The Esophagogastric Junction in Health and Disease

描述(由申请人提供)：胃食道反流病(GERD)在胃肠病学实践中比任何其他疾病都更多的患者遇到。GERD流行病学与人口老龄化和肥胖症流行有关；与这些因素平行的相关卫生保健支出急剧增加。然而，GERD诊断的增加也与扩大诊断标准和缺乏准确的验证生理标准有关，这一趋势导致了误诊和过度治疗。GERD的一个根本原因是食管胃交界处(EGJ)的反流屏障受损，导致更多的反流发作，更大的反流液体积，以及失去在没有伴随液体的情况下选择性地从胃中排出气体的能力。这可能会导致食管炎或一系列非特异性症状。临床上，可疑的GERD通常是根据对质子泵抑制剂(PPI)的症状反应(或无反应)而被“诊断”的。然而，在GERD中并没有持续的胃酸分泌异常，这种管理策略导致了这些药物的大量和昂贵的过度使用。此外，由于PPI几乎肯定可以治愈食管炎(消除了一个主要的诊断标准)，内窥镜作为一种诊断测试的有效性受到了影响，导致患者和医生在治疗失败的频繁情况下感到沮丧。症状可能会持续，因为反流持续存在，尽管酸度较低……或者因为它们与GERD无关。显然，我们需要更好的诊断方法。这项提案将评估两项新技术(3D-高分辨率测压(3D-HRM)和EndoFLIP(R))用于对象化GERD诊断的情况。两者都有可能量化根本原因、机械和生理上的EGJ妥协。3D-HRM是下一代测压技术，旨在精确定义有缺陷的EGJ收缩形态。EndoFlip(R)是量化GERD中EGJ膨胀性异常的开创性技术，最初由该研究小组描述。我们的基本假设是，这些尖端诊断技术可以改善GERD的管理，这些诊断技术对于选择针对机械性EGJ功能障碍的新疗法的患者和校准这些新疗法的应用都是必不可少的。

DESCRIPTION (provided by applicant): Gastroesophageal reflux disease (GERD) accounts for more patient encounters in gastroenterology practices than any other disease entity. GERD epidemiology is linked to both an aging population and the obesity epidemic; related health care expenditures have increased precipitously paralleling these factors. However, the increase in GERD diagnoses is also related to broadened diagnostic criteria and the lack of accurate verifying physiological criteria, trends contributing to both erroneous diagnosis and excessive treatment. One root cause of GERD is impairment of the reflux barrier at the esophagogastric junction (EGJ) leading to more episodes of reflux, greater refluxate volume, and loss of the ability to selectively vent gas from the stomach without accompanying fluid. This can cause esophagitis or a host of nonspecific symptoms. Clinically, suspected GERD is often "diagnosed" based on symptomatic responses (or failure to respond) to proton pump inhibitors (PPIs). However, there is no consistent abnormality of gastric acid secretion in GERD and this management strategy has led to the substantial and costly overuse of these medications. Furthermore, because PPIs almost certainly heal esophagitis (eliminating a major diagnostic criterion), the utility of endoscopy as a diagnostic test is compromised leading to frustration among both patients and physicians in the frequent scenario of therapeutic failure. Symptoms may persist because reflux persists, albeit with less acidity...or because they are unrelated to GERD. Clearly, we need better diagnostics. This proposal will evaluate the use of two novel technologies (3D- high resolution manometry (3D-HRM) and EndoFLIP(R)) to objectify GERD diagnostics. Both have the potential to quantify the root-cause mechanical and physiological EGJ compromises. 3D-HRM is next- generation manometry technology designed to precisely define defective EGJ contractile morphology. EndoFlip(R) is pioneering technology to quantify EGJ distensibility abnormalities in GERD, initially described by this research group. Our underlying hypothesis is that GERD management can be improved with these cutting-edge diagnostics that are essential both to select patients for novel therapies targeting mechanical EGJ dysfunction and to calibrate the application of these novel therapies.