Esophageal symptoms are common and may indicate the presence of gastroesophageal reflux disease (GERD), structural processes, motor dysfunction, behavioral conditions, or functional disorders. ...Esophageal physiologic tests are often performed when initial endoscopic evaluation is unrevealing, especially when symptoms persist despite empiric management. Commonly used esophageal physiologic tests include esophageal manometry, ambulatory reflux monitoring, and barium esophagram. Functional lumen imaging probe (FLIP) has recently been approved for the evaluation of esophageal pressure and dimensions using volumetric distension of a catheter-mounted balloon and as an adjunctive test for the evaluation of symptoms suggestive of motor dysfunction. Targeted utilization of esophageal physiologic tests can lead to definitive diagnosis of esophageal disorders but can also help rule out organic disorders while making a diagnosis of functional esophageal disorders. Esophageal physiologic tests can evaluate obstructive symptoms (dysphagia and regurgitation), typical and atypical GERD symptoms, and behavioral symptoms (belching and rumination). Certain parameters from esophageal physiologic tests can help guide the management of GERD and predict outcomes. In this ACG clinical guideline, we used the Grading of Recommendations Assessment, Development and Evaluation process to describe performance characteristics and clinical value of esophageal physiologic tests and provide recommendations for their utilization in routine clinical practice.
How to Set Up a Successful Motility Lab Yadlapati, Rena; Chen, Joan W.; Khan, Abraham
Gastroenterology,
April 2020, 2020-Apr, 2020-04-00, 20200401, Volume:
158, Issue:
5
Journal Article
Eosinophilic esophagitis (EoE) is an allergen‐driven chronic inflammatory condition, characterized by symptoms related to esophageal dysfunction and confirmed histologically by esophageal mucosal ...eosinophilia. Since its first description in the 1990s, the incidence and prevalence of EoE have been on the rise. It is known to affect all ages of various ethnic backgrounds and both sexes; however, it is most seen in White males. Children with EoE often present with abdominal pain, nausea, vomiting, and failure to thrive, whereas adults with EoE typically present with dysphagia and food impaction. Diagnosis of EoE requires histologic confirmation of elevated esophageal eosinophils in a symptomatic patient, and only after secondary causes have been excluded. Because EoE is a chronic and progressively fibrostenotic disease, treatment goals include resolution of symptoms, induction and maintenance of disease remission, and prevention and possibly reversal of fibrostenotic complications, while minimizing treatment‐related adverse effects and improving quality of life. Treatment strategies include the “3 D's”—drugs, diet, and dilation. Standard drug therapies include proton‐pump inhibitors and topical corticosteroids. Dietary therapies include elemental diet, allergy testing–directed elimination diet, and empiric elimination diets. Endoscopic esophageal dilation for EoE strictures can alleviate esophageal symptoms but has no effect on mucosal inflammation. Recent progress in EoE research has made possible evidence‐based clinical guidelines. Ongoing pharmacologic trials show promise for novel biologic agents in the treatment of refractory EoE.
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FZAB, GIS, IJS, KILJ, NLZOH, NUK, OILJ, SAZU, SBCE, SBMB, UL, UM, UPUK, VSZLJ
The purpose of this American Gastroenterological Association (AGA) Institute Clinical Practice Update is to review the available evidence and expert advice regarding the clinical management of ...patients with suspected extraesophageal gastroesophageal reflux disease.
This article provides practical advice based on the available published evidence including that identified from recently published reviews from leading investigators in the field, prospective and population studies, clinical trials, and recent clinical guidelines and technical reviews. This best practice document is not based on a formal systematic review. The best practice advice as presented in this document applies to patients with symptoms or conditions suspected to be related to extraesophageal reflux (EER). This expert review was commissioned and approved by the AGA Institute Clinical Practice Updates Committee (CPUC) and the AGA Governing Board to provide timely guidance on a topic of high clinical importance to the AGA membership and underwent internal peer review by the CPUC and external peer review through standard procedures of Clinical Gastroenterology and Hepatology. These Best Practice Advice (BPA) statements were drawn from a review of the published literature and from expert opinion. Because systematic reviews were not performed, these BPA statements do not carry formal ratings of the quality of evidence or strength of the presented considerations.
