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Identifying a microbiome pattern in gastric cancer (GC) is hugely debatable due to the variation resulting from the diversity of the studied populations, clinical scenarios, and metagenomic approach. H. pylori remains the main microorganism impacting gastric carcinogenesis and seems necessary for the initial steps of the process. Nevertheless, an additional non-H. pylori microbiome pattern is also described, mainly at the final steps of the carcinogenesis. Unfortunately, most of the presented results are not reproducible, and there are no consensual candidates to share the H. pylori protagonists. Limitations to reach a consistent interpretation of metagenomic data include contamination along every step of the process, which might cause relevant misinterpretations. In addition, the functional consequences of an altered microbiome might be addressed. Aiming to minimize methodological bias and limitations due to small sample size and the lack of standardization of bioinformatics assessment and interpretation, we carried out a comprehensive analysis of the publicly available metagenomic data from various conditions relevant to gastric carcinogenesis. Mainly, instead of just analyzing the results of each available publication, a new approach was launched, allowing the comprehensive analysis of the total sample amount, aiming to produce a reliable interpretation due to using a significant number of samples, from different origins, in a standard protocol. Among the main results, Helicobacter and Prevotella figured in the “top 6” genera of every group. Helicobacter was the first one in chronic gastritis (CG), gastric cancer (GC), and adjacent (ADJ) groups, while Prevotella was the leader among healthy control (HC) samples. Groups of bacteria are differently abundant in each clinical situation, and bacterial metabolic pathways also diverge along the carcinogenesis cascade. This information may support future microbiome interventions aiming to face the carcinogenesis process and/or reduce GC risk.

Background Intestinal and diffuse gastric adenocarcinomas differ in clinical, epidemiological and molecular features. However, most of the concepts related to the intestinal-type are translated to gastric adenocarcinoma in general; thus, the peculiarities of the diffuse-type are underappreciated. Results Besides its growing importance, there are many gaps about the diffuse-type carcinogenesis and, as a result, its epidemiologic and pathogenetic features remain poorly understood. Conclusions Alternative hypotheses to explain these features are discussed, including the role of the gastric microbiota, medical therapies, and modifications in the stomach’s microenvironment.

Background adoptive immunotherapy is a promising cancer therapy. Immune cells are capable of recognizing and destroying cancer cells and represent a powerful strategy, however, this approach remains technically complicated, due to the need to select and isolate immune cells from these, present cancer antigens to those cells, expanding and reinjecting them. Lymph nodes recovered during gastric cancer surgery may represent an option for immunotherapy, since they harbor an enormous amount of immune cells, which have already been presented to cancer antigens. The advantage of selecting only cancer-negative lymph has not been determined yet. The status of immune checkpoints in the immune cells within the lymph nodes was analyzed in order to try to solve this problem. Materials and methods Tissue microarrays were constructed and automated immunostaining for PD-1 and PD-L1 was performed on 143 lymph nodes from 70 patients with gastric adenocarcinoma. Results In positive nodes, PD-L1 was only positivity in cancer cells (6%) and PD-1 was positive for B lymphocytes (60%), T lymphocytes (70%) and one case in cancer cells (2.5%). In negative nodes, most cases were positive for PD-1 in B (73.1%) and T (71.65%) lymphocytes. Conclusions Expression of PD-1 and PD-L1 in gastric cancer lymph nodes was demonstrated for the first time. PD-1 is expressed in positive and negative nodes, which could activate the PD-1 pathway. Lymphocytes from tumor-free lymph nodes were negative for PD-L1, and this might represent an advantage for selecting these lymph nodes as a potential source of immune cells for adoptive immunotherapy.

Highlights • This is a borderline tumor with indolent biological behavior. • There are still multiple poorly understood factors that can dictate its malignant transformation and prognosis. • Here, a rare tumor whose age and survival are tangent the literature reports describe. • There is a need for a long and rigorous segment to identify possible long-term metastases., Introduction Frantz’s Tumor or Solid Pseudopapillary Neoplasm (SPN) is rare with a solid-cystic pattern, and most common in young women. Presentation of case This study based on guidelines for case reports (SCARE) reports a case of SPN in a teenager aged 13 years at the diagnosis time, attended at a teaching public hospital in Brazil, which evolved into liver metastases. Clinical, laboratory, therapeutic and imaging data were collected from the physical chart and analyzed in light of current publications on the topic. The first consultation occurred in January 2012, where weight loss, fever, vomiting, left-sided hypochondrium and epigastric pain were reported. Imaging exams evidenced an expansive heterogeneous process in the pancreatic tail; however, laboratory exams and tumor markers did not present alteration in relation to reference values. In March of 2012, she underwent caudal body pancreatectomy, splenectomy, segmental colectomy and colo-coloanastomosis as a function of the intraoperative findings. After 63 months, right-sided hepatectomy was performed to resect metastases. Currently, she is undergoing outpatient monitoring, without complaint or alterations in imaging and laboratory exams, totaling 100 months of global survival. Discussion This is an interesting case report of a rare tumor, in so far as without any adjuvant chemotherapies, an 8-year long survival time could be achieved in this particular type of tumor despite initially large tumor expansion and later liver metastases. Conclusion Additional epidemiological studies, molecular and clinical trials are required to increase knowledge on SPN.

Gastric cancer remains one of the most lethal cancers. The incidence and mortality rates are quite similar. The main reason for the high mortality is diagnosis at advanced stages of disease, when treatment options are poor. One of the supposed strategies to overcome late-stage diagnosis is identifying people at high risk with the aim of establishing rigorous clinical control, including routine endoscopy and biopsies. Hereditary gastric cancer (HGC) syndromes, though representing a sizeable group to monitor for prevention or, at least, for early diagnosis, are apparently extremely rare. The low rate of HGC diagnosis might be related to the low rates of suspicion, insufficient familiarity about clinical diagnosis criteria, and the supposed conditional necessity of a molecular diagnosis. In this review, we will discuss simple measures to increase HGC diagnosis by applying three rules that might provide an opportunity for precision care to benefit the families affected by this disease.

