OLIGOMETASTASIS IN GASTRIC CANCER TREATMENT: IS THERE A PLACE FOR THE SURGEON?

Metastatic gastric cancer traditionally hinders surgical treatment options, confining them to palliative procedures. The presence of metastases in these tumors is classified as M1, irrespective of their characteristics, quantity, or location. However, oligometastatic disease emerged as an intermediate state between localized and widely disseminated cancer. It exhibits diverse patterns based on metastatic disease extent, type, and location. Adequately addressing this distinctive metastatic state necessitates tailored strategies that surpass the realm of palliative care. Differentprimary tumor types present discernible scenarios of oligometastatic disease, including preferred sites of occurrence and chronological progression. Due to the novelty of this theme and the heterogeneity of the disease, uncertainties still exist, and the ability to provide confident guidelines is challenging. Currently, there are no effective predictors to determine the response and provide clear indications for surgical interventions and systemic treatments in oligometastatic disease. Treatment decisions are commonly based on apparent disease control by systemic therapies, with a short observation period and imaging assessments. Nonetheless, the inherent risk of misinterpretation remains a constant concern. The emergence of novel technologies and therapeutic modalities, such as immunotherapy, cellular therapy, and adoptive therapies, holds the potential to reshape the landscape of surgical treatment for the oligometastatic disease in gastric cancer, expanding the surgeon's role in this multidisciplinary approach. Prospective tools for patient selection in oligometastatic gastric cancer are being explored. Using non-invasive, cost-effective, widely available imaging techniques that provide real-time information may revolutionize medical practice, ensuring precision medicine accessibility, even in resource-constrained small healthcare facilities. Incorporating molecular classifications, liquid biopsies, and radiomic analysis in a complementary protocol will augment patient selection precision for surgical intervention in oligometastasis. Hopefully, these advancements will render surgeries unnecessary in many cases by providing highly effective alternative treatments.

Advance Care Planning and Goals of Care Discussion: Barriers from the Perspective of Medical Residents.

BACKGROUND: Advance care planning (ACP) and goals of care discussion involve the exploration of what is most important to a person to prepare for health-care decision making. Despite their well-established benefits, they are still not frequently performed in clinical oncology practice. This study aims to describe the barriers to discussion goals of care with oncology patients from the perspective of medical residents. METHODS: This cross-sectional and qualitative study applied the "Decide-Oncology" questionnaire, adapted to Portuguese language, to assess barriers to goals of care discussion among medical residents from three university hospitals in Brazil. Residents were asked to rank the importance of various barriers to discuss goals of care (ranging from 1-extremely unimportant to 7-extremely important). RESULTS: Twenty-nine residents answered the questionnaire (30.9%). The most reported barriers were related to patients and their families' difficulty in understanding and accepting the diagnosis and the prognosis as well as patients' desire to receive full active treatment. Furthermore, the physician and external factors such as lack of training and lack of time to have these conversations were also very important barriers. The identification of the key barriers that limit the discussion of ACP and early palliative care referrals can certainly help to prioritize the next steps for future studies aimed at improving ACP and goals of care discussions.

Oligometastasis in gastric cancer treatment: is there a place for the surgeon? / Oligometástases no tratamento do câncer gástrico: existe um lugar para o cirurgião?

ABSTRACT Metastatic gastric cancer traditionally hinders surgical treatment options, confining them to palliative procedures. The presence of metastases in these tumors is classified as M1, irrespective of their characteristics, quantity, or location. However, oligometastatic disease emerged as an intermediate state between localized and widely disseminated cancer. It exhibits diverse patterns based on metastatic disease extent, type, and location. Adequately addressing this distinctive metastatic state necessitates tailored strategies that surpass the realm of palliative care. Differentprimary tumor types present discernible scenarios of oligometastatic disease, including preferred sites of occurrence and chronological progression. Due to the novelty of this theme and the heterogeneity of the disease, uncertainties still exist, and the ability to provide confident guidelines is challenging. Currently, there are no effective predictors to determine the response and provide clear indications for surgical interventions and systemic treatments in oligometastatic disease. Treatment decisions are commonly based on apparent disease control by systemic therapies, with a short observation period and imaging assessments. Nonetheless, the inherent risk of misinterpretation remains a constant concern. The emergence of novel technologies and therapeutic modalities, such as immunotherapy, cellular therapy, and adoptive therapies, holds the potential to reshape the landscape of surgical treatment for the oligometastatic disease in gastric cancer, expanding the surgeon's role in this multidisciplinary approach. Prospective tools for patient selection in oligometastatic gastric cancer are being explored. Using non-invasive, cost-effective, widely available imaging techniques that provide real-time information may revolutionize medical practice, ensuring precision medicine accessibility, even in resource-constrained small healthcare facilities. Incorporating molecular classifications, liquid biopsies, and radiomic analysis in a complementary protocol will augment patient selection precision for surgical intervention in oligometastasis. Hopefully, these advancements will render surgeries unnecessary in many cases by providing highly effective alternative treatments.

