The Variation of the Fetal Esophageal Mucosa at the End of Gestation may be a Possible Etiopathogenic Factor for Barrett's Esophagus

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.

Development of adenocarcinoma after radiofrequency ablation of barrett's esophagus associated to fundoplication and suppression-duodenal diversion procedure: a lesson to be learned / Adenocarcinoma em esôfago de barrett após ablação por radiofrequência associada a fundoplicatura e diversão duodenal

ABSTRACT Despite endoscopic eradication therapy being an effective and durable treatment for Barrett's esophagus-related neoplasia, even after achieving initial successful eradication, these patients remain at risk of recurrence and require ongoing routine examinations. Failure of radiofrequency ablation and argon plasma coagulation is reported in 10-20% of cases.

RESUMO Apesar de a terapia de erradicação endoscópica ser um tratamento eficaz e durável para a neoplasia relacionada ao esôfago de Barrett (BE), mesmo após a erradicação inicial bem-sucedida, esses pacientes permanecem em risco de recorrência e requerem exames de rotina contínuos. A falha na ablação por radiofrequência e na coagulação com plasma de argônio é relatada em 10-20% dos casos.

Endoscopic ablation combined with fundoplication plus acid suppression-duodenal diversion procedure for long segment barrett´s esophagus: early and long-term outcome / Ablação endoscópica combinada com fundoplicatura associada a diversão duodenal no esôfago de barrett longo: resultados precoce e de longo prazo

ABSTRACT BACKGROUND: The addition of endoscopic ablative therapy plus proton pump inhibitors or fundoplication is postulated for the treatment of patients with long-segment Barrett´s esophagus (LSBE); however, it does not avoid acid and bile reflux in these patients. Fundoplication with distal gastrectomy and Roux-en-Y gastrojejunostomy is proposed as an acid suppression-duodenal diversion procedure demonstrating excellent results at long-term follow-up. There are no reports on therapeutic strategy with this combination. AIMS: To determine the early and long-term results observed in LSBE patients with or without low-grade dysplasia who underwent the acid suppression-duodenal diversion procedure combined with endoscopic therapy. METHODS: Prospective study including patients with endoscopic LSBE using the Prague classification for circumferential and maximal lengths and confirmed by histological study. Patients were submitted to argon plasma coagulation (21) or radiofrequency ablation (31). After receiving treatment, they were monitored at early and late follow-up (5-12 years) with endoscopic and histologic evaluation. RESULTS: Few complications (ulcers or strictures) were observed after the procedure. Re-treatment was required in both groups of patients. The reduction in length of metaplastic epithelium was significantly better after radiofrequency ablation compared to argon plasma coagulation (10.95 vs 21.15 mms for circumferential length; and 30.96 vs 44.41 mms for maximal length). Intestinal metaplasia disappeared in a high percentage of patients, and histological long-term results were quite similar in both groups. CONCLUSIONS: Endoscopic procedures combined with fundoplication plus acid suppression with duodenal diversion technique to eliminate metaplastic epithelium of distal esophagus could be considered a good alternative option for LSBE treatment.

RESUMO RACIONAL: A adição de terapia ablativa endoscópica associado a inibidores da bomba de prótons ou fundoplicatura tem sido postulada para o tratamento de pacientes com esôfago de Barrett de segmento longo (EBSL), no entanto, essa conduta não evita o refluxo ácido/biliar nesses pacientes. A fundoplicatura com gastrectomia distal e gastrojejunostomia em Y de Roux (FGD-Y) foi proposta como procedimento de supressão de ácido, demonstrando excelentes resultados no seguimento a longo prazo. Não há relatos na literature com a combinação dessa estratégia terapêutica. OBJETIVOS: Determinar os resultados precoces e a longo prazo observados em pacientes com EBSL com ou sem dysplasia de baixo grau, submetidos a FGD-Y, combinado com terapia endoscópica. MÉTODOS: Estudo prospectivo incluindo pacientes com EBSL, empregando a classificação de Praga, sendo o comprimento circunferencial (C) e máximo (M) e confirmado por estudo histológico. Os pacientes foram submetidos à coagulação com plasma de argônio (CPA, 21 pacientes) ou ablação por radiofrequência (ARF, 31 pacientes). Após o tratamento, eles foram seguidos precoce e tardiamente (5-12 anos), mediante avaliação endoscópica e histológica. RESULTADOS: Foram observadas poucas complicações após o procedimento (úlcera ou estenose). Re-tratamento foi necessário em ambos os grupos de pacientes. A redução do comprimento do epitélio metaplásico foi significativamente melhor após ARF em comparação com CPA (10,95 versus 21,15 mm para C e 30,96 versus 44,41 mm para M). A metaplasia intestinal desapareceu em elevada porcentagem de pacientes, e os resultados histológicos a longo prazo foram bastante semelhantes em ambos os grupos. CONCLUSÕES: Procedimentos endoscópicos combinados com fundoplicatura e gastrectomia distal e gastrojejunostomia em Y de Roux, para eliminar o epitélio metaplásico do esôfago distal podem ser considerados uma boa opção alternativa para o tratamento da EBSL.

An unusual case of extensive polypoid high-grade dysplasia in Barrett's esophagus

Barrett's esophagus (BE) is a known precursor of dysplasia and adenocarcinoma. Endoscopic resection and surgery are the techniques used to treat these kinds of lesions. However, endoscopic resection is considered the first choice for the management of superficial lesions. Dysplasia in BE most commonly appears like a flat lesion but here we describe an unusual case of dysplasia and superficial adenocarcinoma looking like an extensive polypoid lesion.

