Clinical and pathologic characteristics of gastric adenocarcinoma associated with Epstein-Barr virus in a region with a high incidence of gastric cancer in Colombia.

INTRODUCTION AND AIMS: Epstein-Barr virus (EBV) infection is an etiologic factor in EBV-associated gastric carcinoma (EBVaGC). The aim of our study was to describe the clinical and histopathologic characteristics of EBV infection in intestinal-type gastric adenocarcinoma samples. MATERIAL AND METHODS: Of 180 paraffin-embedded gastrectomy samples, 28 were studied. Chromogenic in situ hybridization was performed to detect EBV. Sociodemographic and histopathologic data were obtained from the patients' clinical histories. RESULTS: A total of 21.4% of the samples were positive for EBV. The predominant morphologic characteristic was the lace pattern, with dense inflammatory infiltration. Fifty percent of the EBVaGC+ patients were men, and the median age of the positive patients was 59 years (range: 50-75); 77.2% of the EBVaGC- patients were men, and the median age of the negative patients was 66 years (range: 34-89). Helicobacter pylori infection was associated with 10.7% of the EBVaGC+ patients and 53.6% of the EBVaGC- patients. In the EBVaGC+ patients, the cardia was the most frequent tumor location (17.9%), 7.1% had histologic grades 2 and 3, and 17.9% presented with Borrmann classification type III. In the EBVaGC- patients, the cardia and fundus were the most frequent tumor locations (71.4%), 35.7% had histologic grade 2, and 39.3% and 21.4% presented with Borrmann classification type III and IV, respectively. CONCLUSIONS: The present study describes the clinical and histopathologic characteristics associated with EBVaGC positivity. Those data may aid in the selection of cases that are candidates for analysis through molecular methods aimed at identifying EBV infection in intestinal-type gastric adenocarcinoma.

Impacto do status da infecção pelo vírus de Epstein-Barr e do perfil de instabilidade de microssatélites no prognóstico de pacientes portadores de adenocarcinomas gástricos / Impact of Epstein-Barr virus infection status and microsatellite instability profile on the prognosis of patients with gastric adenocarcinomas

A determinação acurada do prognóstico tumoral ainda é um desafio no tratamento oncológico. Estudos sugerem que dois dos subtipos moleculares de adenocarcinomas gástricos (AdGs), talvez tenham melhor prognóstico quando comparados aos demais: aqueles caracterizados pela presença do vírus Epstein-Barr (AdG-EBV) e aqueles com instabilidade de microssatélites de DNA (AdG-MSI). No Brasil, a distribuição destes subtipos ainda não foi profundamente investigada, e não sabemos o impacto prognóstico dos mesmos na nossa população, que possui aspectos étnicos e epidemiológicos próprios. O objetivo deste trabalho é determinar a prevalência e a relevância clínica/prognóstica dos subtipos EBV e MSI, em uma coorte de pacientes portadores de AdG tratados no A.C.Camargo Cancer Center. A coorte incluiu 198 pacientes diagnosticados entre 2016 a 2020, dos quais foram coletadas amostras de biópsias tumorais (195/198) e fluidos gástricos (167/198). A presença do DNA de EBV foi avaliada por qPCR e o status de MSI foi determinado a partir de dados de sequenciamento de exoma das amostras tumorais (MSIseq/NGS classifier). Na avaliação prognóstica utilizamos análise de sobrevida pelo método de Kaplan-Meier e Log Rank (R v. 4.1.2). Para as análises estatísticas utilizamos principalmente os testes de qui-quadrado e exato de Fisher na análise de fatores clínicos (SPSS v. 25). A prevalência observada na coorte para EBV+ e MSI+ foi exatamente a mesma: 7,1% (14/198 casos), similar a outros relatos da literatura. A média de idade para pacientes EBV+ e EBV- foi similar (respectivamente, 60 e 61,7 anos), e o sexo predominante para os dois grupos foi o masculino (85,7% para EBV+ e 60,3% para EBV-). Quanto aos casos MSI+, a média de idade foi de 74,3 anos e maioria do sexo feminino (71,4%, p= 0,016), enquanto os pacientes MSI- tiverem média de 60,6 anos e o sexo masculino prevalente (64,7%). A distribuição dos casos EBV+ e MSI+ quanto aos subtipos de Lauren, foi respectivamente, 9 28,6% e 69,2% para intestinal, 57,1% e 15,4% para difuso, e 14,3% e 15,4 % para o subtipo misto. Observamos relação significativa entre esta classificação e o status MSI (p=0,017), mas não para a presença de EBV. O impacto prognóstico foi avaliado pela sobrevida câncer específica (CE) e sobrevida livre de recidiva em 05 anos nas condições: (A) excluindo os casos metastáticos ao diagnóstico e (B) excluindo também os com estadiamento TNM IV. Não observamos diferenças estatísticas entre os grupos, o que talvez seja fruto de uma casuística ainda limitada frente à baixa frequência de EBV e MSI em nossa população. Entretanto, os casos EBV+ não apresentaram recidiva da doença, sugerindo um impacto positivo da presença de EBV. Além disso, avaliamos a relação entre a ancestralidade genômica e os AdGs EBV e MSI, onde a ancestralidade predominante principal foi a europeia, seguida da asiática, mas não observamos efeito da ancestralidade quanto ao prognóstico dos subtipos. Ademais, avaliamos a carga mutacional tumoral (CMT) e as assinaturas mutacionais onde se destacou a associação com o status MSI+, grupo no qual foram identificadas as assinaturas correspondentes à deficiência em MMR e idade mais avançada. Os pacientes MSI+ tinham idade mais elevada, o que pode ter afetado o prognóstico inicial. Entretanto, os casos MSI+ com CMT alta se distinguem do resultado da coorte total e apresentaram o prognóstico mais favorável. Dessa forma pudemos aprofundar a compreensão dos AdGs EBV e MSI, contribuir para o detalhamento molecular desta população no Brasil

The accurate determination of tumor prognosis still challenges cancer treatment. Studies have suggested that two of the molecular subtypes of gastric adenocarcinomas (GaCs) may have a better prognosis when compared to the others: those characterized by the presence of the Epstein-Barr virus (GaC-EBV) and those with DNA microsatellite instability (GaC-MSI). In Brazil, the distribution of these subtypes has not been thoroughly investigated, and we do not know their prognostic impact on our population, which has its own ethnic and epidemiological aspects. This study aims to determine the prevalence and clinical/prognostic relevance of the EBV and MSI subtypes in a cohort of patients with GaC treated at the A.C.Camargo Cancer Center. The cohort includes 198 patients recruited between 2016 and 2020, from whom tumor biopsies (195/198) and gastric fluid samples (167/198) were collected. The presence of EBV DNA was assessed by qPCR and MSI status was determined from exome sequencing data from tumor samples (MSIseq/NGS classifier). In the prognostic evaluation, we used survival analysis by the Kaplan-Meier and Log Rank method (R v. 4.1.2). For statistical analyses, we used Chisquare and Fisher's exact tests (SPSS v. 25). The prevalence observed in the cohort for EBV+ and MSI+ was the same: 7.1% (14/198 cases), similar to other reports in the literature. The mean age for EBV+ patients was 60 years and for EBV-, 61.7 years, and the predominant sex for both groups was male (85.7% for EBV+ and 60.3% for EBV-). As for the MSI+ cases, the mean age was 74.3 years and the majority were female (71.4%), while the MSI- patients had a mean age of 60.6 years and the male gender was prevalent (64.7%). The Lauren's subtypes distribution of EBV+ and MSI+ cases were respectively, 28.6 and 69.2% for intestinal, 57.1 and 15.4% for diffuse, and 14.3 and 15.4% for the subtype mixed. We observed a significant relationship between this classification and MSI status (p=0.017), but not for the presence of EBV. The prognostic impact was assessed by overall survival and recurrence-free survival at 05 years in the following conditions: (A) excluding metastatic cases at diagnosis and (B) also excluding those with TNM stage IV. We did not observe statistical differences between the groups, which may be an effect of a limited cohort. However, EBV+ cases did not show disease recurrence, suggesting a preliminary positive impact of the presence of EBV in protecting against recurrences in GaC. In addition, we evaluated the relationship between genomic ancestry and the GaCs EBV and MSI, where the main predominant ancestry was European, followed by Asian. And we did not observe an effect of ancestry on the prognostic panorama of the subtypes. In addition, tumor mutation burden (TMB) and mutational signatures were evaluated to complement the molecular profile. There is an association highlighted for MSI+ status with the signatures corresponding to MMR deficiency and older age. This age factor was verified and the MSI+ patients were older, which affected the initial prognosis. However, MSI+ cases with high TMB differ from the result of the total cohort and presented the most favorable prognosis. In this way, we were able to deepen the understanding of GaCs EBV and MSI in order to contribute to their management in Brazil