Gastroenterologists should be aware of potential extraesophageal manifestations of gastroesophageal reflux disease (GERD) and should inquire about such disorders including laryngitis, chronic cough, asthma, and dental erosions in GERD patients to determine whether GERD may be a contributing factor to these conditions.
Development of a multidisciplinary approach to extraesophageal (EER) manifestations is an important consideration because the conditions are often multifactorial, requiring input from non-gastroenterology (GI) specialties. Results from diagnostic testing (ie, bronchoscopy, thoracic imaging, laryngoscopy, etc) from non-GI disciplines should be taken into consideration when gastroesophageal reflux (GER) is considered as a cause for extraesophageal symptoms.
Currently, there is no single diagnostic tool that can conclusively identify GER as the cause of EER symptoms. Determination of the contribution of GER to EER symptoms should be based on the global clinical impression derived from patients’ symptoms, response to GER therapy, and results of endoscopy and reflux testing.
Consideration should be given toward diagnostic testing for reflux before initiation of proton pump inhibitor (PPI) therapy in patients with potential extraesophageal manifestations of GERD, but without typical GERD symptoms. Initial single-dose PPI trial, titrating up to twice daily in those with typical GERD symptoms, is reasonable.
Symptom improvement of EER manifestations while on PPI therapy may result from mechanisms of action other than acid suppression and should not be regarded as confirmation for GERD.
In patients with suspected extraesophageal manifestation of GERD who have failed one trial (up to 12 weeks) of PPI therapy, one should consider objective testing for pathologic GER, because additional trials of different PPIs are low yield.
Initial testing to evaluate for reflux should be tailored to patients’ clinical presentation and can include upper endoscopy and ambulatory reflux monitoring studies of acid suppressive therapy.
Testing can be considered for those with an established objective diagnosis of GERD who do not respond to high doses of acid suppression. Testing can include pH-impedance monitoring while on acid suppression to evaluate the role of ongoing acid or non-acid reflux.
Alternative treatment methods to acid suppressive therapy (eg, lifestyle modifications, alginate-containing antacids, external upper esophageal sphincter compression device, cognitive-behavioral therapy, neuromodulators) may serve a role in management of EER symptoms.
Shared decision-making should be performed before referral for anti-reflux surgery for EER when the patient has clear, objectively defined evidence of GERD. However, a lack of response to PPI therapy predicts lack of response to anti-reflux surgery and should be incorporated into the decision process.
Eosinophilic esophagitis is a chronic allergen driven immune mediated disease that is increasingly recognized as a leading cause of dysphagia and foregut symptoms in children and adults. Much ...knowledge has been gained in recent years on the genetic and environmental risk factors for this disease, the associated inflammatory milieu, and the long term complications from esophageal remodeling. In this review we will highlight recent progress made in research into this disease, focusing on adults. We will discuss ongoing efforts to develop a minimally invasive technique that may obviate the need for repeated endoscopic assessment of disease activity. Moreover, we will review studies using novel tools such as mucosal impedance and functional lumen imaging as potential surrogate markers for mucosal integrity and esophageal remodeling. With regard to the treatment of eosinophilic inflammation, we will discuss the controversies surrounding responsiveness to proton pump inhibitors in some patients. Therapeutic trials continue to support the use of topical glucocorticoids and empiric food elimination diets as first line treatments. We will discuss ongoing efforts to optimize the elimination diet protocol to decrease the level and duration of food restrictions. Looking ahead, our growing knowledge on the pathogenesis of eosinophilic esophagitis has enabled further advancement of promising targeted biologic therapies.
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BFBNIB, CMK, NMLJ, NUK, PNG, SAZU, UL, UM, UPUK
AIM To assess reference values in the literature for esophageal distensibility and cross-sectional area in healthy and diseased subjects measured by the functional lumen imaging probe(FLIP). METHODS ...Systematic search and review of articles in Medline and Embase pertaining to the use of FLIP in the esophagus was conducted in accordance with the PRISMA guidelines. Cross-sectional area and distensibility at the esophagogastric junction(EGJ) were abstracted for normal subjects, achalasia, and gastroesophageal reflux disease(GERD) patients, stratified by balloon length and volume of inflation.RESULTS Six achalasia studies(n = 154), 3 GERD(n = 52), and 5 studies including healthy controls(n = 98) were included in the systematic review. Normative data varied widely amongst studies of healthy volunteers. In contrast, studies in achalasia patients uniformly demonstrated low point estimates in distensibility ≤ 1.6 mm2/mmH g prior to treatment that increased to ≥ 3.4 mm2/mmH g following treatment at 40 mL bag volume. In GERD patients, distensibility fell to the range of untreated achalasia(≤ 2.85 mm2/mm Hg) following fundoplication.CONCLUSION FLIP may be a useful tool in assessment of treatment efficacy in achalasia. The drastic drop in EGJ distensibility after fundoplication suggests that FLIP measurements need to be interpreted in the context of esophageal body motility and highlights the importance of pre-operative screening for dysmotility. Future studies using standardized FLIP protocol and balloon size are needed.
