NK-кB mRNA及PPAR-γ mRNA在Barrett食管、食管腺癌的发病中的表达

目的 研究NF-кB及PARR-γ在Barrett食管及食管腺癌中转录水平的表达,探讨Barrett食管(BE)及食管腺癌的发病机制.方法 采用real-time PCR法检测正常食管上皮、Barrett食管黏膜及食管腺癌标本中NF-кB mRNA及PARR-γ mRNA表达情况.结果 NF-γB mRNA在BE及食管腺癌中表达均增强,其表达率平均为正常鳞状上皮的1.2058倍(P<0.01)和1.7212倍(P<0.01);PARR-γ mRNA在BE及食管腺癌中表达明显增强,其表达率分别为正常鳞状上皮的5.9130倍(P<0.01)和2.0314(P<0.01).结论 NF-кB及PARR-γ转录水平明显增高说明两者的表达上调在BE及食管腺癌的发生发展中可能起着重要作用.     

Barrett食管的内镜诊断与治疗

Barrett食管（Barrett esophagus,BE）是目前所知的唯一的食管腺癌的癌前病变。近20年来,尤其在西方国家,食管腺癌的发病率逐年升高,因此Barrett食管越来越受到关注。     

Barrett食管与腺癌

Barrett食管（Barrett’s esophagus,BE）是食管腺癌和部分贲门癌的癌前病变。目前大多数的研究认为胃．食管反流是其病因。过去三十多年中,欧美等国食管腺癌与贲门癌的发病率逐渐增加,而食管鳞癌与胃远端腺癌的发病率却逐渐下降。有报道食管腺癌在白人男性和女性中的发病率分别增加了463％和335％。BE发病率的增长速度比其他上皮恶性肿瘤都快得多,因此,这一癌前病变倍受国内外学者重视。现就目前有关BE与腺癌的一些关注热点作一介绍。     

Barrett''''s食管(BE)研究进展

Batter's食管是指食管下段正常复层鳞状上皮被化生的单层柱状上皮所取代的一种病理现象.如受累长度＞3 cm称为长段BE(Short-segment Barrett′s esopha-gus,LSBE),＜3 cm称为短段BE(Long-segment Barrett′sesophagus,SSBE).BE是食管腺癌和部分贲门癌的癌前病变之一,近年来Barrett相关食管腺癌(即BAD)的发病率有增高趋势.本文就这一疾病韵若干研究进展做一简要综述.     

Barrett食管的诊断和随访

近 20多年,食管腺癌和贲门癌的发病率在西方国家和亚洲地区均呈上升趋势,尤其是北美和西欧 [1]。食管腺癌的发生和 Barrett食管 (BE)有直接的关系。大量的研究发现,食管末端的腺癌几乎都产生于 BE,而 40％的贲门（胃－食管交界处）癌同 BE有关 [2,3]。 　　一、 BE的定义 :BE是在 1950年由一位名叫 Norman.Barrett的英国心胸外科医生首次报道,并以他的名字命名 [4]。 　　BE的最初定义 [5]：食管远端的正常鳞状上皮被柱状上皮所替代,其受累长度≥ 3cm,也称为长节段 BE（ Long－ segment Barrett's Esophagus,LSBE) [6]。 …     

Barrett食管的病因与流行病学

Barrett食管（BE）是一种具有重要临床意义的食管疾病。它与食管腺癌的发生密切相关，是一种主要的食管腺癌癌前病变，欧美近年来食管一胃交界部腺癌发生率明显升高，为所有恶性肿瘤中增长速度最快的一种，食管的原发性腺癌中约50％来自BE。     

Barrett食管的研究现状

Barrett食管（BE）是指食管远端复层鳞状上皮被单层柱状上皮所取代的一种病理学现象，又称食管下段柱状上皮化。因为首先是由英国著名的外科医生Dorman Barrett提出，所以后来这种病变即以他的名字命名。BE在欧洲和北美常见，亚洲人和黑人少见。西方国家食管腺癌比鳞癌更常见，在西欧国家近30年来食管腺癌发病率上升了8倍，上升率超过任何一种实体肿瘤。在亚洲食管腺癌也呈上升趋势。BE病人中每年约有0．5％发展为腺癌，由于BE与食管腺癌的发生关系密切，因此，BE成为近年来研究的热点。     

