The Variation of the Fetal Esophageal Mucosa at the End of Gestation may be a Possible Etiopathogenic Factor for Barrett's Esophagus / La Variación de la Mucosa Esofágica Identificada al Final de la Gestación Puede ser un Posible Factor Etiopatogénico para el Esófago de Barrett

SUMMARY: Barrett's esophagus is a condition where the distal third of the esophagus changes its epithelial lining from non- keratinized stratified squamous to simple columnar. This cross-sectional descriptive study was conducted to characterize the esophageal mucosa in the third trimester of pregnancy and determine possible variants in its development and was carried out in the Morphology Laboratory of the Health Faculty of the Industrial University of Santander, Colombia, with 45 human fetuses in the third trimester of gestation (weeks 25-40). A section of the distal esophagus and the first portion of the cardial region of the stomach were obtained, and the histological sections were subjected to a fixation process with 5 % formaldehyde solution. The sections were stained with hematoxylin and eosin and were evaluated for the presence of epithelial change or glands in the esophageal lamina propria. The change from non- keratinized stratified squamous epithelium to simple columnar epithelium was observed in the esophageal mucosa in five fetuses (11.1 %). In 15 cases (33.3 %), the presence of mucous glands underlying the epithelium was determined. In two fetuses, simple columnar epithelium was observed in the esophageal mucosa and underlying submucosal glands (4.4 %). The lack of replacement of the columnar epithelium by squamous epithelium in the distal third of the esophagus and the presence of mucous glands in the last third of gestation may suggest the presentation of Barret's esophagus in adulthood and thus, a predisposition to develop esophageal adenocarcinoma.

El esófago de Barrett es una afección en la que el tercio distal del esófago cambia su revestimiento epitelial de escamoso estratificado no queratinizado a columnar simple. Este estudio descriptivo de corte transversal tiene como objetivo caracterizar la mucosa esofágica en el tercer trimestre del embarazo y determinar posibles variantes en su desarrollo y se realizó en el laboratorio de Morfología de la Facultad de Salud de la Universidad Industrial de Santander-Colombia, con 45 fetos humanos en el tercer trimestre de gestación (semanas 25-40). Se obtuvo una sección del esófago distal y la primera porción de la región cardial del estómago y las secciones histológicas se sometieron a un proceso de fijación con solución de formaldehído al 5 %. Los cortes se tiñeron con hematoxilina y eosina y se evaluaron determinando la presencia de cambio epitelial y glándulas en la lámina propia del esófago. El cambio de epitelio escamoso estratificado no queratinizado a epitelio cilíndrico simple se observó en la mucosa esofágica en cinco fetos (11,1 %). En 15 casos (33,3 %) se determinó la presencia de glándulas mucosas subyacentes al epitelio. En dos fetos se observó epitelio cilíndrico simple en la mucosa esofágica y glándulas submucosas subyacentes (4,4 %). La falta de reemplazo del epitelio cilíndrico por epitelio escamoso en el tercio distal del esófago y la presencia de glándulas mucosas en el último tercio de la gestación pueden sugerir la presentación de esófago de Barrett en la edad adulta y una predisposición a desarrollar adenocarcinoma de esófago.

Exploring the clinical relevance of "Angico Gum": an effective biopolymer for topical protection of oesophageal mucosa in gastroesophageal reflux disease patients.

OBJECTIVES: Angico gum (AG) (Anadenanthera colubrina var. Cebil [Griseb.] Altschul) is utilized by some Brazilian communities to alleviate symptoms from gastroesophageal reflux disease. Here, we aimed to investigate the "in vitro" topical protective capacity of AG on human esophageal mucosa. METHODS: Biopsies of the distal esophageal mucosa were collected from 35 patients with heartburn (24 non-erosive and 11 with erosive oesophagitis (EE)) and mounted in Üssing chambers. AG was applied topically, followed by exposure with acid solution (pH 2.0 or pH 1.0), where transepithelial electrical resistance (TER) and The transepithelial permeability for fluorescein was assessed. The incubation of the AG labeled with FITC in the esophageal mucosa was localized by fluorescence microscopy. KEY FINDINGS: Pretreatment with AG prevented the drop in TER induced by acid solution, as well as significantly decreases the fluorescein permeability in non-erosive patients. The protective effect of AG was sustained for up to 120 min both in biopsies of non-erosive and erosive esophagitis. Confocal microscope images showed mucosal luminal adherence of FITC-labeled AG. CONCLUSION: AG had a prolonged topical protective effect against acid solution in mucosal biopsies of patients with non-erosive and erosive esophagitis.

