Tuberous Sclerosis Complex with rare associated findings in the gastrointestinal system: a case report and review of the literature.

BACKGROUND: Tuberous Sclerosis Complex (TSC) is a complex and heterogeneous genetic disease that has well-established clinical diagnostic criteria. These criteria do not include gastrointestinal tumors. CASE PRESENTATION: We report a 45-year-old patient with a clinical and molecular diagnosis of TSC and a family history of cancer, presenting two rare associated findings: gastrointestinal polyposis and pancreatic neuroendocrine tumor. This patient was subjected to a genetic test with 80 cancer predisposing genes. The genetic panel revealed the presence of a large pathogenic deletion in the TSC2 gene, covering exons 2 to 16 and including the initiation codon. No changes were identified in the colorectal cancer and colorectal polyposis genes. DISCUSSION AND CONCLUSIONS: We describe a case of TSC that presented tumors of the gastro intestinal tract that are commonly unrelated to the disease. The patient described here emphasizes the importance of considering polyposis of the gastrointestinal tract and low grade neuroendocrine tumor as part of the TSC syndromic phenotype.

The impact of polymyxin B dosage on in-hospital mortality of patients treated with this antibiotic.

OBJECTIVE: To assess the impact of dosage on in-hospital mortality of patients receiving intravenous polymyxin B. METHODS: A retrospective cohort study was performed from January 2003 to December 2009. Patients ≥ 18 years receiving intravenous polymyxin B for ≥ 72 h were analysed. Clinical covariates were assessed and data were retrieved from medical records. Subgroup analyses were performed in patients with microbiologically confirmed infections and in patients with bacteraemia. Renal toxicity was also assessed. Logistic regression models (LRMs) were performed for the entire cohort and subgroups. RESULTS: A total of 276 patients were included. The overall in-hospital mortality was 60.5% (167 of 276). The final LRM showed that severe sepsis or septic shock [adjusted odds ratio (aOR) 4.07; 95% confidence interval (CI) 2.22-7.46], presence of mechanical ventilation (aOR 3.14; 95% CI 1.73-5.71), Charlson co-morbidity score (aOR 1.25; 95% CI 1.09-1.44) and age (aOR 1.02; 95% CI 1.01-1.04) were independently associated with increased in-hospital mortality, while ≥ 200 mg/day polymyxin B was associated with lower risk for this outcome (aOR 0.43; 95% CI 0.23-0.79). The effect of ≥ 200 mg/day polymyxin B on in-hospital mortality was higher in both subgroups (microbiologically documented infections and bacteraemia). Patients receiving ≥ 200 mg/day of polymyxin B had significantly higher risk of severe renal impairment. CONCLUSION: A dosage of ≥ 200 mg/day polymyxin B was associated with lower in-hospital mortality. The benefit of these higher doses outweighed the risk of severe renal dysfunction during therapy. Large prospective studies including pharmacokinetic/pharmacodynamic analysis are still required to define the best dosage regimens of polymyxin B.

Principais tópicos em oncogenética / Main subjects in oncogenetics

Introdução: O câncer é um distúrbio genético no qual ocorre a perda do controle da proliferação celular. De maneira geral, podemos dividir os casos de câncer em esporádicos (mutações somáticas restritas ao tumor), que são a maioria, e hereditários (mutações germinativas presentes em todas as células do indivíduo), que em conjunto correspondem a aproximadamente a 10% de todos os casos. É importante compreender o papel da Oncogenética na identificação de pacientes com risco aumentado para desenvolvimento de câncer para possibilitar medidas de detecção precoce, de prevenção e de tratamento, diferenciadas das recomendadas para a população em geral. Métodos: Foi realizada revisão da literatura através dos sites de busca PubMed e Scielo, bem como através de literatura e Guidelines pertinentes à área da Oncogenética. Resultados: A indicação de investigação genética molecular deve ser baseada em uma suspeita de câncer hereditário, sugerida pela história de câncer do paciente e de sua família. Os critérios de indicação variam para as diversas síndromes hereditárias. Assim, torna-se importante o aconselhamento genético pré e pós-teste, a fim de direcionar a investigação mais indicada para cada caso e permitir que o paciente possa realizar escolhas informadas e adaptar-se ao risco e/ou à condição que esse diagnóstico traz à sua vida. Conclusão: A fim de tornar a oncogenética acessível à população em risco, é necessário capacitar mais profissionais no aconselhamento genético, buscar um maior acesso aos exames moleculares especialmente no serviço público de saúde, garantir a qualidade dos testes realizados por diferentes centros e a adequada interpretação de seus resultados.

Introduction: Cancer is a genetic disorder in which occurs a loss of control of cell proliferation. In general, we can divide cancer cases into sporadic (tumor-restricted somatic mutations), which are the majority, and hereditary (germ mutations present in all the cells of the individual), which together account for approximately 10% of all cases. It is important to understand the role of Oncogenetics in identifying patients at increased risk for cancer development in order to enable early detection, prevention and treatment measures, unlike those recommended for the general population. Methods: A review of the literature was performed through PubMed and Scielo databases, as well as through literature and guidelines considered relevant to the area of Oncogenetics. Results: The indication of molecular genetic research should be based on a suspected hereditary cancer, suggested by the patient's and his family's cancer history. The indication criteria vary for the various hereditary syndromes. Thus, pre and post-test genetic counseling becomes important in order to direct the most appropriate investigation for each case, allowing the patient to make informed decisions and to adapt to the risk and / or to the condition this diagnosis brings to his / her life. Conclusion: In order to make Oncogenetics accessible to the population at risk, it is necessary to train more professionals in genetic counseling, to seek greater access to molecular tests, especially in the public health service, to ensure the quality of the tests carried out by different centers and also to provide adequate interpretation of the results.

Tratamento quimioterápico antineoplásico em idosos / Antineoplastic chemotherapic treatment in elderly

Este artigo destaca aspectos da avaliação do paciente idoso com câncer, considerando o risco de toxicidade a tratamentos quimioterápicos.

This article highlights the assessment of older patients with cancer regarding their risk of toxicity to chemotherapy.

Testes genéticos em síndromes de câncer hereditário: como proceder? / Genetic tests in hereditary cancer syndromes: how to proceed?

Este artigo destaca aspectos importantes associados ao aconselhamento genético em pacientes portadores de mutações determinantes de risco aumentado para o desenvolvimento de neoplasias e suas indicações.

This article highlights important aspects about genetic counseling in patients with genetic cancer susceptibility conditions and its indications.