Clinical Risk Factors for Barretts Esophagus in a Primary Care Setting

描述（由申请人提供）：大多数食管腺癌（EAC）患者在癌症诊断前不知道存在巴雷特食管（BE），57%的患者从未报告胃食管反流病（GERD）的慢性症状，这是目前筛查的触发因素。因此，大多数有发展EAC风险的患者从未接受BE筛查，并且患有晚期不可治愈的癌症。我们的初步工作一直致力于了解GERD症状，咽喉反流症状和BE之间的关系，使用新的，侵入性较小的筛查方法。我们在一项随机、交叉试验中比较了门诊非镇静小口径内镜与传统镇静内镜，并建立了检测BE的同等准确性和极好的患者耐受性。我们现在第一次有了一种有效的方法，可用于高接受度的人群筛查。Jobe博士的小组系统地筛查了患有咳嗽和声音嘶哑的耳鼻喉科患者的BE。结果表明，这些受试者（未进行常规筛查的人群）的BE患病率与具有典型和慢性GERD症状的人群相当。最后，为了准备多中心患病率研究，创建了巴雷特食管风险联盟（BERC）。BERC由分布在美国各地的10个中心组成，所有参与者都是国际公认的BE流行病学专家。这项工作的下一个关键步骤将是了解BE人群的风险，以便我们能够缩小筛选工作的范围。本R21申请的目的是进一步开发方案机制，以预期针对NIDDK临床试验项目的首个BERC U系列提案，具体目标如下：1）确定国家初级保健人群代表性样本中BE的患病率，作为美国人群的替代; 2）开发预测BE存在的临床风险因素概率模型; 3）构建并验证包含最有效的风险因素的列线图，作为确定内窥镜筛查阈值的指南。该R21提案的重点是进一步开发受试者入组、数据管理、样本量确定的最佳方法，并开发初级保健患者多中心内镜筛查方案，这对大规模试验的最终成功至关重要。公共卫生相关性这项工作通过将一种新的筛查技术纳入一项联合研究中，解决了我们对食管癌风险理解的关键缺陷，该研究将首次确定Barrett食管在美国人群中的患病率和风险。这项工作将使供应商能够识别患有巴雷特食管（导致食管癌的癌前状态）的高风险个体，并将其纳入内窥镜监测。最终结果将是高度集中的风险分层和预防或通过早期发现提高生存率。

DESCRIPTION (provided by applicant): Most patients who develop esophageal adenocarcinoma (EAC) are unaware of the presence of Barrett's esophagus (BE) prior to cancer diagnosis, and 57% have never reported chronic symptoms of gastroesophageal reflux disease (GERD), the current trigger for screening. Thus, the majority of patients who are at risk for the development of EAC are never screened for BE and present with advanced incurable cancer. Our preliminary work has been directed at understanding the relationship between symptoms of GERD, laryngopharyngeal symptoms of reflux, and BE using novel, less invasive methods of screening. We compared in-office unsedated small-caliber endoscopy in a randomized, cross-over trial to conventional sedated endoscopy and established equivalent accuracy in detecting BE with excellent patient tolerability. For the first time, we now have an efficient method to be used for population screening with high acceptance. Dr. Jobe's group has systematically screened otolaryngology patients with cough and hoarseness for BE. Results indicate that the BE prevalence in these subjects, a population not routinely screened, is equivalent to that in a population with classic and chronic GERD symptoms. Finally, in preparation for a multi-center prevalence study, the Barrett's Esophagus Risk Consortium (BERC) was created. BERC consists of 10 centers which are stragically placed across the US, and all participants are internationally recognized experts in BE epidemiology. The next critical step in this work will be to understand the risk for BE an unselected population so that we can narrowly tailor screening efforts. The purpose of this R21 in application is to further develop protocol mechanics in anticipation of the first BERC U-series proposal directed toward the NIDDK Clinical Trials Program with the following specific aims:1) to determine the prevalence of BE within a representative sample of the Nation's primary care population as a surrogate for the US population; 2) develop a clinical risk factor probability model that predicts the presence of BE; 3) construct and validate a nomogram that incorporates the most potent risk factors as a guide for determining endoscopic screening threshold. This R21 proposal centers on further developing the most optimal methods for subject enrollment, data management, sample size determination, and developing a protocol for multi-center endoscopic screening in primary care patients which will be essential to the eventual success of a large scale trial. PUBLIC HEALTH RELEVANCE This work addresses critical deficits in our understanding of esophageal cancer risk by incorporating a novel screening technology into a consortium study which will for the first time, determine the prevalence and risk of Barrett's esophagus in an unselected U.S. population. This work will enable providers to identify high-risk individuals with Barrett's esophagus, the pre-malignant condition which leads to esophageal cancer, and enroll them into endoscopic surveillance. The end result will be highly focused risk stratification and prevention or improved survival through early detection.