El esófago de Barrett (EB) es un precursor conocido de displasia y adenocarcinoma. La resección endoscópica y la cirugía son las técnicas utilizadas para tratar este tipo de lesiones. Sin embargo, la resección endoscópica se considera la primera opción para el manejo de las lesiones superficiales. La displasia en EB aparece más comúnmente como una lesión plana, pero aquí describimos un caso inusual de displasia y adenocarcinoma superficial que parece una lesión polipoide extensa.

Tratamiento endoscópico del esófago de Barrett con displasia de bajo y alto grado / Endoscopic treatment of Barrett's esophagus with low- and high-grade dysplasia

RESUMEN Introducción: El esófago de Barrett es una condición esofágica adquirida, que puede evolucionar a un adenocarcinoma. Con el paso de los años, la terapia endoscópica ha remplazado la cirugía en el tratamiento de esta afección. Objetivos: Mostrar los resultados de la aplicación de la técnica de resección endoscópica de la mucosa y la ablación con Hibrid-APC en pacientes portadores de esófago de Barrett con displasia de bajo o alto grado. Métodos: Se realizó un estudio descriptivo y retrospectivo en 29 pacientes entre los años 2014-2019, en el Servicio de endoscopias del Centro Nacional de Cirugía de Mínimo Acceso. Se estudiaron variables sociodemográficas, se estableció la clasificación endoscópica del esófago de Barrett, se describieron las características de la lesión, el diagnóstico histológico, la terapéutica endoscópica, la presencia de complicaciones, la resección incompleta y recidiva. Se aplicaron técnicas de estadística descriptiva y métodos no paramétricos. Resultados: Predominó el sexo masculino (58,62 %) y el grupo de 41-60 años (58,62 %). El segmento corto con lesiones planas y el largo con lesiones elevadas fueron más frecuentes (37,93 %). Se realizaron 15 resecciones y 14 ablaciones con Hibrid-APC; se observó una estenosis como complicación de la resección endoscópica de la mucosa y recidivas con ambas técnicas (5 pacientes, 17 %), tres relacionadas con la resección y dos con el Hibrid-APC. El Hibrid-APC alcanzó una efectividad terapéutica del 85,71 % y la resección del 80 %. Conclusiones: El tratamiento endoscópico con displasia de bajo y alto grado, mostró ser un procedimiento efectivo y seguro, con bajo porciento de complicaciones y recidivas.

ABSTRACT Introduction: Barrett's esophagus is an acquired esophageal condition that can evolve into an adenocarcinoma. Over the years, endoscopic therapy has replaced surgery in the treatment of this condition. Objectives: to show the results of the application of the endoscopic mucosal resection and Hybrid-APC ablation technique in patients with Barrett's esophagus with low-grade or high-grade dysplasia. Methods: a descriptive and retrospective study was carried out in 29 patients between 2014 and 2019, in the Endoscopy service of the National Center for Minimal Access Surgery. Social and demographic variables were studied; endoscopic classification of Barrett's esophagus was established, as well as the characteristics of the lesion, histological diagnosis, endoscopic therapy, the presence of complications, incomplete resection and recurrence were described. Descriptive statistics techniques and non-parametric methods were applied. Results: male gender (58.62%) and the group aged 41-60 years (58.62%) predominated. The short segment with flat lesions and the long segment with raised lesions were more frequent (37.93%). A number of 15 resections and 14 ablations were performed with Hybrid-APC; one stricture was observed as a complication of endoscopic mucosal resection and recurrences with both techniques (5 patients, 17%), three related to resection and two to Hybrid-APC. The Hybrid-APC achieved a therapeutic effectiveness of 85.71% and the resection one of 80%. Conclusions: endoscopic treatment with low- and high-grade dysplasia proved to be an effective and safe procedure, with a low percentage of complications and recurrences.

Prevalencia del esófago de Barrett y características epidemiológicas de los pacientes

RESUMEN Introducción: El esófago de Barrett es una lesión del esófago con elevado potencial degenerativo; para su diagnóstico se requiere la confirmación histológica de metaplasia intestinal en el esófago. Objetivo: Determinar la prevalencia del esófago de Barrett y las características epidemiológicas de los pacientes con esta afección. Métodos: Se realizó un estudio observacional descriptivo, entre enero del 2018 y junio del 2019, en 14 pacientes con diagnóstico histológico de esófago de Barrett. Las variables estudiadas fueron: edad, sexo, color de la piel, antecedentes epidemiológicos, síntomas y signos, longitud del segmento, de acuerdo con la clasificación de Sharma y presencia de hernia hiatal. Se realizó el diagnóstico histológico según la clasificación de Viena. Se determinó la prevalencia respecto del total de endoscopias digestivas altas realizadas en el periodo; emplearon de estadísticas descriptivas. Resultados: Se obtuvo una prevalencia de 0,37 %. El sexo masculino (78,6 %) y el color de piel blanca (71,4 %) predominaron; la edad media fue de 51,64 años. El consumo de tabaco fue referido por el 50 % de los pacientes. Los síntomas típicos de reflujo gastroesofágico, regurgitación (64,3 %) y pirosis (42,9 %) fueron los más frecuentes. La variedad de segmento corto fue la más observada y la hernia hiatal se encontró en 28,6 % de los casos. Conclusiones: Predominan las características epidemiológicas de ser pacientes masculinos, color de piel blanca, entre la 5ta y 6ta décadas de la vida y síntomas típicos de enfermedad por reflujo gastroesofágico. La prevalencia de la afección es baja.