RESUMO O câncer gástrico metastático representa um desafio para o tratamento cirúrgico, restringindo-se a procedimentos paliativos. A presença de metástases nestes tumores é categorizada como estágio M1, independentemente das características, quantidade e localização. No entanto, a doença oligometastática surgiu como um estado intermediário entre o câncer localizado e o amplamente disseminado. A oligometastática apresenta diversos padrões com base na extensão, tipo e localização da doença metastática. Abordar adequadamente esse estado distintivo requer estratégias adaptadas que ultrapassem o escopo dos cuidados paliativos. Diferentes tipos de tumores primários exibem cenários distintos de oligometastática, incluindo locais preferenciais de ocorrência e progressão cronológica. Devido à novidade desse tema e à heterogeneidade da doença, ainda existem incertezas, e a capacidade de fornecer diretrizes seguras é limitada. Atualmente, não existem preditores eficazes para determinar a resposta e fornecer indicações claras para intervenções cirúrgicas e tratamentos sistêmicos em oligometastática. As decisões de tratamento geralmente se baseiam no controle aparente da doença por meio de terapias sistêmicas, com um curto período de observação e avaliação por imagem. No entanto, o risco inerente de interpretação incorreta continua sendo uma preocupação constante. A emergência de novas tecnologias e modalidades terapêuticas, como imunoterapia, terapia celular e terapias adotivas, tem o potencial de remodelar o panorama do tratamento cirúrgico da oligometastática no câncer gástrico, expandindo o papel do cirurgião nessa abordagem multidisciplinar. Ferramentas prospectivas para a seleção de pacientes com câncer gástrico oligometastático estão sendo exploradas. A utilização de técnicas de imagem não invasivas, rentáveis e amplamente disponíveis, que fornecem informações em tempo real, pode revolucionar a prática médica, garantindo a acessibilidade da medicina de precisão, mesmo em unidades de saúde com recursos limitados. A incorporação de classificações moleculares, biópsias líquidas e análises radiômicas em um protocolo complementar aumentará a precisão da seleção de pacientes para intervenção cirúrgica em oligometástases. Espera-se que esses avanços tornem as cirurgias desnecessárias em muitos casos, proporcionando tratamentos alternativos altamente eficazes.

Advance care planning and goals of care discussion: the perspectives of Brazilian oncologists.

BACKGROUND: Advance care planning (ACP) and goals of care discussions are important instruments that enable respect for patient autonomy, especially in patients with a life-threatening disease, such as cancer. Despite their well-established benefits, ACP and goals of care discussions are still not frequently performed in clinical oncology practice. Understanding the barriers to this topic is the first step toward developing future interventions that are more likely to improve professional practice and patient satisfaction with care. AIM: To explore Brazilian oncologists' barriers to discuss goals of care and advance care planning. METHODS: A cross-sectional study was developed to identify Brazilian oncologists' barriers to discussing goals of care and ACP. The Decide-Oncology questionnaire was used to identify the importance of these barriers according to oncologists' perceptions. Participants were asked to rank the importance of various barriers to discussing goals of care, ranging from 1 (extremely unimportant) to 7 (extremely important). A quantitative analysis using descriptive statistics was used, including median and interquartile intervals and a qualitative analysis based on Bardin content analysis of the two open questions. RESULTS: Sixty-six oncologists participated in this study. Most of them perceived the patient and family's related barriers as the most important, such as patients' difficulty in understanding their diagnosis and accepting their prognosis. Physician and external related factors, such as lack of training and lack of time for this conversation, were also described as important barriers. Participants with formal training regarding goals of care communication and with experience in palliative care perceived the lack of patients' advanced directives as a significant barrier and manifested more willingness to participate in decision-making about goals of care. The lack of access and of support for referral to palliative care was also considered a significant barrier for ACP and goals of care discussion. CONCLUSION: The identification of barriers that limit the discussion of ACP and early palliative care referrals can certainly help to prioritise the next steps for future studies aimed at improving ACP and helping clinicians to better support patients through shared decision-making based on the patient's values and experiences.