Barrett食管临床及内镜特点分析

Barrett食管（BE）与食管腺癌关系密切，是食管腺癌的癌前病变。现对我院近2年来确诊的BE患者的内镜下表现、临床特点及病理情况进行分析。     

血管内皮生长因子和Survivin蛋白在Barrett食管和食管腺癌组织中表达及其相关性研究

Barrett食管（BE）是指食管下段正常的复层鳞状上皮被单层柱状上皮替代的一种病理现象。BE作为食管癌的一种常见癌前病变，与Barrett腺癌（EA）关系密切，约1％的BE可发生恶变。     

老年Barrett食管

Barrett食管（Barrett’s esophagusBE）是指食管下段的复层鳞状上皮被化生的单层柱状上皮所替代的一种病理现象,它是反流性食管炎常见并发症之一,正常人群BE发生率仅1％左右,而有反流性食管炎患者发生率高达10％～15％。BE与食管腺癌发生关系密切,较正常人群发生几率高40～100倍。平均5％～10％BE遵循肠化——不典型增生——腺癌规律逐渐进展为食管腺癌,80％食管腺癌发生于BE,40％贲门腺癌与BE有关。     

Barrett's esophagus-is it bad for your health?

Barrett's esophagus is a clearly recognized risk factor for the development of esophageal adenocarcinoma. Despite the rapidly increasing incidence rate of esophageal adenocarcinoma, the vast majority of patients with Barrett's esophagus will never go on to develop this cancer. Furthermore, esophageal adenocarcinoma is a rare cause of death in Barrett's esophagus patients, and most of these patients die from other causes. While some studies demonstrate that the overall survival of patients with Barrett's esophagus is no different than that of the general population, others have suggested that Barrett's esophagus may be associated with increased mortality. Work by Solaymani-Dodran et al., in the current issue of the American Journal of Gastroenterology, found that all cause mortality was increased by 37% and mortality from causes other than esophageal cancer was increased by 23% compared to the general population, differences that were eliminated when adjusted for ischemic heart disease. Findings such as these point out the need for large, well-done epidemiologic studies of Barrett's esophagus cohorts in order to develop a better understanding of the natural history of this disease.     

Barrett's esophagus

Barrett's esophagus is an acquired condition resulting from severe esophageal mucosal injury. It still remains unclear why some patients with gastroesophageal reflux disease develop Barrett's esophagus whereas others do not. The diagnosis of Barrett's esophagus is established if the squamocolumnar junction is displaced proximal to the gastroesophageal junction and if intestinal metaplasia is detected by biopsy. Despite this seemingly simple definition, diagnostic inconsistencies remain a problem, especially in distinguishing short segment Barrett's esophagus from intestinal metaplasia of the gastric cardia. Barrett's esophagus would be of little importance were it not for its well-recognized association with adenocarcinoma of the esophagus. The incidence of esophageal adenocarcinoma continues to increase and the 5-year survival rate for this cancer remains dismal. However, cancer risk for a given patient with Barrett's esophagus is lower than previously estimated. Current strategies for improved survival in patients with esophageal adenocarcinoma focus on cancer detection at an early and potentially curable stage. This can be accomplished either by screening more patients for Barrett's esophagus or with endoscopic surveillance of patients with known Barrett's esophagus. Current screening and surveillance strategies are inherently expensive and inefficient. New techniques to improve the efficiency of cancer surveillance are evolving rapidly and hold the promise to change clinical practice in the future. Treatment options include aggressive acid suppression, antireflux surgery, chemoprevention, and ablation therapy, but there is still no clear consensus on the optimal treatment for these patients.     

Barrett's esophagus and risk of esophageal adenocarcinoma

Barrett's esophagus is most often seen in white men with chronic heartburn who are generally older than 50 years of age. The prevalence of Barrett's esophagus is 10% to 15% in patients who are undergoing endosocopy for gastroesophageal reflux disease and 1% to 2% in asymptomatic American adults. Barrett's esophagus represents metaplastic columnar tissue with specialized intestinal metaplasia, and this condition carries an increased risk of esophageal adenocarcinoma. Patients with Barrett's esophagus have a risk of esophageal adenocarcinoma 30 to 60 times that of the general population with an incidence rate of over 100 times that of the general population. Esophageal adenocarcinoma has increased dramatically over the past few decades with specialized intestinal metaplasia being the most important risk factor for the development of dysplasia and cancer. Barrett's esophagus develops in the presence of persistent gastroesophageal reflux, which is an independent risk factor for adenocarcinoma. Other risk factors for adenocarcinoma in patients with Barrett's esophagus include length of Barrett's epithelium, low-grade dysplasia, and high-grade dysplasia. New data concerning the pathophysiology and biology of Barrett's epithelium may provide answers to prevent or treat esophageal cancer. This article briefly reviews Barrett's esophagus and focuses on the risk factors associated with its progression to adenocarcinoma.     

