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Brazil is the largest country in South America and the most genetically heterogeneous. The aim of the present study was to determine the prevalence of germline pathogenic variants (PVs) in Brazilian patients with breast cancer (BC) who underwent genetic counseling and genetic testing at a tertiary Oncology Center. We performed a retrospective analysis of the medical records of Brazilian patients with BC referred to genetic counseling and genetic testing between August 2017 and August 2019. A total of 224 unrelated patients were included in this study. Premenopausal women represented 68.7% of the cohort. The median age at BC diagnosis was 45 years. Multigene panel testing was performed in 219 patients, five patients performed single gene analysis or family variant testing. Forty-eight germline PVs distributed among 13 genes were detected in 20.5% of the patients (46/224). Eighty-five percent of the patients (91/224) fulfilled NCCN hereditary BC testing criteria. Among these patients, 23.5% harbored PVs (45/191). In the group of patients that did not meet NCCN criteria, PV detection rate was 3% (1/33). A total of 61% of the patients (28/46) harbored a PV in a high-penetrance BC gene: 19 (8.5%) BRCA1/2 , 8 (3.5%) TP53 , 1 (0.5%) PALB2 . Moderate penetrance genes ( ATM , CHEK2 ) represented 15.2% (7/46) of the positive results. PVs detection was statistically associated (p<0.05) with BC diagnosis before age 45, high-grade tumors, bilateral BC, history of multiple primary cancers, and family history of pancreatic cancer. According to the current hereditary cancer guidelines, 17.4% (39/224) of the patients had actionable variants. Nine percent of the patients (20/224) had actionable variants in non- BRCA genes, it represented 43.5% of the positive results and 51.2% of the actionable variants. Considering the observed prevalence of PVs in actionable genes beyond BRCA1/2 (9%, 20/224), multigene panel testing may offer an effective first-tier diagnostic approach in this population.

Advanced hepatocellular carcinoma is a prevalent and potentially aggressive disease. For more than a decade, treatment with sorafenib has been the only approved therapeutic approach. Moreover, no agent has been proven to prolong survival following the progression of disease after sorafenib treatment. However, in recent years, this scenario has changed substantially with several trials being conducted to examine the effects of immunotherapy and novel targeting agents. Several immune checkpoint inhibitors have shown promising results in early-stage clinical trials. Moreover, phase III trials with large cohorts have demonstrated remarkable improvement in survival with the use of new targeted therapies in second-line treatment. Treatment regimens involving the combination of two immune checkpoint inhibitors as well as immune checkpoint inhibitors and anti-angiogenic targeted therapies have shown potential to act synergistically in clinical trials. Recently, the combination of atezolizumab and bevacizumab evaluated in a phase III clinical trial has demonstrated survival superiority in the first-line treatment; it is the new considered standard of care. In this manuscript, we aimed to review the latest advances in the systemic treatment of advanced hepatocellular carcinoma focusing on immunotherapy and targeted therapies.

As of 2020, the world is facing the great challenge of the COVID-19 (Coronavirus disease 2019) pandemic, caused by the SARS-CoV-2 virus. While the overall mortality is low, the virus is highly virulent and may infect millions of people worldwide. This will consequently burden health systems, particularly by those individuals considered to be at high risk of severe complications from COVID-19. Such risk factors include advanced age, cardiovascular and pulmonary diseases, diabetes and cancer. However, few data on the outcomes of cancer patients infected by SARS CoV-2 exist. Therefore, there is a lack of guidance on how to manage cancer patients during the pandemic. We sought to propose specific recommendations about the management of patients with gastrointestinal malignancies. The Brazilian Gastrointestinal Tumours Group board of directors and members sought up-to-date scientific literature on each tumour type and discussed all recommendations by virtual meetings to provide evidence-based-and sometimes, expert opinion-recommendation statements. Our objectives were to recommend evidence-based approaches to both treat and minimise the risk of COVID-19 for cancer patients, and simultaneously propose how to decrease the use of hospital resources at a time these resources need to be available to treat COVID-19 patients. Overall and tumour-specific recommendations were made by stage (including surgical, locoregional, radiotherapy, systemic treatments and follow-up strategies) for the most common gastrointestinal malignancies: esophagus, gastric, pancreas, bile duct, hepatocellular, colorectal, anal cancer and neuroendocrine tumours. Our recommendations emphasise the importance of treating cancer patients, using the best evidence available, while simultaneously taking into consideration the world-wide health resource hyperutilisation to treat non-cancer COVID-19 patients.

