A fully resolved active musculo-mechanical model for esophageal transport

Esophageal transport is a physiological process that mechanically transports an ingested food bolus from the pharynx to the stomach via the esophagus, a multi-layered muscular tube. This process involves interactions between the bolus, the esophagus, and the neurally coordinated activation of the esophageal muscles. In this work, we use an immersed boundary (IB) approach to simulate peristaltic transport in the esophagus. The bolus is treated as a viscous fluid that is actively transported by the muscular esophagus, which is modeled as an actively contracting, fiber-reinforced tube. A simplified version of our model is verified by comparison to an analytic solution to the tube dilation problem. Three different complex models of the multi-layered esophagus, which differ in their activation patterns and the layouts of the mucosal layers, are then extensively tested. To our knowledge, these simulations are the first of their kind to incorporate the bolus, the multi-layered esophagus tube, and muscle activation into an integrated model. Consistent with experimental observations, our simulations capture the pressure peak generated by the muscle activation pulse that travels along the bolus tail. These fully resolved simulations provide new insights into roles of the mucosal layers during bolus transport. In addition, the information on pressure and the kinematics of the esophageal wall due to the coordination of muscle activation is provided, which may help relate clinical data from manometry and ultrasound images to the underlying esophageal motor function

A continuum mechanics-based musculo-mechanical model for esophageal transport

In this work, we extend our previous esophageal transport model using an immersed boundary (IB) method with discrete fiber-based structural model, to one using a continuum mechanics-based model that is approximated based on finite elements (IB-FE). To deal with the leakage of flow when the Lagrangian mesh becomes coarser than the fluid mesh, we employ adaptive interaction quadrature points to deal with Lagrangian-Eulerian interaction equations based on a previous work (Griffith and Luo [1]). In particular, we introduce a new anisotropic adaptive interaction quadrature rule. The new rule permits us to vary the interaction quadrature points not only at each time-step and element but also at different orientations per element. This helps to avoid the leakage issue without sacrificing the computational efficiency and accuracy in dealing with the interaction equations. For the material model, we extend our previous fiber-based model to a continuum-based model. We present formulations for general fiber-reinforced material models in the IB-FE framework. The new material model can handle non-linear elasticity and fiber-matrix interactions, and thus permits us to consider more realistic material behavior of biological tissues. To validate our method, we first study a case in which a three-dimensional short tube is dilated. Results on the pressure-displacement relationship and the stress distribution matches very well with those obtained from the implicit FE method. We remark that in our IB-FE case, the three-dimensional tube undergoes a very large deformation and the Lagrangian mesh-size becomes about 6 times of Eulerian mesh-size in the circumferential orientation. To validate the performance of the method in handling fiber-matrix material models, we perform a second study on dilating a long fiber-reinforced tube. Errors are small when we compare numerical solutions with analytical solutions. The technique is then applied to the problem of esophageal transport. We use two fiber-reinforced models for the esophageal tissue: a bi-linear model and an exponential model. We present three cases on esophageal transport that differ in the material model and the muscle fiber architecture. The overall transport features are consistent with those observed from the previous model. We remark that the continuum-based model can handle more realistic and complicated material behavior. This is demonstrated in our third case where a spatially varying fiber architecture is included based on experimental study. We find that this unique muscle fiber architecture could generate a so-called pressure transition zone, which is a luminal pressure pattern that is of clinical interest. This suggests an important role of muscle fiber architecture in esophageal transport

A mechanics--based perspective on the function of human sphincters during functional luminal imaging probe manometry