ABSTRACT Introduction: Barrett's esophagus is an injury to the esophagus with high degenerative potential; histological confirmation of intestinal metaplasia in the esophagus is required for its diagnosis. Objective: To determine the frequency and epidemiological characteristics of patients with Barrett's esophagus. Methods: An observational and descriptive study was conducted between January 2018 and June 2019 in 14 patients with a histological diagnosis of Barrett's esophagus. The variables studied were: age, sex, skin color, epidemiological history, symptoms and signs, segment length according to the Sharma classification and presence of hiatal hernia, as well as the histological diagnosis according to the Vienna classification. The prevalence was determined with respect to the total number of upper gastrointestinal endoscopies performed in the period; descriptive statistical techniques were used. Results: A prevalence of 0,37 % was obtained. Males (78,6 %) and white skin color (71,4 %) predominated; the mean age was 51,64 years. Smoking was reported by 50 % of patients. Typical symptoms of gastroesophageal reflux, regurgitation (64,3 %) and heartburn (42,9 %) were the most frequent. The short segment variety was the most observed and hiatal hernia was found in 28,6 % of cases. Conclusions: The epidemiological characteristics of male patients, white skin color, between the 5th and 6th decades of life and typical symptoms of gastroesophageal reflux disease predominate.

Risk of preneoplastic lesions in mucosal projections of different sizes of the columnar epithelium in the lower esophagus / Risco de lesões pré-neoplásicas em projeções de mucosa de diferentes tamanhos do epitélio colunar no esôfago inferior

ABSTRACT BACKGROUND: Barrett's esophagus is an acquired condition that predisposes to the development of esophageal adenocarcinoma. AIMS: The aim of this study was to establish an association between the endoscopic and the histopathological findings regarding differently sized endoscopic columnar epithelial mucosa projections in the low esophagus, under 3.0 cm in the longitudinal extent. METHODS: This is a prospective study, including 1262 patients who were submitted to upper gastrointestinal endoscopy in the period from July 2015 to June 2017. The suspicious projections were measured and subdivided into three groups according to the sizes encountered (Group I: <0.99 cm; Group II: 1.0-1.99 cm; and Group III: 2.0-2.99 cm), and biopsies were then performed. RESULTS: There was a general prevalence of suspicious lesions of 6.42% and of confirmed Barrett's lesions of 1.17%, without a general significant statistical difference among groups. However, from Groups I and II to Group III, the differences were significant, showing that the greater the lesion, the higher the probability of Barrett's esophagus diagnosis. The absolute number of Barrett's lesions was 7, 9, and 6 for Groups I, II, and III, respectively. CONCLUSIONS: The findings led to the conclusion that even projections under 3.0 cm present a similar possibility of evolution to Barrett's esophagus. If, on the one hand, short segments are more prevalent, on the other hand, the long segments have the higher probability of Barrett's esophagus diagnosis, which is why biopsies are required in all suspicious segments.

RESUMO RACIONAL: O esôfago de Barrett é uma condição adquirida que predispõe ao desenvolvimento de adenocarcinoma de esôfago. OBJETIVOS: Estabelecer uma associação entre os achados endoscópicos e histopatológicos em relação às projeções endoscópicas da mucosa epitelial colunar de diferentes tamanhos no esôfago, abaixo de 3,0 centímetros de extensão longitudinal. MÉTODOS: Foi realizado um estudo prospective incluindo 1262 pacientes submetidos à endoscopia digestiva alta, no período de julho de 2015 a junho de 2017. As projeções suspeitas foram medidas, subdivididas em 3 grupos de acordo com os tamanhos encontrados (Grupo I: <0,99 cm; Grupo II: 1,0 cm-1,99 cm; Grupo III: 2,0 cm-2,99 cm) e biópsias foram então realizadas. RESULTADOS: Houve prevalência geral de lesões suspeitas de 6,42% e de lesões de Barrett confirmadas de 1,17%, sem diferença estatística geral significativa entre os grupos. Porém, dos Grupos I e II, para o Grupo III, as diferenças foram significativas, mostrando que quanto maior a lesão, maior a probabilidade de diagnóstico de esôfago de Barrett. O número absoluto de lesões de Barrett foi 7, 9 e 6 para os grupos I, II e III, respectivamente. CONCLUSÕES: Os achados permitiram concluir que mesmo projeções abaixo de 3,0 cm apresentam possibilidade semelhante de evolução para o esôfago de Barrett. Se, por um lado os segmentos curtos são mais prevalentes, por outro os segmentos longos têm maior probabilidade de diagnóstico de esôfago de Barrett, razão pela qual são necessárias biópsias em todos os segmentos suspeitos.

Current Status and Challenges of Research on Biomarkers of Barrett’s Esophagus in Risk Stratification / 胃肠病学

Barrett’s esophagus (BE) is the recognized precancerous lesion and risk factor for esophageal adenocarcinoma (EAC), and has a high miss diagnosis rate and low survival rate when malignantly transformed into EAC, moreover, there are only limited monitoring method and treatment. Therefore, the screening of biomarkers is highly expected, especially the risk stratification biomarkers related to the progression of malignant transformation of BE. Such biomarkers can help to determine early, quickly and accurately the disease process, and guide the stratified management and precise treatment of BE, reduce the malignancy rate and mortality. This article focused on the dynamic evolutionary process of intra‑tumor heterogeneity, and reviewed the current status and challenges of research on BE biomarkers in risk stratification from the genetics, epigenetics and serology perspectives.

