopsy of the tubular esophagus and excludes intestinal metaplasia of the cardia. Endoscopically, BE is determined, when 'gastric-appearing mucosa' or apparent 'columnar lined esophagus' is evident proximal to the esophagogastric junction. Histologically, BE has double muscularis mucosae, and contains a mixture cell types; gastric-fundic type epithelium, junctional type epithelium, and specialized columnar epithelium (SCE). Especially SCE is distinctive features of BE, available for diagnosis. On the other hand, BE is premalignant condition for the adenocarcinoma of the esophagus, therefore the features of the BE are researched to prevent and find out earlier development of adenocarcinoma. In this review, we referred to the definition of BE with some topics.     

氩离子凝固术治疗巴瑞特食管的临床观察

目的探讨内镜下氩离子凝固术(APC)治疗Barrett食管(BE)的临床疗效。方法选择21003年5月至2004年2月经内镜检查及病理组织学检查诊断的BE患者22例,在内镜下行APC治疗,氩离子凝固治疗单次启动延续时间及启动次数视病灶大小、数目情况而定,一般以内镜下整个病灶凝固为止,所有病例1～3个月内复查内镜。结果22例BE患者中1例失访,1例未到复查时间,其余20例BE患者至复查时17例(85％)胃镜下未见复发,2例在原来部位有散在BE上皮残留,1例在其他部位有新BE上皮生长。结论APC是经内镜非接触性治疗BE的新方法,操作方便,短期疗效较好。     

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.     

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.     

Barrett's esophagus complicating scleroderma

Two patients with scleroderma whose esophageal involvement was associated with longstanding reflux esophagitis were found to also have Barrett's esophagus. Since Barrett's esophagus is a premalignant condition, these patients with scleroderma should be considered at high risk for the development of adenocarcinoma of the esophagus.     

Barrett食管治疗的临床证据

目的针对Barrett食管的治疗方法，进行证据检索和评价，为临床医生和患者提供有关Barrett食管治疗的最新循证医学证据。 方法计算机检索MEDLINE（1978～2006）、CBMdisc（1978～2006）及Cochrane图书馆（2005年第3期），查找与Barrett食管治疗有关的临床随机对照试验、系统评价等，并对所搜集的证据进行评价。 结果Barrett食管的治疗方法包括饮食干预、改变生活方式、药物治疗、内镜下治疗及外科手术治疗等，可依据患者病情选择不同治疗方法。 结论内镜下治疗已取得很大进展，多种治疗方法联用可取得良好效果。     

Poor results of 5-aminolevulinic acid-photodynamic therapy for residual high-grade dysplasia and early cancer in barrett esophagus after endoscopic resection

BACKGROUND AND STUDY AIMS: The aim of the study was to evaluate the efficacy of photodynamic therapy (PDT) in the treatment of residual high-grade dysplasia or early cancer (HGD/EC) after endoscopic resection in Barrett esophagus. PATIENTS AND METHODS: Study patients were separated into group A, with proven residual HGD/EC, and group B with possible HGD/EC (positive lateral margins in the endoscopic resection specimen, without HGD/EC in the remaining Barrett esophagus). PDT treatment consisted of 5-aminolevulinic (5-ALA) photosensitization (40 mg/kg) followed by illumination of the Barrett esophagus with a total light dose of 100 J/cm (2). Complete remission was defined as the absence of HGD/EC in biopsies taken in two consecutive follow-up endoscopies. The percentage regression of Barrett esophagus, as well as the recurrence rate of HGD/EC, was calculated. RESULTS: 20 patients underwent PDT (group A, 11; group B, 9). Mild complications were seen in 4/26 procedures. The overall success rate was 15/20 (75 %). There was a significant difference in success rate between group A (55 %) and group B (100 %); P = 0.03. All patients had residual Barrett esophagus after PDT; the median regression percentage was 50 % (IQR 25 - 70 %). Recurrence of HGD/EC occurred in four patients (two each in groups A and B) after a median follow up of 30 months. CONCLUSIONS: In this selected group of patients, the addition of 5-ALA-PDT after endoscopic resection for HGD/EC had a disappointing success rate in patients who had residual HGD/EC after endoscopic resection. Most patients undergoing 5-ALA-PDT have residual Barrett mucosa after PDT and 5-ALA-PDT does not seem to prevent recurrences during follow-up.     

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.     

多环黏膜切除术治疗Barrett食管的临床研究

目的研究内镜下应用多环黏膜切除术（multiband mucosectomy,MBM）治疗Barrett食管。方法采用前瞻性研究的方法,在窄波成像（narrow band imaging,NBI）下确认Barrett食管病变范围,用多环黏膜切除器吸引病灶,套扎橡皮圈后用圈套器电切。3个月复查胃镜,评估疗效。结果134例Barrett食管患者共切除病灶206块。急性并发症出血发生率6.7%（9/134）,无一例发生穿孔。术后30d内（迟发性并发症）出血发生率1.5%（2/134）,出现食管狭窄症状39.8%（53/133）;30d后（远期并发症）主要为食管狭窄,发生率2.3%（3/133）。术后3个月复查胃镜,病灶完整切除率98.5%（131/133）。结论内镜下MBM术治疗Barrett食管,简便、安全、有效。     

Endoscopic and histologic diagnosis of Barrett esophagus

Endoscopy plays an important role in the identification, diagnosis, and treatment of Barrett esophagus. Short-segment (<2-3 cm) and traditional long-segment (>2-3 cm) Barrett esophagus are distinguished solely on the length of metaplastic tissue above the esophagogastric junction. The histologic hallmark of intestinal metaplasia is required to confirm diagnosis. Biopsy specimens obtained from tissue of presumed Barrett esophagus or an irregular Z line confirm metaplastic glandular mucosa and permit evaluation of dysplastic or neoplastic changes. In the appropriate clinical setting, the use of adjunctive diagnostic techniques may facilitate the diagnosis of Barrett esophagus and sequelae such as dysplasia. Chromoendoscopy with high-resolution or magnified endoscopy is simple, safe, and desirable for surveillance but requires additional procedural time. The use of light-induced fluorescence endoscopy and light-scattering spectroscopy (i.e., optical biopsy) is appealing for the diagnosis and characterization of suspicious lesions. Adjunctive endoscopic techniques and adherence to a protocol for performing biopsies facilitate the early detection and subsequent surveillance of Barrett esophagus.     

Barrett's esophagus: a multifaceted condition.

Five patients with Barrett's esophagus, each with a differing presentation, serve as the basis of this report. Hiatal hernia is noted to be frequently present in Barrett's esophagus, and the incidence of adenocarcinoma is thought to be distinctly increased. The condition is easily diagnosed by fiberoptic endoscopy and verified by direct biopsy. The increasing use of fiberoptic panendoscopy may lead to an increased frequency of diagnosis of the columnar cell-lined lower esophagus and its complications.