Estadiaje ganglionar en el adenocarcinoma gástrico / Lymph node stage in gastric adenocarcinoma

Resumen Objetivos: El sistema linfático del estómago es complejo y multidireccional, siendo difícil predecir el patrón de diseminación linfática en el adenocarcinoma (ADC) gástrico. Los objetivos de este trabajo son determinar si el analizar los grupos ganglionares de la pieza quirúrgica por separado tiene implicaciones en el estadiaje, además estudiar la afectación de diferentes grupos ganglionares. Materials y Método: Estudio observacional retrospectivo de pacientes intervenidos de gastrectomía y linfadenectomía con intención curativa por ADC en un hospital de referencia (2017-2021).,_Se han comparado aquellos pacientes cuya pieza quirúrgica se estudió en su totalidad (grupo A) con aquellos en los que se separaron los grupos ganglionares para su análisis (grupo B). En el grupo B, se ha analizado la afectación ganglionar de diferentes grupos ganglionares en base a la localización tumoral y el estadio pT. Resultados: Se incluyeron 150 pacientes. La media de ganglios analizados fue significativamente mayor cuando se separaron los grupos ganglionares (grupo B) (24,01 respecto a 20,49). La afectación ganglionar fue del 45,8%, 58,3% y 55,5% en los tumores de tercio superior, medio e inferior respectivamente, y los grupos difirieron en base a la localización tumoral. El riesgo de afectación ganglionar fue significativamente mayor y hubo más grupos ganglionares perigástricos afectos cuanto mayor era el estadio pT. Conclusiones: Separar los grupos ganglionares previo a su análisis aumenta el número de ganglios analizados mejorando el estadiaje ganglionar. Existen diferentes rutas de drenaje linfático dependiendo de la localización tumoral y la afectación ganglionar aumenta de forma paralela al estadio pT.

Objectives: The lymphatic system of the stomach is complex and multidirectional, making it difficult to predict the pattern of lymphatic spread in gastric adenocarcinoma (GAC). The aim of this paper is to determine if analyzing the lymph node groups of the surgical specimen separately has implications in the pathological staging, as well as to study the involvement rate of different lymph node groups. Material and Method: Retrospective observational study of patients who underwent curative intent gastrectomy and lymphadenectomy for GAC in a reference hospital (2017-2021). Those patients whose surgical specimen was studied as a whole (group A) were compared with those in whom the lymph node groups were separated by surgeons before analysis (group B). In group B, the involvement of different lymph node groups was analyzed based on tumor location and pT stage. Results: 150 patients were included. The mean number of lymph nodes analyzed was significantly higher when the lymph node groups were separately analyzed (group B) (24.01 compared to 20.49). Lymph node involvement was 45.8%, 58.3%, and 55.5% in tumors of the upper, middle, and lower third, respectively, and the involved groups differed depending on the tumor location. The higher the pT stage was, the risk of lymph node involvement was significantly higher and there were more perigastric lymph node groups affected. Conclusions: Separating lymph node groups prior to their analysis increases the number of lymph nodes analyzed and therefore improves lymph node staging. There are different lymphatic drainage routes depending on the tumor location and lymph node involvement increases in parallel with the pT stage.

Predictors of anastomotic leak after total gastrectomy in patients with adenocarcinoma.

BACKGROUND: Esophagojejunal anastomotic leakage (EJAL) is among the most feared complications after gastric cancer surgery; they entail an uncertain prognosis and relate with increased morbidity and mortality. Factors associated with their development are not well determined, and their diagnosis and treatment vary between institutions. MATERIAL AND METHODS: Retrospective case-control study of patients operated of total gastrectomy with Roux-en-Y esophagojejunostomy from January 2002 to December 2018. We divided our sample into two groups based on the presence of EJAL, and compared demographic, clinical, and histologic variables. We performed a logistic regression model to search risk factors associated with EJAL and described the management offered in our center. RESULTS: We included 58 patients of which 8 (13.7%) presented clinically relevant EJAL. On the comparative analysis, albumin levels and diffuse histology presented a statistically significant difference between groups and presented association with EJAL in the logistic regression model. Regarding treatment of EJAL, ten patients (55.5%) required only conservative measures, whereas eight patients (44.4%) warranted an endoscopic or surgical intervention. CONCLUSION: Our retrospective analysis identified some factors that may be associated with the development of EJAL after gastric cancer surgery. High suspicion and prompt identification of this complication is essential to improve postoperative outcomes in this group.

INTRODUCCIÓN: Las fugas de la anastomosis esófago-yeyunal se encuentran entre las más temidas complicaciones de la cirugía para cáncer gástrico. Estas conllevan un mal pronóstico con una alta mortalidad y morbilidad. Los factores asociados a su desarrollo no están bien determinados y su diagnóstico, y tratamiento varían ampliamente entre instituciones. MATERIAL Y MÉTODOS: Estudio retrospectivo de casos y controles en pacientes operados de gastrectomía total con esófago-yeyuno anastomosis en Y de Roux en el periodo de enero 2002 a diciembre 2018. Nuestra muestra fue dividida en dos grupos con base al desarrollo de fuga de anastomosis en el postoperatorio. Se realizó un análisis comparativo de características demográficas, clínicas y histológicas. Se realizó además una regresión logística para identificar factores de riesgo asociados al desarrollo de fuga de anastomosis en nuestra serie. RESULTADOS: Incluimos a 58 pacientes de los cuales 8 (13.7%) presentaron fuga de anastomosis clínicamente relevante. En el estudio comparativo: Niveles disminuidos de albúmina e histología difusa fueron significativamente mayores en el grupo de fuga y se asociaron en el modelo de regresión logística. En cuanto al tratamiento, diez pacientes (55%) requirieron únicamente tratamiento conservador, mientras que ocho pacientes (44.4%) fueron sometidos a maniobras endoscópicas o quirúrgicas. CONCLUSIÓN: Nuestro análisis retrospectivo identifico factores asociados al desarrollo de fuga de anastomosis posterior a cirugía de cáncer gástrico. Una alta sospecha diagnóstica es esencial para mejorar el pronóstico de estos pacientes.

Desenvolvimento de metodologia para identificação de fungos através de metabarcoding aplicada em amostras humanas de adenocarcinoma gástrico e carcinoma epidermoide de pênis / Development of methodology for fungi identification through metabarcoding applied in gastric adenocarcinoma and penile epidermoid carcinoma of human sample

O microbioma humano compreende material genético da microbiota de um local do corpo e tem influência direta ou indireta na manutenção da homeostase. O distúrbio da microbiota pode estar relacionado ao desenvolvimento de doenças. A população fúngica ainda é muito pouco estudada no contexto do microbioma. No presente estudo, foi desenvolvida uma metodologia para identificação de fungos por metabarcoding. A metodologia desenvolvida foi aplicada em mostras de pacientes portadores de adenocarcinoma gástrico ou carcinoma epidermoide de pênis. De modo geral, em ambos os tumores foi verificada a redução de diversidade fúngica conforme a evolução do estadiamento patológico. Também foram verificados resultados não concordantes ao analisar espécies diferencialmente abundantes em dados de sequenciamento da região ITS2 e de WGS nas amostras de lavado gástrico. Este trabalho reforça a importância em se estudar os fungos e sua associação com doenças como o câncer e incentiva próximos estudos através do desenvolvimento de uma metodologia específica para o micobioma.

