The Esophagogastric Junction in Health and Disease

描述（由申请人提供）：胃食管反流病（GERD）在胃肠病学实践中占比任何其他疾病实体更多的患者。GERD流行病学与人口老龄化和肥胖流行有关；相关的卫生保健支出与这些因素同时急剧增加。然而，胃食管反流病诊断的增加也与诊断标准的扩大和缺乏准确的可验证的生理标准有关，这种趋势导致了错误的诊断和过度的治疗。GERD的一个根本原因是食管胃交界的反流屏障受损，导致反流发作次数增加，反流体积增大，并失去选择性地从胃中排出气体而不伴有液体的能力。这可引起食管炎或一系列非特异性症状。临床上，疑似胃食管反流的诊断通常基于对质子泵抑制剂（PPIs）的症状反应（或无反应）。然而，在反流中胃酸分泌没有一致的异常，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PPIs几乎肯定可以治愈食管炎（消除了一个主要的诊断标准），内窥镜作为诊断测试的效用受到损害，导致患者和医生在治疗失败的频繁情况下感到沮丧。症状可能持续存在，因为反流持续存在，尽管酸度降低…或者因为它们与反流无关。显然，我们需要更好的诊断方法。该提案将评估使用两种新技术（3D-高分辨率测压法（3D- hrm）和EndoFLIP(R)）来客观诊断GERD。两者都有可能量化根本原因的机械和生理EGJ损害。3D-HRM是下一代压力测量技术，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，这些尖端的诊断方法可以改善胃食管反流的管理，这对于选择针对机械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至关重要的。

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.