Despite being one of the most studied cancer-related infections, the relationship between Helicobacter pylori infection and gastric adenocarcinoma (GC) remains, in some points, obscure. Based on a critical analysis of the available literature regarding stomach microbiota, we aimed to shed light to a possible new interpretation of the current understanding about the Helicobacter pylori-related GC carcinogenesis. We analyzed data from the literature on Helicobacter pylori and other potential carcinogenic pathogens, in both benignant conditions and gastric adenocarcinoma. Helicobacter pylori is the dominant microorganism in benignant conditions as non-complicated gastritis. In atrophic gastritis, metaplasia and, mainly, in gastric adenocarcinoma, a strong reduction in Helicobacter pylori abundance, and increased occurrence of other microorganisms is strongly demonstrated by metagenomic experiments. While causing peptic disease and keeping the stomach's high acidity, Helicobacter pylori infection avoids gastric infection by carcinogenic intestinal microbiota. Nevertheless, Helicobacter pylori persistence may also provoke an atrophic gastritis, a condition that causes its own decline, due to a microenvironment modification, including reduced acidity, resulting in Helicobacter pylori substitution by a cancer-prone microbiota. This new interpretation might result in a dramatic modification on clinical management of Helicobacter pylori-related gastric disease.

Background : The II Brazilian Consensus on Gastric Cancer of the Brazilian Gastric Cancer Association BGCA (Part 1) was recently published. On this occasion, countless specialists working in the treatment of this disease expressed their opinion in the face of the statements presented. Aim : To present the BGCA Guidelines (Part 2) regarding indications for surgical treatment, operative techniques, extension of resection and multimodal treatment. Methods: To formulate these guidelines, the authors carried out an extensive and current review regarding each declaration present in the II Consensus, using the Medline/PubMed, Cochrane Library and SciELO databases initially with the following descriptors: gastric cancer, gastrectomy, lymphadenectomy, multimodal treatment. In addition, each statement was classified according to the level of evidence and degree of recommendation. Results : Of the 43 statements present in this study, 11 (25,6%) were classified with level of evidence A, 20 (46,5%) B and 12 (27,9%) C. Regarding the degree of recommendation, 18 (41,9%) statements obtained grade of recommendation 1, 14 (32,6%) 2a, 10 (23,3%) 2b e one (2,3%) 3. Conclusion : The guidelines complement of the guidelines presented here allows surgeons and oncologists who work to combat gastric cancer to offer the best possible treatment, according to the local conditions available. RESUMO Racional: O II Consenso Brasileiro de Câncer Gástrico da Associação Brasileira de Câncer Gástrico ABCG (Parte 1) foi recentemente publicado. Nesta ocasião inúmeros especialistas que atuam no tratamento desta doença expressaram suas opiniões diante declarações apresentadas. Objetivo: Apresentar as Diretrizes da ABCG (Parte 2) quanto às indicações de tratamento cirúrgico, técnicas operatórias, extensão de ressecção e terapia combinada. Métodos: Para formulação destas diretrizes os autores realizaram extensa e atual revisão referente a cada declaração presente no II Consenso, utilizando as bases Medline/PubMed, Cochrane Library e SciELO, inicialmente com os seguintes descritores: câncer gástrico, gastrectomia, linfadenectomia, terapia combinada. Ainda, cada declaração foi classificada de acordo com o nível de evidência e grau de recomendação. Resultados: Das 43 declarações presentes neste estudo, 11 (25,6%) foram classificadas com nível de evidência A, 20 (46,5%) B e 12 (27,9%) C. Quanto ao grau de recomendação, 18 (41,9%) declarações obtiveram grau de recomendação 1, 14 (32,6%) 2a, 10 (23,3%) 2b e um (2,3%) 3. Conclusão: O complemento das diretrizes aqui presentes possibilita que cirurgiões e oncologistas que atuam no combate ao câncer gástrico possam oferecer o melhor tratamento possível, de acordo com as condições locais disponíveis.