The human microbiome comprises genetic material from the microbiota of a body site and has a direct or indirect influence on the maintenance of homeostasis. The disturbance of the microbiota may be related to the development of diseases. The fungal population is still very little studied in the context of the microbiome. In this study, a methodology was developed to identify fungi by metabarcoding. The methodology developed was applied to samples from patients with gastric adenocarcinoma or squamous cell carcinoma of the penis. In general, in both tumors, a reduction in fungal diversity was observed according to the evolution of the pathological staging. Discordant results were also found when analyzing differentially abundant species in sequencing data from the ITS2 region and WGS in gastric lavage samples. This work reinforces the importance of studying fungi and their association with diseases such as cancer and encourages further studies through the development of a specific methodology for the mycobiome

Caracterización clínica, histológica y endoscópica del cáncer gástrico en el Hospital de Especialidades Dr. Abel Gilbert Pontón, Ecuador / Clinical, histological, and endoscopic characterization of gastric cancer at the Hospital de Especialidades Dr. Abel Gilbert Pontón, Ecuador

Resumen Introducción: El cáncer gástrico, a nivel mundial, tiene una incidencia variable y es una de las causas más frecuentes de muerte. En Ecuador ocupa el segundo lugar de muerte en los hombres y la cuarta en las mujeres por cáncer gástrico. Objetivos: Establecer las características sociodemográficas, clínicas, histológicas y endoscópicas, y determinar una correlación entre la localización e histología en una población de pacientes con cáncer gástrico en el Hospital de Especialidades de Guayaquil, Dr. Abel Gilbert Pontón. Materiales y métodos: Estudio de prevalencia analítico y prospectivo. Se incluyeron las endoscopias digestivas altas de consulta externa y emergencia con signos de sospecha de cáncer gástrico realizadas en el Hospital de Especialidades de Guayaquil, Dr. Abel Gilbert Pontón, Ecuador, entre enero de 2018 y diciembre de 2019. Resultados: En el estudio se incluyeron 62 pacientes con diagnóstico de adenocarcinoma gástrico, el sexo masculino representó el 72,6 % en relación con el sexo femenino, con el 27,4 %; el rango de edad fue entre los 27 y 95 años, el promedio de edad es de 60,96 ± 15,1 y la edad de mayor presentación fue de 60 a 70 años. El síntoma que predominó fue el dolor, en un 98,4 %, y la pérdida de peso, en un 64,5 %; su localización más frecuente fue el antro (50,0 %), su morfología de mayor presentación es el Borrmann tipo III y, con respecto al tipo histológico, se encontró el tipo intestinal (64,5 %) y el difuso (29,0 %). El tipo intestinal se presentó en edad más avanzada en un 60 %-69 %, fue más frecuente en el cuerpo (71,4 %) y su localización fue más proximal, en comparación con el tipo difuso, que se presentó más en edad temprana (27-39 años), fue más frecuente en el antro (32,3 %) y su localización fue más distal. Conclusiones: El cáncer gástrico se diagnostica en estadios avanzados, más en hombres que en mujeres y se puede afirmar que en nuestro hospital la localización del cáncer gástrico tipo intestinal se presentó en edades avanzadas, más frecuentemente a nivel proximal y en la clasificación del cáncer gástrico avanzado Borrmann tipo III, lo cual podría tener influencia en el tratamiento y pronóstico. Además, los resultados obtenidos justifican la implementación de programas de detección oportuna y tratamiento de esta grave enfermedad.

Abstract Introduction: Gastric cancer is one of the most common causes of death worldwide, with a varying incidence. In Ecuador, it is the second leading cause of death in men and the fourth in women. Objectives: To establish the socio-demographic, clinical, histological, and endoscopic characteristics of patients with gastric cancer and to determine the correlation between location and histology in this population treated at the Hospital de Especialidades Guayaquil Dr. Abel Gilbert Pontón. Materials and methods: Analytical and prospective prevalence study. Outpatient and emergency upper gastrointestinal endoscopies with signs of suspected gastric cancer performed at the Hospital de Especialidades Guayaquil Dr. Abel Gilbert Pontón - Ecuador between January 2018 through December 2019 were included. Results: The study included 62 patients diagnosed with gastric adenocarcinoma. 72.6% were male and 27.4% were female; the age range was between 27 and 95 years, with an average of 60.96 ± 15.1 years, the age of onset being between 60 and 70 years. Pain was the most frequent symptom in 98.4% of cases, followed by weight loss in 64.5%. The antrum was the most common site of cancer (50.0%), and Borrmann type III was the most common morphology. Intestinal cancer was found in 64.5% of cases, while diffuse gastric cancer was found in 29.0%. Intestinal cancer was more common in older ages (60-69%) and the most frequent site of presentation was the body of the stomach (71.4%) with a proximal location. In contrast, diffuse gastric cancer was more frequent in younger patients aged between 27-39 years, more often in the antrum (32.3%) at a more distal location. Conclusions: Gastric cancer is more often found in men and is usually diagnosed in advanced stages. Intestinal gastric cancer was most commonly seen at advanced ages in our hospital, most frequently at the proximal site and in the Borrmann type III according to the classification of advanced gastric cancer, affecting its treatment and prognosis. The results obtained support the implementation of programs to diagnose and treat this severe disease in a timely manner.

Avaliação da composição da microbiota gástrica e sua correlação com o conteúdo de fibras na dieta de pacientes com adenocarcinoma gástrico e controles sem câncer / Evaluation of gastric microbiota composition and its correlation with fiber content in the diet of patients with gastric adenocarcinoma and cancer-free controls

O adenocarcinoma gástrico é uma das neoplasias mais incidentes no Brasil e no mundo. Sua etiologia é de causa multifatorial. Em relação à dieta, o grau de processamento empregado na produção dos alimentos, condiciona o perfil de nutrientes. Desta forma, em populações com estilo de vida ocidental é crescente o consumo de alimentos ultraprocessados que pode condicionar uma dieta menos diversa, com contribuição de gorduras saturadas, carboidratos simples e consequente baixa ingestão de fibras. As fibras alimentares exercem efeitos protetores e parecem ter papel auxiliar na diminuição da ocorrência de alguns tipos de câncer, como o colorretal; efeito este ligado a interação entre as fibras e o microbioma intestinal. Porém, apesar do estômago ser um órgão colonizado por bactérias, pouco se sabe sobre interrelação entre a dieta e principalmente a ingestão de fibras alimentares e sua ação sobre o microbiota gástrica de pacientes portadores de adenocarcinoma gástrico, visto que os estudos se limitam principalmente a análises a nível intestinal. Dessa forma, o estudo aqui apresentado teve como objetivo apresentar evidências biológicas da relação entre a ingestão de fibras alimentares com a composição da microbiota gástrica de lavado gástrico de indivíduos com adenocarcinoma gástrico e controles endoscópicos. Tais evidências incluíram desde a caracterização da ingestão alimentar e diferenças entre os grupos avaliados, até a correlação entre as variáveis dietéticas com o perfil taxonômico de bactérias estomacais. Para quantificação dietética utilizamos um questionário de frequência alimentar e convertemos a quantidade de gramas de alimentos em contribuição do percentual calórica da dieta de acordo com o grau de processamento e em gramas de fibras para cada 1000 kcal ingerida, com bases em tabelas de composição de alimentos. Para análise de microbiota, após extração de DNA do suco gástrico, foi utilizado a abordagem de sequenciamento do gene codificador do rRNA sub-unidade 16s. Para o primeiro módulo desse trabalho identificamos que o grupo com câncer possui uma maior ingestão de alimentos ultraprocessados e menor ingestão de fibras, quando comparado com os controles. Por meio de um modelo de regressão logística multinomial, essas diferenças resultam em: uma maior ingestão de fibras insolúveis e menor de alimentos ultraprocessados estar mais associada com o grupo controle endoscópico, quando comparado com os indivíduos com câncer (OR 2,651, IC 95% 1,069-6,573, p=0,035) e (OR 2,521, IC 95% 1,076-5,905, p=0,033) respectivamente. Em termos de composição da microbiota estomacal, no grupo adenocarcinoma gástrico identificamos que as fibras totais possuem uma correlação positiva com o filo Firmicutes (rô= 0.53; p= 0,021). Este mesmo tipo de fibras possui correlação forte e negativa com o filo Proteobacteria (rô= −0.58; p= 0,011). No grupo de controles endoscópicos, as fibras insolúveis apresentaram uma correlação negativa com as Proteobactérias. A nível de gênero, de acordo com o algoritmo de Lefse, identificamos 17 gêneros diferencialmente abundantes no grupo controle com alta ingestão de fibras (Q4 = >14g/ 1000kcal), versus com baixa ingestão (Q1= <8,5g/1000 kcal), com destaque para os gêneros Mogibacterium, Prevotella 7, Fusobacterium e Actinomyces, que se mostraram enriquecidos na dieta rica em fibras. Para o grupo com câncer, no quartil 1 observamos 4 gêneros diferencialmente abundantes, sendo eles: Butyrivibrio, Helicobacter e Stomatobaculum. Comparando indivíduos do grupo AdG do Q1 (N=24) versus Controles do Q4 (N=26), o gênero Abiotrophia foi mais abundante nos controles, e Escherichia_shigella, um gênero patogênico, foi mais frequente no AdG. Na diversidade total, evidenciamos uma maior influência das fibras no grupo controle. Por fim, concluímos que as fibras alimentares podem influenciar a microbiota antes do desenvolvimento da doença, visto que, no grupo controle endoscópicos os achados mostraram não apenas uma maior riqueza total de gêneros bacterianos, mas uma maior abundância de bactérias específicas. Esses resultados bem distintos entre casos e controles podem estar associados com o fato, dos indivíduos com câncer já terem uma doença instalada, com consequente disbiose. Destacamos nos controles com alto consumo de fibras, uma maior abundância de gêneros produtores de ácidos graxos de cadeia curta e importante atividade imunomodulatória. Já no grupo AdG identificamos gêneros com um perfil pró-inflamatório, como a Helicobacter

