Barretts Esophagus

巴雷特食管

• 批准号: 8763662
• 负责人: Michael Cook
• 金额: $ 35.04万
• 依托单位: DIVISION OF CANCER EPIDEMIOLOGY AND GENETICS
• 依托单位国家: 美国
• 资助国家: 美国
• 起止时间: 至
• 项目状态: 未结题
• 来源: https://reporter.nih.gov/project-details/8763662
• 关键词: Alcohols; Androgens; Barrett Epithelium; Barrett Esophagus; Biological; Body mass index; Boston; Breath Tests; Case-Control Studies; Cells; Chemicals; Collaborations; Costs and Benefits; Data; Databases; Diagnosis; Diagnostic; Disease; Endoscopy; Epidemiologic Studies; Epithelium; Equation; Esophageal Adenocarcinoma; Esophagitis; Esophagus; Estrogens; Etiology; Exposure to; Future; Gastroenterology; Gastroesophageal reflux disease; General Population; General Practices; Goals; Heterogeneity; Hormones; Incidence; Individual; Lesion; Malignant Neoplasms; Malignant neoplasm of esophagus; Manuscripts; Medical center; Medicare; Metabolic syndrome; Metaplasia; Metaplastic; Modality; Natural History; Non-Steroidal Anti-Inflammatory Agents; Patients; Population; Population Study; Prognostic Marker; Publications; Publishing; Reflux; Relative (related person); Research; Research Personnel; Resources; Risk; Risk Factors; Serum; Somatomedins; Squamous Cell; Staging; Survival Rate; Time; Tissues; Tobacco smoking; Triage; United States; Universities; Work; adiponectin; base; bile salts; clinical practice; cohort; comparative; disorder control; disorder risk; follow-up; high risk; indexing; prognostic; volatile organic compound; volunteer; waist circumference

This project covers a broad range of studies which focus on elucidating risk factors for, and the natural history of, esophageal adenocarcinoma (esophageal cancer) and the precursor lesion Barretts esophagus (aka Barrett esophagus). Barretts esophagus is a metaplastic change in the lower esophagus which is characterized by the replacement of the native squamous cell epithelium with a glandular-type of epithelium. This metaplastic change is thought to be primarily the result of genotoxic damage induced by gastroesophageal refluxacid and bile salts reflux up into the esophagus, exposing cells not equipped to deal with these reactive chemicals. Re-epithelization with the metaplastic Barretts epithelium provides for a tissue which is better able to withstand the exposure to such compounds. However, it also increases the risk of esophageal adenocarcinoma approximately 10-50 fold that of the general population. The incidence of esophageal adenocarcinoma has increased over 650% in the United States over the last 35 years and most individuals present with late stage malignancies, resulting in a 5-year survival rate of less than 20%. This indicates that researchers need to be able to better identify those at high risk and Barretts esophagus is a good starting point. However, although this metaplasia greatly increases the risk of esophageal adenocarcinoma relative to the general population, the absolute risk remains low at around 0.5% or 1 in 200 patient years of follow-up. This is because approximately 90% of individuals who develop esophageal adenocarcinoma are diagnosed at their first (index) endoscopy. Thus, not only do we need to be able to better identify those with high risk (Barretts esophagus) in the general population, we also need to be able to triage these individuals into high and low risk groups so that surveillance resources can be focused on those who most need them, which would make the cost-benefit equation of surveillance endoscopy more attractive. Therefore, the ultimate goals of all the studies within this project seek to better understand the natural history of this disease, risk factors for progression, diagnostic markers and modalities with high sensitivity, and prognostic biomarkers for efficient triaging of risk.The Barrett's Breath Test Pilot (CAS ID:10592) is assessing the utility of quantifying volatile organic compounds (VOCs) in the breath for a future epidemiologic study. Specially, it is assessing what the intraclass correlation coefficients are for VOCs over a 98 day period, with three time points with biological duplicates taken from each of five volunteers. The Barrett's Esophagus Consortium project (CAS ID:10593) is a pooling project that brings together and harmonizes data from five case-control studies of Barrett's esophagus. We have already assessed the exposures tobacco smoking (published in Gastroenterology), and body mass index and waist circumference (published in Gut). We are currently working on analyses of alcohol, GERD and NSAID use; adiponectin; and insulin-like growth factors (IGFs) in relation to this precursor metaplasia for publication. The Esophageal Cancer in SEER-Medicare project (CAS ID:10633) is assessing metabolic syndrome in relation to Barrett's esophagus (manuscript submitted for publication) and esophageal adenocarcinoma , as well as the comparative utility of staging modalities in relation to survival following diagnosis of esophageal adenocarcinoma. We are also assessing whether there is heterogeneity in the natural history of esophageal adenocarcinoma.The CPRD EAC Progression Study is an analysis in collaboration with our colleagues at Boston University and will enable us to assess whether metabolic syndrome is a risk factor for progression from Barretts esophagus to esophageal adenocarcinoma. This analysis is based in the Clinical Practice Research Datalink (CPRD) which was formerly called the General Practice Research Database (GPRD). In the Hormones in Barrett's Esophagus project (CAS ID:10638) we are assessing androgens and estrogens in serum from Barrett's esophagus patients and gastroeosphageal reflux disease controls in the BEEDS study based at the National Naval Medical Center. The Kaiser BE Cohort project will enable us to assess different risk factors for progression from Barretts esophagus to esophageal adenocarcinoma. Currently, a majority of evidence for Barretts esophagus patients comes from studies of risk factors for esophageal adenocarcinoma but a majority of such patients are never previously diagnosed with Barretts esophagus. Thus a disconnect may exist in the population for study and the population under surveillance. These analyses will provide evidence that is directly applicable for a Barretts esophagus population undergoing surveillance. All of these projects are closely aligned to the aims of elucidating the etiology of Barrett's esophagus and esophageal adenocarcinoma as well as providing potential utility for diagnostics and prognostics.