Retrospective analysis of the clinical effects of endoscopic mucosal dissection on treatment of early esophagogastric precancerous lesions.

INTRODUCTION: The purpose of this study was to conduct a retrospective study about the clinical effects of endoscopic mucosal dissection on the treatment of early esophagogastric precancerous lesions. METHODS: A total of 132 patients with early esophagogastric precancerous lesions who were diagnosed and treated with concurrent surgery in our hospital from January 2018 to December 2019 were included in this retrospective study. Patients were divided into endoscopic mucosal resection (EMR) group (n = 58) and endoscopic submucosal dissection (ESD) group (n = 74) according to different surgical methods. The data in the two groups were compared and analyzed in terms of surgical indicators, treatment status and incidence of postoperative complications. RESULTS: There were statistically significant differences between the two groups in the whole block cutting rate, fractional cutting rate and complete cutting rate (P < 0.05). The mean operation time of ESD group was significantly longer than that of EMR group (P < 0.05). There were no significant differences in the intraoperative bleeding rate, blood loss, average specimen area, length of hospital stay and treatment cost between the two groups (P > 0.05). The incidence and recurrence of postoperative complications, including bleeding, perforation and stenosis in the two groups, were observed within 1 year of postoperative follow-up. The incidence of complications in ESD group was slightly higher than that in EMR group, and the local recurrence rate in ESD group was lower than that in EMR group (P > 0.05). CONCLUSION: ESD is an alternative surgical treatment for patients with early esophagogastric precancerous lesions.

Disodium cromoglycate treatment reduces TH2 immune response and immunohistopathological features in a murine model of Eosinophilic Esophagitis.

Eosinophilic esophagitis (EoE) is an emergent chronic disease of the esophagus. The immunopathological process in EoE is characterized by Th2 immune response and prominent eosinophilic influx, in response to common food allergens. The classical treatment consists of allergen elimination diet and systemic/topical corticosteroid therapy. Nevertheless, patients do not always comply to treatment, and the prolonged corticosteroid therapy can cause side effects, therefore, there is an immediate need for new therapeutic approach for EoE. Disodium cromoglicate (DSCG) is a substance broadly used in allergic asthma treatment, and a well-known mast cell activation stabilizer. However, its effect in EoE have not been evaluated yet. This study aimed to assess the effects of DSCG treatment in an EoE experimental model. Male Balb/C mice were subcutaneously sensitized for five days with OVA, and subsequently orally OVA-challenged, DSCG administration was performed between the OVA-challenges. DSCG treatment not only reduced eosinophilic and mast cell influx, as well as reduced fibrosis. In addition, tslp, GATA3, IL-5, FoxP3 and IL-10 mRNA expression were reduced in esophageal mucosa, associated with lower Th2 (CD3+CD4+GATA3+IL4+) and B cells (CD19+CD40+) number in peripheral lymphoid organs. In conclusion, the data demonstrate DSCG treatment was effective in reducing mast cell activation and Th2 immune response, important immunopathological EoE features. Therefore, the use of DSCG as an EoE treatment can be considered a promising therapeutic approach to treat this disease.

L-arginine-induced esophagitis, report of six cases.

Background: Drug-induced esophagitis is an uncommon diagnosis in the pediatric population. The following is a report of six adolescents with L-arginine-induced esophagitis. Case reports: All patients were under treatment with L-arginine for short stature. After using the prescribed medication for 1-3 months, all cases started with severe retrosternal pain, odynophagia, and dysphagia. The upper gastrointestinal endoscopies showed ulcers located in the mid esophageal mucosa. Conclusions: In the presence of acute severe odynophagia, dysphagia, and retrosternal pain, drug-induced esophagitis should be considered as a possible diagnosis. Treatment includes liquid diet, pain control, sucralfate, omeprazole, and interruption of L-arginine. In addition, the physician should explain preventive measures focused on patient and family education on the drug side effects and precise instructions on how to take medications, as well as a careful balance of risk and benefits of any medication. At present, there are no clinical trials that support the use of L-arginine in treatment of short stature.

