Potential role of immunotherapy in advanced non-small-cell lung cancer

Immuno checkpoint inhibitors have ushered in a new era with respect to the treatment of advanced non-small-cell lung cancer. Many patients are not suitable for treatment with epidermal growth factor receptor tyrosine kinase inhibitors (eg, gefitinib, erlotinib, and afatinib) or with anaplastic lymphoma kinase inhibitors (eg, crizotinib and ceritinib). As a result, anti-PD- 1/PD-L1 and CTLA-4 inhibitors may play a novel role in the improvement of outcomes in a metastatic setting. The regulation of immune surveillance, immunoediting, and immunoescape mechanisms may play an interesting role in this regard either alone or in combination with current drugs. Here, we discuss advances in immunotherapy for the treatment of metastatic non-small-cell lung cancer as well as future perspectives within this framework.Pierre Fabr

TRASTUZUMAB IN METASTATIC BREAST CANCER: SYSTEMATIC REVIEW OF COST-EFFECTIVENESS ANALYSES

Objective: To conduct a systematic review of cost-effectiveness analyses of trastuzumab in patients with metastatic breast cancer overexpressing human epidermal growth factor receptor 2.Methods: A systematic review for the years 1998 to 2013 was conducted. A survey of the scientific literature was performed using six electronic databases, two search tools on the internet and a manual search of references using search strategies for each database. The selected studies were assessed for quality according to specific methodology. Data analysis was performed by converting the costs and by observations made from the incremental cost-effectiveness ratios of trastuzumab.Results: From a detailed analysis of 521 retrieved articles, 13 articles were selected for this review. The treatment regimens adopted for cost-effectiveness were varied. Eight studies compared treatment with trastuzumab as first line for metastatic disease, and five studies compared treatment with trastuzumab as the second line. All the studies were using trastuzumab as second-line treatment was not considered a cost-effective intervention. The analyses used different thresholds to determine whether treatment with trastuzumab was cost-effective as well as to determine differences in modeling costs, outcomes and treatment patterns.Conclusion: The use of trastuzumab, alone or combined, was cost-effective as first-line treatment. Differences were found in the quality of the included studies. Conducting new cost-effectiveness analyses of trastuzumab in metastatic breast cancer is required, in alliance with political, social and administrative factors, to help decision makers concerning its incorporation

Expressão de p53, Ki-67 e c-erb B2 em adenomas hipofisários secretores de prolactina e/ou hormônio de crescimento

Os eventos subcelulares implicados na formação e comportamento dos adenomas hipofisários não são completamente compreendidos. Neste estudo nós investigamos a presença de p53, Ki-67 e c-erb B2 em 38 adenomas hipofisários com positividade imuno-histoquímica para GH e prolactina (n=26, 68,4%), para prolactina (n=9, 23,7%) e para GH (n=3, 7,8%). A análise revelou os seguintes resultados: 24 tumores (63,2%) expressaram positividade variável para c-erb B2, 11 (28,9%) expressaram positividade para p53 e 11 tumores (28,9%) foram variavelmente positivos para Ki-67. Nossos resultados demonstraram elevada percentagem de tumores secretores de GH/prolactina, prolactina e GH com positividade imuno-histoquímica para c-erb B2. Desde que este receptor de membrana está relacionado aos fatores de crescimento EGF e TGFalfa e ambos têm efeito definido no crescimento tumoral, nossos dados sugerem possível função para o c-erb B2 na evolução destes tumores.The subcellular events implicated on the formation and behavior of pituitary adenomas are not fully understood. In this study we investigated the presence of p53, Ki-67 and c-erb B2 in 38 pituitary adenomas with immunohistochemical positivity for GH and prolactin (n=26; 68.4%), for prolactin (n=9; 23.7%) and for GH (n=3. 7.8%). The analyses revealed the following results: 24 (63.2%) tumors expressed variable positivity for c-erb B2, 11 (28.9%) expressed p53 positivity and 11 (28.9%) tumors were variably positive for Ki-67. Our results demonstrated a high percentage of GH/prolactin-, prolactin- and GH-secreting tumors with immunohistochemical positivity for c-erb B2. Once this membrane receptor is related to growth factors EGF and TGFalpha and both have a definite effect on tumor growth, our data suggest a possible role for c-erb B2 on the evolution of these tumors