Planejamento antecipado de cuidados: guia prático / Advance care planning: a practical guide / Planificación anticipada de atención: una guía práctica

Resumo O planejamento antecipado de cuidados é um processo de discussões entre profissionais de saúde e pacientes que permite a tomada de decisão compartilhada quanto a objetivos de cuidados de saúde, atuais e/ou futuros, com base nos desejos e valores do paciente e em questões técnicas do cuidado. É considerado fundamental na prestação de cuidados de excelência em fim de vida, permitindo que profissionais de saúde alinhem os cuidados prestados com o que é mais importante para o paciente. Apesar de seus benefícios, ainda é muito pouco realizado na prática clínica, especialmente no Brasil. Considerando a necessidade de guias práticos de planejamento antecipado de cuidados adaptados à realidade brasileira, pautados em estratégias de comunicação empática, este estudo é uma proposta de guia baseada em revisão integrativa da literatura (PubMed e SciELO), com recomendações de evidências atuais, incluindo instrumentos validados para o português (Brasil), para facilitar sua implementação na prática clínica.

Abstract Advance care planning is a process of discussion between healthcare professionals and patients that enables shared decision-making on current and/or future healthcare goals, based on patients' desires and values and technical care issues. Advance care is considered essential in the provision of quality terminal care, allowing healthcare professionals to align the care provided with what is most important to the patient. Despite its benefits, it is still underused in clinical practice, especially in Brazil. Considering the need for practical guides for advance care planning adapted to the Brazilian reality, drawing on empathetic communication strategies, this study is a guide proposal based on an integrative literature review (PubMed and SciELO), with recommendations of current evidence, including instruments validated for Portuguese (Brazil), to facilitate its implementation in clinical practice.

Resumen La planificación anticipada de atención es un proceso de discusión entre los profesionales de la salud y los pacientes que permite la toma de decisiones relacionadas a los objetivos de atención médica actuales y/o futuros, basadas en los deseos y valores del paciente y en cuestiones técnicas de la atención. Resulta ser una apropiada atención terminal, ya que estos profesionales pueden adecuar la atención con los deseos del paciente. Pese a sus beneficios, es poco realizada en la práctica clínica, especialmente en Brasil. Dada la necesidad de guías prácticas para la planificación anticipada de atención, adaptadas a la realidad brasileña y basadas en estrategias comunicativas empáticas, este estudio propone una guía a partir de una revisión integradora de la literatura (PubMed y SciELO), con recomendaciones de evidencia actual, incluidos instrumentos validados para el portugués brasileño para facilitar su aplicación en la práctica clínica.

Influence of FPGS, ABCC4, SLC29A1, and MTHFR genes on the pharmacogenomics of fluoropyrimidines in patients with gastrointestinal cancer from the Brazilian Amazon.

PURPOSE: Fluoropyrimidines are one of the most used drug class to treat cancer patients, although they show high levels of associated toxicity. This study analyzed 33 polymorphisms in 17 pharmacogenes involved with the pharmacogenomics of fluoropyrimidines, in gastrointestinal cancer patients undergoing fluoropyrimidine-based treatment in the Brazilian Amazon. METHODS: The study population was composed of 216 patients, 92 of whom have an anatomopathological diagnosis of gastric cancer and 124 of colorectal cancer. The single nucleotide polymorphisms (SNP) were genotyped by allelic discrimination using the TaqMan OpenArray Genotyping technology, with a panel of 32 customized assays, run in a QuantStudio ™ 12K Flex Real-Time PCR System (Applied Biosystems, Life Technologies, Carlsbad USA). Ancestry analysis was performed using 61 autosomal ancestry informative markers (AIMs). RESULTS: The study population show mean values of 48.1% European, 31.1% Amerindian, and 20.8% African ancestries. A significant risk association for general and severe toxicity was found in the rs4451422 of FPGS (p = 0.001; OR 3.40; CI 95% 1.65-7.00 and p = 0.006; OR 4.63; CI 95% 1.56-13.72, respectively) and the rs9524885 of ABCC4 (p = 0.023; OR 2.74; CI 95% 1.14-6.65 and p = 0.024; OR 5.36; IC 95% 1.24-23.11, respectively) genes. The rs760370 in the SLC29A1 gene (p = 0.009; OR 6.71; CI 95% 1.16-8.21) and the rs1801133 in the MTHFR toxicity (p = 0.023; OR 3.09; CI 95% 1.16-8.21) gene also demonstrated to be significant, although only for severe toxicity. The results found in this study did not have statistics analysis correction. CONCLUSION: Four polymorphisms of the ABCC4, FPGS, SLC29A1, and MTHFR genes are likely to be potential predictive biomarkers for precision medicine in fluoropyrimidine-based treatments in the population of the Brazilian Amazon, which is constituted by a unique genetic background.