Introducción: La esofagitis inducida por medicamentos es un diagnóstico poco frecuente en pacientes pediátricos. A continuación, se describe una serie de seis casos de pacientes menores de 15 años con esofagitis inducida por L-arginina. Casos clínicos: Los seis casos se encontraban en tratamiento con L-arginina por talla baja e iniciaron con dolor retroesternal, odinofagia y disfagia de rápida instalación. Cuatro de ellos acudieron al servicio de urgencias por la intensidad de los síntomas. Los hallazgos en la endoscopia del tubo digestivo alto fueron úlceras en la mucosa del esófago a la altura del tercio medio, zona de estrechez natural por la compresión del bronquio izquierdo. Conclusiones: En presencia de odinofagia, disfagia, dolor retroesternal y el antecedente de la ingesta de L-arginina, la esofagitis inducida por fármacos debe considerarse como una posibilidad diagnóstica. El tratamiento está basado en el manejo del dolor, sucralfato, omeprazol, así como la suspensión del medicamento y medidas preventivas centradas en la educación del paciente y los familiares sobre los riesgos y beneficios de un medicamento y la forma correcta de administrarlo.

L-arginine-induced esophagitis, report of six cases / Reporte de seis casos de esofagitis inducida por L-arginina

Abstract Background: Drug-induced esophagitis is an uncommon diagnosis in the pediatric population. The following is a report of six adolescents with L-arginine-induced esophagitis. Case reports: All patients were under treatment with L-arginine for short stature. After using the prescribed medication for 1-3 months, all cases started with severe retrosternal pain, odynophagia, and dysphagia. The upper gastrointestinal endoscopies showed ulcers located in the mid esophageal mucosa. Conclusions: In the presence of acute severe odynophagia, dysphagia, and retrosternal pain, drug-induced esophagitis should be considered as a possible diagnosis. Treatment includes liquid diet, pain control, sucralfate, omeprazole, and interruption of L-arginine. In addition, the physician should explain preventive measures focused on patient and family education on the drug side effects and precise instructions on how to take medications, as well as a careful balance of risk and benefits of any medication. At present, there are no clinical trials that support the use of L-arginine in treatment of short stature.

Resumen Introducción: La esofagitis inducida por medicamentos es un diagnóstico poco frecuente en pacientes pediátricos. A continuación, se describe una serie de seis casos de pacientes menores de 15 años con esofagitis inducida por L-arginina. Casos clínicos: Los seis casos se encontraban en tratamiento con L-arginina por talla baja e iniciaron con dolor retroesternal, odinofagia y disfagia de rápida instalación. Cuatro de ellos acudieron al servicio de urgencias por la intensidad de los síntomas. Los hallazgos en la endoscopia del tubo digestivo alto fueron úlceras en la mucosa del esófago a la altura del tercio medio, zona de estrechez natural por la compresión del bronquio izquierdo. Conclusiones: En presencia de odinofagia, disfagia, dolor retroesternal y el antecedente de la ingesta de L-arginina, la esofagitis inducida por fármacos debe considerarse como una posibilidad diagnóstica. El tratamiento está basado en el manejo del dolor, sucralfato, omeprazol, así como la suspensión del medicamento y medidas preventivas centradas en la educación del paciente y los familiares sobre los riesgos y beneficios de un medicamento y la forma correcta de administrarlo.

Eosinophilic esophagitis: Current concepts in diagnosis and treatment.

