Barretts Esophagus

巴雷特食管

• 批准号: 9339193
• 负责人: Michael Cook
• 金额: $ 40.97万
• 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/9339193
• 关键词: Adenocarcinoma; Algorithms; Androgens; Barrett Epithelium; Barrett Esophagus; Case-Control Studies; Cells; Chemicals; Clinical; Cohort Studies; Costs and Benefits; Data; Databases; Diagnosis; Diagnostic; Disease; Endoscopy; Epithelium; Equation; Esophageal Adenocarcinoma; Esophagitis; Esophagus; Estrogens; Etiology; Exposure to; Gastroenterology; Gastroesophageal reflux disease; General Population; General Practices; Goals; Hepatology; Hormones; Incidence; Individual; Journals; Laboratories; Lesion; Malignant Neoplasms; Malignant neoplasm of esophagus; Manuscripts; Medical History; Medicare; Metabolic syndrome; Metaplasia; Metaplastic; Modality; Natural History; Patients; Population; Prognostic Marker; Publications; Publishing; Reflux; Research; Research Personnel; Resources; Risk; Risk Factors; Squamous Cell; Staging; Survival Rate; Testing; Tissues; Triage; United States; base; bile salts; billing data; cancer epidemiology; case control; clinical practice; cohort; comparative; diagnostic biomarker; disorder control; disorder risk; follow-up; high risk; indexing; inflammatory marker; mortality; prognostic

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 Esophagus Consortium project (CAS ID:10593) is a pooling project that brings together and harmonizes data from eight case-control studies of Barrett's esophagus and fourteen case-control studies of esophageal adenocarcinoma. The consortium has published many articles, details of which can be seen at http://beacon.tlvnet.net/ The Esophageal Cancer in SEER-Medicare project (CAS ID:10633) is assessing metabolic syndrome in relation to Barrett's esophagus (published in Journal of Clinical Gastroenterology) and esophageal adenocarcinoma (manuscript submitted) as well as the comparative utility of staging modalities in relation to survival following diagnosis of esophageal adenocarcinoma (published in Cancer). We are also assessing whether there is are demographic, medical history, and survival differences in esophageal adenocarcinoma by whether there was a prior diagnosis of the precursor condition Barrett's esophagus (submitted for publication). A new project will assess whether we can develop an algorithm to accurately identify diagnoses of esophageal adenocarcinoma using Medicare billing data alone.The CPRD EAC Progression Study has assessed 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). The manuscript has been published in Cancer Epidemiology. In the Hormones in Barrett's Esophagus project (CAS ID:10638) we have assessed circulating androgens and estrogens in Barrett's esophagus patients compared with gastroeosphageal reflux disease controls in the BEEDS study based atthe Walter Reed (published in Clinical Gastroenterology and Hepatology). We are currently assessing similar exposures in a second Barrett's esophagus population for external replication (manuscript being drafted) as well as expansion to esophageal cancer (adenocarcinoma) using three cohort studies.The Kaiser BE Cohort project has enabled us to assess cancer and mortality risks amongst a large Barretts esophagus cohort. These analyses will provide evidence that is directly applicable for a Barretts esophagus population undergoing surveillance. The manuscript has been submitted for publication.The inflammation markers and esophageal adenocarcinoma (CAS 10731) is beinging together esophageal adenocarcinoma cases and controls from seven cohorts. We are assessing a suite of circulating inflammation markers and testing whether these are associated with risk of developing esophageal adenocarcinoma. Laboratory analyses are currently being conducted. 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（食管癌）和前驱病变巴雷特食管（又名巴雷特食管）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，该项目中所有研究的最终目标是寻求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。巴雷特食管联盟项目(CAS ID:10593) 是一个汇集项目，汇集并协调了巴雷特食管的八项病例对照研究和巴雷特食管的十四项病例对照研究的数据。食管腺癌。该联盟发表了许多文章，详细信息请参见 http://beacon.tlvnet.net/ SEER-Medicare 项目中的食管癌 (CAS ID:10633) 正在评估与巴雷特食管相关的代谢综合征（发表于临床胃肠病学杂志）和食管腺癌（已提交手稿）以及分期方式与诊断后生存相关的比较实用性食管腺癌（发表于《癌症》）。我们还通过先前是否诊断过巴雷特食管先兆病症（已提交发表）来评估食管腺癌是否存在人口统计学、病史和生存差异。一个新项目将评估我们是否可以开发一种算法，仅使用医疗保险账单数据来准确识别食管腺癌的诊断。CPRD EAC 进展研究评估了代谢综合征是否是从 Barretts 食管进展为食管腺癌的危险因素。该分析基于临床实践研究数据链 (CPRD)，该数据库以前称为全科实践研究数据库 (GPRD)。该手稿已发表在《癌症流行病学》杂志上。 在 Barrett 食管激素项目 (CAS ID:10638) 中，我们在基于 Walter Reed 的 BEEDS 研究（发表于《临床胃肠病学和肝病学》）中评估了 Barrett 食管患者的循环雄激素和雌激素与胃食管反流病对照的比较。我们目前正在使用三项队列研究评估第二个巴雷特食管人群的类似暴露情况，以进行外部复制（手稿正在起草）以及扩展到食管癌（腺癌）。Kaiser BE 队列项目使我们能够评估这些人群的癌症和死亡风险。一个大的巴雷特食管队列。这些分析将提供直接适用于接受监测的巴雷特食管人群的证据。该手稿已提交出版。炎症标志物和食管腺癌 (CAS 10731) 将来自七个队列的食管腺癌病例和对照结合在一起。我们正在评估一套循环炎症标志物，并测试这些标志物是否与发生食管腺癌的风险相关。目前正在进行实验室分析。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。