Functional luminal imaging probe (FLIP) is used to measure cross-sectional area (CSA) and pressure at sphincters. It consists of a catheter surrounded by a fluid filled cylindrical bag, closed on both ends. Plotting the pressure-CSA hysteresis of a sphincter during a contraction cycle, which is available through FLIP testing, offers information on its functionality, and can provide diagnostic insights. However, limited work has been done to explain the mechanics of these pressure-CSA loops. This work presents a consolidated picture of pressure-CSA loops of different sphincters. Clinical data reveal that although sphincters have a similar purpose (controlling the flow of liquids and solids by opening and closing), two different pressure-CSA loop patterns emerge: negative slope loop (NSL) and positive slope loop (PSL). We show that the loop type is the result of an interplay between (or lack thereof) two mechanical modes: (i) neurogenic mediated relaxation of the sphincter muscle and (ii) muscle contraction proximal to the sphincter which causes mechanical distention. We conclude that sphincters which only function through mechanism (i) exhibition NSL whereas sphincters which open as a result of both (i) and (ii) display a PSL. This work provides a fundamental mechanical understanding of human sphincters. This can be used to identify normal and abnormal phenotypes for the different sphincters and help in creating physiomarkers based on work calculation

Evaluation of Esophageal Motility Utilizing the Functional Lumen Imaging Probe

© 2016 by the American College of Gastroenterology. Objectives:Esophagogastric junction (EGJ) distensibility and distension-mediated peristalsis can be assessed with the functional lumen imaging probe (FLIP) during a sedated upper endoscopy. We aimed to describe esophageal motility assessment using FLIP topography in patients presenting with dysphagia.Methods:In all, 145 patients (aged 18-85 years, 54% female) with dysphagia that completed up per endoscopy with a 16-cm FLIP assembly and high-resolution manometry (HRM) were included. HRM was analyzed according to the Chicago Classification of esophageal motility disorders; major esophageal motility disorders were considered "abnormal". FLIP studies were analyzed using a customized program to calculate the EGJ-distensibility index (DI) and generate FLIP topography plots to identify esophageal contractility patterns. FLIP topography was considered "abnormal" if EGJ-DI was < 2.8 mm 2 /mm Hg or contractility pattern demonstrated absent contractility or repetitive, retrograde contractions.Results:HRM was abnormal in 111 (77%) patients: 70 achalasia (19 type I, 39 type II, and 12 type III), 38 EGJ outflow obstruction, and three jackhammer esophagus. FLIP topography was abnormal in 106 (95%) of these patients, including all 70 achalasia patients. HRM was "normal" in 34 (23%) patients: five ineffective esophageal motility and 29 normal motility. In all, 17 (50%) had abnormal FLIP topography including 13 (37%) with abnormal EGJ-DI.Conclusions:FLIP topography provides a well-tolerated method for esophageal motility assessment (especially to identify achalasia) at the time of upper endoscopy. FLIP topography findings that are discordant with HRM may indicate otherwise undetected abnormalities of esophageal function, thus FLIP provides an alternative and complementary method to HRM for evaluation of non-obstructive dysphagia.Link_to_subscribed_fulltex

Advances in the physiological assessment and diagnosis of GERD

Abstract GERD is a common condition worldwide. Key mechanisms of disease include abnormal oesophagogastric junction structure and function, and impaired oesophageal clearance. A therapeutic trial of acid-suppressive PPI therapy is often the initial management, with endoscopy performed in the setting of alarm symptoms and to exclude other conditions. If symptoms persist and endoscopy does not reveal evidence of GERD, oesophageal function tests are performed, including oesophageal manometry and ambulatory reflux monitoring. However, reflux episodes can be physiological, and some findings on endoscopy and manometry can be encountered in asymptomatic individuals without GERD symptoms. The diagnosis of GERD on the basis of functional oesophageal testing has been previously reported, but no updated expert recommendations on indications and the interpretation of oesophageal function testing in GERD has been made since the Porto consensus over a decade ago. In this Consensus Statement, we aim to describe modern oesophageal physiological tests and their analysis with an emphasis on establishing indications and consensus on interpretation parameters of oesophageal function testing for the evaluation of GERD in clinical practice. This document reflects the collective conclusions of the international GERD working group, incorporating existing data with expert consensus opinion

