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The gut microbiome is interlinked with renal cell carcinoma (RCC) and its response to systemic treatment. Mounting data suggests that certain elements of the gut microbiome may correlate with improved outcomes. New generation sequencing techniques and advanced bioinformatic data curation are accelerating the investigation of specific markers and metabolites that could predict treatment response. A variety of new therapeutic strategies, such as fecal microbiota transplantation, probiotic supplements, and dietary interventions, are currently being developed to modify the gut microbiome and improve anticancer therapies in patients with RCC. This review discusses the preliminary evidence indicating the role of the microbiome in cancer treatment, the techniques and tools necessary for its proper study and some of the current forms with which the microbiome can be modulated to improve patient outcomes.
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The incidence of malignant pleural mesothelioma is expected to increase globally. New treatment options for this malignancy are eagerly awaited to improve the survival and quality of life of patients. The present article highlights the results of recent advances in this field, analyzing data from several relevant trials. The heterogeneous tumor microenvironment and biology, together with the low mutational burden, pose a challenge for treating such tumors. So far, no single biomarker has been soundly correlated with targeted therapy development; thus, combination strategies are often required to improve outcomes. Locally applied vaccines, the expansion of genetically engineered immune cell populations such as T cells, the blockage of immune checkpoints that inhibit anti-tumorigenic responses and chemoimmunotherapy are among the most promising options expected to change the mesothelioma treatment landscape.
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Although a relatively uncommon tumor, cholangiocarcinoma is on the rise globally. Of note, most patients are diagnosed with metastatic disease, and the prognosis is poor with cytotoxic chemotherapy. Strategies targeting specific genomic alterations have demonstrated promising activity in recent years and could represent a new therapeutic avenue for these patients. In this review, we will address the biology and clinical results of FGFR inhibition in intrahepatic cholangiocarcinoma, highlighting limitations associated with treatment and discussing the use of circulating tumor DNA to detect mechanisms of resistance.
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ABSTRACT Introduction: Cytopathologic analysis (CP) and frozen section (FS) are available techniques for intraoperative evaluation of sentinel lymph node in surgeries for breast cancer treatment that will define the need for axillary lymphadenectomy. Objective: To compare CP and FS of axillary sentinel lymph nodes in metastasis detection of patients with breast cancer. Materials and methods: The electronic files from January 2010 and December 2014, from the Centro de Patologia de Curitiba, Parana, Brazil were reviewed, and were included all the cases in which the result of intraoperative exams by both methods, CP and FS, were recorded. The results of intraoperative exams were compared to the histopathology by hematoxylin and eosin (HE) staining. Results: A total of 183 sentinel lymph nodes from 94 patients were included. The mean age was 55 years and mean lymph node size was 11.70 mm. There was one false-positive case in both intraoperative methods and four false-negatives in FS, which were micrometastasis. FS's sensibility, specificity, positive predictive value (PPV) and negative predictive value (NPV) and accuracy were respectively 80%, 99.38%, 94.11%, 96.42% and 97.26%. Regarding CP, there were six false-negative in which four were micrometastasis. CP's sensibility, specificity, PPV and NPV and accuracy were respectively 70%, 99.38%, 93.33%, 96.42% and 97.26%. Conclusion: The results of the present study shows that both CP and FS are reliable techniques for metastasis detection in breast sentinel lymph nodes, and are equivalent in sensibility, specificity, accuracy, PPV and NPV.
RESUMO Introdução: A análise citopatológica (CP) e o método de corte por congelação (CC) são técnicas disponíveis de avaliação intraoperatória do linfonodo sentinela nas cirurgias para tratamento de câncer de mama que vão definir a necessidade de linfadenectomia axilar. Objetivo: Comparar a avaliação CP e os CCs de linfonodos sentinela axilares na pesquisa de metástases em pacientes com câncer mamário. Materiais e método: Foram revisados os arquivos eletrônicos do Centro de Patologia de Curitiba, Paraná, Brasil, de janeiro de 2010 a dezembro de 2014, sendo incluídos os casos em que constavam o resultado do exame intraoperatório por ambos os métodos, CP e CC. Os resultados dos exames intraoperatórios foram comparados com a histopatologia, corada por hematoxilina e eosina (HE). Resultados: Foram incluídos 183 linfonodos sentinelas de 94 pacientes. A idade média foi de 55 anos, e o tamanho médio dos linfonodos, de 11,70 mm. Houve um caso falso positivo nos dois métodos intraoperatórios e quatro falso negativos na CC, entre os quais todos eram micrometástases. Sensibilidade, especificidade, valor preditivo positivo (VPP), valor preditivo negativo (VPN) e acurácia do CC foram, respectivamente, 80%, 99,38%, 94,11%, 96,42% e 97,26%. Já na CP, houve seis falso negativos, entre esses, quatro eram micrometástases. Sensibilidade, especificidade, VPP, VPN e acurácia da CP foram, respectivamente, 70%, 99,38%, 93,33%, 96,42% e 97,26%. Conclusão: Os resultados do presente estudo demonstraram que CP e CC são técnicas confiáveis para detecção de metástase em linfonodos sentinela de mama e se equivalem em sensibilidade, especificidade, acurácia, VPP e VPN.
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OBJECTIVE: Given that only the free non-protein-bound concentration of an antiepileptic drug (AED) crosses the blood-brain barrier, entering the brain and producing an antiepileptic effect, knowledge and measurement of the free drug fraction is important. Such data are sparse, particularly for newer AEDs, and have arisen from the use of disparate methodologies and settings over the past six decades. We report on the protein binding of 25 AEDs that are available for clinical use, along with two pharmacologically active metabolites (carbamazepine-epoxide and N-desmethyl clobazam), using standardized methodology and under set conditions. METHODS: The protein binding of the various AEDs was undertaken in sera of 278 patients with epilepsy. Separation of the free non-protein-bound component was achieved by using ultracentrifugation (Amicon Centrifree Micropartition System) under set conditions: 500 µl serum volume; centrifugation at 1,000 g for 15 min, and at 25°C. Free and total AED concentrations were measured by use of fully validated liquid chromatography/mass spectroscopy (LC/MS) techniques. RESULTS: Gabapentin and pregabalin are non-protein-bound, whereas highly bound AEDs (≥88%) include clobazam, clonazepam, perampanel, retigabine, stiripentol, tiagabine, and valproic acid as well as the N-desmethyl-clobazam (89%) metabolite. The minimally bound drugs (<22%) include ethosuximide (21.8%), lacosamide (14.0%), levetiracetam (3.4%), topiramate, (19.5%) and vigabatrin (17.1%). Ten of the 25 AEDs exhibit moderate protein binding (mean range 27.7-74.8%). SIGNIFICANCE: These data provide a comprehensive comparison of serum protein binding of all available AEDs including the metabolites, carbamazepine-epoxide and N-desmethyl-clobazam. Knowledge of the free fraction of these AEDs can be used to optimize epilepsy treatment.