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.     

Histopathology of columnar-lined esophagus in patients with gastroesophageal reflux disease

BACKGROUND AND AIMS: The question of whether an endoscopically normal-appearing esophagogastric junction should be biopsied in patients with gastroesophageal reflux disease is controversial. We have addressed this issue using endoscopy and histopathology. METHODS: A total of 114 consecutive patients (58 males) with symptoms of gastroesophageal reflux disease prospectively underwent endoscopy, including biopsy sampling from the esophagogastric junction. Endoscopically visible columnar-lined esophagus was defined by the presence of gastric-type mucosa above the level of the rise of the gastric folds. Histopathology was conducted using the Paull-Chandrasoma classification. RESULTS: Of the 114 patients, 85 (74.6%) had endoscopically visible columnar-lined esophagus of length < or =0.5 cm (n = 82), 1 cm (n = 2) and 7 cm (n = 1); 29 patients (25.4%) had a normal endoscopic junction. All patients had histopathologic columnar-lined esophagus. Intestinal metaplasia and low-grade dysplasia was identified in 26 (22.8%) and 5 (4.4%) individuals, respectively, and was not statistically different in endoscopically normal vs. abnormal junction (P = 0.408 for intestinal metaplasia, P = 0.775 for low grade dysplasia). Intestinal metaplasia was independent from endoscopic esophagitis (P = 0.398) and hiatal hernia (P = 0.405). CONCLUSIONS: Columnar-lined esophagus cannot be excluded by endoscopy. In patients with gastroesophageal reflux disease, biopsy sampling of normal-appearing junction is recommended for histopathologic exclusion of intestinal metaplasia and low-grade dysplasia.     

Barrett食管患者幽门螺杆菌感染率的Meta分析

目的分析Barrett食管患者幽门螺杆菌感染率及caga阳性的幽门螺杆菌感染率，并与内镜检查正常者和胃食管反流病患者比较，探讨幽门螺杆菌（Helicobacter pylori，Hp）感染与Barrett食管的关系。方法计算机检索MEDLINE和EMbase数据库至2008年2月，纳入比较Barrett食管患者和内镜检查正常者及胃食管反流病（gastroesophageal reflux disease，GERD）患者Hp感染率的病例对照研究或队列研究。统计分析采用RevMan4．2．8，计算比值比OR（95％CI）。结果共纳入19篇文献，包括16篇病例对照研究和3篇队列研究。病例对照研究分析结果显示，Barrett食管患者比内镜检查正常者Hp感染率低[OR0．56，95％CI（0．40，0．79）]，与GERD患者相比差异无统计学意义[OR0．86，95％CI（0．74，1．00）]。队列研究的分析结果显示，Barrett食管患者与内镜检查正常者及GERD患者相比Hp感染率差异无统计学意义[OR1．12，95％CI（0．77，1．61）；OR1．10，95％CI（0．32，3．83）]。cagA阳性Hp感染率较内镜正常者及GERD患者低[OR0．30，95％CI（0．12，0．74）；OR0．55，95％CI（0．33，0．94）]。病例对照研究长节段较短节段Barrett食管Hp感染率低[OR0．32，95％CI（0．16，0．66）]。而队列研究结果显示，长节段较短节段Barrett食管患者Hp感染率差异无统计学意义[OR0．66，95％CI（0．29，1．48）]。结论Barrett食管患者和GERD患者Hp感染率无差别，Barrett食管患者Hp感染率，特别是cagA阳性Hp菌株感染率较内镜检查正常者明显减少。     

P物质在BARRETT食管黏膜组织中的表达

目的研究P物质在BARRETT食管（BE）黏膜组织中的表达,探讨其在BE发病中的作用。方法应用免疫组织化学方法测定P物质在正常对照组（n=25）及BE组（n=58）中的表达,并比较P物质在不同化生程度、伴或不伴胆汁反流BE组中表达的差异。结果 P物质在BE中的表达低于对照组,且胃化生（＋）BE组P物质表达高于肠化生（＋）BE组,差异均有显著性（t=9.98、3.25,P〈0.05）;伴胆汁反流BE组P物质表达明显低于不伴胆汁反流BE组（t=3.04,P〈0.05）,而伴胆汁反流BE组肠化生阳性率高于不伴胆汁反流BE组,差异有显著性（χ2=4.99,P〈0.05）。结论 BE组存在P物质分泌失调,其可能在BE的发生发展中起着一定作用;胆汁反流可能影响BE黏膜P物质的分泌,而与肠化生的发生可能有关。     

Role of minimally invasive surgery in the modern treatment of Barrett's esophagus

Gastroesophageal reflux disease (GERD) is a highly prevalent disease. Population studies have demonstrated that a significant proportion of individuals weekly experience GERD symptoms. Barrett's esophagus (BE), defined by the presence of intestinal metaplasia (columnar epithelium with goblet cells), is considered a consequence of chronic reflux. This review defines the role of surgery in the modern treatment of BE, taking into consideration the pathophysiology of the disease and the new endoscopic procedures available at present.     