Gastric adenocarcinoma is one of the most common neoplasms in Brazil and in the world. Its etiology has a multifactorial cause. In relation to diet, the degree of processing used in food production conditions the nutrient profile. Thus, in populations with a Western lifestyle, the consumption of ultra-processed foods is increasing, which can lead to a less diverse diet, with the contribution of saturated fats, simple carbohydrates and consequent low fiber intake.Dietary fibers have protective effects and seem to have an auxiliary role in reducing the occurrence of some types of cancer, such as colorectal; This effect is linked to the interaction between fibers and the intestinal microbiome. However, despite the stomach being an organ colonized by bacteria, little is known about the interrelationship between diet and especially dietary fiber intake and its action on the gastric microbiota of patients with gastric adenocarcinoma, since studies are mainly limited to intestinal analyses. Thus, the study presented here aimed to present biological evidence of the relationship between dietary fiber intake and the composition of the gastric microbiota of gastric lavage from individuals with gastric adenocarcinoma and endoscopic controls. Such evidence ranged from the characterization of food intake and differences between the groups evaluated, to the correlation between dietary variables with the taxonomic profile of stomach bacteria. For dietary quantification, we used a food frequency questionnaire and converted the amount of grams of food into the contribution of the caloric percentage of the diet according to the degree of processing and in grams of fiber for each 1000 kcal ingested, based on food composition tables. For microbiota analysis, after extracting DNA from gastric juice, the approach of sequencing the gene encoding the 16s rRNA subunit was used. For the first module of this work, we identified that the cancer group has a higher intake of ultra-processed foods and lower fiber intake when compared to controls. Using a multinomial logistic regression model, these differences result in: a higher intake of insoluble fiber and lower intake of ultra-processed foods being more associated with the endoscopic control group when compared to individuals with cancer (OR 2.651, 95% CI 1.069 -6.573, p=0.035) and (OR 2.521, 95% CI 1.076-5.905, p=0.033) respectively. In terms of the composition of the stomach microbiota, in the gastric adenocarcinoma group we identified that the total fibers have a positive correlation with the Firmicutes phylum (rô = 0.53; p = 0.021). This same type of fiber has a strong and negative correlation with the Proteobacteria phylum (rô= −0.58; p=0.011). In the group of endoscopic controls, insoluble fibers showed a negative correlation with Proteobacteria. At the genus level, according to the Lefse algorithm, we identified 17 differentially abundant genus in the control group with high fiber intake (Q4 = >14g/ 1000kcal), versus low intake (Q1= <8.5g/1000 kcal), with emphasis on the genera Mogibacterium, Prevotella 7, Fusobacterium and Actinomyces, which were enriched in the fiber-rich diet. For the cancer group, in quartile 1 we observed 4 differentially abundant genera, namely: Butyrivibrio, Helicobacter and Stomatobaculum. Comparing individuals from the Q1 AdG group (N=24) versus Q4 controls (N=26), the Abiotrophia genus was more abundant in the controls, and Escherichia_shigella, a pathogenic genus, was more frequent in AdG. In total diversity, we evidenced a greater influence of fibers in the control group. Finally, we conclude that dietary fiber can influence the microbiota before the development of the disease, since, in the endoscopic control group, the findings showed not only a greater total richness of bacterial genus, but also a greater abundance of specific bacteria. These very different results between cases and controls may be associated with the fact that individuals with cancer already have an installed disease, with consequent dysbiosis. We highlight in controls with high fiber consumption, a greater abundance of genus producing short-chain fatty acids and important immunomodulatory activity. In the AdG group, we identified genus with a pro-inflammatory profile, such as Helicobacter.

Avaliação do microambiente tumoral em adenocarcinomas gástricos a partir de dados de expressão gênica / Evaluation of the tumor microenvironment in gastric adenocarcinomas using gene expression data

O câncer gástrico (CG) tem grande importância clínica devido a suas altas taxas de incidência e mortalidade estando entre os cinco tipos de câncer mais frequentes no mundo. O CG encontra-se associado ao diagnóstico tardio, que, somado a agressividade da doença, resulta em sobrevida mediana curta. A principal forma de tratamento é a cirurgia em conjunto com a quimioterapia. Mais recentemente, o tratamento com imunoterpia foi aprovado para casos de CG avançado metastático. O CG é usualmente classificado nos subtipos histológicos difuso e intestinal, porém, devido à sua alta heterogeneidade genética, pode ser também classificado em quatro subtipos moleculares (CIN, MSI, GS e EBV). Ambos aspectos de classificação estão associados a diferentes prognósticos e taxas de sobrevida, mas ainda não são suficientes para direcionar ou predizer quais pacientes respondem melhor a uma ou outra terapia. Neste contexto, outro fator relacionado à patogênese da doença, resposta a tratamento e prognóstico é o contexto imunológico do microambiente tumoral, como a composição e orientação funcional das células do infiltrado inflamatório associado ao tumor. Por meio de um método analítico de deconvolução aplicado a dados de expressão gênica é possível estimar a proporção de diferentes tipos celulares, além de seus aspectos funcionais. Neste trabalho, foi feito um levantamento das ferramentas e listas de genes marcadores de células imunes a fim de definir qual teria a melhor performance na estimação da proporção de células imunes em amostras de CG. Não observamos diferenças na composição do infiltrado inflamatório entre os subtipos histológios; já entre os subtipos moleculares de CG as proporções de linfóctios T CD8 se destacaram como maiores nos subtipos EBV e MSI, por exemplo. Foi então proposta uma classificação baseada em assinaturas mutacionais que conseguiu resgatar pacientes que apresentaram melhor prognóstico. O contexto imunológico nos pacientes com alta atividade mutacional (S4) apresentou elementos de que ser mais responsivo com maior expressão de genes associados à resposta imune citotóxica e do mecanismo de escape pelos checkpoints imunes. Além disso, há indícios de que há formação das estruturas terciárias de linfócitos pela correlação entre as quantidades estimadas de linfócitos T e B. Já o grupo com baixa atividade da assinatura (S4), associado a um pior prognóstico, apresentou maiores quantidades de linfócitos Treg. A avaliação global do microambiente tumoral, seus aspectos moleculares e imunológicos, proporciona dados mais informativos para estratificação dos pacientes quanto ao prognóstico e podem ser utilizadas em breve na prática clínica para direcionamento terapêutico.

Gastric cancer (GC) has great clinical importance due to its high incidence and mortality rates, being among the five most frequent types of cancer in the world. GC is associated with late diagnosis which, added to the aggressiveness of the disease, results in a short median survival. The main form of treatment is surgery in conjunction with chemotherapy. Recently, immunotherapy treatment has been approved for advanced metastatic GC. GC is usually classified into diffuse and intestinal histological subtypes, however, due to its high genetic heterogeneity, it can also be classified into four molecular subtypes (CIN, MSI, GS and EBV). Both classification are associated with different prognosis and survival rates, but they are still not sufficient to direct or predict which patients respond better to one or another therapy. In this context, another factor related to the pathogenesis of the disease, response to treatment and prognosis is the immunological context of the tumor microenvironment, such as the composition and functional orientation of the cells of the inflammatory infiltrate associated with the tumor. Through an analytical method of deconvolution applied to gene expression data, it is possible to estimate the proportion of different cell types, in addition to their functional aspects. In this work, the tools and lists of immune cell marker genes were surveyed in order to define which one would perform better in estimating the proportion of immune cells in GC samples. We did not observe differences in the composition of the inflammatory infiltrate between the histological subtypes; among the CG molecular subtypes, the proportions of T CD8 lymphocytes stood out as higher in the EBV and MSI subtypes, for example. A classification based on mutational signatures was then proposed, which managed to rescue patients with a better prognosis. The immunological context in these patients with high mutational activity (S4) showed elements of being more responsive with greater expression of genes associated with the cytotoxic immune response and the escape mechanism by immune checkpoints. In addition, there is evidence that there is formation of tertiary lymphocyte structures by the correlation between the estimated amounts of T and B lymphocytes. The group with low mutational signature activity (S4), on the other hand, associated with a worse prognosis, had higher amounts of Treg lymphocytes. The global assessment of the tumor microenvironment, its molecular and immunological aspects, provides more informative data for stratifying patients regarding prognosis and may soon be used in clinical practice for therapeutic guidance.

