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.     

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。     

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.     

Detection of Barrett's epithelium by acoustic microscopy

Barrett's esophagus is associated with increased risk of adenocarcinoma of the gastroesophageal junctional region. The presence of goblet cells (intestinal metaplasia) in columnar cell-lined esophageal mucosa defines Barrett's change. The diagnosis of Barrett's esophagus is based on the presence of intestinal metaplasia in a biopsy from an endoscopically visualized abnormal columnar epithelium. In this pilot study, acoustic microscopy was used to identify the mucosal structure of 10 distal esophageal biopsies. Sections cut at 5 microm of archival paraffin blocks on glass slides were used for this study. Acoustic microscopy permitted the identification of low- and high-power images of epithelial architecture and cellular detail, including Barrett's epithelium. This modality of visualization has the potential to detect lesions such as Barrett's metaplasia, low- and high-grade dysplasia and early carcinoma. If it can be applied to in vivo endoscopy, acoustic microscopy has the potential to increase the accuracy of the diagnosis of Barrett's esophagus, dysplasia and malignancy by providing a method of accurately directing biopsies at endoscopy.     

Endoscopic therapy for Barrett's esophagus

With the increase in the rate of esophageal adenocarcinoma in the United States and the Western world matched with the high morbidity and mortality of esophagectomy, there is an increasing need for new and effective techniques to treat and prevent esophageal adenocarcinoma. A wide variety of endoscopic mucosal ablative techniques have been developed for early esophageal neoplasia. However, long-term control of neoplasic risk has not been demonstrated. Most studies show that specialized intestinal metaplasia may persist underneath neo-squamous mucosa, posing a risk for subsequent neoplastic progression. In this article we review current published literature on endoscopic therapies for the management of Barrett's esophagus.     

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.     

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.     

Endoscopic diagnosis of Barrett's esophagus

In Japan Barrett's mucosa is defined as columnar lined esophagus (CLE). The prevalence of Barrett's esophagus and Barrett's adenocarcinoma is very low. But in Western countries Barrett's mucosa is defined as CLE with intestinal metaplasia, and many cases of Barrett's esophagus and Barrett's adenocarcinoma are reported. The definite endoscopic diagnosis of Barrett's mucosa cannot be so easy. We investigated the positional relationship between the esophageal hiatus, squamo-columnar junction, and longitudinal vessels in persons who underwent esophagogastroduodenoscopy. Subepithelial longitudinal vessels were found at the lower esophagus in all cases. In no cases were the longitudinal vessels observed under the gastric mucosa beyond the esophageal hiatus. It is peculiar to the esophagus to be able to observe subepithelial longitudinal vessels in the vicinity of the esophago-gastric junction. When longitudinal vessels are found only under the columnar epithelium at the oral side over the esophageal hiatus from the stomach, this indicates Barrett's epithelium. Thus the definite diagnosis of Barrett's epithelium can be made by endoscopy.     

食管胃结合部癌前病变和早期癌的研究进展

Siewert将在食管胃连接部上下5 cm范围内发生的肿瘤定义为食管胃结合部肿瘤,包括远端食管腺癌、真正意义上的贲门癌和近端胃癌。传统上认为远端食管腺癌起源于Barrett食管黏膜,与反流相关疾病关系密切;贲门腺癌起源于贲门黏膜,与幽门螺杆菌感染关系密切;而近端胃癌则与幽门螺杆菌和肠化具有较强的关联性。反流相关疾病、Barrett食管和肠上皮化生、幽门螺杆菌感染等与食管胃结合部肿瘤的关系一直是该部位肿瘤的研究热点,但是也存在强烈的争议。随着食管胃结合部解剖学和组织学发展成熟,结合早期发现该部位癌变倾向,使得关于食管胃结合部癌变的病因、分子机制、解剖学及组织学上的探讨越来越深入明朗。因此在早期发现该部位病变并加以干预可以有效地帮助临床和科研工作者解决困扰,同时显著提高肿瘤患者的生存率。     

Barrett's esophagus: screening and prognosis

The diagnostic criteria for Barrett's disease have changed very considerably during the last 10 years. Classically, the definition asked for columnar epithelium in the lower esophagus extending for at least 3 cm proximally. Now, the diagnosis rests on the finding of specialised intestinal metaplasia, i.e. columnar epithelium with goblet cells, in the esophagus, regardless of the extension. This is important because it is this type of metaplasia that is associated with an increased risk for the development of esophageal adenocarcinoma and esophageal adenocarcinoma is the tumor with the fastest rising incidence in the western world in recent years. The criteria of the current definition of Barrett's esophagus are described in detail and the implications this change in definition carries for screening and surveillance of patients is discussed.     