Endoscopic therapeutic effect on Barrett esophagus with special intestinal metaplasia / 中华消化内镜杂志

Objective:To evaluate the endoscopic therapeutic effect on Barrett esophagus (BE) with special intestinal metaplasia.Methods:A retrospective analysis was performed on data of 56 patients of BE with special intestinal metaplasia who were diagnosed in Renmin Hospital of Wuhan University from January 2017 to December 2019 and treated with endoscopic radiofrequency ablation (ERFA) or endoscopic mucosal resection (EMR). The postoperative bleeding rate, feeding obstruction rate, operative time, hospital stay and residual or recurrent intestinal metaplasia lesions were studied.Results:There were no significant differences between the ERFA group ( n=43) and the EMR group ( n=13) in terms of age, gender, length of BE, preoperative gastrointestinal symptoms and comorbidity ( P>0.05). The postoperative bleeding rate [23.1% (3/13) VS 0, P=0.010] and feeding obstruction rate [30.8% (4/13) VS 4.7% (2/43), P=0.022] were higher in the EMR group compared with those in the ERFA group, and the operative time [6.0 (5.6, 6.2) min VS 5.4 (5.2, 5.5) min, Z=4.95, P<0.001] and hospital stay [6.0 (5, 7) d VS 3.5 (3, 4) d, Z=5.76, P<0.001] were longer in the EMR group. There were no significant differences in the incidences of postoperative pain or fever between the two groups ( P>0.05). No residual or recurrent intestinal metaplasia lesions were observed during the follow-up in any EMR patient, and follow-up biopsies after the first treatment in the ERFA group revealed residual intestinal metaplasia lesions in 41.9% (18/43) patients, with a significant difference ( P=0.005). Conclusion:EMR is more thorough in the treatment of BE with special intestinal metaplasia, while ERFA is more widely used in clinical practice for simpler operation, shorter operative time, and less postoperative complications.

Dissecção endoscópica submucosa com incisão circunferencial versus túnel submucoso no tratamento da neoplasia superficial do esôfago / Endoscopic submucosal dissection with circumferential incision versus tunneling method for treatment of superficial esophageal cancer

ABSTRACT BACKGROUND: Endoscopic submucosal dissection (ESD) of esophageal superficial neoplasm is associated with a high en bloc R0 resection rate and low recurrence. OBJECTIVE: We aim to compare the performance and clinical outcomes of ESD via ESD after circumferential incision (ESD-C) versus submucosal tunneling (ESD-T). METHODS: Single-center retrospective analysis of all consecutive patients who underwent ESD for superficial esophageal cancer, between 2009 and 2018. ESD-T was defined as the technique of making the mucosal incisions followed by submucosal tunneling in the oral to anal direction. ESD-C consisted of completing a circumferential incision followed by ESD. Main study outcomes included en bloc and R0 resection rates. Secondary outcomes included procedural characteristics, curative resection rate, local recurrence and adverse events. RESULTS: A total of 65 procedures (23 ESD-T and 42 ESD-C) were performed for ESCC (40; 61.5%) and BE-neoplasia (25; 38.5%). There were no statistically significant differences between patients who underwent ESD-T versus ESD-C in en bloc (91.3% vs 100%, P=0.12), R0 (65.2% vs 78.6%, P=0.24), curative resection rates (65.2% vs 73.8%, P=0.47) and mean procedure time (118.7 min with vs 102.4 min, P=0.35). Adverse events for ESD-T and ESD-C were as follows: bleeding (0 versus 2.4%; P=0.53), perforation (4.3% vs 0; P=0.61), esophageal stricture (8.7% versus 9.5%; P=0.31). Local recurrence was encountered in 8.7% after ESD-T and 2.4% after ESD-C (P=0.28) at a mean follow-up of 8 and 2.75 years, respectively (P=0.001). CONCLUSION: ESD-T and ESD-C appear to be equally effective with similar safety profiles for the management of superficial esophageal neoplasms.

RESUMO CONTEXTO: A dissecção endoscópica submucosa (DES) no tratamento da neoplasia superficial do esôfago está associada a uma alta taxa de ressecção R0 em bloco e baixa taxa de recorrência. OBJETIVO: O objetivo deste estudo é comparar o desempenho e os resultados clínicos da DES com incisão circunferencial (DES-C) versus com DES com túnel submucoso (DES-TS). MÉTODOS: Estudo retrospectivo de banco de dados coletados prospectivamente de um centro especializado em DES, investigando pacientes consecutivos submetidos à DES por câncer de esôfago superficial, entre 2009 e 2018. DES-TS foi definida como a técnica de realizar primeiro incisões na mucosa seguida de tunelamento submucoso no sentido oral para anal. DES-C consistiu em completar uma incisão circunferencial seguida da dissecção submucosa. As principais variáveis do estudo incluíram taxas de ressecção em bloco e R0. Os resultados secundários incluíram características do procedimento, taxa de ressecção curativa, recorrência local e eventos adversos. RESULTADOS: Um total de 65 procedimentos (23 DES-TS e 42 DES-C) foram realizados para CCE de esôfago (40; 61,5%) e neoplasia associada ao EB (25; 38,5%). Não houve diferenças estatisticamente significativas entre os pacientes submetidos a DES-TS versus DES-C nas taxas de ressecção em bloco (91,3% vs 100%, P=0,12), R0 (65,2% vs 78,6%, P=0,24), taxas de ressecção curativa (65,2% vs 73,8%, P=0,47) e tempo médio do procedimento (118,7 min com vs 102,4 min, P=0,35). Os eventos adversos para DES-TS e DES-C foram os seguintes: sangramento (0 vs 2,4%; P=0,53), perfuração (4,3% vs 0; P=0,61), estenose esofágica (8,7% vs 9,5%; P=0,31). A recorrência local foi encontrada em 8,7% após DES-TS e 2,4% após DES-C (P=0,28) em um seguimento médio de 8 e 2,75 anos, respectivamente (P=0,001). CONCLUSÃO: DES-TS e DES-C demostram ser igualmente eficazes com perfil de segurança semelhante para o tratamento das neoplasias superficiais do esôfago.