High risk of malignancy in familial Barrett's esophagus: presentation of one family

Barrett's esophagus is an acquired condition fundamentally related to the presence of severe and prolonged pathologic acid and biliary gastro-esophageal reflux. However, genetic factors may also play a role in some cases. The aim of this study is to present 3 generations of a Spanish family with the largest number of members so far reported with Barrett's esophagus or esophageal adenocarcinoma. Of the 24 members of this family studied over 3 generations, 6 patients developed esophageal adenocarcinoma, 4 Barrett's esophagus, 6 clinical symptoms of gastro-esophageal reflux disease without Barrett's esophagus, and 8 were asymptomatic. In conclusion, patients with familial Barrett's esophagus get the disease more severely with a high rate of malignancy and, therefore, the endoscopic surveillance should be closer than in cases of nonfamilial Barrett's esophagus.     

Advances in Barrett's esophagus and esophageal adenocarcinoma

Despite advances in diagnosis and therapy, esophageal adenocarcinoma remains an aggressive and usually lethal tumor. This review focuses on the epidemiology of esophageal adenocarcinoma and its presumed precursor lesion, Barrett's esophagus; the pathogenesis of the cancer; advances in treatment of adenocarcinoma and Barrett's esophagus; and strategies for cancer prevention. Emphasis is placed on recent literature. Although the absolute number of cases of adenocarcinoma in the United States is still small, the incidence of this cancer has increased dramatically in the last 40 years, and adenocarcinoma is now the predominant form of esophageal cancer in this country. Recent evidence suggests that Barrett's esophagus is more prevalent in asymptomatic individuals than previously appreciated. The pathogenesis of Barrett's esophagus is poorly understood. Given that some subjects will have repeated bouts of severe erosive esophagitis and never develop Barrett's esophagus, host factors must play an important role. The utility of neoadjuvant radiation and chemotherapy in those with adenocarcinoma, although they are widely practiced, is not of clear benefit, and some authorities recommend against it. Ablative therapies, as well as endoscopic mucosal resection, hold promise for those with superficial cancer or high-grade dysplasia. Most series using these modalities feature relatively short follow-up, and longer-term data will be necessary to better describe the effects of these therapies. The value of chemoprevention in subjects with dysplastic Barrett's esophagus by use of cyclooxygenase 2 inhibitors, nonsteroidal anti-inflammatory drugs, or proton pump inhibitors is unknown. Similarly, although endoscopic screening is widely practiced, its value in patients with chronic gastroesophageal reflux disease symptoms is of unproven value, and recommending bodies are divided as to its practice.     

Cdx2和MUC2在反流性食管炎、Barrett食管和食管腺癌中的表达

目的研究Cdx2和MUC2在反流性食管炎、Barrett食管和食管腺癌中表达，探讨3种食管黏膜疾病的内在关系。方法选取反流性食管炎30例、Barrett食管18例及食管腺癌25例作为研究对象，以正常食管上皮黏膜25例作为对照，采用免疫组化方法检测Cdx2和MUC2的表达，对结果进行统计分析。结果Cdx2和MUC2在反流性食管炎、Barrett食管及食管腺癌中的蛋白阳性表达率均较正常对照组明显增高（P〈0．05）。Cdx2在正常食管黏膜上皮中无表达，在反流性食管炎、Barrett食管及食管腺癌中的阳性表达率分别为26．7％、66．7％和28．0％，在Barrett食管中表达明显高于反流性食管炎（P〈0．05），亦明显高于食管腺癌（P〈0．05）；MUC2在正常食管黏膜上皮和反流性食管炎组织无表达，在Barrett食管及食管腺癌中的阳性表达率分别为61．1％和24．0％，Barrett食管中表达率明显高于食管腺癌（P〈0．05）。两者表达情况相似。结论Cdx2是肠上皮化生的始动因素，MUC2的表达是肠上皮化生的晚发事件。Cdx2和MUC2在反流性食管炎、Barrett食管和食管腺癌组织中的表达情况支持这3种食管黏膜疾病间有密切的关系。     

Hiatal hernia size,Barrett's length,and severity of acid reflux are all risk factors for esophageal adenocarcinoma

