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1.
Demystifying Esophageal Lichen Planus: A Comprehensive Review of a Rare Disease You Will See in Practice.
Jacobs, JW, Kukreja, K, Camisa, C, Richter, JE
The American journal of gastroenterology. 2022;(1):70-77
Abstract
Lichen planus (LP) is a chronic inflammatory disorder that often affects the skin, hair, nails, and mucus membranes. Although esophageal involvement has traditionally been felt to be rare, recent reports suggest that it is often unrecognized or misdiagnosed. The diagnoses of esophageal lichen planus can be challenging and is suspected based on patients' endoscopic and histologic findings and in the context of their clinical history and physical examination. Physicians must have an index of suspicion, particularly in older white women and in those patients with an atypical esophagitis or stricturing disease, which do not respond to traditional treatment. Currently, there are limited data on esophageal lichen planus patients, and no formal management guidelines for this disease, which all gastroenterologists will see in practice. This article reviews the etiology and histopathology of LP and provides a comprehensive discussion of the clinical features, diagnosis, and management of esophageal disease from the gastroenterologist's perspective. Finally, we address the esophageal complications of LP.
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Development and Validation of Web-Based Tool to Predict Lamina Propria Fibrosis in Eosinophilic Esophagitis.
Hiremath, G, Sun, L, Correa, H, Acra, S, Collins, MH, Bonis, P, Arva, NC, Capocelli, KE, Falk, GW, King, E, et al
The American journal of gastroenterology. 2022;(2):272-279
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Abstract
INTRODUCTION Approximately half of esophageal biopsies from patients with eosinophilic esophagitis (EoE) contain inadequate lamina propria, making it impossible to determine the lamina propria fibrosis (LPF). This study aimed to develop and validate a web-based tool to predict LPF in esophageal biopsies with inadequate lamina propria. METHODS Prospectively collected demographic and clinical data and scores for 7 relevant EoE histology scoring system epithelial features from patients with EoE participating in the Consortium of Eosinophilic Gastrointestinal Disease Researchers observational study were used to build the models. Using the least absolute shrinkage and selection operator method, variables strongly associated with LPF were identified. Logistic regression was used to develop models to predict grade and stage of LPF. The grade model was validated using an independent data set. RESULTS Of 284 patients in the discovery data set, median age (quartiles) was 16 (8-31) years, 68.7% were male patients, and 93.4% were White. Age of the patient, basal zone hyperplasia, dyskeratotic epithelial cells, and surface epithelial alteration were associated with presence of LPF. The area under the receiver operating characteristic curve for the grade model was 0.84 (95% confidence interval: 0.80-0.89) and for stage model was 0.79 (95% confidence interval: 0.74-0.84). Our grade model had 82% accuracy in predicting the presence of LPF in an external validation data set. DISCUSSION We developed parsimonious models (grade and stage) to predict presence of LPF in esophageal biopsies with inadequate lamina propria and validated our grade model. Our predictive models can be easily used in the clinical setting to include LPF in clinical decisions and determine its effect on treatment outcomes.
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Salivary Trefoil Factor Family (TFF) Peptides and Their Roles in Oral and Esophageal Protection: Therapeutic Potential.
Hoffmann, W
International journal of molecular sciences. 2021;(22)
Abstract
Human saliva is a complex body fluid with more than 3000 different identified proteins. Besides rheological and lubricating properties, saliva supports wound healing and acts as an antimicrobial barrier. TFF peptides are secreted from the mucous acini of the major and minor salivary glands and are typical constituents of normal saliva; TFF3 being the predominant peptide compared with TFF1 and TFF2. Only TFF3 is easily detectable by Western blotting. It occurs in two forms, a disulfide-linked homodimer (Mr: 13k) and a high-molecular-mass heterodimer with IgG Fc binding protein (FCGBP). TFF peptides are secretory lectins known for their protective effects in mucous epithelia; the TFF3 dimer probably has wound-healing properties due to its weak motogenic effect. There are multiple indications that FCGBP and TFF3-FCGBP play a key role in the innate immune defense of mucous epithelia. In addition, homodimeric TFF3 interacts in vitro with the salivary agglutinin DMBT1gp340. Here, the protective roles of TFF peptides, FCGBP, and DMBT1gp340 in saliva are discussed. TFF peptides are also used to reduce radiotherapy- or chemotherapy-induced oral mucositis. Thus, TFF peptides, FCGBP, and DMBT1gp340 are promising candidates for better formulations of artificial saliva, particularly improving wound healing and antimicrobial effects even in the esophagus.