Influence of different adhesive systems on the pull-out bond strength of glass fiber posts

This in vitro study evaluated the tensile bond strength of glass fiber posts (Reforpost - Angelus-Brazil) cemented to root dentin with a resin cement (RelyX ARC - 3M/ESPE) associated with two different adhesive systems (Adper Single Bond - 3M/ESPE and Adper Scotchbond Multi Purpose (MP) Plus - 3M/ESPE), using the pull-out test. Twenty single-rooted human teeth with standardized root canals were randomly assigned to 2 groups (n=10): G1- etching with 37% phosphoric acid gel (3M/ESPE) + Adper Single Bond + #1 post (Reforpost - Angelus) + four #1 accessory posts (Reforpin - Angelus) + resin cement; G2- etching with 37% phosphoric acid gel + Adper Scotchbond MP Plus + #1 post + four #1 accessory posts + resin cement. The specimens were stored in distilled water at 37°C for 7 days and submitted to the pull-out test in a universal testing machine (EMIC) at a crosshead speed of 0.5 mm/min. The mean values of bond strength (kgf) and standard deviation were: G1- 29.163 ± 7.123; G2- 37.752 ±13.054. Statistical analysis (Student's t-test; a=0.05 showed no statistically significant difference (

Acute traumatic subdural haematomas : study of 110 cases

Apresentamos uma série consecutiva de 110 pacientes com hematoma subdural agudo traumático (HSDA) admitidos no serviço de emergência do HBDF no período de 1°-janeiro a 1°-dezembro-1994. Todos os pacientes foram atendidos de acordo com o mesmo protocolo. Houve predominância do sexo masculino (79%), com idade variando entre 14 e 70 anos, sendo os atropelamentos (34%) e os acidentes automobilísticos (20%) as causas mais comuns. A maioria dos pacientes (85,7%) foi admitida muito grave, com 8 pontos ou menos na Escala de Coma Glasgow (ECG), o que influenciou diretamente na mortalidade. A tomografia computadorizada de crânio foi o exame diagnóstico de escolha que mostrou serem as contusões e o inchaço cerebral ("swelling") as lesões intracranianas associadas mais freqüentes. A cirurgia foi realizada em 45,1% dos pacientes, e, em sua maioria, através de craniotomia fronto-têmporo-parietal ampla, com drenagem do hematoma, seguida de plástica da dura-mater. Em 54,9% as condições clínicas não permitiram a realização da cirurgia; neste grupo, cerca de 69,6% estavam em coma profundo à admissão, com 3 pontos na ECG. A letalidade cirúrgica foi de 61,2% e esteve diretamente relacionada à condição clínica inicial e à idade do paciente. A letalidade, incluindo todos os pacientes cirúrgicos e não cirúrgicos com HSDA, mesmo aqueles admitidos já com sinais de falência de tronco cerebral, foi de 79,5%. Além destes pacientes que faleceram, cerca de 7% evoluíram sem seqüelas ou com seqüelas mínimas; outros 11,4% com seqüelas de moderadas a paves e 2,1 % permaneceram em estado vegetativo persistente. Nossos dados estão de acordo com os da literatura no que se refere a elevada taxa de morbidade e mortalidade dos pacientes com HSDA.We report a series of 110 patients with acute traumatic subdural hematoma (ASDH) admitted at HBDF emergency within 1994 (January Is1 to December PJ.All patients were treated according to the same protocol. There was a predominance of males (79%), with ages ranging from 14 to 70, being car accidents (20%) and car-pedestrian accidents (34%) the most frequent causes The majority of patients (85.7%) was admitted in very serious condition, with a score of 8 points on the Glasgow Coma Scale (GCS) or lesser, which directly influenced the mortality rates. CT scan was the diagnostic procedure of choice, and it showed contusion and brain swelling to be the most frequent associated intracranial lesions. Surgery was carried out in 45.1% of cases and, in most instances, through an ample fronto-temporo-parietal craniotomy, with hematoma drainage and dural reconstitution. In 54.9% of cases, clinical conditions did not allow surgery and in this group, 69.6