El Hybrid-APC en el tratamiento endoscópico del esófago de Barrett / The Hybrid-APC in the endoscopic treatment of Barrett'sesophagus

RESUMEN Fundamento: debido al riesgo de evolución insatisfactoria de los pacientes con esófago de Barrett hacia el adenocarcinoma esofágico, es necesaria la aplicación de técnicas seguras y efectivas que logren prevenir el desenlace hacia lesiones malignas esofágicas. El Hybrid-APC (Argón plasma coagulación) es una de estas técnicas que permiten detener la historia natural del esófago de Barrett en su etapa inicial. Objetivo: realizar una revisión y reflexión acerca del tratamiento endoscópico del esófago de Barrett con el Hybrid-APC. Métodos: se realizó una búsqueda en los motores Google, PudMed, SciELO regional, SciELO Public Health, National Library of Medicine PudMed. En la estrategia de la búsqueda se utilizaron los términos: esófago de Barrett, tratamiento endoscópico, Hybrid-APC. Se evaluaron los documentos en extensos y se desarrolló un documento resumen de la información recolectada. En la búsqueda bibliográfica realizada se encontraron 20 trabajos relacionados con esófago de Barrett, tratamiento endoscópico 10 y específico del uso del Hybrid-APC cinco. Resultados: los estudios reportaron la efectividad y seguridad de la ablación con el Hybrid-APC en el tratamiento endoscópico del esófago de Barrett con displasia de bajo grado; y en la displasia de alto grado y carcinoma in situ remanente, luego de una resección mucosa endoscópica. Conclusiones: el tratamiento endoscópico del esófago de Barrett con Hybrid-APC, se considera una técnica alternativa para detener la evolución de esta enfermedad hacia el adenocarcinoma. Esto generará motivación para entrenamientos y su puesta en práctica de forma generalizada.

ABSTRACT Background: due to the risk of unsatisfactory evolution of patients with Barrett's esophagus (EB) towards esophageal adenocarcinoma, it is necessary to apply safe and effective techniques that prevent the outcome towards esophageal malignant lesions. The Hybrid-APC (argon plasma coagulation) is one of these techniques that allow stopping the natural history of EB in its initial stage. Objective: to conduct a review and reflection on the endoscopic treatment of Barrett's esophagus with the Hybrid-APC. Methods: a search was conducted on Google, PudMed, SciELo regional, SciELo Public Health, National Library of Medicine PudMed engines. The search strategy used the terms: Barrett's esophagus, endoscopic treatment, Hybrid-APC. Extensive documents were evaluated and a summary document of the information collected was developed. The literature search found 20 works related to Barrett's esophagus, ten on endoscopic treatment, and five on specific to the use of Hybrid-APC. Results: studies reported the effectiveness and security of the ablation with the Hybrid-APC in the endoscopic treatment of Barrett's esophagus with low degree dysplasia, and in the high degree dysplasia and remnant carcinoma in situ, after the endoscopic mucous resection. Conclusions: the endoscopic treatment of Barrett's esophagus with Hybrid-APC is considered an alternative technique to stop the evolution of this pathology towards adenocarcinoma. This will generate motivation for training and its implementation in a generalized way.

Progress in Study on Relationship Between Microbiome Dysbiosis and Pathogenesis of Esophageal Diseases / 胃肠病学

With the development of the genomic sequencing of human commensal microbiome and bioinformatics, the role of esophageal microbiome in the pathogenesis of gastroesophageal reflux disease (GERD), Barrett's esophagus (BE), esophageal adenocarcinoma (EAC), and esophageal squamous cell carcinoma (ESCC) has been attracted much attention. Esophageal microbiome are relatively stable, but changes such as age, diet, use of drugs, oral hygiene, smoking, etc. can break the balance between esophageal microbiome and host immunity, and lead to persistent dysbacteriosis, increasing the risk of local inflammation and systemic inflammation and ultimately lead to the progression of many diseases. This article reviewed the progress in study on relationship between microbiome dysbiosis and pathogenesis of esophageal diseases.

High Expression of GADD45B Induced by Acid and Bile Acid is A Potential Prognostic Marker for Barrett's Esophagus-associated Adenocarcinoma / 胃肠病学

Background: Esophageal mucosal injury induced by gastroesophageal reflux is a key link to the development of Barrett's esophagus-associated adenocarcinoma. However, the molecular mechanism is still not elucidated. Aims: To investigate the role of differentially expressed genes (DEGs) after stimulating esophageal cells with acid and bile acid in the development of esophageal adenocarcinoma (EAC). Methods: The DEGs were obtained through bioinformatics methods after stimulating esophageal cells with low pH and deoxycholic acid, and GO, KEGG enrichment analysis were performed. Protein-protein interaction (PPI) network was performed to screen the hub genes, and their relationships with prognosis and tumor stage of EAC patients were analyzed. The role of co-expressed genes of GADD45B in EAC was also analyzed. Results: Thirty-one overlapping DEGs were obtained after stimulating esophageal cells with low pH and deoxycholic acid, which mainly enriched in the cytokine-cytokine receptor interaction, transcription factors activity, and regulation of cell proliferation and apoptotic process. High expression of GADD45B was correlated with the survival prognosis and tumor stage of EAC patients. GADD45B and its co-expressed genes were involved in the production of tumor necrosis factor. Conclusions: The high expression of GADD45B induced by acid and bile acid is correlated with the prognosis and tumor stage of EAC patients, and is a potential diagnosis and treatment target for Barrett's esophagus-associated adenocarcinoma.