The prevalence of gastroesophageal reflux disease (GERD) symptoms increased approximately 50% until the mid-1990s, when it plateaued. The incidence of complications related to GERD including ...hospitalization, esophageal strictures, esophageal adenocarcinoma, and mortality also increased during that time period, but the increase in esophageal adenocarcinoma has since slowed, and the incidence of strictures has decreased since the mid-1990s. GERD is responsible for the greatest direct costs in the United States of any gastrointestinal disease, and most of those expenditures are for pharmacotherapy. Risk factors for GERD include obesity, poor diet, lack of physical activity, consumption of tobacco and alcohol, and respiratory diseases.
Introduction
Ineffective esophageal motility (IEM) is the most commonly diagnosed abnormality on high-resolution manometry (HRM). However, the clinical significance of IEM and associated reflux ...burden remains unclear.
Aim
Our primary aim was to compare reflux patterns between IEM versus normal motility on HRM.
Methods
HRM and reflux studies in patients with IEM and normal motility were retrospectively reviewed. Esophageal pressure topography parameters, reflux variables, and patient-reported outcome questionnaires were explored.
Results
A total of 239 patients with IEM were explored. Of these, 146 underwent reflux monitoring. Additionally, 100 patients with normal HRM all of whom had undergone reflux monitoring were included. IEM patients were more likely to have an abnormal number of reflux events compared to normal (22.7% vs. 9.0%,
p
< 0.01). Including only off-proton pump inhibitor (PPI) testing, IEM patients had higher mean total acid exposure time (AET) and total reflux events compared to normal motility (
p
= 0.02). Within IEM patients, higher AET modestly correlated with increased percentage of impaired swallows. Increased reflux events modestly correlated with higher impaired swallows and decreased lower esophageal sphincter (LES) resting pressure. Reflux burden increased with higher esophagogastric junction (EGJ) subtype, driven mostly by subtype III, although there was no difference in the distribution of EGJ subtypes between the IEM and normal HRM cohorts.
Conclusions
Patients with HRM diagnosis of IEM may be more prone to acid reflux while off-PPI and non-acid reflux while on-PPI. Reflux burden appears to be worse in IEM patients who have lower resting LES pressure, higher EGJ subtype, or higher percentage of impaired swallows.
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EMUNI, FIS, FZAB, GEOZS, GIS, IJS, IMTLJ, KILJ, KISLJ, MFDPS, NLZOH, NUK, OBVAL, OILJ, PNG, SAZU, SBCE, SBJE, SBMB, SBNM, UKNU, UL, UM, UPUK, VKSCE, ZAGLJ
Dysregulation of protein translation is a key driver for the pathogenesis of many cancers. Eukaryotic initiation factor 4A (eIF4A), an ATP-dependent DEAD-box RNA helicase, is a critical component of ...the eIF4F complex, which regulates cap-dependent protein synthesis. The flavagline class of natural products (
, rocaglamide A) has been shown to inhibit protein synthesis by stabilizing a translation-incompetent complex for select messenger RNAs (mRNAs) with eIF4A. Despite showing promising anticancer phenotypes, the development of flavagline derivatives as therapeutic agents has been hampered because of poor drug-like properties as well as synthetic complexity. A focused effort was undertaken utilizing a ligand-based design strategy to identify a chemotype with optimized physicochemical properties. Also, detailed mechanistic studies were undertaken to further elucidate mRNA sequence selectivity, key regulated target genes, and the associated antitumor phenotype. This work led to the design of
(Zotatifin), a compound with excellent physicochemical properties and significant antitumor activity that supports clinical development.
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