Marcação imunoistoquímica de CDX2 e Ki67 no adenocarcinoma gástrico / CDX2 and Ki67 immunohistochemistry marking in gastric adenocarcinoma

Introdução: A proteína CDX2 é um fator de transcrição específico do intestino, que está presente no tecido gástrico apenas quando há uma metaplasia intestinal. A metaplasia intestinal é uma lesão precursora do adenocarcinoma gástrico. O Ki67 é um biomarcador de proliferação celular. Objetivo: Verificar a presença da proteína CDX2 no adenocarcinoma gástrico. Comparar a expressão da CDX2 entre os diferentes graus de diferenciação e entre os níveis de proliferação celular. Método: A partir de 62 blocos histológicos contendo amostras de adenocarcinoma gástricos (4 bem diferenciados, 30 moderadamente diferenciados e 28 pouco diferenciados), foi feita a construção de blocos multiamostrais (TMA). Procedeu-se a marcação imunoistoquímica com os anticorpos escolhidos e realizou-se a leitura da área positiva imunocoradas. Resultados: 31 amostras foram positivas para a CDX2 e 31 negativas, sem diferença significativa entres os graus de diferenciação (p = 0,576). 38 amostras foram classificadas como de baixo grau de proliferação celular e 24 como de alto grau. Não houve diferença estatística de grau de proliferação celular entre os graus de diferenciação (p = 0,676). O grau de proliferação celular variou dependendo da expressão da CDX2 (p = 0,036). Conclusão: A expressão da proteína CDX2 esteve presente em 50% dos adenocarcinomas gástricos. Não houve diferença estatística da expressão do CDX2 entres os graus de diferenciação do adenocarcinoma gástrico. A proliferação celular variou dependendo da expressão da CDX2, havendo um maior nível de proliferação celular nas amostras que apresentaram expressão positiva para CDX2

Background: CDX2 protein is an intestinal specific transcription factor that is present in the gastric tissue only when there is intestinal metaplasia. Intestinal metaplasia is a gastric adenocarcinoma precursor injury. Ki67 is a cell proliferation biomarker. Objective: Verify the presence of CDX2 protein in gastric adenocarcinoma. Compare the CDX2 expression between the differentiation degree groups and between the cell proliferation degrees. Methods: It was collected 62 paraffin blocks containing the gastric adenocarcinoma samples (4 well differentiated adenocarcinoma, 30 moderately differentiated and 28 poorly differentiated). It was made the tissue microarrays blocks (TMA), so it was proceeded to immunohistochemical staining with the anti-CDX2 and the anti-Ki67 antibodies and it was accomplished the read of the positive immune-stained area. Results: 31 samples were positive for CDX2 expression, and 31 were negative. There was no statistical difference of the CDX2 expression between the differentiation degree groups (p = 0.576). 38 samples were classified as low degree of cell proliferation and 24 as high degree. There was no statistical difference of the cell proliferation degree between the differentiation degree groups (p = 0.676). The degree of cell proliferation ranged depending on the CDX2 expression (p = 0.036). Conclusion: Protein CDX2 expression was observed in 50% of gastric adenocarcinoma samples. There was no statistical difference of the CDX2 expression between the differentiation degree groups. The cell proliferation ranged depending of CDX2 expression, with a higher index of cell proliferation in the positive CDX2 expression samples

Comportamiento clínico, endoscópico e histológico del cáncer gástrico diagnosticado en el Hospital "Dr. Mario Muñoz Monroy" / Histological, endoscopic and clinical behavior of gastric cancer diagnosed in the Hospital "Dr. Mario Muñoz Monroy"

RESUMEN Introducción: en los últimos años, se aprecia a nivel global un aumento del cáncer gástrico. La mayoría de los tumores gástricos primarios son malignos. En Matanzas, existe un incremento de esta patología. Objetivo: determinar el comportamiento clínico, endoscópico e histológico del cáncer gástrico diagnosticado. Materiales y métodos: se realizó un estudio observacional, descriptivo y prospectivo en el Departamento de Gastroenterología del Hospital "Dr. Mario Muñoz Monroy", de la ciudad de Matanzas, en el período de enero del 2017 a octubre del 2019. El universo fue 25 pacientes que presentaron cáncer gástrico por diagnóstico endoscópico e histológico. Resultados: el grupo de edad más afectado correspondió a los pacientes entre 61 y 70 años, (44 %). El sexo masculino predominó en un 68 %. Los factores de riesgo de mayor incidencia, fueron la dieta inadecuada y el hábito de fumar. Las manifestaciones clínicas más relevantes fueron: epigastralgia, plenitud gástrica y pérdida de peso. La variedad hística que predominó fue el adenocarcinoma difuso y la localización el antro. Conclusiones: el cáncer gástrico constituye un problema de salud que, al actuar sobre los factores de riesgo se puede disminuir su incidencia; con un diagnóstico precoz se logrará disminuir la mortalidad (AU).

ABSTRACT Introduction: an increase of gastric cancer is appreciated in the world in the last years. Most of the primary gastric tumors are malignant. There is an increase of this disease also in Matanzas. Objective: to determine the histological, endoscopic and clinical behavior of the diagnosed gastric cancer. Materials and methods: a prospective, descriptive and observational study was carried out in the Department of Gastroenterology of the Hospital "Mario Munoz Monroy, of Matanzas, in the period from January 2017 to October 2019. The universe were 25 patients presenting gastric cancer by histologic and endoscopic diagnosis. Results: The most affected age group was the one of patients among 61 and 70 years old (44 %). Male sex predominated in 68 %. The risk factors having higher incidence were an inadequate diet and smoking. The more relevant clinical manifestation were epigastralgia, gastric fullness and weight loss. The predominating tissue variety was the diffuse adenocarcinoma and antrum location. Conclusions: gastric cancer is a health problem the incidence of which could be reduced when acting on its risk factors; with a precocious diagnosis mortality will be reduced (AU).

Morbimortalidad por cáncer gástrico en un servicio de cirugía general / Morbidity and mortality from gastric cancer in a general surgery service

RESUMEN Introducción: El cáncer de estómago representa la segunda causa más frecuente de muerte relacionada con neoplasias en el mundo, es responsable del 8 al 10 por ciento de todas las muertes por cáncer. Objetivo: Determinar la morbilidad y la mortalidad por cáncer gástrico en el servicio de cirugía del Hospital Universitario "General Calixto García". Métodos: Se realizó un estudio observacional descriptivo, transversal. El universo estuvo conformado por 145 pacientes que cumplieron con los criterios de inclusión. Se utilizaron métodos estadísticos descriptivos y cálculos con valores porcentuales. Resultados: El 67,6 por ciento de los pacientes pertenecían al sexo masculino, mientras que 87 se ubicaron en los grupos de edades entre 60 y 79 años. El 37,2 por ciento de los pacientes presentaron lesión ulcerada infiltrante de acuerdo a la clasificación endoscópica de Borrmann. El adenocarcinoma gástrico fue el tipo histológico más encontrado. La técnica quirúrgica más empleada fue la gastrectomía subtotal, y la gastroyeyunostomía. La complicación postoperatoria más frecuente la constituyó la bronconeumonía con 35 pacientes. La mayoría de los pacientes egresaron vivos. Conclusiones: La investigación sugiere que el diagnóstico precoz y la cirugía en la actualidad es la única modalidad con potencial curativo y puede elevar la calidad de vida y mejorar los índices de morbimortalidad en la población(AU)

ABSTRACT Introduction: Stomach cancer is the second leading cause of death related to neoplasms worldwide. It is responsible for 8-10 percent of all cancer-related deaths. Objective: To determine the morbidity and mortality for gastric cancer in the surgery service of General Calixto García University Hospital. Methods: A descriptive, cross-sectional and observational study was carried out. The universe consisted of 145 patients who met the inclusion criteria. Descriptive statistical methods and calculations with percentage values were used. Results: 67.6 percent of the patients belonged to the male sex, while 87 were located in the age groups between 60 and 79 years. 37.2 percent of the patients presented an infiltrating ulcerated lesion according to Borrmann endoscopic classification. Gastric adenocarcinoma was the most common histological type. The most used surgical technique was subtotal gastrectomy, followed by gastrojejunostomy. The most frequent postoperative complication was bronchopneumonia, accounting for 35 patients. Most of the patients were discharged alive. Conclusions: Research suggests that early diagnosis and surgery are currently the only modality with curative potential and can raise the quality of life as well as improve morbidity and mortality rates among the population(AU)

Caracterización de los pacientes operados por adenocarcinoma gástrico en el Hospital "Dr. Carlos J Finlay". 2009-2016 / Characterization of patients operated on for gastric adenocarcinoma at "Dr. Carlos J. Finlay" Hospital from 2009 to 2016