Diagnosis of esophagogastric tumors

It has been suggested that certain histological criteria may serve to indicate a good prognosis in patients with esophageal carcinoma. These include absence of subepithelial extension of the carcinoma cells, stage no higher than m2, and no neoplastic involvement near the resection margin. As endoscopic mucosal resection is becoming an accepted treatment option in this type of tumor, prognostic parameters of this type are of particular interest. By contrast, when metastases are detected in the celiac lymph nodes, it implies that the tumor is unresectable and that palliative treatment is required. Endoscopic ultrasound (EUS)-guided fine-needle aspiration has been found to be the most cost-effective option in this setting. Although autofluorescence endoscopy is being tested as a new technique for endoscopic diagnosis, its value is at present unclear. However, such developments may lead to improved diagnosis in the future, particularly in relation to the initial stages of carcinoma. For the moment, EUS is still the most widely accepted method for early diagnosis and staging. Esophageal squamous-cell carcinoma appears to be commonly associated with head and neck cancer, but the cost-effectiveness of surveillance is a matter of controversy. With regard to Barrett's esophagus and adenocarcinoma, p53 staining in areas of low-grade dysplasia appears to be helpful for predicting progression to high-grade dysplasia. The prevalence of short-segment Barrett's esophagus increases with age, but the length of the segment does not increase with time; the length probably depends on individual conditions, not merely on elapsed time. Helicobacter pylori infection appears to be associated with intestinal metaplasia at the esophagogastric junction. However, the most recent data appear to suggest that this scenario (usually termed "carditis") may be different from intestinal metaplasia in the lower esophagus, related to acid reflux. A follow-up program might be able to detect Barrett's esophagus adenocarcinoma at earlier stages, but only a minority of Barrett's esophagus patients are likely to be detected before neoplasia has developed. Gastric cancer appears to develop in individuals with H. pylori infection, but not in uninfected persons. In addition, those with severe gastric atrophy, corpus-predominant gastritis, and intestinal metaplasia may be at greater risk for gastric cancer. This again raises the question of H. pylori eradication in asymptomatic individuals with infection, and surveillance of patients with severe intestinal metaplasia. The most recent data appear to support the notion that healing of MALT lymphoma depends not only on H. pylori eradication and on the stage of the tumor, but also on individual factors (possibly immunology-related).     

CK7、CK20对短节段Barrett食管与贲门部肠上皮化生的诊断价值探讨

目的利用细胞角质蛋白(CK)中的CK7/CK20免疫组化染色反应的不同,对胃镜、病理检查难以区分的短节段Barrett食管(SSBE)及贲门部肠上皮化生(CIM)诊断价值进行探讨。方法根据肠上皮化生(IM)的部位将观察对象分为4组:SSBE伴IM组、CIM组、长节段Barrett食管(LSBE)伴IM组和胃窦部肠上皮化生(GA-IM)组,各组病理检查组织分别进行粘液组织化学AB-PAS、HID-AB染色以及CK7/CK20免疫组织化学染色,并进行各组胃食管反流(GERD)症状及Hp感染情况对比。结果SSBE伴IM与LSBE伴IM CK7/CK20免疫组织化学染色反应相同,以Barrett′s类型为主(72.2%),明显高于CIM(27.3%),差异显著(P<0.01),具有GERD症状者Barrett′s类型发生率(88.9%)较高,明显高于胃类型(14.6%)者,差异有显著意义(P<0.01),CIM与GA-IM CK7/CK20免疫组织化学染色相似,以胃类型为主,与SSBE伴IM及LSBE伴IM比较有显著差异(P<0.01),SSBE伴IM与LSBE伴IM肠化类型主要为Ⅲ型,分别为66.7%,75.0%,与CIM及GA-IM比较差异显著(P<0.01),而CIM与GA-IM肠化类型主要为Ⅰ、Ⅱ型。各组Hp感染率无明显差异(P>0.05)。结论CK7/CK20免疫组化染色反应表现为Barrett′s类型或胃类型对SSBE与CIM的鉴别有重要价值,CK7/CK20免疫组化染色反应表现为Bar-rett′s类型,同时结合有GERD症状,Ⅲ型IM有助于SSBE诊断。反之,CK7/CK20免疫组化染色反应表现为胃类型,无GERD症状,以及Ⅰ、Ⅱ型IM,则提示CIM。     

