The long-term objective of this research proposal is to understand the role of anatomical and mechanical variables of the esophagogastric junction (EGJ) in the pathogenesis of gastroesophageal reflux disease (GERD). The candidate is currently in the first year of a tenure track faculty appointment in the Division of Gastroenterology and Hepatology at Northwestern University Medical School. He is seeking support for full time mentored research. His mentor, Dr. Peter Kahrilas is an NIH funded internationally-recognized expert on esophageal physiology and division head in the department of Gastroenterology and Hepatology. In addition, the candidate will be enrolled in the K30 sponsored Master of Science in Clinical Investigation Program at the Graduate School of Northwestern University. The proposed research study is to define the anatomical and mechanical variables of the EGJ as they relate to GERD. The EGJ is a complex anatomic zone whose functional integrity is sum of its many parts. To date, much of the research on the competence of the EGJ in GERD has been focused on the lower esophageal sphincter. Our hypothesis is that acquired anatomic changes inclusive of, but not restricted to hiatal hernia may alter the mechanical characteristics of the EGJ and affect the propensity to reflux. One such variable that will be studied is compliance. Increased compliance may exacerbate reflux in two ways: 1) lowering the incremental increase in intra-abdominal pressure required to open the relaxed or hypotensive EGJ, and 2) the relaxed EGJ may open wider than normal under a given physiological circumstance resulting in a reduced discriminative resistance for liquid as opposed to gas reflux. Compliance will be determined using a customized barostat technique and then correlated with hiatal hernia size, intra-abdominal LES length, angle of His and gastroesophageal flap valve grade. In addition, we will be attempting to improve standard pH monitoring technique by measuring acid exposure at the SCJ and converting data to hydrogen ion concentration exposure. These changes will improve diagnostic accuracy of pH monitoring and also help determine the relationship between anatomical and mechanical variants and acid reflux.

National Institute of Health (NIH)
National Institute of Diabetes and Digestive and Kidney Diseases (NIDDK)
Mentored Patient-Oriented Research Career Development Award (K23)
Project #
Application #
Study Section
Diabetes, Endocrinology and Metabolic Diseases B Subcommittee (DDK)
Program Officer
Podskalny, Judith M,
Project Start
Project End
Budget Start
Budget End
Support Year
Fiscal Year
Total Cost
Indirect Cost
Northwestern University at Chicago
Internal Medicine/Medicine
Schools of Medicine
United States
Zip Code
Kwiatek, Monika A; Mirza, Faiz; Kahrilas, Peter J et al. (2009) Hyperdynamic upper esophageal sphincter pressure: a manometric observation in patients reporting globus sensation. Am J Gastroenterol 104:289-98
Pandolfino, John E; Ghosh, Sudip K; Rice, John et al. (2008) Classifying esophageal motility by pressure topography characteristics: a study of 400 patients and 75 controls. Am J Gastroenterol 103:27-37
Pandolfino, John E; Zhang, Qing; Ghosh, Sudip K et al. (2007) Acidity surrounding the squamocolumnar junction in GERD patients: ""acid pocket"" versus ""acid film"". Am J Gastroenterol 102:2633-41
Ghosh, Sudip K; Kahrilas, Peter J; Lodhia, Nilesh et al. (2007) Utilizing intraluminal pressure differences to predict esophageal bolus flow dynamics. Am J Physiol Gastrointest Liver Physiol 293:G1023-8
Ghosh, Sudip K; Pandolfino, John E; Rice, John et al. (2007) Impaired deglutitive EGJ relaxation in clinical esophageal manometry: a quantitative analysis of 400 patients and 75 controls. Am J Physiol Gastrointest Liver Physiol 293:G878-85
Pandolfino, John E; Kim, Hyon; Ghosh, Sudip K et al. (2007) High-resolution manometry of the EGJ: an analysis of crural diaphragm function in GERD. Am J Gastroenterol 102:1056-63
Pandolfino, J E; Ghosh, S K; Zhang, Q et al. (2007) Upper sphincter function during transient lower oesophageal sphincter relaxation (tLOSR);it is mainly about microburps. Neurogastroenterol Motil 19:203-10
Pandolfino, John E; Ghosh, Sudip K; Zhang, Qing et al. (2006) Quantifying EGJ morphology and relaxation with high-resolution manometry: a study of 75 asymptomatic volunteers. Am J Physiol Gastrointest Liver Physiol 290:G1033-40
Pandolfino, John E; El-Serag, Hashem B; Zhang, Qing et al. (2006) Obesity: a challenge to esophagogastric junction integrity. Gastroenterology 130:639-49
Pandolfino, John E; Zhang, Qing G; Ghosh, Sudip K et al. (2006) Transient lower esophageal sphincter relaxations and reflux: mechanistic analysis using concurrent fluoroscopy and high-resolution manometry. Gastroenterology 131:1725-33

Showing the most recent 10 out of 26 publications