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Eosinophilic Esophagitis: Etiology and Therapy.
Patel, RV, Hirano, I, Gonsalves, N
Annual review of medicine. 2021;:183-197
Abstract
Eosinophilic esophagitis (EoE) is a relatively recently identified but now frequently encountered antigen/immune-mediated disease which places significant burden on patients and the healthcare system. With its growing prevalence and recognition by healthcare providers in multiple disciplines, substantial progress has been made regarding the diagnostic criteria, clinical evaluation, tools for disease assessment, and immune pathways related to pathogenesis. Current treatment goals focus on the amelioration of inflammation and prevention of remodeling consequences using proton pump inhibitors, swallowed topical steroids, elimination diets, and esophageal dilation. Ongoing research holds promise for more efficacious and targeted therapies as well as a personalized approach to the care of patients with EoE.
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Does Pepsin Saliva Concentration (Peptest™) Predict the Therapeutic Response of Laryngopharyngeal Reflux Patients?
Lechien, JR, Bobin, F, Dequanter, D, Rodriguez, A, Le Bon, S, Horoi, M, Thill, MP, Salem, C, Muls, V, Saussez, S
The Annals of otology, rhinology, and laryngology. 2021;(9):996-1003
Abstract
OBJECTIVE To study the profile and the therapeutic response of patients with laryngopharyngeal reflux (LPR) at the hypopharyngeal-esophageal multichannel intraluminal impedance-pH monitoring (HEMII-pH) according to the initial pepsin saliva concentration. METHODS From January 2018 to January 2020, patients with positive LPR diagnosis at the HEMII-pH were consecutively recruited from 3 European Hospitals. Saliva pepsin concentration (Peptest™) was measured during the HEMII-pH testing period and patients were classified into 2 groups: negative versus positive Peptest. The clinical outcomes, that is, gastrointestinal and HEMII-pH findings, reflux symptom score-12 (RSS-12), and 3-month therapeutic response, were compared between groups. RESULTS A total of 124 patients completed the study. Among them, 30 patients had negative Peptest. Pharyngeal reflux events occurred outside 1-hour post-meal time in 74.0%, after the meals in 20.5% and nighttime in 5.5%. The pepsin saliva level was not significantly associated with the reflux events preceding the sample collection. Patients with positive Peptest had better improvement of RSS-12 digestive and respiratory subscores and oral, pharyngeal, and laryngeal findings compared with patients with negative Peptest. CONCLUSION Patients with high saliva pepsin concentration had no stronger gastrointestinal, HEMII-pH, or clinical outcomes compared with those with low or undetectable saliva pepsin concentration.
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A review of optimal evaluation and treatment of suspected esophageal food impaction.
Lake, M, Smoot, D, O'Halloran, P, Shortsleeve, M
Emergency radiology. 2021;(2):401-407
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Abstract
Fluoroscopy-guided esophageal disimpaction of ingested food is a safe, effective, and cost-efficient alternative to endoscopically guided disimpaction. Patients with suspected esophageal impaction usually require fluoroscopy to confirm the diagnosis and determine the level of obstruction, which guides further management. Proximal esophageal food impactions at or near the cricopharyngeus muscle require an ENT intervention. Food impactions from the cervical esophagus to the aortic arch require a GI intervention. Obstructions distal to the aortic arch can usually be managed by the radiologist with a fluoroscopy-guided disimpaction. The use of intravenous glucagon to relax the mid and distal esophageal smooth muscle, combined with an effervescent agent, and water comprises this "combination" therapy to relieve an acute esophageal food impaction. This paper reviews the indications, contraindications, technique, and 32 years of experience with fluoroscopy-guided esophageal disimpaction at our institution. A retrospective chart review of our experience includes 252 patients with a 56% success rate that obviated more expensive and invasive procedures. Only one complication of a minor mucosal tear of no clinical consequence was encountered. Radiologists should be familiar with the presentation and management of this common diagnosis.
