THE ESOPHAGOGASTRIC JUNCTION IN HEALTH AND DISEASE

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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.