Objective: to assess the socioeconomic and demographic profiles of patients hospitalized with a diagnosis of diabetic foot in a tertiary hospital in Belem-PA, Brazil, as well as to evaluate risk factors for lower limb amputations in such patients, classifying them according to the Wagner and PEDIS classifications. Methods: we conducted a descriptive, cross-sectional, unicentric, and analytical study carried out through a structured questionnaire. Results: the study consisted of 57 patients, aged between 48 and 84 years old, 66.7% being male. The average income ranged between one and three (61.4%) minimum wages and below one minimum wage (31.6%). Type II Diabetes Mellitus was predominant (86.0%). Concerning comorbidities, arterial hypertension displayed the highest proportion (62.3%), followed by dyslipidemia (52.8%). Smokers comprised 35.1% of the sample. Infectious diabetic foot (50.9%) and mixed diabetic foot (49.1%) were the most common. Of the 20 patients with previous amputation, 90% had undergone minor amputation, and 10%, major ones. Callosity (92.6%) was the most prevalent deformity. Fifty-four (94.7%) patients underwent surgery, those being debridement (24.1%), minor amputation (37.0%) and major amputation (38.9%). During hospitalization, 78.9% of individuals did not require ICU stay. Hospitalization time varied between three and 59 days, and 78.9% of hospitalized patients did not progress to death, but 43.1% of patients submitted to major amputations died. Conclusion: patients with diabetic foot followed-up have a low socioeconomic profile; most of them underwent surgical procedures, whether major or minor, due to the higher prevalence of infectious diabetic foot and/or non-adherence to non-operative treatment. RESUMO Objetivo: traçar o perfil socioeconômico demográfico de pacientes internados com diagnóstico de pé diabético em um hospital terciário de Belém-PA, bem como avaliar os fatores de riscos para amputações de membros inferiores classificando-os de acordo com os critérios de Wagner e PEDIS. Métodos: estudo descritivo, transversal, unicêntrico e analítico realizado mediante questionário estruturado com perguntas objetivas e com posterior análise estatística descritiva de pacientes diagnosticados com pé diabético em um hospital terciário de Belém-PA. Resultados: estudo foi composto por 57 pacientes, com idade variando entre 48 e 84 anos, sendo 66,7% masculino. A renda medida oscilou entre 01 a 03 salários. O Diabetes Mellitus do tipo II foi predominante (86,0%). HAS foi a doença associada mais prevalente (62,3%), seguida da Dislipidemia (52,8%). Havia 35,1% fumantes. O tipo mais comum de pé diabético foi o neuropático (59,6%), seguido pelo infeccioso (50,9%) e o misto (49,1%). O tempo de hospitalização variou entre 03 e 59 dias. 43,1% dos pacientes que foram submetidos a amputações maiores faleceram. Conclusão: a ocorrência de pé diabético foi maior nos pacientes do sexo masculino com mais de 50 anos de idade. Predominaram pacientes de baixa renda e com pouca escolaridade. A maioria dos pacientes foram acometidos por pé diabético do tipo II e padrão infeccioso e, que necessitaram de intervenção. A maioria dos pacientes foi admitido com classificações mais avançadas de Wagner e PEDIS, o que estava associado à altas taxas de amputações, impactando nos desfechos de mortalidade.

Objetivo: Identificar as alterações biomecânicas nos pés de pacientes internados com diagnóstico de pé diabético em um hospital terciário de Belém-PA, bem como avaliar os fatores de riscos sóciodemográficos relacionados Métodos: estudo descritivo, transversal, unicêntrico e analítico realizado mediante questionário estruturado com perguntas objetivas e com posterior análise estatística descritiva dos resultados obtidos de pacientes diagnosticados com pé diabético em um hospital terciário de Belém-PA. Resultados: Estudo foi composto por 57 pacientes, com idade variando entre 48 e 84 anos, sendo 66.7% masculino. A renda medida oscilou entre 01 a 03 salários. O Diabetes Mellitus do tipo II foi predominante (86.0%). HAS obteve maior proporção (62.3%), seguida da Dislipidemia (52.8%). O tipo mais comum de pé diabético foi o neuropático (59.6%). A calosidade representou a alteração biomecânica mais frequente seguida por deformidades como proeminências ósseas, dedo em garra e sobreposição de dedos. Conclusão: O presente estudo revelou que no HUJBB em Belém-Pará a ocorrência de pé diabético foi maior nos pacientes do sexo masculino com mais de 50 anos de idade. Predominaram pacientes de baixa renda, com pouca escolaridade, portador de Diabetes tipo II e significativo acometimento neuropático do pé, denotando a contínua necessidade de inspecionar os pe?s e orientar a seleção de calcados como medidas preventivas de complicações biomecânicas e amputações.

Background: Since the publication of the first Brazilian Consensus on Gastric Cancer (GC) in 2012 carried out by the Brazilian Gastric Cancer Association, new concepts on diagnosis, staging, treatment and follow-up have been incorporated. Aim: This new consensus is to promote an update to professionals working in the fight against GC and to provide guidelines for the management of patients with this condition. Methods: Fifty-nine experts answered 67 statements regarding the diagnosis, staging, treatment and prognosis of GC with five possible alternatives: 1) fully agree; 2) partially agree; 3) undecided; 4) disagree and 5) strongly disagree A consensus was adopted when at least 80% of the sum of the answers “fully agree” and “partially agree” was reached. This article presents only the responses of the participating experts. Comments on each statement, as well as a literature review, will be presented in future publications. Results: Of the 67 statements, there was consensus in 50 (74%). In 10 declarations, there was 100% agreement. Conclusion: The gastric cancer treatment has evolved considerably in recent years. This consensus gathers consolidated principles in the last decades, new knowledge acquired recently, as well as promising perspectives on the management of this disease.

4056 Background: Epstein–Barr virus (EBV) discriminates a molecular group of gastric cancer (GC) that seems to have peculiar treatment responses and prognosis. Nevertheless, the gene expression pattern of such tumors needs additional investigations due to the heterogeneity of the tumor microbiome and the small number of studied samples. Biological networks analysis of gene expression patterns, in this complex scenario, might lead to the discovery of putative "hubs" genes, supposed to have important roles in cancer occurrence and consequences. This study aimed to explore the biological value of hub genes in EBV-positive gastric cancer patients. Methods: Fresh tumor samples collected during gastrectomies from individuals with gastric adenocarcinoma (n = 41, 59.0±11.0 years) were included. Gene expression of tumor samples was evaluated in the Illumina sequencing platform. A weighted correlation network analysis (WGCNA) was used to find highly correlated gene patterns. The gene's correlation to EBV status was also explored, including eight EBV positive and 33 EBV negative cases. Gene Ontology (GO) term enrichment was performed to predict the involved biological functions. The expression level of the hubs gene was measured by differential expression analysis. Results: A gene cluster including 636 genes able to discriminate EBV status (ρ = 0.65, p-value = 6e-05) was identified. GO analysis (padj 1 and padj< 0.05). The top hub genes were LAPTM5, PTPN22, C1QA, CD84, CD53, ADAMDEC1, DPYD, TYROBP, RARRES3, IFI16, CYBB, CMKLR1, PHF21A, GPNMB, and C1QC, according to cluster significance and gene expression level. In positive EBV-GC, all hub genes were overexpressed (FC 1.24 - 2.49) (Table). The average area under the ROC curve (AUC) for hub genes was 0.9 (0.84-0.99). Overexpression of LAPTM5 (p-value = 0.013) and DPYD (p-value =0.0065) and low expression of ADAMDEC1 (p-value = 0.05) were strongly related to poor survival outcome. Conclusions: EBV-positive status was correlated with overexpression of hub genes. Genes found in this investigation have high sensitivity and specificity to discriminate EBV status in GC. Some of them seem to be related to patients' survival, opening an avenue for future scientific explorations in this field. The biological network's approach may be a promising tool for mining target genes for potential clinical applications. [Table: see text]