Diagnóstico, tratamento e seguimento do esôfago de Barrett: revisão sistemática / Diagnosis, treatment and follow-up of barretts esophagus: a systematic review

ABSTRACT BACKGROUND: Barrett's esophagus (BE) is a premalignant condition that raises controversy among general practitioners and specialists, especially regarding its diagnosis, treatment, and follow-up protocols. OBJECTIVE: This systematic review aims to present the particularities and to clarify controversies related to the diagnosis, treatment and surveillance of BE. METHODS: A systematic review was conducted on PubMed, Cochrane, and SciELO based on articles published in the last 10 years. PRISMA guidelines were followed and the search was made using MeSH and non-MeSH terms "Barrett" and "diagnosis or treatment or therapy or surveillance". We searched for complete randomized controlled clinical trials or Phase IV studies, carried out with individuals over 18 years old. RESULTS: A total of 42 randomized controlled trials were selected after applying all inclusion and exclusion criteria. A growing trend of alternative and safer techniques to traditional upper gastrointestinal endoscopy were identified, which could improve the detection of BE and patient acceptance. The use of chromoendoscopy-guided biopsy protocols significantly reduced the number of biopsies required to maintain similar BE detection rates. Furthermore, the value of BE chemoprophylaxis with esomeprazole and acetylsalicylic acid was relevant, as well as the establishment of protocols for the follow-up and endoscopic surveillance of patients with BE based predominantly on the presence and degree of dysplasia, as well as on the length of the follow-up affected by BE. CONCLUSION: Although further studies regarding the diagnosis, treatment and follow-up of BE are warranted, in light of the best evidence presented in the last decade, there is a trend towards electronic chromoendoscopy-guided biopsies for the diagnosis of BE, while treatment should encompass endoscopic techniques such as radiofrequency ablation. Risks of ablative endoscopic methods should be weighted against those of resective surgery. It is also important to consider lifetime endoscopic follow-up for both short and long term BE patients, with consideration to limitations imposed by a range of comorbidities. Unfortunately, there are no randomized controlled trials that have evaluated which is the best recommendation for BE follow-up and endoscopic surveillance (>1 cm) protocols, however, based on current International Guidelines, it is recommended esophagogastroduodenoscopy (EGD) every 5 years in BE without dysplasia with 1 up to 3 cm of extension; every 3 years in BE without dysplasia with >3 up to 10 cm of extension, every 6 to 12 months in BE with low grade dysplasia and, finally, EGD every 3 months after ablative endoscopic therapy in cases of BE with high grade dysplasia.

RESUMO CONTEXTO: O esôfago de Barrett (EB) é uma condição que aumenta o risco de ocorrência de displasias e câncer no esôfago, a qual apresenta inúmeras controvérsias entre médicos generalistas e até especialistas, em especial no que tange o seu diagnóstico, tratamento e seguimento. OBJETIVO: Tentar esclarecer as controvérsias relacionadas ao estabelecimento do diagnóstico, tratamento, seguimento e vigilância do EB. MÉTODOS: Foi realizado revisão sistemática da literatura fundamentada apenas em ensaios clínicos randomizados e controlados (completos ou em fase IV), em indivíduos maiores que 18 anos, publicados nos últimos 10 anos, por meio de busca, nas bases de dados: PubMed, Cochrane e SciELO (utilizando os termos MeSH e não-MeSH: "Barrett" no título AND diagnosis or treatment or therapy or surveillance" em todos os campos). RESULTADOS: Um total de 42 ensaios clínicos controlados e randomizados foram identificados e selecionados após aplicação dos critérios de inclusão e exclusão. Evidenciou-se, principalmente, o surgimento de técnicas seguras, alternativas à endoscopia digestiva alta (EDA) tradicional para aprimorar a detecção do esôfago de Barrett, associadas a boa aceitação por parte dos pacientes, quando realizadas por meio de acesso nasal. Ainda, o uso de protocolo de biópsias guiadas por cromoendoscopia eletrônica favoreceu reduzir significativamente o número de biópsias necessárias para alcançar as melhores taxas de identificação histológica do EB. Ademais, foi evidenciado que o uso de esomeprazol 40 mg 2x/dia associado ao ácido acetil salicílico 300 mg/dia pode ter efeito protetivo em relação ao desenvolvimento de câncer no EB, além de ser identificado protocolos de seguimento e vigilância endoscópica dos pacientes com EB >1 cm fundamentados, especialmente, no grau de displasia e comprimento do EB (EB sem displasia com 1 a 3 cm = EDA a cada 5 anos; EB sem displasia com >3 a 10 cm = EDA a cada 3 anos; EB com displasia de baixo grau = EDA a cada 6 a 12 meses; EB com displasia de alto grau = realização de terapia endoscópica ablativa e EDA a cada 3 meses). CONCLUSÃO: Foi verificado a necessidade do desenvolvimento de mais ensaios clínicos randomizados e controlados relacionados ao tema, especialmente no que tange o estabelecimento do seguimento e vigilância do EB, entretanto, na luz das melhores evidências apresentadas na última década, o diagnóstico de EB deve seguir, idealmente, protocolos de biópsias guiadas por cromoendoscopia eletrônica. Ademais, o tratamento deve ser fundamentado primeiramente em técnicas endoscópicas, especialmente aquelas terapias com radiofrequência, e quando associado a displasia de alto grau, deverá ser ponderado quanto aos riscos de se insistir em métodos endoscópicos ablativos ou considerar um tratamento cirúrgico ressectivo. Por fim, reforça-se a necessidade de todo paciente com EB >1 cm permanecer em seguimento endoscópico por toda a sua vida, conforme protocolos pré-estabelecidos, exceto se apresentar comorbidades limitantes que impediriam a realização de alguma conduta mais intervencionista. Infelizmente, não há ensaios clínicos randomizados que avaliaram qual é a melhor recomendação de protocolo para o seguimento endoscópico de EB (>1cm), porém, baseado nas atuais Guidelines Internacionais, é recomendado esofagogastroduodenoscopia (EGD) a cada 5 anos em EB sem displasia com 1 a 3 cm de extensão; a cada 3 anos em EB com displasia com 3 a 10 cm de extensão, a cada 6 a 12 meses em EB com displasia de baixo grau e, finalmente, EGD a cada 3 meses após terapia ablativa endoscópica nos casos de EB com displasia de alto grau.

