THE ESOPHAGOGASTRIC JUNCTION IN HEALTH AND DISEASE

描述(逐字摘自申请人摘要)：胃食道反流 疾病(GERD)是一种常见的疾病，影响着数百万美国人，并导致 通过对食道和胃交界处的解剖和生理扰动 (EGJ)。GERD在美国的经济影响从年度 用于药物治疗的40亿美元支出。虽然很有效， 医学治疗本质上是补偿性的，而不是潜在的治愈。 做手术。然而，抗反流手术的一个问题一直是不可预测的。 术后吞咽困难和腹胀与打嗝能力减弱有关。 因此，这个修订后的RO1应用程序代表了 胃肠病专家(Kahrilas医生)、外科医生(Joehl医生)和机械师 工程师(Brasseur博士)研究GERD和 Nissen胃底折叠术的外科治疗具体目标#1解决方案 顺行的EGJ功能，而特定的目的#2研究反流的机制。 顺行EGJ功能将通过“食道压力测试”进行量化。 在同时进行透视的情况下使用测压，同时吞咽已定义的 粘弹性特性。这些数据会伴随着吞咽困难 问卷调查。来自对照组的数据将与GERD患者的数据进行比较，并 抗反流手术后2例。特定目标#1的潜在假设 这是一个EGJ的数学模型，嵌入在一台计算机中 实验室“，并基于可获得的最佳解剖学和生理学数据 将提高对术后吞咽困难的认识和预防。特定的 目标2专注于扩展我们对相互作用的研究 GERD病理生理学中的解剖学和生理学因素 调查方法包括使用恒压计创建测量的 术中胃扩张程度和EGJ顺应性 透视EGJ，采用胃内空气充气的方法研究 一过性LES松弛的生理学和高分辨率测压地形图 EGJ的几何形状和机动性。一个潜在的假设是， TLESR诱发反流患者的最佳手术处理不同 而不是括约肌扩张的病人。最终的目标是量身定做 个体化GERD的外科治疗 对那个病人进行生理学研究，希望这将改善 提高抗反流手术的疗效，减少并发症。

DESCRIPTION (Verbatim from Applicant's Abstract): Gastroesophageal reflux disease (GERD) is a common disorder, affecting millions of Americans and caused by anatomical and physiological perturbations of the esophagogastric junction (EGJ). The economic impact of GERD in the US is evident by the annual expenditure of >$4 billion for pharmaceutical treatments. Although effective, medical therapy is by nature compensatory, as opposed to potentially curative surgery. However, a problem with antireflux surgery has been unpredictable postoperative dysphagia and bloating related to a diminished ability to belch. Thus, this revised RO1 application represents a collaborative effort by a gastroenterologist (Dr Kahrilas), a surgeon (Dr Joehl), and a mechanical engineer (Dr Brasseur) to study perturbations of the EGJ imposed by GERD and by surgical treatments of GERD (Nissen fundoplication). Specific aim #1 addresses antegrade EGJ function while specific aim #2 investigates mechanisms of reflux. Antegrade EGJ function will be quantified with an "esophageal stress test" using manometry with concurrent fluoroscopy while swallowing boluses of defined viscoelastic properties. These data will be complimented by a dysphagia questionnaire. Data from controls will be compared to that of GERD patients and patients after antireflux surgery. The underlying hypothesis of specific aim #1 is that a mathematical model of the EGJ, embedded within a "computer laboratory" and based on the best anatomical and physiological data obtainable will improve understanding and prevention of post-surgical dysphagia. Specific aim #2 is focused aboutextending our investigations into the interplay between anatomical and physiological factors in the pathophysiology of GERD. Investigational methodologies include using a barostat to create measured degrees of gastric distension and to ascertain EGJ compliance during fluoroscopy of the EGJ, using intragastric air insufflation to study the physiology of transient LES relaxations and high resolution manometry to map the geometry and mobility of the EGJ. An underlying hypothesis is that the optimal surgical management of a patient with tLESR induced reflux is different than of the patient with a patulous sphincter. The ultimate goal is to tailor the surgical management of GERD for the individual patient based on physiological studies of that patient with the hope that this will improve the efficacy and reduce the complications of antireflux surgery.