e16056 Background: FLOT perioperative have emerged as a new standard for locally advanced gastric cancer (LAGC). Nevertheless, the molecular consequences of such therapy remain obscure. Aiming to investigate changes in the tumor transcriptional landscape in LAGC patients treated with FLOT, a comprehensive analysis of messenger RNA (mRNAs) and long noncoding RNA (lncRNAs) expression was developed using next-generation sequencing (NGS). Methods: Paired tumor and non-tumor fresh samples, including 17 patients with intestinal-type LAGC submitted to neoadjuvant FLOT treatment (treated group) and 13 who did not receive neoadjuvant therapy (untreated group), were sequenced and compared. Differential expression analyses were performed using the DESeq2 package. Criteria for differentially expressed (DE) lncRNAs and mRNAs were|Log2(Fold-Change)| > 2; and adjusted p-value < 0.05. In silico analyses were adopted to identify DE lncRNAs with transcription factors (TFs) and RNA-binding proteins (RPBs). Kyoto Encyclopedia of Genes and Genomes (KEGG) pathway analysis and gene ontology (GO) was also performed to elucidate these target proteins’ and mRNAs biological’s roles. Results: In tumor samples from the untreated group, 4443 mRNAs and 961 lncRNAs DE were found, in which 293 mRNAs and 148 lncRNAs accurately discriminated (the area under the curve ROC > 0.9) tumor and non-tumor tissues. Only 265 mRNAs and 29 lncRNAs DE were detected in treated patients, indicating that neoadjuvant therapy led to changes in expression patterns, making tumor tissues similar to non-tumor tissues. Subsequent analyzes identified that non-tumor tissues (treated vs. untreated) showed similar expression profiles. Among tumor samples, 34 mRNAs and 54 lncRNAs DE were found, in which 7 mRNAs and 16 lncRNAs can discriminate between treated and untreated tumors, indicating the effect of neoadjuvant treatment is predominant in the tumor. GO evaluation of genes was significant for 83 terms for biological process. The most annotated terms were the regulation of catalytic activity. We also observed that DE lncRNAs interact with TFs and RBPs were enriched in related cancer development and progression pathways, including transcriptional dysregulation and cellular senescence. Conclusions: Despite the need for further validation to better understand the transcriptional landscape related to neoadjuvant treatment, the present study highlights the functional relevance of lncRNAs in tumor biology and, mainly, shed light on the molecular effects of FLOT neoadjuvant treatment, that might help to guide future investigations aiming to establish personalized management of GC.

O câncer gástrico é um importante problema de saúde pública, considerado o quinto câncer mais diagnosticado no mundo. A metástase peritoneal é uma das principais causas de mortalidade relacionadas ao câncer gástrico. A hipermetilação de genes supressores de tumor é um fator promissor para o desenvolvimento de biomarcadores preditivos. Em tumores gástricos, a expressão reduzida do gene supressor CDH1 contribui para a invasão tumoral e desencadeamento de metástases. Nosso objetivo foi avaliar o perfil de metilação da região promotora do gene CDH1 como indicador de metástase peritoneal em pacientes com câncer gástrico. O perfil de metilação de CDH1 foi avaliado em 47 amostras de lavados peritoneais de pacientes com câncer gástrico por PCR de sequenciamento de bissulfito (BSP). Trinta e três sítios CpGs na região do promotor CDH1 foram avaliados individualmente. Amostras com ≥ 10% de sítios CpGs metilados foram consideradas hipermetiladas. A análise estatística foi realizada pelo teste Exato de Fisher, utilizando o programa R-Studio (p≤0,05). Vinte e nove (62%) amostras apresentaram hipermetilação na região promotora de CDH1, com metilação preferencial nos sítios CpGs localizados na região 5' a montante do gene. A análise estatística mostrou que a hipermetilação de CDH1 foi significativamente diferente em pacientes com estágios avançados de profundidade de invasão do tumor (p=0,03). Nossos resultados sugerem que a análise de metilação do gene CDH1 é uma ferramenta útil na predição de progressão e invasividade tumoral em pacientes com câncer gástrico e pode ter um grande impacto para o campo da medicina de precisão do câncer.

The search for cancer biomarkers is frequently based on comparisons between tumors and adjacent-to-tumor samples. However, even after histological confirmation of been free of cancer cells, these adjacent-to-tumor samples might harbor molecular alterations which are not sufficient to cause them to look like cancer, but can differentiate these cells from normal cells. When comparing them, potential biomarkers are missed, and mainly the opportunity of finding initial aberrations presents in both tumors and adjacent samples, but not in true normal samples from non-cancer patients, resulting in misinterpretations about the carcinogenic process. Nevertheless, collecting adjacent-to-tumor samples brings trumps to be explored. The addition of samples from non-cancer patients opens an opportunity to increase the finds of the molecular cascade of events in the carcinogenic process. Differences between normal samples and adjacent samples might represent the first steps of the carcinogenic process. Adding samples of non-cancer patients to the analysis of molecular alterations relevant to the carcinogenic process opens a new window of opportunities to the discovery of cancer biomarkers and molecular targets.

