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.

Agency
National Institute of Health (NIH)
Institute
National Institute of Diabetes and Digestive and Kidney Diseases (NIDDK)
Type
Research Project (R01)
Project #
5R01DK056033-12
Application #
8536256
Study Section
Clinical, Integrative and Molecular Gastroenterology Study Section (CIMG)
Program Officer
Hamilton, Frank A
Project Start
2001-04-01
Project End
2016-08-31
Budget Start
2013-09-01
Budget End
2014-08-31
Support Year
12
Fiscal Year
2013
Total Cost
$320,079
Indirect Cost
$110,191
Name
Northwestern University at Chicago
Department
Internal Medicine/Medicine
Type
Schools of Medicine
DUNS #
005436803
City
Chicago
State
IL
Country
United States
Zip Code
60611
Lin, Zhiyue; Xiao, Yinglian; Li, Yuwen et al. (2017) Novel 3D high-resolution manometry metrics for quantifying esophagogastric junction contractility. Neurogastroenterol Motil 29:
Yadlapati, Rena; Kahrilas, Peter J (2017) When is proton pump inhibitor use appropriate? BMC Med 15:36
Kou, W; Pandolfino, J E; Kahrilas, P J et al. (2017) Could the peristaltic transition zone be caused by non-uniform esophageal muscle fiber architecture? A simulation study. Neurogastroenterol Motil 29:
Carlson, D A; Kahrilas, P J (2017) Editorial: when to be suspicious of malignancy-associated pseudoachalasia. Aliment Pharmacol Ther 46:198
Kahrilas, Peter J; Pandolfino, John E (2017) Treatments for achalasia in 2017: how to choose among them. Curr Opin Gastroenterol 33:270-276
Kou, Wenjun; Griffith, Boyce E; Pandolfino, John E et al. (2017) A continuum mechanics-based musculo-mechanical model for esophageal transport. J Comput Phys 348:433-459
Kahrilas, Peter J; Katzka, David; Richter, Joel E (2017) Clinical Practice Update: The Use of Per-Oral Endoscopic Myotomy in Achalasia: Expert Review and Best Practice AdviceĀ From the AGA Institute. Gastroenterology 153:1205-1211
Kou, Wenjun; Pandolfino, John E; Kahrilas, Peter J et al. (2017) Simulation studies of the role of esophageal mucosa in bolus transport. Biomech Model Mechanobiol 16:1001-1009
Nativ-Zeltzer, N; Logemann, J A; Zecker, S G et al. (2016) Pressure topography metrics for high-resolution pharyngeal-esophageal manofluorography-a normative study of younger and older adults. Neurogastroenterol Motil 28:721-31
Kahrilas, Peter J (2016) Transoral Incisionless Fundoplication for the Treatment of Gastroesophageal Reflux Disease. Gastroenterol Hepatol (N Y) 12:400-2

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