The Esophagogastric Junction in Health and Disease

健康与疾病中的食管胃连接处

• 批准号: 8231238
• 负责人: Peter James Kahrilas
• 金额: $ 32.71万
• 依托单位: NORTHWESTERN UNIVERSITY AT CHICAGO
• 依托单位国家: 美国
• 财政年份: 2001
• 资助国家: 美国
• 起止时间: 2001-04-01 至 2016-08-31
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/8231238
• 关键词: Accounting; Acidity; Adult; Affect; Aging; Anatomy; Calibration; Chest Pain; Clinical; Complex; Deglutition; Development; Diagnosis; Diagnostic; Diagnostic tests; Dilatation - action; Disease; Disease Management; Distal; Encapsulated; Endoscopy; Epidemic; Epidemiology; Esophageal; Esophagitis; Esophagogastric Junction; Esophagus; Failure; Frustration; Functional disorder; Funding; Fundoplication; Gases; Gastric Acid; Gastroenterology; Gastroesophageal reflux disease; Goals; Healed; Health; Health Expenditures; Heartburn; Hernia; Hiatal Hernia; Human; Hydromorphone; Impairment; Indium; Inferior esophageal sphincter structure; Investigation; Length; Link; Liquid substance; Manometry; Measurement; Measures; Mechanics; Medical; Methods; Modeling; Morphology; Movement; Muscle; Muscle Contraction; Obesity; Pathogenesis; Pathway interactions; Patients; Pharmaceutical Preparations; Physicians; Physiological; Physiology; Plant Roots; Population; Predisposition; Procedures; Proton Pump Inhibitors; Reflux; Relaxation; Research; Research Project Grants; Resolution; Respiratory Diaphragm; Rest; Sensory; Solutions; Sphincter; Stomach; Symptoms; System; Techniques; Technology; Testing; Therapeutic; Tissues; Vent; Viscosity; aging population; base; design; disease diagnosis; healing; imaging probe; improved; instrument; new technology; next generation; novel; pressure; response; sample fixation; tool; trend

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.

描述（由申请人提供）：在胃肠病学实践中，与任何其他疾病实体相比，胃食管反流病 (GERD) 所遇到的患者数量更多。 GERD 流行病学与人口老龄化和肥胖流行有关；与这些因素同时发生的相关医疗保健支出也急剧增加。然而，GERD诊断的增加也与诊断标准的扩大和缺乏准确验证的生理标准有关，导致错误诊断和过度治疗的趋势。 GERD 的根本原因之一是食管胃交界处 (EGJ) 的反流屏障受损，导致更多的反流发作、更多的反流液量以及选择性地从胃中排出气体而不伴随液体的能力丧失。这可能会导致食管炎或一系列非特异性症状。临床上，疑似 GERD 通常是根据对质子泵抑制剂 (PPI) 的症状反应（或无反应）来“诊断”的。然而，GERD 患者的胃酸分泌并没有一致的异常，这种管理策略导致了这些药物的大量且昂贵的过度使用。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），因此内窥镜检查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，尽管酸度较低……或者因为它们与胃食管反流病无关。显然，我们需要更好的诊断。该提案将评估两种新技术（3D 高分辨率测压法 (3D-HRM) 和 EndoFLIP(R)）的使用，以客观化 GERD 诊断。两者都有可能量化 EGJ 机械和生理损害的根本原因。 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，可以通过这些尖端诊断来改善 GERD 管理，这些诊断对于选择针对机械性 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。 公众健康相关性：胃食管反流病 (GERD) 是一种日益常见的疾病，影响约 10% 的美国成年人口，并与衰老和肥胖有关。 GERD 具有独特治疗意义的根本原因之一是食管胃交界处 (EGJ) 的反流屏障功能退化，但目前尚无准确评估这一点的诊断测试。该提案将评估两项新技术，以改善 EGJ 的诊断评估并合理化具体疗法。