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.     

Histology of Barrett's esophagus and dysplasia

This article explores issues related to the diagnosis of Barrett's esophagus (BE) in endoscopic biopsies and dysplasia in Barrett's epithelium. The definitions of BE, including long- and short-segment BE, are reviewed, with an emphasis on the significance of intestinal metaplasia (IM). IM of the gastroesophageal junction and cardia is reviewed and problems in its distinction from short-segment BE are discussed. In addition, the article reviews the classification of dysplasia in Barrett's mucosa, with reference to problematic areas, such as sampling error and interobserver variability. Biomarkers and their role in the diagnosis of dysplasia and stratification of risk are summarized.     

Barrett's esophagus: pathogenesis, treatment, and prevention

Esophageal adenocarcinoma is the most common type of esophageal cancer seen in the United States and Western Europe. Barrett's esophagus (BE) is a well-known risk factor for esophageal adenocarcinoma and is believed to be found in 6% to 12% of patients undergoing endoscopy for gastroesophageal reflux disease and in more than 1% of all patients undergoing endoscopy. This article focuses on the pathogenesis, treatment, and prevention of BE.     

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.     

Barrett's esophagus in children

Barrett's esophagus (BE) is a condition of esophageal dysplasia in which the tubular esophagus is lined with columnar instead of squamous mucosa--not with just any type of columnar mucosa, but with a specialized type with goblet cells. It is considered to be an acquired phenomenon secondary to acid exposure from gastro-esophageal reflux (GER). This report shows a review of BE of children and our data about BE from the study of 19 handicapped children with GER. 3 had intestinal dysplasia with goblet cells (BE). The % time of pH under 4 on 24-hour pH monitoring was significantly lower in the patients with esophagitis including BE than in them with normal esophagus. BE of our study seemed to be reversible after the surgery and anti-acid therapy. It is suggested that BE is not a rare condition even in children and biopsy specimens should be taken to establish the diagnosis.     

Pathogenesis of Barrett's esophagus--new findings in the experimental studies of duodenal reflux models

Duodeno-gastro-esophageal reflux has been thought to induce Barrett's esophagus. Recently, we designed a new duodenal reflux model using rats, and studied sequential morphological changes of esophageal mucosa leading to Barrett's esophagus. A specialized columnar epithelium (SCE) developed 20 weeks after operation. Barrett's epithelium originated from pyloric-foveolar metaplasia of stem cells in the basal layer of the esophageal squamous epithelium. The pyloric-foveolar metaplasia was then followed by the appearance of goblet cells, becoming a typical SCE. The expression of homeobox gene Cdx2 was seen in this process, thereby suggesting a role of Cdx2 in intestinal differentiation of Barrett's esophagus. We noticed the pyloric-foveolar metaplasia followed by the appearance of goblet cells is common to entire gut in regenerative process, and proposed a concept of GRCL (gut regenerative cell lineage), and an implication of GRCL in digestive tract carcinogenesis was discussed.     

Gastroesophageal reflux disease and Barrett's esophagus

Several articles have been published during the last year that may affect the management of patients with gastroesophageal reflux disease (GERD) and/or Barrett's esophagus in the near future. A new method of measuring esophageal pH has been introduced that does not require an indwelling transnasal catheter and may allow a more physiological assessment of esophageal acid exposure. Several articles discussed the use of endoscopic antireflux procedures, and a sham-controlled randomized study was published concerning the Stretta procedure. A long-term follow-up study and a decision analysis study have again fueled the debate concerning the relevance of surveillance of Barrett's patients, whereas other studies focused on techniques that may improve the detection of specialized intestinal metaplasia and dysplasia within the Barrett's segment. Finally, several studies have reported promising results with the endoscopic treatment of Barrett's metaplasia and early neoplasia using ablation techniques or endoscopic resection modalities. This review summarizes the most important articles in the field of GERD and Barrett's esophagus that have been published in peer-reviewed journals during the last year that are relevant to the practicing endoscopist.     

Barrett's esophagus: Clinical issues

Barrett's esophagus has been defined conceptually as the condition in which any extent of metaplastic columnar epithelium that predisposes to cancer development replaces the stratified squamous epithelium that normally lines the distal esophagus. The condition develops as a consequence of gastroesophageal reflux disease. Barrett's metaplasia has clinical importance primarily because of its malignant predisposition, and virtually all of the contentious clinical issues in Barrett's esophagus are related in some way to its cancer risk. This article considers some key clinical issues that impact the management of patients with Barrett's esophagus.     

Circumferential endoscopic mucosal resection in Barrett's esophagus with high-grade intraepithelial neoplasia or mucosal cancer. Preliminary results in 21 patients

BACKGROUND AND STUDY AIMS: Treatment by endoscopic mucosal resection (EMR) has been established for early lesions in Barrett's esophagus. However, the remaining Barrett's esophagus epithelium remains at risk of developing further lesions. The aim of this study was to evaluate the efficacy of circumferential endoscopic mucosectomy (circumferential EMR)s in removing not only the index lesion (high-grade intraepithelial neoplasia (HGIN) or mucosal cancer), but also the remaining Barrett's esophagus epithelium. PATIENTS AND METHODS: A total of 21 patients were included in the study (11 men, 10 women), who had Barrett's esophagus and either HGIN (n = 12) or mucosal cancer (n = 9). Of the patients, 17/21 were at high surgical risk and five had refused surgery. On the basis of preprocedure endosonography their lesions were classified as T1N0 (n = 19) or T0N0 (n = 2). The lesions and the Barrett's esophagus epithelium were removed by polypectomy after submucosal injection of 10-15 ml of saline; a double-channel endoscope was used in 15/21 cases. Circumferential EMR was performed in two sessions, the lesion and the surrounding half of the circumferential Barrett's esophagus mucosa being removed in the first session. In order to prevent the formation of esophageal stenosis, the second half of the Barrett's esophagus mucosa was resected 1 month later. RESULTS: Complications occurred in 4/21 patients (19 %), consisting of bleeding which was successfully managed by endoscopic hemostasis in all cases. No strictures were observed during follow-up (mean duration 18 months) and endoscopic resection was considered complete in 18/21 patients (86 %). For three patients, histological examination showed incomplete removal of tumor: one of these underwent surgery; two received chemoradiotherapy, and showed no evidence of residual tumor at 18 months' and 24 months' follow-up, respectively. Two patients in whom resection was initially classified as complete later presented with local recurrence and were treated again by EMR. Barrett's esophagus mucosa was completely replaced by squamous cell epithelium in 15/20 patients (75 %). CONCLUSIONS: Circumferential EMR is a noninvasive treatment of Barrett's esophagus with HGIN or mucosal cancer, with a low complication rate and good short-term clinical efficacy. Further studies should focus on long-term results and on technical improvements.     

Increased DNA adducts in Barrett's esophagus and reflux-related esophageal malignancies

BACKGROUND: DNA adduct formation can initiate carcinogenic processes. AIM: To examine the pre-malignant condition of Barrett's esophagus by measuring the DNA adducts. METHODS: DNA adducts were measured in the proximal and distal esophagus of patients with Barrett's esophagus (n = 9), patients with adenocarcinoma in the distal esophagus/esophagogastric junction (n = 28), and in control group of patients (n = 8) using the 32-P-postlabeling method. The average levels of DNA adducts are expressed as mean adducts/10(9) nucleotides + standard error of the mean. RESULTS. The average DNA adduct levels in the distal esophagus were significantly higher in both the Barrett's esophagus (24.5 +/- 7.9) and the adenocarcinoma (12.0 + 3.0) than in the control patients (0.1 +/- 0.08), P < 0.001. In the proximal esophagus, the DNA adduct levels were approximately equal in the Barrett's esophagus (7.0 +/- 1.0) and in the adenocarcinoma group (6.4 +/- 0.65). However, the levels in the proximal esophagus in both groups were significantly higher than in the control group (2.1 +/- 0.67), P < 0.05. CONCLUSIONS: Patients with Barrett's esophagus and patients with esophageal/esophagogastric junction adenocarcinoma had significantly more DNA adducts than the control group. These results support the current concept of the carcinogenic potential of chronic gastroesophageal reflux, and the pre-malignant condition of Barrett's esophagus.     

