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Pathophysiological Mechanisms of GASTRO-ESOPHAGEAL Reflux Following Sleeve Gastrectomy. OBJECTIVE: to evaluate the mechanisms associated with reflux events following sleeve gastrectomy (SG). SUMMARY BACKGROUND DATA: Gastro-esophageal reflux (GERD) post-SG is a critical issue due to symptom severity, impact on quality of life, requirement for re-operation, and potential for Barrett's esophagus. The pathophysiology is incompletely delineated. METHODS: Post-SG patients, stratified into asymptomatic and symptomatic, underwent protocolized nuclear scintigraphy (n=83), 24-hour esophageal pH monitoring, and stationary manometry (n=143) to characterize reflux patterns. Ten patients underwent fasting and post-prandial concurrent manometry and pH for detailed analysis of reflux events. RESULTS: Baseline demographics between cohorts were similar: Age 47.2 ± 11.6 vs. 44.1 ± 11.3 years (p=0.121); females 73.2% vs. 90.8% (p=0.005); excess weight loss (EWL) 53.8 ± 28.1% vs. 57.4 ± 25.5% (p=0.422), follow-up duration 12.3 vs. 7.4 months (p=0.503). Nuclear scintigraphy delineated bolus-induced deglutitive reflux events (29.6% vs. 62.5%, p=0.005) and post-prandial reflux events (4(IQR2) vs. 4(IQR 3) events, p=0.356). Total acid exposure was significantly elevated in the symptomatic population (7.7% vs. 3.6%, p<0.001), especially fasting acid exposure (6.0% vs.1.3%, p<0.001). pH/manometry analysis demonstrated acute elevations of the gastro-esophageal pressure gradient (>10mmHg) underpinned most reflux events. Swallow-induced intragastric hyper-pressurization was associated with individual reflux events in most patients (90% in fasting state and 40% post-prandial). CONCLUSIONS: We found reflux to be strongly associated with SG and identified three unique categories. Bolus-induced deglutitive and post-prandial reflux occurred in most patients. Elevated fasting esophageal acid exposure mediated symptoms. Frequent, significant elevation in the gastro-esophageal pressure gradient was the mechanism of reflux and appeared to relate to the non-compliant proximal stomach.