Eosinophilic esophagitis is an immune-allergic pathology of multifactorial etiology (genetic and environmental) that affects both pediatric and adult patients. Its symptoms, which include heartburn, regurgitation, and esophageal stenosis (with dysphagia being more frequent in eosinophilic esophagitis in young adults and children), are similar to those of gastroesophageal reflux disease, causing delays in diagnosis and treatment. Although endoscopic findings such as furrows, esophageal mucosa trachealization, and whitish exudates may suggest its presence, this diagnosis should be confirmed histologically based on the presence of more than 15 eosinophils per high-power field and the exclusion of other causes of eosinophilia (parasitic infections, hypereosinophilic syndrome, inflammatory bowel disease, among others) for which treatment could be initiated. Currently, the 3 "D"s ("Drugs, Diet, and Dilation") are considered the fundamental components of treatment. The first 2 components, which involve the use of proton pump inhibitors, corticosteroids, immunosuppressants and empirical diets or guided food elimination based on allergy tests, are more useful in the initial phases, whereas endoscopic dilation is reserved for esophageal strictures. Herein, the most important aspects of eosinophilic esophagitis pathophysiology will be reviewed, in addition to evidence for the various treatments.

CHROMOENDOSCOPY USING TOLUIDINE BLUE PLUS LUGOL'S SOLUTION FOR EARLY DIAGNOSIS OF ESOPHAGEAL PREMALIGNANT LESIONS AND SUPERFICIAL NEOPLASMS IN HIGH-RISK PATIENTS.

BACKGROUND: Esophageal cancer is the eighth most common cancer. The prognosis is bleak in patients with advanced stages. Patients with early disease have a better prognosis than those with advanced stage. There are several techniques for the screening of premalignant and superficial lesions including chromoendoscopy. OBJECTIVE: This article aimed to determine the effectiveness of chromoendoscopy with toluidine blue combined with Lugol's solution for diagnosis of esophageal premalignant and superficial neoplastic lesions in high risk patients. METHODS: Routine white light upper endoscopy was performed. Toluidine blue was sprayed from the gastroesophageal junction to 20 cm of the dental arch. Then the uptake dye areas were characterized. Later Lugol's solution was sprayed. Areas with less-intense staining were characterized. Biopsy of the toluidine blue capturing areas and areas with less-intense staining of Lugol's solution were taken. In the cases where lesions were not evidenced after application of dyes, biopsies four quadrants of the esophageal mucosa were taken. The samples were evaluated by a digestive pathologist. RESULTS: Barrett's esophagus was the most common premalignant lesion and the early neoplastic lesion was adenocarcinoma with a sensitivity of 100%, specificity 85.7%, positive predictive value 30%, negative predictive value 100%, positive likelihood ratio 7 negative likelihood ratio 0. CONCLUSION: Chromoendoscopy with toluidine blue combined with Lugol's solution is a useful tool in the screening of esophageal premalignant lesions and superficial neoplasms.

Utilização da cromoendoscopia com azul de toluidina mais solução de Lugol para diagnóstico precoce de lesões pré-malignas esofágicas e neoplasias superficiais em pacientes de alto risco / Chromoendoscopy using toluidine blue plus lugol's solution for early diagnosis of esophageal premalignant lesions and superficial neoplasms in high-risk patients

ABSTRACT BACKGROUND: Esophageal cancer is the eighth most common cancer. The prognosis is bleak in patients with advanced stages. Patients with early disease have a better prognosis than those with advanced stage. There are several techniques for the screening of premalignant and superficial lesions including chromoendoscopy. OBJECTIVE: This article aimed to determine the effectiveness of chromoendoscopy with toluidine blue combined with Lugol's solution for diagnosis of esophageal premalignant and superficial neoplastic lesions in high risk patients. METHODS: Routine white light upper endoscopy was performed. Toluidine blue was sprayed from the gastroesophageal junction to 20 cm of the dental arch. Then the uptake dye areas were characterized. Later Lugol's solution was sprayed. Areas with less-intense staining were characterized. Biopsy of the toluidine blue capturing areas and areas with less-intense staining of Lugol's solution were taken. In the cases where lesions were not evidenced after application of dyes, biopsies four quadrants of the esophageal mucosa were taken. The samples were evaluated by a digestive pathologist. RESULTS: Barrett's esophagus was the most common premalignant lesion and the early neoplastic lesion was adenocarcinoma with a sensitivity of 100%, specificity 85.7%, positive predictive value 30%, negative predictive value 100%, positive likelihood ratio 7 negative likelihood ratio 0. CONCLUSION: Chromoendoscopy with toluidine blue combined with Lugol's solution is a useful tool in the screening of esophageal premalignant lesions and superficial neoplasms.

