The Esophagogastric Junction in Health and Disease

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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.