Background: The II Brazilian Consensus on Gastric Cancer by the Brazilian Gastric Cancer Association (ABCG) was recently published. On this occasion, several experts in gastric cancer expressed their opinion before the statements presented. Aim: To present the ABCG Guidelines (part 1) regarding the diagnosis, staging, endoscopic treatment and follow-up of gastric cancer patients. Methods: To forge these Guidelines, the authors carried out an extensive and current review regarding each statement present in the II Consensus, using the Medline/PubMed, Cochrane Library and SciELO databases with the following descriptors: gastric cancer, staging, endoscopic treatment and follow-up. In addition, each statement was classified according to the level of evidence and degree of recommendation. Results: Of the 24 statements, two (8.3%) were classified with level of evidence A, 11 (45.8%) with B and 11 (45.8%) with C. As for the degree of recommendation, six (25%) statements obtained grade of recommendation 1, nine (37.5%) recommendation 2a, six (25%) 2b and three (12.5%) grade 3. Conclusion: The guidelines presented here are intended to assist professionals working in the fight against gastric cancer with relevant and current information, granting them to be applied in the daily medical practice. RESUMO Racional: O II Consenso Brasileiro de Câncer Gástrico da Associação Brasileira de Câncer Gástrico (ABCG) foi recentemente publicado. Nesta ocasião, inúmeros especialistas que atuam no tratamento desta doença expressaram sua opinião diante declarações apresentadas. Objetivo: Apresentar as Diretrizes da ABCG (Parte 1) quanto ao diagnóstico, estadiamento, tratamento endoscópico e seguimento dos pacientes com câncer gástrico. Métodos: Para formulação destas Diretrizes os autores realizaram extensa e atual revisão referente a cada declaração presente no II Consenso, utilizando as bases Medline/PubMed, Cochrane Library e SciELO com os seguintes descritores: câncer gástrico, estadiamento, tratamento endoscópico e seguimento. Ainda, cada declaração foi classificada de acordo com o nível de evidência e grau de recomendação. Resultados: Das 24 declarações, duas (8,3%) foram classificadas com nível de evidência A, 11 (45,8%) B e 11 (45,8%) C. Quanto ao grau de recomendação, seis (25%) declarações obtiveram grau de recomendação 1, nove (37,5%) grau 2a, seis (25%) 2b e três (12,5%) 3. Conclusão: As diretrizes aqui presentes têm a finalidade de auxiliar os profissionais que atuam no combate ao câncer gástrico com informações relevantes e atuais, permitindo que sejam aplicadas na prática médica diária.

Although the small bowel is a vast organ with a highly proliferative epithelium, the incidence of small bowel cancers is surprisingly low. Many factors could be involved in this unexpected cancer incidence, including difficult access to the exploration of the small bowel mucosa, which might lead to missed diagnoses of non-obstructive and non-bleeding small tumours. Moreover, possible factors that influence the low incidence include more efficient machinery of DNA replication and DNA repair enzymes, peculiarities in microbiota components, competence of the immune system, and the speed of intestinal transit. Importantly, the answer for the enigmatic risk of driver mutations caused by replication errors may be hidden in the small bowel, which is an obscure part of digestive tract that is usually inaccessible by endoscopic or colonoscopic conventional investigations. These observations warrant the necessity of an urgent exploration of small bowel features, including the evaluation of DNA replication controls and expression of DNA repair genes, in order to shed light on these obscure events.

A neoplasia gástrica é doença heterogênea e multifatorial, com incidência e mortalidade variando geograficamente. Aproximadamente 60% dos diagnósticos em pacientes de países ocidentais ocorrem nos estádios III ou IV. Nestes doentes, o melhor tratamento consiste na realização de procedimento cirúrgico. OBJETIVO: Identificar os aspectos epidemiológicos de pacientes diagnosticados com adenocarcinoma gástrico T4b. MÉTODOS: Estudo observacional, transversal, retrospectivo, de fonte secundária, dos pacientes diagnosticados com adenocarcinoma gástrico T4b através de estadiamento patológico. Foram analisados 815 prontuários, sendo 27 pacientes estudados. As variáveis investigadas foram: aspectos demográficos, principais queixas, fatores de risco, acesso ao serviço de saúde, aspectos cirúrgicos, morbidade, mortalidade e sobrevida. RESULTADOS: Vinte e dois eram homens (81,5%) e cinco mulheres (18,5%) com idade variando de 38 a 87 e média de 58,78 anos. O tempo de acesso ao serviço, em meses, variou de 1 a 120, com média de 12,5. Os sinais e sintomas mais prevalentes foram: perda de peso 23 (85,2%), epigastralgia 22 (81,5%), vômitos 16 (59,3%) e plenitude gástrica 12 (44,4%). A frequência de acometimento das estruturas adjacentes foi: pâncreas oito (29,6%), fígado sete (25,9%), cólon transverso seis (22,2%), intestino delgado seis (22,2%), mesocólon três (11,1%), baço um (3,7%) e vesícula biliar um (3,7%). Morbidades pós-operatórias ocorreram em 51,85% dos pacientes. Houve associação significativa entre mortalidade cirúrgica e ocorrência de fístula/deiscência, choque séptico e sangramento. A sobrevida ao final de seis meses foi de 63,27%. CONCLUSÃO: A média do tempo entre início dos sintomas e acesso ao serviço de saúde especializado foi elevada. Mais da metade dos pacientes apresentaram morbidades pós-operatórias. Os pacientes que apresentaram fístula/deiscência, sangramentos e choque séptico tiveram associação significativa com mortalidade cirúrgica. A sobrevida ao final de seis meses foi de 63,27%. Gastric neoplasia is a heterogeneous and multifactorial disease and its incidence and mortality vary widely based on geographic location. Approximately 60% of the diagnoses of patients from occidental countries were made on the stages III and IV. The best treatment still is to realize a surgical procedure. AIM: Identify the epidemiological aspects of the patients diagnosed with T4b gastric adenocarcinoma. METHODS: The study was observational, transversal and retrospective; it was also based on secondary sources from patients diagnosed with T4b gastric adenocarcinoma, through pathologic stages. A total of 815 charts were analyzed and 27 patients studied. The variables were: demographic aspects, main symptoms, risk factors, access to health system, surgical aspects, morbidity, mortality and survival. RESULTS: Were included 22 men (81,5%) and five woman (18,5%), in the age group between 38 and 87 years old - median age of 58. The time, in months, to access the health system varied from one to 120, average of 12,5 months. The most prevalent signs and symptoms were: weight loss 23 (85,2%), epigastric pain 22 (81,5%), vomit 16 (59,3%) and gastric fullness 12 (44,4%). The frequency of the affected adjacent body structures was: pancreas 8 (29,6%), liver 7 (25,9%), transverse colon 6 (22,2%), small intestine 6 (22,2%), mesocolon 3 (11,1%), spleen 1 (3,7%) and gallbladder 1 (3,7%). Postoperative morbidity occurred in 51, 85% of the patients. There were a significative association between surgical mortality and the occurrence of fistula/ dehiscence, septic shock and bleeding. The survival rate after six months was 63,27%. CONCLUSION: The mean time between onset of symptoms and access to specialized health services was high. More than half of the patients had postoperative morbidities. Patients who had fistula / dehiscence, bleeding and septic shock were significantly associated with surgical mortality. The survival rate after six months was 63.27%. UFPA - Universidade Federal do Pará