RESUMEN Introducción: El cáncer gástrico ocupa hoy el cuarto lugar de incidencia mundial de cáncer y es la segunda causa de muerte por cáncer en el mundo. Objetivo: Caracterizar a los pacientes operados con adenocarcinoma gástrico en el Hospital "Dr. Carlos J. Finlay". 2009-2016. Material y Métodos: Se realizó un estudio descriptivo retrospectivo a los pacientes operados con adenocarcinoma gástrico en un periodo de 8 años. Resultados: Prevalecieron los pacientes geriátricos del sexo masculino. La forma más frecuente de presentación fue la úlcera gástrica en 54,7%. Predominaron los tumores del antro en 72,0%, moderadamente diferenciados en 61,3% de pacientes. La mayoría de los tumores se encontraban en estadio IIIA. De los procedimientos quirúrgicos predominó la gastrectomía distal en 56,0% y los procederes exeréticos en 68,0% de pacientes. La mortalidad operatoria fue de 6,0%, con prevalencia del shock hipovolémico. Conclusiones: Predominaron los pacientes geriátricos del sexo masculino cuya técnica quirúrgica fue la gastrectomía distal. Como forma clínica sobresalió la úlcera gástrica, así como los tumores del antro en estadio IIIA, moderadamente diferenciados. El estadio avanzado y los procedimientos paliativos se relacionaron de manera significativa con la mortalidad.

ABSTRACT Introduction: Gastric cancer is the fourth most common cancer at present and the second leading cause of cancer-related mortality worldwide. Objective: The aim of this study is to characterize the patients with gastric adenocarcinoma operated on at "Dr. Carlos J. Finlay" Hospital during the period between 2009 and 2016. Material and Methods: A descriptive retrospective study was conducted in patients operated on for gastric adenocarcinoma in an eight-year period. Results: Male geriatric patients prevailed in the study. Gastric ulcer was the most frequent form of presentation in 54,7 %. Tumors of the antrum predominated in 72,0 %, with moderate degree of differentiation in 61,3 % of patients. The majority of tumors were in stage IIIA. The most used surgical methods were distal gastrectomy which was performed in 56,0 % of patients and exeretic procedures that were carried out in 68,0 % of patients. Operative mortality was 6,0 % with prevalence of hypovolemic shock. Conclusion: There was a predominance of male geriatric patients who underwent the surgical technique of distal gastrectomy. Gastric ulceration was the most common clinical form of presentation as well as tumors of the antrum in stage IIIA, in which there was a moderate degree of differentiation. Advanced stage tumors and palliative procedures were significantly related to mortality.

Clinical usefulness of extending the proximal margin in total gastrectomies for gastric adenocarcinoma. / Utilidad clínica de la ampliación del margen proximal en gastrectomías totales por adenocarcinoma gástrico.

INTRODUCTION AND AIMS: Surgical resection with negative margins is part of the curative treatment of gastric adenocarcinoma. Positive surgical margins are associated with worse outcome. The aim of the present study was to determine the clinical usefulness of extending the proximal surgical margin in patients undergoing total gastrectomy for gastric adenocarcinoma. MATERIALS AND METHODS: A retrospective analysis of patients that underwent total gastrectomy within the time frame of 2002 and 2017 was conducted. Patients diagnosed with adenocarcinoma that underwent curative surgery were included. Patients were divided into three groups, depending on proximal surgical margin status: negative margin (R0), positive margin with additional resection to achieve negative margin (R1-R0), and positive margin (R1). Demographic and clinical variables were analyzed. The outcome measures to evaluate were recurrence, disease-free survival, and overall survival. RESULTS: Forty-eight patients were included in the study. Thirty-seven were classified as R0, 9 as R1-R0, and 2 as R1. Fifty-two percent of the patients had clinical stage III disease. The overall surgical mortality rate was 2% and the morbidity rate was higher than 29%. The local recurrence rate was 0% in the R1-R0 group vs. 50% in the R1 group (p = 0.02). Disease-free survival was 49 months in the R1-R0 group vs. 32 months in the R1 group (p = 0.6). Overall survival was 51 months for the R1-R0 group vs. 35 months for the R1 group (p = 0.5). CONCLUSIONS: Intraoperative extension of the positive surgical margin improved the local recurrence rate but was not associated with improvement in overall survival or disease-free survival and could possibly increase postoperative morbidity.

Dieta e adenocarcinoma gástrico: o papel das frutas, vegetais, leite e derivados, azeite, oleaginosas, leguminosas e cereais / Diet and gastric adenocarcinoma: the role of fruits, vegetables, dairy, olive oil/ vegetable oil, oilseeds, legumes and cereals

INTRODUÇÃO: O adenocarcinoma gástrico (AdG) é uma neoplasia maligna com alta taxa de mortalidade no mundo, embora as taxas de incidência estejam diminuindo. Em 2018 foram estimados 1.333.701 novos casos de câncer gástrico (GC) no mundo (BRAY et al. 2018). No Brasil para 2018-2019 foram estimados 21.290 novos casos (Ministério da Saúde 2018). OBJETIVO: Este estudo avaliou o consumo de frutas, hortaliças, laticínios, azeite de oliva/ óleo vegetal, oleaginosas, leguminosas e cereais e sua associação com o AdG. MATERIAIS E MÉTODOS: Estudo caso-controle realizado pelo Departamento de Epidemiologia e Estatística do A.C. Camargo Cancer Center, durante o período de abril de 2016 a fevereiro de 2019. Foram incluídos os indivíduos com idade entre 18 e 75 anos de ambos os sexos. Os casos foram pacientes com diagnóstico confirmado histologicamente de AdG (C16, CID-O3) diagnosticados e tratados no A.C. Camargo Cancer Center. Os grupos controles foram divididos em: controles 1: pacientes do departamento de endoscopia; Controles 2: pacientes do Departamento de Prevenção (adultos saudáveis). Todos os controles foram pareados com os casos por sexo e faixa etária. Uma entrevista para avaliar informações sociodemográficas, questionário de frequência alimentar e hábitos de vida foi aplicada em casos e controles. A análise estatística foi realizada por meio dos testes Qui-quadrado, Univariada e Regressão Logística Múltipla. O projeto foi aprovado pelo comitê de ética em pesquisa do A.C. Camargo Cancer Center sob o número 2169/ 16C. RESULTADOS: Foram analisados 211 casos, 143 controles 1 e 285 controles 2. Quanto às características demográficas, os casos foram semelhantes aos controles 1 e 2 para as variáveis estado civil, ocupação e atividades físicas. Nas análises univariadas, o consumo de vegetais, laticínios simples e amarelos, frutas cítricas e frutas em geral foram vistos como um fator de proteção entre os casos e controle 2. Os vegetais escuros também apresentaram fator de proteção entre casos versus controle 1 e controle 2. Na análise multivariada a análise entre casos versus controle 1, ex e fumante atual (OR=1,81; IC95% 1,10-2,97; OR=4,64; IC95% 1,96-10,98), e o consumo de oleaginosas acima de 6g / dia (OR=2,60; IC95% 1,30-5,16) foram os fatores independentes associados ao AdG. Enquanto o consumo de vegetais verde-escuros acima de 17,4 g/ dia teve um efeito protetor. Na análise de regressão de modelo múltiplo entre casos versus controle 2, os fatores independentes associados ao AdG foram ser ex-fumante e fumante atual (OR=2,16; IC95% 1,37-3,39; OR=2,99; IC95% 1,58-5,66), respectivamente e o consumo de álcool > 47g / dia (OR=2,98; IC95% 1,39-6,39). Ser de etnia não branca apresentou fator de proteção para o AdG (OR=0,53; IC95% 0,35-0,80) e o consumo diário de frutas foi fator protetor independente, quando ajustado pelo IMC, consumo de oleaginosas, consumo de vegetais crucíferos e grau de escolaridade. CONCLUSÃO: Nossos resultados mostraram que o consumo de vegetais verde-escuros e frutas foi associado à redução da chance para o AdG. Além disso, o consumo de álcool, tabaco e oleaginosas acima de 6g/dia foram fatores que aumentaram a chance para o AdG (AU)