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Pharmacological treatments for eosinophilic esophagitis: current options and emerging therapies.
Lucendo, AJ
Expert review of clinical immunology. 2020;(1):63-77
Abstract
Introduction: The epidemiology of eosinophilic esophagitis (EoE) has increased rapidly to represent a common cause of chronic and recurrent esophageal symptoms. Current treatment options have limitations so the development of novel therapies is a matter of growing interest.Areas covered: This article provides an up-to-date discussion of current therapies and investigational options for EoE. Established anti-inflammatory treatments for EoE at present include dietary therapy, proton pump inhibitors and swallowed topic steroids, which should be combined with endoscopic dilation in case of strictures. Refractoriness, high recurrence rates, and need for long-term therapies have promoted the investigation of novel, esophageal-targeted formulas of topic corticosteroids, and monoclonal antibodies (including mepolizumab, reslizumab, QAX576, RPC4046, dupilumab, omalizumab, infliximab, and vedolizumab) for EoE, with some having been demonstrated as effective and safe in the short term. Several additional promising therapies are also discussed.Expert opinion: Several therapeutic targets have shown efficacy and will be approved to treat EoE, especially corticosteroid-sparing options and those for patients with multiple Th2-associated diseases. Personalized therapeutic strategies for initial and maintenance treatments of EoE must be rationally designed, to reduce the burden of disease and answer meaningfully the needs of all stakeholders involved in EoE.
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Extraesophageal syndrome of gastroesophageal reflux: relationships with lung disease and transplantation outcome.
Chan, WW, Ahuja, N, Fisichella, PM, Gavini, S, Rangan, V, Vela, MF
Annals of the New York Academy of Sciences. 2020;(1):95-105
Abstract
Gastroesophageal reflux disease (GERD) is prevalent and may be associated with both esophageal and extraesophageal syndromes, which include various pulmonary conditions. GERD may lead to pulmonary complications through the "reflux" (aspiration) or "reflex" (refluxate-triggered, vagally mediated airway spasm) mechanisms. While GERD may cause or worsen pulmonary disorders, changes in respiratory mechanics due to lung disease may also increase reflux. Typical esophageal symptoms are frequently absent and objective assessment with reflux monitoring is often needed for diagnosis. Impedance monitoring should be considered in addition to traditional pH study due to the involvement of both acidic and weakly acidic/nonacidic reflux. Antireflux therapy may improve outcomes of some pulmonary complications of GERD, although careful selection of a candidate is paramount to successful outcomes. Further research is needed to identify the optimal testing strategy and patient phenotypes that would benefit from antireflux therapy to improve pulmonary outcomes.
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Promotion of Regular Oesophageal Motility to Prevent Regurgitation and Enhance Nutrition Intake in Long-Stay ICU Patients. A Multicenter, Phase II, Sham-Controlled, Randomized Trial: The PROPEL Study.