Comprehensive analysis of germline mutations in northern Brazil: a panel of 16 genes for hereditary cancer-predisposing syndrome investigation.

BACKGROUND: Next generation sequencing (NGS) has been a handy tool in clinical practice, mainly due to its efficiency and cost-effectiveness. It has been widely used in genetic diagnosis of several inherited diseases, and, in clinical oncology, it may enhance the discovery of new susceptibility genes and enable individualized care of cancer patients. In this context, we explored a pan-cancer panel in the investigation of germline variants in Brazilian patients presenting clinical criteria for hereditary cancer syndromes or familial history. METHODS: Seventy-one individuals diagnosed or with familial history of hereditary cancer syndromes were submitted to custom pan-cancer panel including 16 high and moderate penetrance genes previously associated with hereditary cancer syndromes (APC, BRCA1, BRCA2, CDH1, CDKN2A, CHEK2, MSH2, MSH6, MUTYH, PTEN, RB1, RET, TP53, VHL, XPA and XPC). All pathogenic variants were validated by Sanger sequencing. RESULTS: We identified a total of eight pathogenic variants among 12 of 71 individuals (16.9%). Among the mutation-positive subjects, 50% were diagnosed with breast cancer and had mutations in BRCA1, CDH1 and MUTYH. Notably, 33.3% were individuals diagnosed with polyposis or who had family cases and harbored pathogenic mutations in APC and MUTYH. The remaining individuals (16.7%) were gastric cancer patients with pathogenic variants in CDH1 and MSH2. Overall, 54 (76.05%) individuals presented at least one variant uncertain significance (VUS), totalizing 81 VUS. Of these, seven were predicted to have disease-causing potential. CONCLUSION: Overall, analysis of all these genes in NGS-panel allowed the identification not only of pathogenic variants related to hereditary cancer syndromes but also of some VUS that need further clinical and molecular investigations. The results obtained in this study had a significant impact on patients and their relatives since it allowed genetic counselling and personalized management decisions.

Refusal of medical treatment by older adults with cancer: a systematic review.

The literature about the factors associated with cancer treatment refusal, especially by the older patients is scarce. Therefore, this study aimed to identify predictive factors associated with treatment refusal by older patients with cancer. A systematic review was conducted using three databases, Medline, Web of Science, and Scopus with the key concepts, "refusal treatment" and "cancer" and "decision making" and "elderly" or "aged". The search took place in July 2020 and it included articles published in the last 5 years. Of the 211 articles found, 22 were included in the review. Most studies have focused on head and neck and breast cancer treatment decisions and used a quantitative design. The majority of studies evaluated refusal of surgery interventions. Important factors associated with refusal cancer treatment include gender, marital status, race, having government insurance, advanced cancer, poor performance status (cancer stage III or IV) and Charlson Comorbidity Index ≥2. Thus, there are socio-demographic and clinical variables associated with treatment refusal. More studies with the elderly are needed. Understanding these factors may be useful to recognize situations where active education and support can help elderly patients accept optimal care.

Gastric Cancer Microbiome.

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.

Brazilian gastric cancer association guidelines (part 2): update on treatment / Diretrizes da associação brasileira de câncer gástrico (parte 2): atualização sobre o tratamento

ABSTRACT 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.

The diffuse-type gastric cancer epidemiology enigma.

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.

Hepatic metastasis in Frantz's tumor: A case report.

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.

Hereditary gastric cancer: Three rules to reduce missed diagnoses.

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.

Current Perspectives on Circulating Tumor DNA, Precision Medicine, and Personalized Clinical Management of Cancer.

Circulating tumor DNA (ctDNA) has recently emerged as a minimally invasive "liquid biopsy" tool in precision medicine. ctDNA-genomic DNA fragments that are released into the bloodstream after the active secretion of microvesicles or tumor cell lysis reflects tumor evolution and the genomic alterations present in primary and/or metastatic tumors. Notably, ctDNA analysis might allow the stratification of patients, the monitoring of the therapeutic response, and the establishment of an opportunity for early intervention independent of detection by imaging modalities or clinical symptoms. As oncology moves towards precision medicine, the information in ctDNA provides a means for the individual management of the patient based on their tumor's genetic profile. This review presents current evidence on the potential role for ctDNA in helping to guide individualized clinical treatment decisions for patients with melanoma, castration-resistant prostate cancer, breast cancer, metastatic colorectal cancer, and non-small cell lung cancer.

The Small Bowel Cancer Incidence Enigma.

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.

Ii brazilian consensus on gastric cancer by the brazilian gastric cancer association / Ii consenso brasileiro de câncer gástrico realizado pela associação brasileira de câncer gástrico

ABSTRACT 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.

RESUMO Racional: Desde a publicação do primeiro Consenso Brasileiro sobre Câncer Gástrico em 2012 realizado pela Associação Brasileira de Câncer Gástrico (ABCG), novos conceitos sobre o diagnóstico, estadiamento, tratamento e seguimento foram incorporados. Objetivo: Promover uma atualização aos profissionais que atuam no combate ao câncer gástrico (CG) e fornecer diretrizes quanto ao manejo dos pacientes portadores desta afecção. Métodos: Cinquenta e nove especialistas responderam 67 declarações sobre o diagnóstico, estadiamento, tratamento e prognóstico do CG com cinco alternativas possíveis: 1) concordo plenamente; 2) concordo parcialmente; 3) indeciso; 4) discordo e 5) discordo fortemente. Foi considerado consenso a concordância de pelo menos 80% da soma das respostas "concordo plenamente" e "concordo parcialmente". Este artigo apresenta apenas as respostas dos especialistas participantes. Os comentários sobre cada declaração, assim como uma revisão da literatura serão apresentados em publicações futuras. Resultados: Das 67 declarações, houve consenso em 50 (74%). Em 10 declarações, houve concordância de 100%. Conclusão: O tratamento do câncer gástrico evoluiu consideravelmente nos últimos anos. Este consenso reúne princípios consolidados nas últimas décadas, novos conhecimentos adquiridos recentemente, assim como perspectivas promissoras sobre o manejo desta doença.

Suicide journey of H. pylori through gastric carcinogenesis: the role of non-H. pylori microbiome and potential consequences for clinical practice.

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.

Traps and trumps from adjacent-to-tumor samples in gastric cancer research.

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.

GEJ cancers: gastric or esophageal tumors? searching for the answer according to molecular identity.

The 7th edition of Union for International Cancer Control (UICC) staging system moved gastroesophageal junction (GEJ) cancers from gastric to esophageal group. Since clinical management is strongly influenced by this staging system, we looked at molecular fingerprints of GEJ tumors and compared to gastric and esophageal profiles. We aimed at elucidating whether GEJ cancers cluster with gastric or esophageal groups according to mRNA and microRNA expression pattern, since this might represent tumor identity. The clinical and expression data were downloaded from The Cancer Genome Atlas (TCGA) with 395 stomach, 184 esophagus and 521 colon samples for mRNA analyses and 392 stomach, 175 esophagus and 459 colon samples for microRNA comparisons. Both Principal Component Analysis (PCA) and Heat Map plots were performed in R platform, using Log2 transformation of RPKM normalized data. Differential Expression Analysis was also performed in R, using RAW data and the DESeq2 package. The mRNAs and microRNAs were tagged as differentially expressed if they met the following criteria: i) FDR adjusted p-value < 0.05; and ii) |Log2 (fold-change)| > 2. Esophagus squamous cell carcinoma (ESCC) clustered apart of the others tumors, while adenocarcinomas (AC) clustered all together according to both mRNAs and microRNAs expression patterns. The HMs of the differentially expressed mRNAs and microRNAs also demonstrated that ESCC belongs to a different group, while AC molecular signature of esophagus looks like AC of the cardia and non cardia regions. Even distal gastric cancers are quite similar to AC of the lower esophagus, demonstrating that esophagus AC relies much closer to gastric cancers than to esophagus cancers. By using robust molecular fingerprints, it was strongly demonstrated that GEJ tumors looks more like gastric cancers than esophageal cancers, despite of tumor heterogeneity.

Insights into gastric neuroendocrine tumors burden.

Type 1 gastric neuroendocrine tumors (gNETs) are usually small lesions, restricted to mucosal and sub-mucosal layers of corpus and fundus, with low aggressive behavior, for the majority of cases. Nevertheless, some cases present aggressive behavior. The increasing incidence of gNETs brings together a new relevant problem: how to identify potentially aggressive type 1 gNETs. The challenging problem seems to be finding out signs or features able to predict potentially aggressive cases, allowing a tailored approach, since the involved societies dedicated to provide guidelines for management of these neoplasms apparently failed in producing staging systems able to accurately predict prognosis of these tumors. Additionally, it is also important to try to find out explanations for increasing incidence, as well as to identify potential targets aiming to reach better control of this neoplasia. Here, we discuss potential pathways implicated in aggressive behavior, as well as new strategies to improve clinical management of these tumors.