INTRODUCTION: Gastric adenocarcinoma (AdG) is a malignant neoplasm with a high mortality rate in the world, although incidence rates are declining. In 2018 was estimated 1.333.701 new cases of gastric cancer (GC) (BRAY et al. 2018). In Brasil for 2018-2019 it was estimated 21.290 new cases (Ministério da Saúde, 2018). AIM: This study evaluated the consumption of fruits, vegetables, milk, dairy products, olive oil/vegetable oil, oilseeds, legumes and cereals and its association to AdG. MATERIALS AND METHODS: A case-control study has been carried on by the Department of Epidemiology and Statistics, A.C.Camargo Cancer Center, during april 2016 ­ february 2019. Inclusion criteria was cases aged 18-75 years of both genders. Cases were patients with histologically confirmed diagnosis of AdG (C16, ICD-O3) diagnosed and treated at A.C.Camargo Cancer Center. There are two controls groups: Controls 1: patients from the Departament of Endoscopy; Controls 2: patients from the Prevention Department (healthy adults). All controls were matched with cases by gender and age group. An interview to evaluate socio demographic information, food frequency questionnaire and lifestyle habits was applied in cases and controls. Statistical analysis was performed using Chi-square test, Univariated and Multiple Logistic Regression Models. This project was approved by the Ethics Committee A.C. Camargo Cancer Center (nº 2169/16C). RESULTS: There were analyzed 211 cases, 143 controls 1 and 285 control 2. Regarding demographic characteristics, the cases were similar to the controls 1 and 2 for the variables marital status, occupation and physical activities. In the univariated analyzes, the consumption of vegetables, simple and yellow dairy, citric and general fruits were seen as a protective factor between cases and control 2. Dark vegetables also have shown protective factor between cases versus control 1 and control 2. In the multivariate analysis between cases versus control 1, former and current smoker (OR=1.81; IC95% 1,10-2,97; OR=4.64; IC95% 1,96-10,98, and the consumption of oilseeds above 6g/ day (OR=2.60; IC95% 1,30-5,16) were being the independent factors associated to AdG. While the consumption of dark green vegetables above 17,4 g/ day had a protective effect. In the multiple model regression analysis between cases versus control 2, the independent factors associated to AdG were being former and current smoker (OR=2,16; IC95%1 1,37-3,39; OR=2,99; IC95% 1,58-5,66) respectively, and alcohol consumption >47g/ day (OR=2,98; IC95% 1,39-6,39). Being of no white ethnicity showed a protective factor for AdG (OR=0,53; IC95% 0,35-0,80) and daily consumption of fruits was an independent protective factor when adjusted by BMI, consumption of oilseeds, consumption of cruciferous vegetables and educational level. CONCLUSION: Our results showed that consumption of dark green vegetables and fruits were associated with reduced risk for AdG. In addition, the consumption of alcohol and tobacco were factors that increased the risk of AdG (AU)

Nível de atividade física e estilo de vida associados ao risco de adenocarcinoma gástrico: um estudo caso-controle em Belém-Pará, Norte do Brasil / Level of physical activity and lifestyle associated with the risk of gastric adenocarcinoma: a case-control study in Belém-Pará, North of Brasil

Introdução: O câncer gástrico entre todos os tipos de câncer é o quinto mais incidente no mundo, representando 5,7% de todos os novos casos previstos em 2018. Embora sua incidência tenha sofrido um declínio durante as últimas décadas, as taxas de mortalidade ainda se mantêm em patamares elevados em países em desenvolvimento, como o Brasil. A investigação dos fatores associados ao estilo de vida como atividade física poderá identificar o padrão de risco em uma população. Dessa forma o objetivo deste estudo foi analisar o nível de atividade física habitual e sua associação ao risco de adenocarcinoma gástrico em Belém-Pará, Norte do Brasil. Metodologia: Trata-se de um estudo do tipo caso-controle de base hospitalar, desenvolvida em dois hospitais de referência em câncer em Belém, Pará, Norte do Brasil. Foram aplicados questionários referentes aos dados sociodemográficos, de estilo de vida e de atividade física, no período entre julho/2017 e abril/2019, em indivíduos entre 18 e 75 anos. Para avaliar a atividade física habitual foi utilizado o questionário de BAQ, sendo avaliada o exercício físico (EFL), a atividade física ocupacional (AFO) e de lazer e locomoção (ALL). Para análise descritiva foram utilizadas frequências relativa e absoluta, e medidas de tendência central e dispersão. Aplicou-se o teste de associação Qui-quadrado e para cálculo da OR foram usados modelos de regressão logística binária univariada e múltipla. Assumiu-se o nível descritivo de 5% (p<0.05) para a significância estatística. Resultados: Observou-se que 5 anos antes da entrevista, aqueles que realizaram EFL no nível do 2º tercil tiveram 71% menos chances de desenvolver o câncer gástrico (p= 0,012). Os indivíduos com maiores níveis de ALL à 10, 15 e 20 anos antes do diagnóstico de cancer gástrico tiveram 76%, 78% e 81% menos chances respectivamente. Conclusão: A atividade física relacionada ao EFL e/ou ALL foi um fator independente e protetor, e foi associada inversamente ao câncer gástrico em todos os anos (AU)

Introduction: Gastric cancer among all cancers is the fifth most common cancer in the world, accounting for 5.7% of all new cases predicted in 2018. Although its incidence has declined in recent decades, mortality rates still remain at high levels in developing countries, such as Brazil. Investigation of lifestyle factors such as physical activity may identify the risk pattern in a population. Thus, the aim of this study was to analyze the level of habitual physical activity and its association with the risk of gastric adenocarcinoma in Belém-Pará, North of Brazil. Methodology: This is a hospital-based case-control study developed in two reference hospitals for cancer in Belém, Pará,North of Brazil. Questionnaires referring to sociodemographic, lifestyle and physical activity data were applied between July / 2017 and April / 2019, in individuals between 18 and 75 years of age. o assess habitual physical activity, we used the BAQ questionnaire, which assessed physical exercise (EFL), occupational physical activity (AFO) and leisure and locomotion (ALL). Relative and absolute frequencies and central tendency and dispersion measurements were used for descriptive analysis. The Chi-square association test was applied and univariate and multiple binary logistic regression models were used for OR analysis. The descriptive level of 5% (p <0.05) was assumed for the statistical significance. Results: It was observed that 5 years before the interview, those who underwent EFL at the 2nd percentile level were 71% less likely to develop gastric cancer (p = 0.012). Individuals with the highest ALL levels at 10, 15, and 20 years before the diagnosis of gastric cancer were 76%, 78%, and 81% less likely, respectively. Conclusion: EFL and / or ALL-related physical activity was an independent and protective factor, and was inversely associated with gastric cancer in all years (AU)

Investigação de assinaturas mutacionais em adenocarcinomas gástricos e avaliação de Seu possível impacto prognóstico / Investigation of mutational signatures in gastric adenocarcinoma and evaluation of its possible prognostic impact

Adenocarcinomas gástricos (AdGs) são neoplasias de grande agressividade e alta incidência no Brasil. Os altos índices mundiais de mortalidade dos AdGs se devem aos poucos sinais clínicos da doença em seus estágios iniciais, o que leva uma detecção tardia na maioria dos casos. Sendo o AdG uma doença de forte componente genético e ambiental em sua etiologia, a busca por processos causadores de mutações somáticas que contribuem para a sua formação e progressão pode permitir avanços no prognóstico e na determinação de abordagens terapêuticas. Devido à escassez de estudos que associam características moleculares à clínica, além da inexistência de dados moleculares em grande escala obtidos da população brasileira, este trabalho teve por objetivo analisar o perfil mutacional de amostras de AdG em busca de assinaturas moleculares que possam ser associadas a aspectos clínicos de interesse Foram identificadas seis assinaturas mutacionais, através do signeR, para uma coorte de 756 amostras. O subtipo molecular MSI, a ausência de metástase linfonodal (N0) e de recidiva (Tumor Free) demonstraram associação com três assinaturas signeR-S1, singeR-S2 e signeR-S4, associadas aos processos de falha no mecanismo de reparo de DNA (via MMR) e desaminação espontânea da 5-metil-citosina. De maneira complementar, este grupo de assinaturas também demonstraram-se associados com uma melhor sobrevida, maior número de células T CD8+, além de uma expressão aumentada de genes de perfil citotóxico. Estes resultados, em conjunto, sugerem que o grupo de pacientes enriquecidos para estas assinaturas, possuem um contexto imunológico favorável à imunoterapia (AU)

