Project Summary/Abstract: This administrative supplement follows strategy for parent grant 5U01DK074035-12 Gastroparesis (GP) presents with chronic upper GI dysmotility symptoms in the setting of delayed gastric emptying without any mechanical obstruction. Inconsistencies exist between subjective symptom severity and objective evidence of GP, while the availabilities of therapeutic options are very limited. Hence the pathophysiology, clinical course, outcomes and treatment strategies require further investigation. Our response to the NIDDK Gastroparesis Consortium (U01) under RFA-DK-16-010 has the following aims: 1) To complete approved studies initiated by the GpCRC which entails enrolling GP patients to Gastroparesis Registry 3 with their clinical data and bio-samples as well as obtain gastric tissue under the pathological basis of gastroparesis (PBG) protocol, when some patients undergo surgery for failed medical therapy. This data collection will contribute more knowledge about pathogenesis, pathomorphology, symptoms severity grading, complications, and treatment outcomes in patients with GP as well as gastroparesis-like presentation but normal gastric emptying. 2) We plan to continue our very successful enrollment of patients qualified for the BESST study (Buspirone for Early Satiety and Symptoms of Gastroparesis: A Multicenter, Randomized, Placebo-Controlled, Double-Masked Trial. 3) It is also our goal to initiate a very innovating, challenging and interesting study titled: Pyloric Sphincter Abnormalities in Patients with Gastroparesis (PSAGS). The objective of this study is to determine any potential pyloric sphincter abnormalities in GP patients when compared with healthy controls. We aim to determine how prevalent these abnormalities are by using three tests : a) measure pyloric sphincter diameter, cross-sectional area, pressure, compliance, and distensibility using endoluminal functional luminal imaging probe (EndoFLIP™) technology; b) assess the regularity and a strength of stomach gastric slow waves and accommodation status by electrogastrography (EGG) with water load satiety testing (WLST) and; c) obtain recordings of gastric emptying, small bowel transit time (SBTT), and colon transit time (CTT) captured by wireless motility capsule (WMC). In addition as a new diagnostic strategy, we propose to determine whether endoscopy guided core biopsy samples of antral muscularis propria in GP patients can provide sufficient tissue for full histologic analysis to specifically address status of interstitial cell of Cajal, myenteric plexus neurons and smooth muscle pathology. Therefore we will investigate whether this endoscopic method can safely replace surgically obtained gastric smooth muscle tissue and correlate ICC findings with symptoms, gastric emptying and treatment outcome. This information is crucial in order to be able to provide pathophysiological analysis in patients with mild to moderate GP symptoms, who did not reach a severe enou...