BackgroundMetastatic gastric cancer (GC) is an incurable and aggressive disease with a poor prognosis. Immunotherapy is an attractive approach for treating patients with cancer, and studies using immunotherapy have shown promising results in melanoma, kidney and non-small cell lung cancers, among others.Case presentationWe present a case of a 50-year-old woman with metastatic GC whose cancer had progressed after first-line chemotherapy and who received pembrolizumab as an experimental treatment. Molecular analyses showed that her tumor was negative for PD-L1 expression, contained microsatellite stability and several focal somatic copy number alterations. The patient experienced an almost complete response after eleven cycles of treatment. Her symptoms related to the disease disappeared, and the medication was well tolerated.ConclusionsDespite reports of promising responses in some patients, immunotherapy is not suitable for all patients; therefore, we explored the molecular characteristics that could explain the exceptional response and clinical benefits observed in our patient.

Ao refletir sobre as mídias contemporâneas e sua facilidade em produzir e consumir conteúdo dentro do ciberespaço, observa-se que existe a possibilidade desse fluxo estar influenciando a representação identitária local, em especial a identidade do município de Ielmo Marinho no Rio Grande do Norte. Assim, existe nesse intercurso uma importante lacuna para investigação, no que diz respeito a identificação e construção da identidade do ielmomarinhense. Nesse sentido, ao constatar a acessibilidade e a expansão do YouTube, como uma mídia alternativa, bem como as escassas informações e pesquisas pertinentes ao município de Ielmo Marinho, verificou-se a relevância de investigar a possível relação entre os discursos midiáticos no YouTube e as representações identitárias desse município. Dessa forma, o presente estudo de doutoramento teve como objetivo geral perceber e descrever as representações identitárias do ielmomarinhense, conforme estão plasmadas nos discursos midiáticos por meio do YouTube (envolvidos no ciberespaço), que estamparam o espaço social do município entre os anos de 2009 a 2018. Com o intuito de auxiliar no alcance desse objetivo central, autores como Hall (2011); Silva (2014); Woodward (2014); Chartier (1990; 1991); Canclini (1998; 2008); Castells (1999a) e Pollak (1992) foram os balizadores teóricos desse estudo, para as discussões em termos de identidade, diferença e representação, enquanto que para os apontamentos acerca das investigações midiáticas no YouTube e as noções conceituais do ciberespaço, tomou-se como base Gibson (1984), Lévy (1996; 2000), Lemos (2002; 2009; 2015), Castells (1999b; 2003), Burgess e Green (2009). Como estratégia para desenhar o percurso metodológico, este estudo, diante dos seus objetivos propostos se classifica como uma pesquisa de caráter exploratório-descritivo, pautada na abordagem qualitativa, sob o suporte do viés quantitativo. Para organização e posterior análise dos materiais, o estudo norteou-se a partir de dois procedimentos técnicos distintos, inicialmente utilizou-se o método histórico e etnográfico, para a reconstrução da história de Ielmo Marinho, em que foram realizados estudos a partir dos documentos que retratam a história do município a luz de Santos (2015) e Fernandes (2013; 2018). Em um segundo momento, como auxílio a identificação do objeto de estudo, que foram os discursos midiáticos presentes no YouTube, utilizou-se a etnografia virtual (on-line) em congruência com estudos estatísticos. Com isso, a pesquisa obteve como corpus de análise uma amostra de 163 vídeos publicados no YouTube entre 2009 e 2018. Os materiais apreendidos foram analisados e interpretados a partir da análise de conteúdo de Bardin (2011). Nesse sentido, com relação aos resultados encontrados, observou-se que no município de Ielmo Marinho habitam tantas representações identitárias no que se convencionou de identidade ielmomarinhense que por vários motivos ela não é construída a partir de um discurso homogêneo, caracterizando-a como uma identidade híbrida. A mesma é caracterizada por elementos que se associam as características rurais do município, suas festividades religiosas, a economia local voltada ao abacaxi e o envolvimento de agentes públicos em casos de corrupção. Sendo assim, este estudo identificou que os discursos midiáticos presentes no YouTube podem sim participar da configuração do espaço social, atribuindo valores e criando sentido para a representação identitária do ielmomarinhense.

