Barretts Esophagus

巴雷特食管

基本信息

批准号：
8565475
负责人：
Michael Cook
金额：
$ 38万
依托单位：
DIVISION OF CANCER EPIDEMIOLOGY AND GENETICS
依托单位国家：
美国
项目类别：
财政年份：
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/8565475
关键词：
Androgens Barrett Epithelium Barrett Esophagus Biological Biological Markers Breath Tests Case-Control Studies Cells Chemicals Costs and Benefits Data Diagnosis Diagnostic Disease Endoscopy Epidemiologic Studies Epithelium Equation Esophageal Adenocarcinoma Esophagus Estrogens Etiology Exposure to Future Gastroenterology General Population Goals Hormones Incidence Individual Lesion Malignant Neoplasms Malignant neoplasm of esophagus Medical center Medicare Metabolic syndrome Metaplasia Metaplastic Modality Natural History Patients Publications Publishing Reflux Relative (related person)Research Personnel Resources Risk Risk Factors Serum Squamous Cell Staging Survival Rate Time Tissues Tobacco smoking Triage United States base bile salts clinical practice comparative disorder control disorder risk follow-up high risk indexing prognostic volatile organic compound volunteer waist circumference

项目摘要

This project covers a broad range of studies which focus on elucidating risk factors for and natural history of esophageal adenocarcinoma and the precursor lesion Barretts 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 we are now drafting an analysis of BMI and waist circumference 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, as well as the comparative utility of staging modalities in relation to survival following diagnosis of esophageal adenocarcinoma. The Hormones in Barrett's Esophagus project (CAS ID:10638) is 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. 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.

该项目涵盖广泛的研究，重点是阐明食管腺癌和巴雷特食管前驱病变的危险因素和自然史。巴雷特食管是下食管的化生性改变，其特征是天然鳞状细胞上皮被腺型上皮取代。这种化生变化被认为主要是胃食管反流酸和胆汁盐回流到食管引起的基因毒性损伤的结果，暴露出不具备处理这些反应性化学物质的细胞。化生Barretts上皮的再上皮形成提供了能够更好地承受暴露于此类化合物的组织。然而，它也会使患食管腺癌的风险增加约10-50倍于普通人群。过去 35 年来，美国食管腺癌的发病率增加了 650% 以上，大多数人已处于晚期恶性肿瘤，导致 5 年生存率低于 20%。这表明研究人员需要能够更好地识别高危人群，而巴雷特食管是一个很好的起点。然而，尽管相对于一般人群，这种化生大大增加了食管腺癌的风险，但绝对风险仍然较低，约为 0.5% 或随访 200 个患者年中就有 1 个。这是因为大约 90% 的食管腺癌患者是在第一次（索引）内窥镜检查中被诊断出来的。因此，我们不仅需要能够更好地识别普通人群中的高风险人群（巴雷特食管），还需要能够将这些人分为高风险组和低风险组，以便将监测资源集中于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，该项目所有研究的最终目标旨在更好地了解这种疾病的自然史、进展的危险因素、高灵敏度的诊断标志物和模式，以及用于有效分类风险的预后生物标志物。 Barrett 呼吸测试飞行员 (CAS ID:10592) 正在评估量化呼吸中挥发性有机化合物 (VOC) 的实用性，以用于未来的流行病学研究。具体来说，它正在评估 98 天内 VOC 的组内相关系数，其中三个时间点从五名志愿者中每人采集生物重复数据。 Barrett 食管联盟项目 (CAS ID:10593) 是一个汇集项目，汇集并协调五项 Barrett 食管病例对照研究的数据。我们已经评估了吸烟的暴露情况（发表在《胃肠病学》上），现在我们正在起草一份与这种前体化生相关的 BMI 和腰围分析报告，以供发表。 SEER-Medicare 项目中的食管癌 (CAS ID:10633) 正在评估与 Barrett 食管相关的代谢综合征，以及食管腺癌诊断后分期方式与生存相关的比较效用。巴雷特食管激素项目 (CAS ID:10638) 正在国家海军医疗中心的 BEEDS 研究中评估巴雷特食管患者和胃食管反流病对照者血清中的雄激素和雌激素。所有这些项目都与阐明巴雷特食管和食管腺癌的病因以及为诊断和预后提供潜在实用性的目标密切相关。