该项目涵盖了广泛的研究，重点是阐明食道腺癌（食管癌）和前体病变贝雷特食管（aka barrett食管）的自然史的危险因素和自然史。 巴雷特食道是下食道的一种化生变化，其特征是用上皮的腺体型替换天然鳞状细胞上皮。这种化生变化被认为主要是胃食管反流酸引起的遗传毒性损伤的结果，而胆汁盐会反流入食道，暴露于无法处理这些反应性化学物质的细胞。用化生式贝雷特上皮的重新上述为组织提供了能够承受这种化合物的暴露的组织。但是，这也增加了食管腺癌的风险约为一般人群的10-50倍。在过去的35年中，美国食管腺癌的发病率在美国增加了650％以上，大多数人出现了晚期恶性肿瘤，导致5年的存活率低于20％。这表明研究人员需要能够更好地识别高风险的人，而巴雷特食管是一个很好的起点。然而，尽管这种化学大大增加了食管腺癌相对于普通人群的风险，但绝对风险在200名患者随访年中的0.5％或1个左右较低。这是因为在第一次（指数）内窥镜检查中诊断出患食道腺癌的患者中约有90％。因此，我们不仅需要能够更好地识别普通人群中患有高风险的人（Barretts食管），而且我们还需要能够将这些人分为高和低风险群体，以便可以将监视资源重点放在那些最需要它们的人，这将使监视内窥镜检查的成本效益方程更具吸引力。因此，该项目中所有研究的最终目标旨在更好地了解这种疾病的自然历史，进展的危险因素，诊断标记和具有高灵敏度的方式以及预后的生物标志物，以有效地对风险进行危险。 （CAS ID：10592）正在评估呼吸中量化挥发性有机化合物（VOC）的实用性，以进行未来的流行病学研究。特别是，它正在评估98天内的类内相关系数对VOC的含量是什么，三个时间点具有从五名志愿者中的每一个中取出的生物学重复项。巴雷特的食道联盟项目（CAS ID：10593）是一个合并项目，它汇集了五项对巴雷特食管的病例对照研究的数据。我们已经评估了烟草吸烟（发表在胃肠病学上），体重指数和腰围（发表在肠道上）。我们目前正在研究酒精，GERD和NSAID使用的分析；脂联素;与这种前体化学的发表有关的胰岛素样生长因子（IGF）。 Seer-Medicare项目中的食道癌（CAS ID：10633）正在评估与Barrett的食道有关（手稿供发表）和食管腺癌以及诊断性食管生存后的分期模式比较实用性的代谢综合征（手稿）和食管腺癌。腺癌。我们还在评估食管腺癌的自然史上是否存在异质性。CPRDEAC进度研究是与波士顿大学同事合作的分析到食管腺癌。该分析基于临床实践研究数据链接（CPRD），该研究数据库以前称为通用实践研究数据库（GPRD）。在Barrett的食管项目（CAS ID：10638）的激素中，我们正在评估Barrett食管患者的血清中的雄激素和雌激素，以及基于国家海军医疗中心的BEEDS研究中的BEEDS Replux疾病控制。 Kaiser BE队列项目将使我们能够评估从Barretts食管到食道腺癌的不同危险因素。目前，大多数证据表明，巴雷特食管患者的证据来自对食管腺癌的危险因素的研究，但大多数此类患者以前从未被诊断出患有巴雷特食管食管。因此，人口中可能存在脱节，以进行研究和监视的人口。这些分析将提供直接适用于接受监视的食道食管人群的证据。所有这些项目都与阐明Barrett食管和食管腺癌的病因的目的紧密一致，并为诊断和预后提供了潜在的实用性。