The Esophagogastric Junction in Health and Disease

描述（由申请人提供）：胃食管反流病（GERD）在胃肠病学实践中比任何其他疾病实体占更多的患者遭遇。GERD流行病学与人口老龄化和肥胖流行有关;相关的医疗保健支出与这些因素平行急剧增加。然而，GERD诊断的增加也与扩大的诊断标准和缺乏准确的验证生理标准有关，这些趋势导致错误诊断和过度治疗。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、更大的反流液量和选择性地从胃排出气体而不伴随液体的能力丧失。这可能导致食管炎或一系列非特异性症状。临床上，疑似GERD通常是根据质子泵抑制剂（PPI）的症状反应（或无反应）进行“诊断”的。然而，在GERD中没有一致的胃酸分泌异常，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几乎肯定会治愈食管炎（消除主要诊断标准），因此内窥镜检查作为诊断测试的效用受到影响，导致患者和医生在治疗失败的常见情况下感到沮丧。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。本提案将评价两种新技术（3D-高分辨率测压（3D-HRM）和EndoFLIP（R））的使用，以客观化GERD诊断。两者都有可能量化根本原因机械和生理EGJ损害。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扩张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，GERD管理可以通过这些尖端诊断来改善，这些诊断对于选择针对机械EGJ功能障碍的新疗法的患者以及校准这些新疗法的应用至关重要。 公共卫生相关性：胃食管反流病（GERD）是一种越来越常见的医学疾病，影响约10%的美国成年人口，并与衰老和肥胖有关。具有独特治疗意义的GERD的一个根本原因是食管胃交界处（EGJ）的反流屏障功能退化，但目前没有准确评估这一点的诊断测试。该提案将评估两种新技术，以改善EGJ的诊断评估并使特定治疗合理化。

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. PUBLIC HEALTH RELEVANCE: Gastroesophageal reflux disease (GERD) is an increasingly common medical condition affecting about ten percent of the adult US population and linked to both aging and obesity. One root cause of GERD with unique treatment implications is degradation of the reflux barrier function of the esophagogastric junction (EGJ), but there are currently no diagnostic tests that accurately assess this. This proposal will evaluate two novel technologies to improve diagnostic assessment of the EGJ and rationalize specific therapies.