Caracterización demográfica de la población con esófago de Barrett en dos instituciones médicas de Bogotá, Colombia / Demographic characterization of the population with Barretts esophagus in two medical centers of Bogotá, Colombia

Resumen Introducción: el esófago de Barrett es un trastorno en el que ocurre un cambio del epitelio escamoso estratificado del esófago por uno columnar especializado, lo cual se da como consecuencia del reflujo gastroesofágico crónico. En Colombia no se conoce la prevalencia actual de esta patología, ni se ha caracterizado a la población que la padece. El presente estudio tiene como objetivo conocer cuáles son las características demográficas principales de la población diagnosticada con esófago de Barrett en dos instituciones médicas de Bogotá. Material y métodos: se realizó un estudio de corte transversal multicéntrico, en el cual se evaluaron los reportes de endoscopias y de histopatología de 3000 pacientes que asistieron a estas instituciones por cualquier indicación. A partir de estos reportes se tomaron los datos requeridos. Asimismo, se realizó un análisis estadístico descriptivo de dichos datos. Resultados: la prevalencia del esófago de Barrett en la muestra es del 0,73 %. Se observó, además, que la correlación endoscópico-patológica es baja (28,5 %). De los casos diagnosticados, el rango de edad más frecuente se ubica entre los 60 y 80 años, con una edad promedio de 65,5 años. Asimismo, existe una predominancia de esta patología en el sexo femenino (63,6 %), en personas con un índice de masa corporal (IMC) >25 kg/m² y en aquellas con antecedentes de tabaquismo, sin historial de consumo de alcohol. En la mayoría de pacientes, se realizó la endoscopia por síntomas de reflujo gastroesofágico (50 %). La longitud del segmento observado no fue reportada en una gran cantidad de endoscopias. Conclusiones: en las instituciones analizadas, el esófago de Barrett es una patología de muy baja prevalencia y predominante en mujeres de edad avanzada con síntomas de reflujo gastroesofágico, sobrepeso y antecedente de tabaquismo.

Abstract Introduction: Barrett's esophagus occurs when the stratified squamous epithelium of the esophagus changes to a specialized columnar epithelium as a result of chronic gastroesophageal reflux. Its current prevalence in Colombia is unknown and the population suffering from it has not been characterized. The present study aims to determine the main demographic characteristics of the population diagnosed with Barrett's esophagus treated at two medical centers in Bogotá, Colombia. Materials and methods: A multicenter cross-sectional study was conducted to assess the endoscopy and histopathology reports of 3,000 patients who underwent this procedure for any reason. A descriptive statistical analysis of the data was performed. Results: The prevalence of Barrett's esophagus in the sample was 0.73%. The endoscopic-histology correlation was low (28.5%). Of the diagnosed cases, the most frequent age range was 60-80 years, with an average age of 65.5 years. This condition is predominant in the female sex (63.6%), in people with a BMI over 25 kg/m², with a history of smoking, and no history of alcohol consumption. Most patients underwent endoscopy for symptoms associated with gastroesophageal reflux (50%). The length of the observed segment was not reported in most endoscopies. Conclusions: In the medical centers included in this study, Barrett's esophagus is a rare pathology, found predominantly in elderly women with symptoms of gastroesophageal reflux, overweight, and with a history of smoking.