Heyland, DK, Marquis, F, Lamontagne, F, Albert, M, Turgeon, AF, Khwaja, KA, Garland, A, Hall, R, Chapman, MG, Kutsiogannis, DJ, et al
Critical care medicine. 2020;(3):e219-e226
Abstract
OBJECTIVES To evaluate the effect of esophageal stimulation on nutritional adequacy in critically ill patients at risk for enteral feeding intolerance. DESIGN A multicenter randomized sham-controlled clinical trial. SETTING Twelve ICUs in Canada. PATIENTS We included mechanically ventilated ICU patients who were given moderate-to-high doses of opioids and expected to remain alive and ventilated for an additional 48 hours and who were receiving enteral nutrition or expected to start imminently. INTERVENTIONS Patients were randomly assigned 1:1 to esophageal stimulation via an esophageal stimulating catheter (E-Motion Tube; E-Motion Medical, Tel Aviv, Israel) or sham treatment. All patients were fed via these catheters using a standardized feeding protocol. MEASUREMENTS AND MAIN RESULTS The co-primary outcomes were proportion of caloric and protein prescription received enterally over the initial 7 days following randomization. Among 159 patients randomized, the modified intention-to-treat analysis included 155 patients: 73 patients in the active treatment group and 82 in the sham treatment group. Over the 7-day study period, the percent of prescribed caloric intake (± SE) received by the enteral route was 64% ± 2 in the active group and 65% ± 2 in sham patients for calories (difference, -1; 95% CI, -8 to 6; p = 0.74). For protein, it was 57% ± 3 in the active group and 60% ± 3 in the sham group (difference, -3; 95% CI, -10 to 3; p = 0.30). Compared to the sham group, there were more serious adverse events reported in the active treatment group (13 vs 6; p = 0.053). Clinically important arrhythmias were detected by Holter monitoring in 36 out of 70 (51%) in the active group versus 22 out of 76 (29%) in the sham group (p = 0.006). CONCLUSIONS Esophageal stimulation via a special feeding catheter did not improve nutritional adequacy and was associated with increase risk of harm in critically ill patients.
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Esophagogastric junction outflow obstruction: Characterization of a new entity? Clinical, manometric, and neuroimmunological description.
Furuzawa-Carballeda, J, Coss-Adame, E, Romero-Hernández, F, Zúñiga, J, Uribe-Uribe, N, Aguilar-León, D, Valdovinos, MA, Núñez-Álvarez, CA, Hernández-Ramírez, DF, Olivares-Martínez, E, et al
Neurogastroenterology and motility. 2020;(8):e13867
Abstract
OBJECTIVE To determine the differences between clinical, manometric, and neuroimmunological profile of esophagogastric junction outflow obstruction (EGJOO) and achalasia patients. METHODS Seven EGJOO and 27 achalasia patients were enrolled in a blind cross-sectional study. Peripheral blood (PB) of 10 healthy donors and 10 lower esophageal sphincter (LES) muscle biopsies from organ transplant donors were included as controls. The presence of ganglion cells, cells of Cajal, Th22/Th7/Th2/Th1/Tregs/Bregs/pDCregs in tissue, and PB was assessed by immunohistochemistry and flow cytometry. Serum concentration of IL-22/IL-17A/IL-17F/IL-4/IFN-γ/IL-1β/IL-6/IL-23/IL-33/TNF-α/IL-10 was determined using bioplex plates. ANAs and antineuronal antibodies were evaluated by immunofluorescence and Western blot. KEY RESULTS EGJOO and achalasia patients had lower ganglion cells and cells of Cajal percentage vs. controls, while fibrosis was present only in achalasia patients. EGJOO and controls had lower cell percentage of Th22/Th17/Th2 vs. achalasia. EGJOO tissue had lower Th1/Treg cell number vs. achalasia, but higher levels vs. control group. Bregs and pDCregs percentage was higher in EGJOO vs. control group. Percentage of PB subpopulations in EGJOO was not significantly different from control group. Serum cytokine levels were higher for IL-1β/IL-6/TNF-α, while IL-17A levels were lower in EGJOO vs. achalasia and control group. EGJOO group was negative for ANAs, while in achalasia group, 54% were positive. GAD65 and PNMa/Ta2 antibodies were present in achalasia, whereas Yo and recoverin were positive in EGJOO group. CONCLUSIONS AND INFERENCES Although EGJOO shares some clinical characteristics with achalasia, the neuroimmunological profile is completely different, suggesting that EGJOO might be a different entity.