Gastric Adenocarcinomas (GAs) are highly aggressive neoplasms with a high in- cidence in Brazil. The hight world mortality rates of GA are due to few clinical signs of the disease in its early stages which lead to late detection. Because of a strong genetic and environmental component in GA etiology, the search for the causative somatic mutations processes that contribute to their initiation and pro- gression may allow advances in prognosis and in the establishment of therapeutic approaches. Due to the lack of studies that associate molecular characteristics with clinical features, as well as the lack of large scale molecular studies in the Brazilian population, this study aims to analyze the mutational profile of GAs samples from Brazilian and global populations, looking for molecular signatures that may be associated with relevant clinical aspects. The signeR algorithm de- tected six mutational signatures in a cohort of 756 samples. Three signatures (signeR-S1 S2 and S4) were associated with failure in DNA repair mechanisms (MMR pathway) and spontaneous deamination of 5-methylcytosine and had cor- relation with microsatellite instability (MSI) molecular subtype. Those signatures were also associated with better clinical outcomes like the absence of lymph node metastasis (N0) and longer disease-free survival. Furthermore, those signatures were also associated with a particular lymphocyte infiltration pattern, enriched for T CD8+ lymphocytes, and a higher expression of cytotoxic genes. Together, these results suggest that the group of patients enriched for these signatures may have a favorable prognosis due to better anti tumoral effector immune response and that could be further improved with immunotherapy (AU)

Adenocarcinoma gástrico y tumor estromal del estómago sincrónico incidental / Gastric adenocarcinoma and incidental synchronous incidental gastrointestinal stromal tumor

Se presenta el caso de un paciente masculino de 73 años de edad operado por adenocarcinoma del antro gástrico. Se practicó gastrectomía subtotal distal más linfadenectomía D2. Durante el examen anatomopatológico de la pieza quirúrgica se encontró otro tumor pequeño en el espesor de la pared del antro cubierto por mucosa normal, separado del adenocarcinoma. El análisis histológico confirmó otra neoplasia incidental sincrónica, un tumor del estroma gastrointestinal de tipo fusiforme, positivo para el marcador tumoral CD117. El objetivo del trabajo es presentar esta asociación tumoral sincrónica, revisar sus características y las teorías etiopatogénicas actuales de esta condición sincrónica según la literatura especializada(AU)

A case is presented of a 73-year-old male patient who was operated for a gastric adenocarcinoma of the antrum. A distal subtotal gastrectomy plus D2 lymphadenectomy were practiced. During the anatomic and pathologic examination of the surgical piece, a second tiny tumor was found in the wall of the antrum and that was covered with a normal mucosa separated from the adenocarcinoma. The histologic examination confirmed another synchronous incidental neoplasm, a spindle-cell gastrointestinal stromal tumor, positive for the tumor marker CD117. This paper is aimed at presenting synchronous tumor entity, to review its characteristics and the current etiologic and pathogenic theories of this synchronic condition according to the specialized literature(AU)

Cáncer gástrico incipiente gigante: reporte de un caso / A case report: Giant early gastric cancer

Resumen Introducción: El cáncer gástrico es la primera causa de muerte por cáncer, en hombres, en Chile, siendo el adenocarcinoma la variante más frecuente. Caso clínico: Reportamos el caso de un cáncer gástrico incipiente gigante de 7,2 cm en un hombre de 74 años tratado en la Clínica INDISA en Santiago de Chile. El paciente fue sometido exitosamente a una gastrectomía total con linfoadenectomía D2 y esófago-yeyuno anastomosis en Y de Roux. La histología evidenció un adenocarcinoma bien diferenciado, polipoide, invasivo hasta la submucosa, sin compromiso ganglionar. A los 5 años de su cirugía, el paciente se encuentra asintomático y sin recidiva tumoral.

Abstract Introduction: The gastric cancer is the first cause of death from cancer, in men, in Chile, being the adenocarcinoma the most frequent variant. Clinical case: We report the case of a large early gastric cancer of 7.2 cm in a 74-year-old man who was treated in INDISA Clinic in Santiago, Chile. A total gastrectomy with D2 lymphadenectomy with End-to-Side esophagojejunostomy in a Roux-en-Y anastomosis was successfully performed. The histology showed a polypoid well differentiated adenocarcinoma infiltrating up to the submucosa without regional lymph node involvement. Five years after the surgery, he remains asymptomatic and without tumor recurrence.

Comportamiento del cáncer gástrico avanzado diagnosticado por videoendoscopia en el Hospital "Faustino Pérez Hernandez", Matanzas / Behavior of advanced gastric cancer diagnosed by video-endoscopy at the Faustino Pérez Hernández Hospital, Matanzas

Introducción: el cáncer gástrico avanzado constituye la segunda causa de muerte por tumores malignos en el mundo. En los últimos cinco años en la provincia de Matanzas existe un incremento de esta patología. Objetivo: determinar el comportamiento clínico epidemiológico del cáncer gástrico avanzado diagnosticado por videoendoscopía, en el departamento de Gastroenterología del Hospital Universitario "Comandante Faustino Pérez Hernández", de Matanzas en el período de enero del 2014 a enero del 2016. Materiales y Métodos: se realizó un estudio observacional, descriptivo y prospectivo en el Departamento de Gastroenterología del Hospital Universitario "Comandante Faustino Pérez Hernández", de Matanzas en el período de enero del 2014 a enero del 2016. El universo los 28 pacientes que presentaron cáncer gástrico avanzado por diagnóstico endoscópico e histológico. Resultados: el grupo de edad más afectado correspondió a los pacientes con 60 años de edad o más (67,9 %). El sexo masculino predominó, un 57,1 %. Los factores de riesgo de mayor incidencia fueron la dieta inadecuada (65 %) y el hábito de fumar (42,9 %). Las manifestaciones clínicas más relevantes fueron la pérdida de peso, la astenia y la acidez. La variedad histica que predominó fue el adenocarcinoma de tipo intestinal y el antro gástrico resultó ser la localización más frecuente. La mayoría de los pacientes tuvieron positivos el test de ureasa para la infección por Helicobacter pylori. (60,7 %). Conclusiones: la infección por Helicobacter pylori constituye una de las principales causas de cáncer gástrico. El diagnóstico y tratamiento precoz de la infección contribuirán a disminuir su incidencia (AU).

Introduction: the advanced gastric cancer is the second reason of death due to malignant cancer in the world. There it is a surge of this disease in the last five years in the province of Matanzas. Objective: to determine the clinical-epidemiologic behavior of advanced gastric cancer diagnosed by video-endoscopy in the Department of Gastroenterology of the Teaching Hospital "Comandante Faustino Pérez Hernández", of Matanzas, in the period from January 2014 to January 2016. Materials and Methods: an observational, descriptive and prospective study of the department of Gastroenterology of the Teaching Hospital "Comandante Faustino Pérez Hernández", of Matanzas, was carried in the period from January 2014 to January 2016. The universe were 28 patients who had advanced gastric cancer according to the endoscopic and histological diagnosis. Outcomes: the most affected age group was the one of the patients aged 60 years and more (67,9 %).The male sex predominated, with 57,1 %. The risk factors with higher incidence were an inadequate diet (65 %) and smoking (42,9 %). The most relevant clinical manifestations were weight loss, asthenia and heartburn. The predominating histological variety was the intestinal type adenocarcinoma and the gastric antrum was the most frequent location. Most of the patients were positive to the urease test for helicobacter pylori (60,7 %). Conclusions: the infection by Helicobacter pylori is one of the main causes of gastric cancer. The precocious diagnosis and treatment of the infection will favor the reduction of its incidence (AU).

Infección por Helicobacter pylori en el municipio de Palma Soriano durante el período 2008-2014 / Helicobacter pylori infection in Palma Soriano during 2008-2014

Se realizó un estudio descriptivo y retrospectivo de 989 pacientes con diagnóstico endoscópico de gastritis crónica, cuyas biopsias habían sido procesadas en el Departamento de Anatomía Patológica del municipio de Palma Soriano, en Santiago de Cuba, durante el período 2008-2014, con el objetivo de determinar la incidencia de la infección por Helicobacter pylori, para lo cual además se consideraron las variables: edad, sexo, tipos de gastritis, presencia del microorganismo y su asociación con neoplasias malignas. En la serie predominaron el grupo etario de 40-49 años (26,7 %) y el sexo femenino (69,0 %); asimismo, resultó más frecuente la gastritis superficial (57,8 %) y se halló la bacteria en 70,5 % de la muestra, donde solo 0,5 se asoció a neoplasias malignas

A descriptive and retrospective study of 989 patients with endoscopic diagnosis of chronic gastritis whose biopsies had been processed in the Pathology Department of Palma Soriano in Santiago de Cuba, was carried out during 2008-2014, aimed at determining the incidence of the infection due to Helicobacter pylori, for which the variables: age, sex, gastritis types, presence of the organism and its association with malignancies were also considered. In the series the 40-49 years age group (26,7 %) and female sex (69,0 %) prevailed; also, the superficial gastritis was more frequent (57,8 %) and the bacteria was found in 70,5 % of the sample, where only 0,5 was associated to malignancies