Reflux disease and Barrett's esophagus

Gastroesophageal reflux disease (GERD) is a common clinical problem. New information suggests that infection with Helicobacter pylori may protect patients from developing GERD and its complications. Endoscopy may be used by clinicians to tailor GERD therapy, but an empirical trial of a proton-pump inhibitor may be an alternative diagnostic approach. Studies continue to show that laparoscopic antireflux surgery is a cost-effective treatment option for patients requiring maintenance therapy with proton-pump inhibitors. However, the minimally invasive nature of the operation should not alter the indications for antireflux surgery, especially for patients with atypical symptoms. It remains unclear why some patients with GERD develop Barrett's esophagus, whereas others do not. Recent guidelines suggest that patients with long-standing GERD symptoms, especially white men over 50 years of age, should undergo endoscopy at least once to screen for Barrett's esophagus. Debate concerning short-segment Barrett's esophagus continues. Intestinal metaplasia at a normal-appearing gastroesophageal junction may be associated with intestinal metaplasia of the stomach and infection with H. pylori, whereas short tongues of intestinal metaplasia in the esophagus are associated with GERD. Cancer surveillance is indicated in short-segment Barrett's esophagus, as dysplasia may develop in these patients. Barrett's esophagus is the only known risk factor for the development of esophageal adenocarcinoma, but the incidence of adenocarcinoma may be lower than previously reported. New clinical guidelines for endoscopic surveillance suggest that the surveillance interval should be lengthened to every two years in patients without dysplasia. Newer treatment options, such as thermal ablation and photodynamic therapy, continue to show promise, but are not yet ready for routine clinical use.     

Biology of Barrett's esophagus and esophageal adenocarcinoma

The past few years have brought new advances in our understanding of the molecular mechanisms underlying the development of Barrett's esophagus and esophageal adenocarcinoma. Although knowledge of the genetic basis for these conditions has not yet translated into clinically useful biomarkers, the current pace of biomedical discovery holds endless possibilities for molecular medicine to improve the diagnosis and management of patients with these conditions. This article provides a useful conceptual basis for understanding the molecular events involved in the making of Barrett metaplasia and in its neoplastic progression, and provides a rationale for evaluating studies on the application of molecular medicine to the diagnosis and management of patients with Barrett's esophagus and esophageal adenocarcinoma.     

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.     

Reflux of duodenal or gastroduodenal contents induces esophageal carcinoma in rats

We observed the sequential development of columnar lined epithelium associated with adenocarcinoma, squamous dysplasia related with squamous cell carcinoma and adenosquamous carcinoma which were induced by duodeno-esophageal or gastro-duodeno-esophageal reflux in rats. Wistar male rats, weighing approximately 250 g were employed. Animals received total gastrectomy and were reconstructed with esophago-jejunostomy, which causes unavoidable duodeno-esophageal reflux. The animals were sacrificed every 10 weeks after surgery until 50 weeks. Erosions and basal cell hyperplasia were observed in the lower esophageal squamous epithelium at 10 weeks after surgery. At 20 weeks, glandular structures featured with galactose oxidase-Schiff-positive staining (foveolar metaplasia) appeared in the basal layer of esophageal squamous epithelium. At 30 weeks, the glands developed and formed cysts which were stained with concanavalin A (pyloric glandular metaplasia) or/and high iron diamine and alcian blue (intestinal metaplasia). Since 40 weeks after surgery, esophageal carcinomas were found. As adenocarcinomas were surrounded by the columnar-lined epithelium, squamous cell carcinoma and adenosquamous carcinoma were accompanied by squamous dysplasia. Persistent duodeno-esophageal reflux can change the stem cells of squamous epithelium to make columnar-lined cells. As part of the sequence of events leading to the development of columnar-lined epithelium, foveolar metaplasia was observed followed by the appearance of pyloric glandular metaplasia and intestinal metaplasia. Chronic duodenal reflux induces the development of esophageal carcinoma not only adenocarcinoma also squamous cell carcinoma and adenosquamous carcinoma. These pathways of carcinogenesis were different dual patterns.     

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.     

Risk prediction in Barrett’s esophagus – aspects of a combination of molecular and epidemiologic biomarkers reflecting alterations of the microenvironment

Abstract

Barrett’s esophagus (BE) is a chronic, metaplastic lesion of the esophagus and the only known precursor of esophageal adenocarcinoma. The identification of risk factors to assess the risk for BE and their correspondence with hallmarks of malignant progression for early stratification purposes is critically needed. Data legitimate the assumption that aside of reflux symptoms and related conditions, also demographic and environmental factors are thought to be associated with the risk for BE and its progression to esophageal adenocarcinoma. Molecular biomarkers and inflammatory mechanisms are subjects of intensive research and dispone of promising features regarding risk assessment especially for progressive BE. The amount of investigated epidemiologic factors, as well as discovered biomarkers gets confusingly large. Despite the recognized potential relevance of environmental and molecular factors, the efforts to date have resulted in moderately applicable risk estimates. More prospective data is needed to allow an imputation of the mostly retrospectively assessed factors to reappraise their meaningfulness in risk prediction approaches.