OBJECTIVE: The reasons for the development of dysplasia and adenocarcinoma in Barrett's mucosa are not well understood. The aims of this study were to characterize risk factors for the transition from Barrett's esophagus without dysplasia to Barrett's esophagus with high-grade dysplasia or esophageal adenocarcinoma. METHODS: A group of 131 patients with high-grade dysplasia or esophageal adenocarcinoma were selected as case subjects. A first population of 2170 patients without gastroesophageal reflux disease (GERD) and a second population of 1189 patients with Barrett's esophagus served as two control groups. Logistic regression analyses were used to compare the risk factors associated with the occurrence of high-grade dysplasia or esophageal adenocarcinoma. RESULTS: Patients with high-grade dysplasia or esophageal adenocarcinoma shared many characteristics with other forms of severe GERD, such as older age, male gender, and white ethnicity. The length of Barrett's esophagus and the size of hiatus hernia increased the risk for both conditions. Subjects with high-grade dysplasia and adenocarcinoma had more severe acid reflux than patients with other forms of GERD. Smoking and alcohol consumption did not affect the risk for developing high-grade dysplasia or adenocarcinoma in patients with Barrett's esophagus. CONCLUSIONS: High-grade dysplasia and esophageal adenocarcinoma seem to stem from an extreme and unfavorable constellation of all risk factors that are generally held responsible for the development of GERD and Barrett's esophagus.     

Barrett's esophagus and obesity: the missing part of the puzzle

Obesity is a recognized risk factor of gastroesophageal reflux disease (GERD) and esophageal adenocarcinoma. The impact of obesity on the risk of Barrett's esophagus is unclear. This is addressed by a systematic review in this issue of the American Journal of Gastroenterology using additional data given by the authors of individual observational studies. The review suggests that although obesity is a risk factor of Barrett's esophagus, it is probably not a direct effect and is likely to be due to the association with GERD. As obesity is a strong risk factor of esophageal adenocarcinoma, more data are needed in this area. In particular, more research is needed on visceral adipose tissue and risk of esophageal adenocarcinoma, and whether obesity is an important risk factor for the development of neoplasia in those with Barrett's esophagus.     

From reflux esophagitis to Barrett's esophagus and esophageal adenocarcinoma

The occurrence of gastroesophageal reflux disease is common in the human population.Almost all cases of esophageal adenocarcinoma are derived from Barrett's esophagus,which is a complication of esophageal adenocarcinoma precancerous lesions.Chronic exposure of the esophagus to gastroduodenal intestinal fluid is an important determinant factor in the development of Barrett's esophagus.The replacement of normal squamous epithelium with specific columnar epithelium in the lower esophagus induced by the chronic exposure to gastroduodenal fluid could lead to intestinal metaplasia,which is closely associated with the development of esophageal adenocarcinoma.However,the exact mechanism of injury is not completely understood.Various animal models of the developmental mechanisms of disease,and theoretical and clinical effects of drug treatment have been widely used in research.Recently,animal models employed in studies on gastroesophageal reflux injury have allowed significant progress.The advantage of using animal models lies in the ability to accurately control the experimental conditions for better evaluation of results.In this article,various modeling methods are reviewed,with discussion of the major findings on the developmental mechanism of Barrett's esophagus,which should help to develop better prevention and treatment strategies for Barrett's esophagus.     

Gene expression profiling reveals stromal genes expressed in common between Barrett's esophagus and adenocarcinoma

BACKGROUND & AIMS: Barrett's esophagus is a precursor of esophageal adenocarcinoma. DNA microarrays that enable a genome-wide assessment of gene expression enhance the identification of specific genes as well as gene expression patterns that are expressed by Barrett's esophagus and adenocarcinoma compared with normal tissues. Barrett's esophagus length has also been identified as a risk factor for progression to adenocarcinoma, but whether there are intrinsic biological differences between short-segment and long-segment Barrett's esophagus can be explored with microarrays. METHODS: Gene expression profiles for endoscopically obtained biopsy specimens of Barrett's esophagus or esophageal adenocarcinoma and associated normal esophagus and duodenum were identified for 17 patients using DNA microarrays. Unsupervised and supervised approaches for data analysis defined similarities and differences between the tissues as well as correlations with clinical phenotypes. RESULTS: Each tissue displays a unique expression profile that distinguishes it from others. Barrett's esophagus and esophageal adenocarcinoma express a unique set of stromal genes that is distinct from normal tissues but similar to other cancers. Adenocarcinoma also showed lower and higher expression for many genes compared with Barrett's esophagus. No difference in gene expression was found between short-segment and long-segment Barrett's esophagus. CONCLUSIONS: The genome-wide assessment provided by current DNA microarrays reveals many candidate genes and patterns not previously identified. Stromal gene expression in Barrett's esophagus and adenocarcinoma is similar, indicating that these changes precede malignant transformation.