Biliary tract cancers are aggressive malignancies that include gallbladder cancer and tumors of intra- and extrahepatic ducts and have a poor prognosis. Surgical resection remains the main curative therapy. Nevertheless, numerous patients experience recurrence even after radical surgery. This scenario drives the research to identify biliary tract cancer biomarkers despite the limited progress that has been made. Recently, a large number of studies have demonstrated that deregulated expression of microRNAs is closely associated with cancer development and progression. In this review, we highlight the role and importance of microRNAs in biliary tract cancers with an emphasis on utilizing circulating microRNAs as potential biomarkers. Additionally, we report several single-nucleotide polymorphisms inmicroRNAgenes that are associated with the susceptibility of biliary tract tumors.

OBJETIVO: Analisar os aspectos epidemiológicos-cirúrgicos dos pacientes com câncer de vesícula biliar (CAVB) atendidos em um Hospital Universitário de Belém/PA, no período de 1999-2009. MÉTODOS: estudo observacional, retrospectivo, descritivo-analítico de fonte secundária dos pacientes com diagnóstico de CAVB, no período de 1999-2009. Foram analisados 75 prontuários, sendo 34 pacientes estudados. As informações coletadas foram utilizadas para o estadiamento tumoral TNM do CAVB e para a caracterização clínico-cirúrgica da população estudada. RESULTADOS: 79% eram do sexo feminino, com média de idade de 66,2±11 anos e tempo de sintomatologia de 10,8±17,2 meses, não obtendo relação estatística com o estadio da doença. Dor no hipocôndrio direito, náuseas e icterícia predominaram como sinais/sintomas. A litíase biliar esteve presente em 91% dos casos, sendo positiva em 100% dos pacientes com estadios I/II. A sensibilidade ultrassonográfica para sugestionar o CAVB no pré-operatório foi 14,28%. A operação mais executada foi a colecistectomia simples, tendo como achado intra-operatório predominante, invasão hepática. O adenocarcinoma foi o tipo histológico preponderante, com destaque para os estadios III e IV. CONCLUSÃO: A série estudada apresentou alta incidência de litíase biliar, o adenocarcinoma com estadio avançado foi o mais prevalente. acarretando um pequeno índice de operações com intenção curativa, 30% dos pacientes operados, e uma taxa de mortalidade de 21%. A valorização dos sintomas e a investigação precoce por exames de imagem poderiam favorecer o tratamento, em fases iniciais do CAVB, proporcionando um melhor prognóstico para os pacientes operados. OBJECTIVE: To evaluate the epidemiological aspects of surgical patients with gallbladder cancer (GC) enrolled in a University Hospital in Bethlehem (State of Pará - PA), in the period 1999-2009. METHODS: observational, retrospective, descriptive and analytical study of secondary sources of patients with GC in the period 1999-2009. We analyzed 75 medical records, with 34 patients studied. The information collected was used for the TNM tumor staging of GC and to characterize the clinical and surgical population. RESULTS: 79% were female, mean age 66.2 ± 11 years and duration of symptoms was 10.8 ± 17.2 months, with no statistical relationship with the stage of disease. Pain in right upper quadrant, nausea and jaundice prevailed as signs / symptoms. Gallstones were present in 91% of cases and were positive in 100% of patients with stage I / II. The sensitivity of ultrasound to preoperatively suggest GC was 14.28%. The simplest operation performed was cholecystectomy, with the predominant intraoperative finding being hepatic invasion. Adenocarcinoma was the predominant histologic type, especially for stages III and IV. CONCLUSION: The present study showed high incidence of gallstone disease. Advanced stage adenocarcinoma was the most prevalent. This resulted in a low rate of operations with curative intent, in 30% of the patients, and a mortality rate of 21%. The appreciation of symptoms and early investigation by imaging could facilitate treatment in early stages of GC, providing a better prognosis for patients.