RESUMO CONTEXTO: O câncer de esôfago é o oitavo câncer mais comum. O prognóstico é sombrio em pacientes com estágios avançados. Pacientes com doença precoce têm um melhor prognóstico do que aqueles com estágio avançado. Existem várias técnicas para a triagem de lesões pré-malignas e superficiais, incluindo cromoendoscopia. OBJETIVO: Este artigo objetivou determinar a efetividade da cromoendoscopia com azul de toluidina combinada com a solução de Lugol para o diagnóstico de lesões neoplásicas pré-malignas e superficiais esofágicas em pacientes de alto risco. MÉTODOS - A endoscopia de luz branca de rotina foi realizada de forma rotineira. O azul do toluidina foi pulverizado desde a junção gastroesofágica até 20 cm da arcada dentária. As áreas impregnadas pela tintura da tomada foram então caracterizadas. Mais adiante a solução de Lugol foi pulverizada. Áreas com coloração menos intensa foram caracterizadas. Foram realizadas biópsias das áreas de captura de azul de toluidina e áreas com coloração menos intensa da solução de Lugol. Nos casos onde as lesões não foram evidenciadas após a aplicação das tinturas, foram feitas biópsias em quatro quadrantes da mucosa esofágica. As amostras foram avaliadas por um patologista especializado. RESULTADOS: O esôfago de Barrett foi a lesão pré-maligna mais frequente e a lesão neoplásica precoce foi adenocarcinoma com sensibilidade de 100%, especificidade de 85,7%, valor preditivo positivo de 30%, valor preditivo negativo 100%, razão de verossimilhança positiva 7 e razão de verossimilhança negativa 0. CONCLUSÃO: A cromoendoscopia com azul de toluidina combinada com a solução de Lugol é uma ferramenta útil na triagem de lesões pré-malignas esofágicas e neoplasias superficiais.

A novel murine model of esophageal nonerosive reflux disease: from inflammation to impairment in mucosal integrity.

Nonerosive reflux disease (NERD) is a highly prevalent phenotype of the gastroesophageal reflux disease. In this study, we developed a novel murine model of NERD in mice with microscopic inflammation and impairment in the epithelial esophageal barrier. Female Swiss mice were subjected to the following surgical procedure: the transitional region between the forestomach and the glandular portion of the stomach was ligated, and a nontoxic ring was placed around the duodenum near the pylorus. The control group underwent sham surgery. The animals were euthanized at 1, 3, 7, and 14 days after surgery. Survival and body weight were monitored daily. Esophageal wet weight, macroscopic lesion, histopathological alterations, myeloperoxidase (MPO) activity, cytokine levels, transepithelial electrical resistance (TEER), and mucosal permeability were evaluated. The survival rate was 78% at 14 days, with mild loss in body weight. Surgery did not induce erosive esophagitis but instead induced microscopic inflammation and increased esophageal wet weight, IL-6, keratinocyte-derived cytokine (KC) levels, and MPO activity with maximal peak between 3 and 7 days and resolution at 14 days postsurgery. Epithelial esophageal barrier was evaluated in operated mice at 7 and 14 days postsurgery; a decrease in TEER and increase in the esophageal epithelial permeability were observed compared with the sham-operated group. In addition, the inhibition of acid secretion with omeprazole significantly prevented the esophageal inflammation and impairment of barrier function at 7 days postsurgery. Thus we established a novel experimental model of NERD in mice, which can contribute to understanding the pathophysiological events associated with NERD.NEW & NOTEWORTHY In this study, we standardized an experimental model of nonerosive reflux disease (NERD) in mice. This model involves an acute inflammatory response followed by impaired esophageal mucosal integrity, even in the absence of inflammation. Thus this model can serve for evaluation of pathophysiological aspects of NERD and open new perspectives for therapeutic strategies for patients with this disorder.