Esôfago de Barrett: o estado da arte / Barrett's Esophagus: the state of the art

Objetivo: Demonstrar fatores envolvidos nos distúrbios do sono em profissionais que fazem plantões. Métodos: Trata-se de estudo transversal, cuja amostra foi composta de 244 voluntários, plantonistas da área da saúde, sendo 191 do sexo feminino, que responderam a um questionário socioeconômico, associado à aplicação da Escala de Sonolência de Epworth e ao Índice de Qualidade do Sono de Pittsburgh. Os dados foram analisados pelos coeficientes de Spearman e de Kendall Tau, com distribuição de probabilidade gama. Resultados: Houve significância (p<0,05) com o Índice de Qualidade do Sono de Pittsburgh e a atividade física (+0,216), ergonomia (+0,148), filhos (-0,146), valor da remuneração (+0,112) e disfunção durante o dia (+0,352). Também houve significância com a Escala de Sonolência de Epworth e atividade física (+0,138), renda familiar (-0,118), trabalho semanal (-0,151), latência do sono (-0,106), duração do sono (-0,107), eficiência do sono (-0,139) e disfunção durante o dia (+0,170). Por fim, a eficiência do sono teve significiância com profissão (-0,209), tabagismo (+0,402), Escala de Sonolência de Epworth (-0,139) e dissonias com a obesidade (índice de massa corporal >30; razão de chance de 1,40; intervalo de confiança de 95% de 1,02-1,94). Conclusão: As medidas autorrelatadas são prontamente obtidas com questionários validados, como a Escala de Sonolência de Epworth e o Índice de Qualidade do Sono de Pittsburgh, encontrando-se correlações com renda familiar, ter ou não filhos, índice de massa corporal, atividade física, ergonomia, condições de trabalho, tabagismo e componentes biopsicossociais. Em virtude do caráter transversal deste estudo é indispensável mais estudos com maior follow-up

Objective: To demonstrate factors involved in sleep disorders in professionals who take shifts. Methods: This is a cross-sectional study whose sample consists of 244 volunteers, on-duty health workers, 191 females, who answered a socioeconomic questionnaire, associated with application of the Epworth Sleepiness Scale and the Pittsburgh Sleep Quality Index. Data were analyzed with Spearman's and Kendall Tau coefficients, and gamma probability distribution. Results: There was significance (p<0,05) with the Pittsburgh Sleep Quality Index and physical activity (+0,216), ergonomics (+0,148), children (-0,146), the wage (+0,112), dysfunction during the day (+0,352). Also there was significance with the Epworth Sleepiness Scale and physical activity (+0,138), family income (-0,118), weekly workload (-0,151), sleep latency (-0,106), sleep duration (-0,107), sleep efficiency (-0,139), and dysfunction during the day (+0,170). Finally, sleep efficiency was significant with occupation (-0,209), smoking habits (+0,402), Epworth Sleepiness Scale (-0,139), dyssomnia with obesity (body index mass >30; OR of 1,40; CI 95% 1,02-1,94). Conclusion: Self-reported measures are readily obtained with validated questionnaires such as Epworth Sleepiness Scale and Pittsburgh Sleep Quality Index, with correlations with family income, having children or not, body mass index, physical activity, ergonomics, working conditions, smoking habits, and biopsychosocial components. Due to the cross-sectional nature of this study, further research with longer follow-up is indispensable

Research Progress on Related Genes of Gastroesophageal Reflux Disease / 胃肠病学

Gastroesophageal reflux disease (GERD) is a common disease with complex pathogenesis and poor efficacy of traditional treatments. With the development of molecular biotechnology, it is demonstrated that gene polymorphisms such as IL-1B, IL-1RN, PAR-2, and GSTP1 can increase disease susceptibility, while COX-2, CDX-2, MMPs, EGF and other genes can promote the development of GERD into Barrett's esophagus (BE) and esophageal adenocarcinoma (EAC). The study of genetics will contribute to the prevention and treatment of the disease. This article reviewed the role of related genes in the occurrence, development and carcinogenesis of GERD.

Progress in Research on Correlation Between Toll-like Receptors and Barrett's Esophagus / 胃肠病学

Barrett's esophagus (BE), the only recognizable precancerous lesion of esophageal adenocarcinoma (EAC), is a common disease characterized by abnormal transformation of squamous epithelium into intestinal columnar epithelium. Toll-like receptors (TLRs) are important pattern recognition receptors that play a central role in innate and adaptive immunity. TLRs are involved in the identification of almost all pathogens. In addition, TLRs signaling pathway is important for the occurrence and development of BE. This article reviewed the progress in research on the correlation between TLRs and BE.

Postprandial proximal gastric acid pocket and its association with gastroesophageal acid reflux in patients with short-segment Barrett’s esophagus / 浙江大学学报（英文版）（B辑：生物医学和生物技术）

Objective: To determine the characteristics of postprandial proximal gastric acid pockets (PPGAPs) and their association with gastroesophageal acid reflux in patients with Barrett’s esophagus (BE). Methods: Fifteen patients with BE (defined by columnar lined esophagus of ≥1 cm) and 15 healthy individuals that were matched for age, gender, and body mass index, were recruited. The fasting intragastric pH and the appearance time, length, lowest pH, and mean pH of the PPGAP were determined using a single pH electrode pull-through experiment. For BE patients, a gastroesophageal reflux disease questionnaire (GerdQ) was completed and esophageal 24-h pH monitoring was carried out. Results: The PPGAP was significantly longer (5 (3, 5) cm vs. 2 (1, 2) cm) and the lowest pH (1.1 (0.8, 1.5) vs. 1.6 (1.4, 1.9)) was significantly lower in patients with short-segment BE than in healthy individuals. The PPGAP started to appear proximally from the gastroesophageal pH step-up point to the esophageal lumen. The acidity of the PPGAP was higher in the distal segment than in the proximal segment. In short-segment BE patients, there were significant correlations between the acidity and the appearance time and length of the PPGAP. The length and acidity of the PPGAP were positively associated with gastroesophageal acid reflux episodes. The acidity of the PPGAP was associated with the DeMeester scores, the GerdQ scores, and the fasting intragastric pH. Conclusions: In patients with short-segment BE, a PPGAP is commonly seen. Its length and acidity of PPGAP are associated with gastroesophageal acid reflux, the DeMeester score, and the GerdQ score in patients with short-segment BE.