Gastric cancer is the third most frequent type of neoplasia and the second most important cause of cancer-related death in the world. In northern Brazil, the state of Pará shows a high incidence of this disease and the capital ranks among cities with the highest incidence of stomach cancer in the world. To evaluate chromosomal aberrations implicated in gastric carcinogenesis, we analyzed 16 samples of gastric adenocarcinoma by fluorescence in situ hybridization using a chromosome 8 alpha-satellite probe and by direct chromosomal analysis techniques. All lesions were classified as at advanced stages according to the recommendations of the Union Internationale Contre le Cancer (UICC). Trisomy 8 was the main finding of this study, observed in all cases. There was no significant difference between chromosome 8 ploidy and localization, stage, or histological type of adenocarcinoma in our sample. The high incidence of alterations we found in chromosome 8 may be a regional characteristic, related to the high incidence of this neoplasm in Pará state and a strong influence of external factors, such as eating habits. This aberration may comprise a cytogenetic subgroup of this neoplasm. Additional investigations are necessary to confirm the involvement of chromosome 8 and to identify genes in this chromosome related to gastric carcinogenesis.

Gastric cancer is considered to be the fifth highest incident tumor worldwide and the third leading cause of cancer deaths. Developing regions report a higher number of sporadic cases, but there are only a few local studies related to hereditary cases of gastric cancer in Brazil to confirm this fact. CDH1 germline mutations have been described both in familial and sporadic cases, but there is only one recent molecular description of individuals from Brazil. In this study we performed Next Generation Sequencing (NGS) to assess CDH1 germline mutations in individuals who match the clinical criteria for Hereditary Diffuse Gastric Cancer (HDGC), or who exhibit very early diagnosis of gastric cancer. Among five probands we detected CDH1 germline mutations in two cases (40%). The mutation c.1023T > G was found in a HDGC family and the mutation c.1849G > A, which is nearly exclusive to African populations, was found in an early-onset case of gastric adenocarcinoma. The mutations described highlight the existence of gastric cancer cases caused by CDH1 germline mutations in northern Brazil, although such information is frequently ignored due to the existence of a large number of environmental factors locally. Our report represent the first CDH1 mutations in HDGC described from Brazil by an NGS platform.

Gallbladder cancer is a rare malignancy and presents a poor prognosis. MYC and p53 have been implicated in gallbladder carcinogenesis. However, little is known about the molecular mechanisms involved in their regulation in this neoplasia. Here, we evaluated the MYC and TP53 copy numbers in gallbladder tumors and their possible association with protein expression. We also investigated whether MYC may be controlled by mutations and DNA promoter methylation. In the present study, 15 samples of invasive gallbladder carcinomas and six control samples were analyzed. On the other hand, the expression of MYC and p53 was more frequent in gallbladder carcinomas than in control samples (p = 0.002, p = 0.046, respectively). Gain of copies of the MYC and TP53 genes was detected in 86.7 and 50 % of gallbladder carcinomas, respectively. MYC and TP53 amplifications were associated with immunoreactivity of their protein (p = 0.029, p = 0.001, respectively). MYC hypomethylation was only detected in tumoral samples and was associated with its protein expression (p = 0.029). MYC mutations were detected in 80 % of tumor samples. The G allele at rs117856857 was associated with the presence of gallbladder tumors (p = 0.019) and with MYC expression (p = 0.044). Moreover, two tumors presented a pathogenic mutation in MYC exon 2 (rs28933407). Our study highlights that the gain of MYC and TP53 copies seems to be a frequent finding in gallbladder cancer. In addition, gain of copies, hypomethylation and point mutations at MYC may contribute to overexpression of its protein in this type of cancer.

Paulo Pimentel de Assumpcao • Sidney Emanuel Batista dos Santos • Ândrea Kely Campos Ribeiro dos Santos • Samia Demachki • Andre Salim Khayat • Geraldo Ishak • Danielle Queiroz Calcagno • Ney Pereira Carneiro dos Santos • Carolina Barauna de Assumpcao • Monica Barauna de Assumpcao • Vinicius Albuquerque Sortica • Taissa Maira Thomaz Araujo • Fabiano Cordeiro Moreira • Andre Mauricio Ribeiro dos Santos • Rommel Mario Rodriguez Burbano

Gastric neoplasia is a heterogeneous and multifactorial disease and its incidence and mortality vary widely based on geographic location. Approximately 60% of the diagnoses of patients from occidental countries were made on the stages III and IV. The best treatment still is to realize a surgical procedure.Identify the epidemiological aspects of the patients diagnosed with T4b gastric adenocarcinoma.The study was observational, transversal and retrospective; it was also based on secondary sources from patients diagnosed with T4b gastric adenocarcinoma, through pathologic stages. A total of 815 charts were analyzed and 27 patients studied. The variables were: demographic aspects, main symptoms, risk factors, access to health system, surgical aspects, morbidity, mortality and survival.Were included 22 men (81,5%) and five woman (18,5%), in the age group between 38 and 87 years old - median age of 58. The time, in months, to access the health system varied from one to 120, average of 12,5 months. The most prevalent signs and symptoms were: weight loss 23 (85,2%), epigastric pain 22 (81,5%), vomit 16 (59,3%) and gastric fullness 12 (44,4%). The frequency of the affected adjacent body structures was: pancreas 8 (29,6%), liver 7 (25,9%), transverse colon 6 (22,2%), small intestine 6 (22,2%), mesocolon 3 (11,1%), spleen 1 (3,7%) and gallbladder 1 (3,7%). Postoperative morbidity occurred in 51, 85% of the patients. There were a significative association between surgical mortality and the occurrence of fistula/ dehiscence, septic shock and bleeding. The survival rate after six months was 63,27%.The mean time between onset of symptoms and access to specialized health services was high. More than half of the patients had postoperative morbidities. Patients who had fistula / dehiscence, bleeding and septic shock were significantly associated with surgical mortality. The survival rate after six months was 63.27%.

