Etoposide e dexametasona como primeira linha em idosos com comorbidades portadores de Linfoma Difuso de Grandes Células B

-Pacientes idosos com linfoma difuso de grandes células B (LDGCB) são frequentemente excluídos de estudos clínicos. A utilização de terapias curativas muitas vezes é impossibilitada em virtude das comorbidades apresentadas por esta população ao diagnóstico. Nós adotamos um protocolo alternativo de quimioterapia oral combinando um inibidor da topoisomerase II e dexametasona. Apresentamos os resultados parciais com este protocolo em três pacientes portadores de LDGCB com idade superior a 80 anos e comorbidades severas. Todos alcançaram remissão completa com baixa toxicidade. Esses resultados demonstram que protocolos curativos alternativos devem ser testados em pacientes idosos portadores LDGCB a despeito da presença de comorbidades severas

Disparities in early death and survival in children, adolescents, and young adults with acute promyelocytic leukemia in California.

BACKGROUND: Findings from clinical trials and population-based studies have differed with regard to whether mortality within 30 days of diagnosis (early death) of acute promyelocytic leukemia (APL) has decreased in the era of all-trans retinoic acid and anthracycline-based chemotherapy. METHODS: Using data from the California Cancer Registry, the authors investigated 7-day and 30-day mortality and survival in 772 patients who were aged birth to 39 years when they were diagnosed with APL during 1988 to 2011. Logistic regression and Cox proportional models were used to examine the association of early death and survival, respectively, with sociodemographic and clinical factors. RESULTS: The overall 30-day mortality decreased significantly over time, from 26% (1988-1995) to 14% (2004-2011) (P =.004). On multivariable analysis, the odds of 30-day mortality were 3 times as high during 1988 through 1995 than 2004 through 2011 (P =.001). However, 7-day mortality did not improve over time (P =.229). When patients who died within 7 days of diagnosis were excluded, the 30-day mortality during 1996 to 2011 was 3% to 8%, which is similar to levels reported in clinical trials. Higher early death and lower survival were associated with a lack of health insurance (1996-2011) (early death odds ratio, 2.67; P =.031) and Hispanic race/ethnicity (early death odds ratio, 2.13; P =.014). Early death was not found to be associated with age, sex, socioeconomic status, or hospital type. Black patients also experienced worse survival. CONCLUSIONS: The findings of the current study revealed a decreased 30-day mortality during the all-trans retinoic acid era, but 7-day mortality remained high. Efforts to achieve equal outcomes in young patients with APL should focus on improving access to effective treatment, mainly among uninsured patients and those of Hispanic and black race/ethnicity

The use of nanoencapsulation to decrease human skin irritation caused by capsaicinoids

Capsaicin, a topical analgesic used in the treatment of chronic pain, has irritant properties that frequently interrupt its use. In this work, the effect of nanoencapsulation of the main capsaicinoids (capsaicin and dihydrocapsaicin) on skin irritation was tested in humans. Skin tolerance of a novel vehicle composed of chitosan hydrogel containing nonloaded nanocapsules (CH-NC) was also evaluated. The chitosan hydrogel containing nanoencapsulated capsaicinoids (CH-NC-CP) did not cause skin irritation, as measured by an erythema probe and on a visual scale, while a formulation containing free capsaicinoids (chitosan gel with hydroalcoholic solution [CH-ET-CP]) and a commercially available capsaicinoids formulation caused skin irritation. Thirty-one percent of volunteers reported slight irritation one hour after application of CH-NC-CP, while moderate (46% [CH-ET-CP] and 23% [commercial product]) and severe (8% [CH-ET-CP] and 69% [commercial product]) irritation were described for the formulations containing free capsaicinoids. When CH-NC was applied to the skin, erythema was not observed and only 8% of volunteers felt slight irritation, which demonstrates the utility of the novel vehicle. A complementary in vitro skin permeation study showed that permeation of capsaicinoids through an epidermal human membrane was reduced but not prevented by nanoencapsulation

Alterações hemodinâmicas durante ressecção de feocromocitoma por videolaparoscopia. Relato de caso

Feocromocitomas são tumores malignos raros que sintetizam, armazenam e secretam catecolaminas. 85% destes localizam-se na supra-renal. Freqüentemente são passíveis de ressecção curativa. Entretanto, a extirpação desses tumores pode ser potencialmente fatal devido às alterações hemodinâmicas agudas e severas que podem ocorrer no perioperatório. A cirurgia videolaparoscópica é o tratamento de eleição, permitindo uma manipulação menos traumática do tumor e acesso à veia adrenal com menor liberação de catecolaminas. Entretanto, a produção do pneumoperitônio pode levar ao aumento destas. O manejo anestésico no pré e perioperatório continua sendo um desafio, pois as alterações hemodinâmicas variam de um paciente para outro, independente do preparo prévio. Relatamos o caso de um paciente jovem com tumor na supra-renal direita, internado com quadro de pouca repercussão clínica, no qual não foram utilizados bloqueadores adrenérgicos no pré-operatório. As alterações cardiovasculares que ocorrem durante a confecção do pneumoperitônio para ressecção da massa tumoral foram prontamente controladas com o vasodilatador nitroprussiato de sódio e o beta-bloqueador esmolol. Uma revisão bibliográfica sobre as várias técnicas anestésicas e monitorização empregadas no perioperatório foi realizada

Racial/ethnic and socioeconomic survival disparities for children and adolescents with central nervous system tumours in the United States, 2000-2015.

BACKGROUND AND OBJECTIVES: Central nervous system (CNS) malignancy is the commonest cause of cancer death in children and adolescents (0-19 years) in high-income settings. There is limited data on survival inequalities by race/ethnicity and socioeconomic position (SEP), for young patients, we aim to analyse their influence on survival from childhood CNS tumour. METHODS: 9577 children and adolescents diagnosed with primary malignant CNS tumours during 2000-2015, followed up until Dec 31 st, 2015, and reported to cancer registries (Surveillance, Epidemiology and End Results programme) were included in the analysis. Cox regression models estimated the hazard ratios for race/ethnicity, SEP, and individual insurance status, adjusting for sex, age, diagnostic period, and tumour type. Individual-level insurance status data were available from 2007. RESULTS: 62.5 % children and adolescents were non-Hispanic White, 10.6 % were non-Hispanic Black and 26.9 % were Hispanic. Race/ethnicity was strongly associated with survival (p < 0.001), even after adjusting for SEP, with Black (HR = 1.39 [95 %CI 1.23-1.58]) and Hispanic children (HR = 1.40 [95 %CI 1.28-1.54]) having higher hazards of death than White children. This association remained after adjusting for insurance status. There was an apparent positive association between SEP and survival that was largely attenuated after adjustment for insurance status (p = 0.20). Survival was comparable between those privately and Medicaid-insured. CONCLUSIONS: Non-Hispanic Black and Hispanic children had lower survival than their White counterparts. This association, not fully explained by differences in SEP, tumour subtype or health insurance, could be related to racially/ethnically-driven barriers to optimal healthcare, warranting further investigation

T-cell large granular lymphocytic leukemia: treatment experience with fludarabine

OBJECTIVES: The aim of this retrospective study was to investigate the results of T-cell large granular lymphocytic leukemia treatment with fludarabine by assessing the complete hematologic response, the complete molecular response, progression-free survival, and overall survival. METHODS: We evaluated the records of six patients with T-cell large granular lymphocytic leukemia who were treated with fludarabine as a first-, second-, or third-line therapy, at a dose of 40 mg/m2, for three to five days per month and 6 to 8 cycles. RESULTS: Of the six patients investigated with T-cell large granular lymphocytic leukemia who were treated with fludarabine, five (83.3%) were female, and their median age was 36.5 years (range 18 to 73). The median lymphocyte level was 3.4x109/L (0.5 to 8.9). All patients exhibited a monoclonal T-cell receptor gamma gene rearrangement at diagnosis. Two (33.3%) patients received fludarabine as first-line treatment, two (33.3%) for refractory disease, one (16.6%) for relapsed disease after the suspension of methotrexate treatment dueto liver toxicity, and one (16.6%) due to dyspesia. A complete hematologic response was achieved in all cases, and a complete molecular response was achieved in five out six cases (83.3%). During a mean follow-up period of 12 months, both the progression-free survival and overall survival rates were 100%. CONCLUSION: T-cell large granular lymphocytic leukemia demonstrated a high rate of complete hematologic and molecular response to fludarabine, with excellent compliance and tolerability rates. To confirm our results in this rare disease, we believe that fludarabine should be tested in clinical trials as a first-line treatment for T-cell large granular lymphocytic leukemia.

Analgesic Effect of Cathodal Transcranial Current Stimulation Over Right Dorsolateral Prefrontal Cortex in Subjects with Muscular Temporomandibular Disorders: Study Protocol for a Randomized Controlled Trial

BACKGROUND: Temporomandibular disorders are a group of orofacial pain conditions that are commonly identified in the general population. Like many other chronic pain conditions, they can be associated with anxiety/depression, which can be related to changes in the activity of the dorsolateral prefrontal cortex. Some studies have demonstrated clinical improvement in subjects with chronic pain who are given therapeutic neuromodulation. