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.     

Histochemical diagnosis of short segment Barrett's esophagus

Recently, we have many chances of findings of Barrett's esophagus in routine endoscopic examination. It is also reported that we have few frequent findings of typical Barrett's esophagus, long segment Barrett's esophagus (LSBE) which is seen predominantly in Europe and United States, however the frequency of finding of short segment Barrett's esophagus (SSBE) and adenocarcinoma derived from SSBE is gradually increasing in Japan. So it is thought that precise diagnosis of SSBE and the evaluation of potential malignancy of SSBE are needed in the present medical management. The present study has shown the differences of characteristics of mucinous contents and malignant potentials between in SSBE and LSBE by use of biopsy specimen taken by endoscopic procedure. It is well known that Barrett's epithelium is categorized gastric fundic type, junctional type and specialized columnar epithelium, especially Barrett's mucosa is characterized by specialized columnar epithelium, e. g. incomplete epithelial type of intestinal metaplasia. We have set up two characteristic groups, gastric mucin dominant and intestinal mucin dominant by using specific mucin staining for MUC2, MUC5AC, Con A and CD10. In results, we confirmed that 80% of specialized columnar epithelia revealed intestinal mucin dominant in LSBE and 77% revealed gastric mucin dominant as compared with 23%, intestinal mucin dominant. Moreover, we have examined the ability of cell proliferation using Ki67-immunostaining in Barrett's epithelia. It was demonstrated that positive immunoactivity of Ki67 in proliferative zone was shown in 37.5% of gastric mucin dominant and 76.5% of intestinal mucin dominant. The results described above suggested that specialized columnar epithelia with intestinal mucin dominant have a higher potential of malignant transformation. We concluded that the evaluation of characteristics of mucinous contents in specialized columnar epithelia plays an important role in determination of high risk group of carcinogenesis in the case of SSBE.     

Endoscopic diagnosis and surveillance of Barrett's esophagus

There are many questions regarding the screening and surveiliance of BE for which there are currently no answers. Despite the use of models and extrapolations by some authors to suggest that screening and surveiliance for a cancer of such low incidence will never be justified, others argue just as vociferously that given the continued epidemic rise in incidence of this cancer, the uniformly fatal outcome of these cancers if dianosed after symptoms occur, and the enormous pool of patients remaining at risk for future cancer development, a focused and prudent screening and surveillance strategy for Barrett's-related esophageal adenocarcinoma is justified. The data also show that a single screening examination is probably as effective as almost all subsequent surveilance examinations in detecting advanced neoplasia, and much of the current resource use and energy for screening and surveillance in BE should be directed toward screening. Whether screening should be offered or recommended to only older patients (> 50-55 years), whites, and men is unknown, but it is premature to adopt this strategy until better evidence exist supporting a restricted screening policy. Regarding the optimal surveilance frequency and technique, examinations more frequent than every 3 to 5 years are not justifiable, and until proven otherwise, biopsy specimens should be obtained with the largest forceps that can be used with the endoscopic instrument and "saturation" biopsies from the Barrett's obtained. It is unlikely that too many biopsy specimens can be taken. Furthermore, the safety of this approach has been, proven. It is quite likely that the inverse is not true; clinicians likely can do much more harm by taking too few biopsy specimens. It is hoped that the current intense interest in Barrett's neoplasia allows clinicians to address these critical issues in the years to come and resolve this clinical conundrum.     

内镜窄带成像诊断Barrett食管的作用研究

目的 探讨内镜窄带成像在早期发现Barrett仕食管(BE)中的特殊肠上皮化生(SIM)细胞等癌前病变中的作用.方法 2008年6月～12月间,共25例经胃镜检查确诊为内镜BE患者,分别采用普通模式、NBI模式进行观察,并用NBI模式进行BE黏膜腺管开口分型,于改变最明显处取活检行病理检查.结果 在对鳞一柱状上皮交界的病变轮廓、黏膜腺管开口形态及毛细血管结构形态的观察中,NBI显著优于普通内镜;NBI模式下通过Endo分型,其Ⅳ型、V型腺管开口检出SIM的准确性、敏感性、特异性分别为92%、86%及94%.结论 NBI可清晰观察BE黏膜病变轮廓、腺管开口形态及毛细血管结构形态;操作转换简单易行,对BE食管进行靶向活检具有良好指导意义及临床使用价值.     

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.     

Barrett's esophagus

Gastroesophageal reflux disease (GERD) is a condition commonly managed in the primary care setting. Patients with GERD may develop reflux esophagitis as the esophagus repeatedly is exposed to acidic gastric contents. Over time, untreated reflux esophagitis may lead to chronic complications such as esophageal stricture or the development of Barrett's esophagus. Barrett's esophagus is a premalignant metaplastic process that typically involves the distal esophagus. Its presence is suspected by endoscopic evaluation of the esophagus, but the diagnosis is confirmed by histologic analysis of endoscopically biopsied tissue. Risk factors for Barrett's esophagus include GERD, white or Hispanic race, male sex, advancing age, smoking, and obesity. Although Barrett's esophagus rarely progresses to adenocarcinoma, optimal management is a matter of debate. Current treatment guidelines include relieving GERD symptoms with medical or surgical measures (similar to the treatment of GERD that is not associated with Barrett's esophagus) and surveillance endoscopy. Guidelines for surveillance endoscopy have been published; however, no studies have verified that any specific treatment or management strategy has decreased the rate of mortality from adenocarcinoma.     

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.     

Barrett's esophagus: observations on diagnosis and management.

Barrett's esophagus is a premalignant condition that may often pass unrecognized in clinical practice. In adults, this condition is generally believed to be caused by chronic gastroesophageal reflux resulting in a metaplastic change in the epithelium of the esophagus. Diagnosis of Barrett's esophagus is established by careful biopsy of the involved esophageal mucosa. Periodic surveillance is recommended because of the risk of carcinoma. Antireflux surgery has not been shown to result consistently in the regression of the metaplastic epithelium, but potent acid suppression offers a new therapeutic approach that leads to healing of esophagitis and the potential regression of Barrett's epithelium.     

Carcinogenesis of Barrett's esophagus

Barrett's esophagus is a premalignant condition and remains the number one risk factor for developing adenocarcinoma. Gastro-esophageal reflux disease is a strong risk factor for both esophageal adenocarcinoma and the precancerous lesion Barrett's esophagus. Both of these conditions are related to the reflux of acid and bile into the esophagus. This results in inflammation and cell damage which initiates a sequence of events termed the metaplasia-dysplasia sequence in which the squamous epithelium is replaced by columnar epithelium exhibiting increasing degrees of dysplasia and overt malignancy. The underlying disease mechanisms remain unclear, but tumor suppression genes (p53, p16, APC) and, oncogenes (K-ras, cyclin D1, c-erb-2) seem to cause the malignant transformation of Barrett's esophagus, and the genetic or epigenetic alterations of these genes have been reported.     

窄带成像技术诊断Barrett食管的临床应用价值

目的:通过对Barrett食管(BE)在窄带内镜下的图像特征与组织学的一致性进行比较,探讨窄带成像技术(NBI)诊断BE的临床应用价值.方法:对76例临床拟诊BE的患者进行NBI检查,根据黏膜和血管的形态行NBI图像分类,并与组织病理学进行比较.结果:在NBI模式下,对BE诊断的敏感性、特异性、阳性预测值分别为74.2%、78.6%和93.9%,明显高于常规内镜.与组织学比较,无肠化生的BE,NBI下黏膜形态多表现为A型,高级别黏膜内瘤变(HGD)的黏膜形态全表现为D型,而肠化生(SIM)和低级别黏膜内瘤变(LGD)两者的黏膜形态多表现为C型.结论:NBI可明显提高对BE诊断的准确率,且与组织学有较好的一致性.     

Radiologic diagnosis of Barrett's esophagus: Critical analysis of 65 cases

A recent increase in the number of Barrett's esophagis being diagnosed is probably directly related to a proportional increase in endoscopic biopsies of the esophagus and awareness of premalignant potential of Barrett's mucosa. While the endoscopist can detect Barrett's mucosa with fair degree of accuracy, the radiologic diagnosis of Barrett's esophagus still remains a diagnostic challenge despite several well established radiologic features. We reviewed 65 patients with pathologically proven Barrett's esophagus and found a wide spectrum of radiologic features. These include hiatus hernia in 49, gastroesophageal reflux in 38, strictures in 32, esophagitis in 20, and characteristic Barrett's ulcer in 12. In addition ascending or migrating strictures were found in 10, mucosal pattern simulating areae gastricae in 5, cricopharyngeal dysfunction in 4, and fixed spiral folds in 3 patients. This constellation of radiologic features, some of which have not been previously emphasized, should further assist radiologists in suggesting the diagnosis of Barrett's esophagus.     

Barrett's esophagus: chemoprevention

The clinical applicability of the experimental data discussed previously remains questionable, and results of clinical studies on chemoprevention in Barrett's esophagus are needed. The utility of selectively targeting acid exposure, ODC, and COX-2 is not clear, and elucidation of that role will be facilitated by a better understanding of the contribution of these factors in the development of Barrett's cancers. The insights already gained into the basic mechanisms of acid exposure, ODC, and COX-2 in the pathogenesis of Barrett's esophagus and esophageal adenocarcinoma hold promise for the development of future therapies aimed at these molecular targets and their signaling pathways. In preclinical studies, the ability of COX-2 selective NSAIDs and DFMO to inhibit carcinogenesis is encouraging. Results of well-designed, prospective clinical studies, however, are still needed to establish the efficacy of potent acid suppression, COX-2 inhibitors, and DFMO in the prevention of this malignancy.     

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.     

Biomarkers in Barrett's esophagus

This article provides a framework for clinicians who are attempting the difficult task of interpreting the Barrett's biomarker literature with the goal of improving care for their patients. Although many articles. including more that 60 proposed biomarkers, have been published on this subject, only a few describe phase 3 and 4 studies that are of interest to the clinical gastroenterologist (Table 1). For year, dysplasia grade has been the sole means of risk stratification for patients with BE, and it likely will continue to be used in the foreseeable future. The current authors believe that dysplasia classification can be valuable using the team management approach and quality controls described previously. Significant problems, however, have emerged in phase 2 through 4 studies of dysplasia that make it imperative for the Barrett's field to incorporate additional biomarkers as they are validated. These problems include poor reproducibility of dysplasia interpretations, poor predictive value for negative, indefinite, and low-grade dysplasia, and inconsistent results for HGD in different centers, all of which makes it virtually impossible to develop national guidelines for surveillance. Some studies have even suggested that endoscopic biopsy surveillance using dysplasia may not be worthwhile. Currently, flow cytometric tetraploidy and aneuploidy have progressed furthest in biomarker validation (see Table 1). With proper handling, endoscopic biopsy specimens can be shipped to reference laboratories that have the instruments, computer analytic methods, and expertise to reproducibly detect tetraploidy and aneuploidy. The results of phase 4 studies indicate that flow cytometry appears to be useful in detecting a subset of patients who do not have HGD and yet have an increased risk of progression to cancer that cannot be identified by dysplasia grade. For many reasons, the authors anticipate that the number of validated biomarkers will increase substantially in the future. Biopsy repositories are now readily available for phase 3 studies that can evaluate and compare biomarkers. There are initiatives for multi-institutional Barrett's Centers of Excellence that could provide rapid progress in biomarker evaluation. In addition to new candidate biomarkers, the human genome project has provided high-throughput methodologies and methods for computer analysis of data, which can provide the volume and quality control required for clinically useful biomarkers. Currently, 17p (p53) LOH has progressed the furthest among molecular biomarkers. The authors do not recommend its routine clinical use at the present time, however. Finally, it is likely that clinicians will want to follow the results of clinical treatment-response studies and epidemiologic studies that evaluate relationship between clinical interventions or environmental risk and protective factors and surrogate endpoints, especially if the endpoints are progessing well along the phases of biomarker validation. These studies are likely to be of clinical interest because they may becoming the basis for randomized clinical trials to prevent cancer in BE.     

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.