80 Background: Recently, some papers aiming to warn the scientific community regarding possible misinterpretation due to using adjacent to tumor sample tissues as normal controls were published The main motivation for these alerts was the observation of important molecular alterations in tissues nearby a cancer, although been collected from non-tumor areas. Nevertheless the cancer field hypothesis has been recognized many years ago; this concept was not incorporated to current practice in molecular investigations. In this work we aim to investigate potential implications of using adjacent to tumor sample tissues as normal controls. Methods: Gastric Cancer (GC) and Adjacent Tissues (AT) paired fresh samples of 16 patients, and 16 samples from non-cancer patients (NC) were analyzed. miRNA sequencing was performed using Illumina Miseq platform. Statistical analysis was performed in R using DESeq2 tool to identify differential expressed miRNAs. Results: Comparing GC with NC tissue samples, we observed 21 miRNAs differentially expressed (p-value < 0.05 and |Log2(Fold-Change)| > 2), eight were down-regulated and 13 were up-regulated in GC. Comparing AT with NC tissue samples, 16 miRNAs were differentially expressed, two were down-regulated and 14 were up-regulated in AT. In both comparisons, GC and AT samples clustered together and clearly separated from NC samples. Comparing GC with AT samples, hsa-miR-196a-5p was significantly down-regulated in GC. Conclusions: AT tissues harbor molecular alterations distinguishing them from non-cancer patient’s samples. Combined analyses of the groups clearly demonstrated that AT resembles much more cancer profile than NC patient’s tissue prolife. Using AT samples as controls might impair the discovery of possible initial molecular events identifiable exclusively by using samples from non-cancer patients. The current strategy of molecular investigation must be revised.

UNLABELLED:This study aimed to evaluate the relative mRNA expression of Fas receptor (FAS), Fas ligand (FASL), and forkhead box protein 3 (FOXP3) in liver biopsy specimens obtained from patients with viral and non-viral chronic hepatitis and correlate their expression with the fibrosis stage. A total of 51 liver biopsy specimens obtained from HBV (n = 6), HCV (n = 28), and non-viral hepatic disease (NVHD) (n = 9) patients and from individuals with normal liver histology (n = 8) (control-CT) were analyzed. Quantifications of the target genes were assessed using qPCR, and liver biopsies according to the METAVIR classification. The mRNA expression levels of FAS and FASL were lower in the CT group compared to the groups of patients. The increase in the mRNA expression of FAS and FASL was correlated with higher levels of inflammation and disease progression, followed by a decline in tissues with cirrhosis, and it was also associated with increased levels of alanine aminotransferase (ALT) and aspartate aminotransferase (AST). Higher mRNA expression of FOXP3 was observed in the HCV and NVHD groups, with the peak observed among patients with cirrhosis. The increased FOXP3 mRNA expression was positively correlated with increased FAS and FASL mRNA expression and the AST and ALT levels in all patients. CONCLUSIONS:These results suggest that regardless of the cause, the course of chronic liver disease may be modulated by the analyzed genes and correlated with an increase in regulatory T cells during the liver damage followed by hepatocyte destruction by Fas/FasL system and subsequent non specific lymphocytic infiltrate accumulation.

To evaluate the epidemiological aspects of surgical patients with gallbladder cancer (GC) enrolled in a University Hospital in Bethlehem (State of Pará - PA), in the period 1999-2009.observational, retrospective, descriptive and analytical study of secondary sources of patients with GC in the period 1999-2009. We analyzed 75 medical records, with 34 patients studied. The information collected was used for the TNM tumor staging of GC and to characterize the clinical and surgical population.79% were female, mean age 66.2 ± 11 years and duration of symptoms was 10.8 ± 17.2 months, with no statistical relationship with the stage of disease. Pain in right upper quadrant, nausea and jaundice prevailed as signs / symptoms. Gallstones were present in 91% of cases and were positive in 100% of patients with stage I / II. The sensitivity of ultrasound to preoperatively suggest GC was 14.28%. The simplest operation performed was cholecystectomy, with the predominant intraoperative finding being hepatic invasion. Adenocarcinoma was the predominant histologic type, especially for stages III and IV.The present study showed high incidence of gallstone disease. Advanced stage adenocarcinoma was the most prevalent. This resulted in a low rate of operations with curative intent, in 30% of the patients, and a mortality rate of 21%. The appreciation of symptoms and early investigation by imaging could facilitate treatment in early stages of GC, providing a better prognosis for patients.

Thirty-four years old patient, female, husband died of AIDS (Acquired Immunodeficiency Síndrome). She's confined to Hospital Universitário João de Barros Barreto, with a positive tesT for AIDS, fever, 10 kg/month of weight loss, diarrhea with gummy faeces, productive cough, yellowish sputum. The therapy was initiated, symptomatic, associated to Epivir, Saquinavir and AZT. The searching exams for Alcohol Ácid Resistant Bacili and fungi in the sputum were negative. At the hemogram was shown a pancytopenia, the esophagogastroduodenunscopy showed light esophago moniliasis. During commitment presented a perforating acute abdomen chart, the abdominal radiography showed hidroair levels, pneumoperitoneum, enlarced bowels with swollen wall. She was undertaken a surgery with diagnosis hypothesis of cytomegalovirus perforation, which accordin to literature is the most frequent cause of intestinal perforation in patients with AIDS.