Barrett's esophagus

The Barrett's esophagus showing columnar metaplasia upward to the esophagus from the esophago-gastric junction is one of the final appearance of reflux esophagitis and important as a precancerous state of esophageal adenocarcinoma. Especially the Barrett's mucosa with intestinal metaplasia has high potential risk for adenocarcinoma. Although the clinical definition of the esophago-gastric junction is not easy, the criteria of the esophago-gastric junction and the Barrett's mucosa proposed by the Japanese Society for Esophageal Diseases is useful. The gastro-esophageal reflux is important in the development of Barrett's mucosa not only in the classical Barrett's esophagus but also in the short-segment Barrett's.     

The clinical strategy for the Barrett's esophagus

The treatment of Barrett's esophagus is controversial. Current treatments include endoscopic therapy, surgical procedures, gastric acid-suppressive therapy with proton pump inhibitors (PPIs), and cancer chemoprevention such as nonsteroidal anti-inflammatory drugs. Endoscopic therapy combined with gastric acid suppressive therapy can result in squamous reepithelialization of the Barrett's mucosa. Antireflux surgery and PPIs therapy are potential options for the treatment of gastroesophageal reflux symptoms in patients with Barrett's esophagus. But there are no prospective studies that support any alternative approach to treatment. Although chemoprevention therapy may reduce cancer risk in Barrett's esophagus, no randomized controlled trials that prove its efficacy have been reported.     

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.     

Non-biopsy detection of intestinal metaplasia and dysplasia in Barrett's esophagus: a prospective multicenter study

BACKGROUND AND STUDY AIMS: There have been no multicenter studies investigating the use of magnification chromoendoscopy (MCE) for the detection of intestinal metaplasia and dysplasia/cancer in Barrett's esophagus. Our aims were to assess the ability of MCE to predict the histological diagnosis (non-biopsy detection), to compare the yield of MCE-targeted versus random biopsies for dysplasia, and to compare procedure times. PATIENTS AND METHODS: In this prospective multicenter study, patients with known or suspected Barrett's esophagus underwent MCE with indigo carmine dye staining. Three mucosal patterns (ridge/villous, circular, and irregular/distorted) were standardized, based on past experience. Mucosal patterns were noted and target biopsies were obtained only if irregular/distorted patterns were identified. Otherwise, random four-quadrant biopsies were obtained. RESULTS: A total of 56 patients (mean age 64 years, mean length of Barrett's esophagus 2.7cm) were prospectively evaluated: 38 patients (67.8 %) had ridge/villous patterns, four patients (7.1 %) had circular patterns, four patients (7.1 %) had irregular/distorted patterns, and ten patients (17.8 %) had a combination of patterns. Histologically, intestinal metaplasia was not shown in eight patients (14.2 %), nondysplastic Barrett's esophagus was diagnosed in 30 patients (53.5 %), low-grade dysplasia was detected in 12 patients (21.4 %), and high-grade dysplasia was detected in six patients (10.7 %). An irregular/distorted pattern either throughout the entire segment of Barrett's esophagus or in combination with a ridge/villous or circular pattern had a sensitivity or 83 %, a specificity of 88 %, a positive predictive value of 45 %, and a negative predictive value of 98 % for high-grade dysplasia. The yield of high-grade dysplasia was similar for the two techniques but the time taken to perform MCE was less than the time taken to perform random biopsies. CONCLUSION: An irregular/distorted pattern is specific for high-grade dysplasia and so it may not be necessary to perform biopsies in patients with ridge/villous or circular mucosal patterns.     

In vivo endoscopic optical coherence tomography of esophagitis, Barrett's esophagus, and adenocarcinoma of the esophagus

BACKGROUND AND STUDY AIMS: We studied the feasibility of endoscopic optical coherence tomography imaging in esophageal disorders, including Barrett's esophagus and Barrett-related adenocarcinoma. Optical coherence tomography is a high-resolution cross-sectional imaging technique with a resolution of almost 10 microm. PATIENTS AND METHODS: The mucosal architecture of reflux esophagitis (n = 9) and Barrett's esophagus (n = 9) including Barrett-related esophageal cancer (n = 6) was studied by optical coherence tomography imaging. RESULTS: In different stages of reflux esophagitis edema, fibrinoid deposits, or loss of the epithelial layer were observed. Optical coherence tomography images of Barrett's esophagus substantially differed from normal esophagus, reflux esophagitis, and esophageal carcinoma. A stratified structure of the mucosa was still preserved in Barrett's esophagus. However, images of Barrett-related cancer lacked the regular structure of the esophagus. CONCLUSIONS: The high consistency of the first optical coherence tomography findings, the resolution of up to 10 microm, and the distinct pattern of normal, inflammatory, premalignant and malignant tissues make optical coherence tomography a promising method for endoscopically obtained optical biopsy.