Friday, May 9, 2025
5/9/2025
vEsophagus - Predicting surgical outcomes using a virtual esophagus - PROJECT SUMMARY Esophageal motility disorders and gastroesophageal reflux (GERD) are associated with major symptoms (heartburn, chest pain, regurgitation), malnutrition, and aspiration. Nearly 20–30% of the adult population experiences weekly GERD symptoms. Most of the 1 million outpatient visits per year for dysphagia (difficulty swallowing) in the US will require endoscopy which is both invasive and expensive. Additionally, many patients will require further esophageal testing with manometry, reflux testing, and esophagram after endoscopy to identify the underlying cause and identify patients appropriate for surgery. The total expenditure for the management of esophageal disease is estimated to be over $12B/yr and thus, the cost to society is substantial. Esophageal diseases occur when the delicate interplay of neuromyogenic activity, luminal geometry, and esophageal wall mechanics goes awry. Clinical evaluation and management of these disorders utilize endoscopy, esophagram, and high-resolution impedance manometry to characterize anatomy, bolus transit, and neuromuscular function. Although these approaches can identify pathologic patterns for disease classification, they are limited in their ability to guide treatment decisions and determine prognosis due to an inability to assess the effect of physiomechanical factors driving bolus transit. Realizing these limitations, through the past decade, we have integrated physiologic data into physics-based models to simulate esophageal peristalsis and bolus transit. Following multiple iterations and validation, we have generated our current version of the virtual esophagus (vEsophagus). The vEsophagus simulates a virtual twin and effectively resolves the deformation of the esophagus, bolus location, pressure/velocity, stresses/strain in the wall, and neural activation versus time. The scientific premise of this proposal is that we can utilize the vEsophagus to define the physiomechanical perturbations driving poor outcome in patients with achalasia (Aim 1) and GERD (Aim 2) and that we can define an optimal treatment approach using vEsophagus simulations of the virtual twin. We will study patients undergoing directed treatment (POEM, antireflux surgery) in achalasia and GERD patients to determine whether the vEsophagus can define the physiomechanical predictors of disease (Aims 1a & 2a) and can be used to predict outcome after POEM (Aim 1b) and antireflux surgery (Aim 2b). This work will be paradigm shifting due to an entirely new approach to esophageal diseases that focuses on individual patient models (personalized) which can inform treatment selection and prognosis. Tailoring POEM to prevent poor outcomes and complications of blown-out-myotomy and GERD is clinically important, and currently there is no model to guide fundoplication approach to prevent complications of abnormal bolus transit. Our preliminary data provides the rigor to support that we can predict outcome using vEsophagus and we will test this clinically. Eventually, the vEsophagus could replace or reduce clinical trials in humans. It can help predict surgery outcome and could be used to test various motility approaches including pharmacological interventions.
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