Brand Name and Generic Proton Pump Inhibitor Prescriptions in the United States: Insights from the National Ambulatory Medical Care Survey (2006–2010)

Introduction. Proton pump inhibitors (PPI) are one of the most commonly prescribed medication classes with similar efficacy between brand name and generic PPI formulations. Aims. We determined demographic, clinical, and practice characteristics associated with brand name PPI prescriptions at ambulatory care visits in the United States. Methods. Observational cross sectional analysis using the National Ambulatory Medical Care Survey (NAMCS) of all adult (≥18 yrs of age) ambulatory care visits from 2006 to 2010. PPI prescriptions were identified by using the drug entry code as brand name only or generic available formulations. Descriptive statistics were reported in terms of unweighted patient visits and proportions of encounters with brand name PPI prescriptions. Global chi-square tests were used to compare visits with brand name PPI prescriptions versus generic PPI prescriptions for each measure. Poisson regression was used to determine the incidence rate ratio (IRR) for generic versus brand PPI prescribing. Results. A PPI was prescribed at 269.7 million adult ambulatory visits, based on 9,677 unweighted visits, of which 53% were brand name only prescriptions. In 2006, 76.0% of all PPI prescriptions had a brand name only formulation compared to 31.6% of PPI prescriptions in 2010. Visits by patients aged 25–44 years had the greatest proportion of brand name PPI formulations (57.9%). Academic medical centers and physician-owned practices had the greatest proportion of visits with brand name PPI prescriptions (58.9% and 55.6% of visits with a PPI prescription, resp.). There were no significant differences in terms of median income, patient insurance type, or metropolitan status when comparing the proportion of visits with brand name versus generic PPI prescriptions. Poisson regression results showed that practice ownership type was most strongly associated with the likelihood of receiving a brand name PPI over the entire study period. Compared to HMO visits, patient visits at academic medical centers (IRR 4.2, 95% CI 2.2–8.0), physician-owned practices (IRR 3.9, 95% CI 2.1–7.1), and community health centers (IRR 3.6, 95% CI 1.9–6.6) were all more likely to have brand name PPIs. Conclusion. PPI prescriptions with brand name only formulations are most strongly associated with physician practice type

How to select patients for anti-reflux surgery? The ICARUS guidelines (International Consensus regarding preoperative examinations and clinical characteristics assessment to select adult patients for AntiReflUx Surgery)

Objective: Anti-reflux surgery can be proposed in patients with gastro-esophageal reflux disease, especially when proton pump inhibitor use leads to incomplete symptom improvement. However, to date, international consensus guidelines on the clinical criteria and additional technical examinations used in patient selection for anti-reflux surgery are lacking. We aimed at generating key recommendations in the selection of patients for anti-reflux surgery. Design: We included 35 international experts (gastroenterologists, surgeons and physiologists) in a Delphi process and developed 37 statements that were revised by the Consensus Group, to start the Delphi process. Three voting rounds followed where each statement was presented with the evidence summary. The panel indicated the degree of agreement for the statement. When 80% of the Consensus Group agreed (A+/A) with a statement, this was defined as consensus. All votes were mutually anonymous.Results: Patients with heartburn with a satisfactory response to PPIs, patients with a hiatal hernia (HH), patients with esophagitis LA grade B or higher and patients with Barrett’s esophagus are good candidates for anti-reflux surgery. An endoscopy prior to anti-reflux surgery is mandatory and a barium swallow should be performed in patients with suspicion of a HH or short esophagus. Esophageal manometry is mandatory to rule out major motility disorders. Finally, esophageal pH (+/- impedance) monitoring off PPI is mandatory to select patients for anti-reflux surgery, if endoscopy is negative for unequivocal reflux esophagitis. Conclusion: With the ICARUS guidelines, we generated key recommendations for selection of patients for anti-reflux surgery