This review describes the current multidisciplinary management of gastrointestinal stromal tumor (GIST), which is the most common sarcoma of the gastrointestinal tract. Before 2001, surgery was the only effective therapy for GIST. The discovery of the central role of KIT proto-oncogene mutations in the pathogenesis of this tumor, and the development of specific inhibitors of KIT tyrosine kinase (TK) function, has changed the paradigm of treatment for GISTs. Imatinib and sunitinib are TK inhibitors with activity against GISTs. Their major established role in GIST is in the treatment of advanced disease. A growing body of literature and clinical experience support the potential perioperative use of these drugs. The adjuvant use of imatinib is based on retrospective series and limited prospective studies demonstrating that imatinib reduces the risk of recurrence. Ongoing studies are further defining the length of adjuvant therapy, as well as identifying the patients that could achieve the best results. Neoadjuvant treatment often decreases the tumor size, allowing a less morbid surgery, appears to be safe and beneficial for some patients, and therefore deserves further study.

Severe hypercalcemia is a rare metabolic disorder in pediatric medicine. This report describes a rare case of severe hypercalcemia and its clinical manifestations in a 2-year-old toddler. The radiological findings caused by hypercalcemia and osteolysis were emblematic of the osteolytic lesions. Hypercalcemia led to massive pulmonary alveolar calcification. The hypercalcemia was successfully treated with pamidronate, a bisphosphonate drug class. Further investigation resulted in a diagnosis of acute lymphoblastic leukemia (ALL). The patient is currently on chemotherapy and has a favorable prognosis. Although severe hypercalcemia alone is an unusual finding as the first sign for ALL, this should be considered, not to mention the radiological images resulted from calcium deposits.

Many breast cancer patients with HER2 overexpression do not respond to initial therapy with trastuzumab (Herceptin), and the vast majority of those who initially respond to the agent develop resistance to treatment within 1 year. This review will discuss several molecular mechanisms that can lead to the development of trastuzumab resistance, including loss of PTEN, activation of alternative pathways, receptor-antibody interaction block, and circulating HER2 extracellular domain, as well as the possibility of exploring these aberrations as therapeutic targets that could help avoid or overcome resistance to trastuzumab.

Dimethylsulfoxide (DMSO) is an amphipathic molecule composed of a polar domain characterized by the sulfinyl and two nonpolar methyl groups, for this reason it is able to solubilize polar and nonpolar substances and transpose hydrophobic barriers. DMSO is widely used to solubilize drugs of therapeutic applications and studies indicated that 10% v/v concentration did not modify culture viability when used to treat human peripheral blood mononuclear cells (PBMC). However, some DMSO concentrations could influence lymphocyte activation and present anti-inflammatory effects. Therefore, the objective of this study was to evaluate the effect of DMSO on lymphocyte activation parameters. Cell viability analysis, proliferation, and cytokine production were performed on PBMC from six healthy subjects by flow cytometry. The results indicated that 2.5% v/v DMSO concentrations did not modify lymphocytes viability. DMSO at 1% and 2% v/v concentrations reduced the relative proliferation index of lymphocytes and at 5% and 10% v/v concentrations reduced the percentage of total lymphocytes, cluster of differentiation 4+ (CD4+) T lymphocytes and CD8+ T lymphocytes interferon-γ (IFN-γ), tumor necrosis factor-α (TNF-α) and interleukin-2 (IL-2) producers. Thus, it was concluded that DMSO has an in vitro anti-inflammatory effect by reducing lymphocyte activation demonstrated with proliferation reduction and the decrease of cytokine production.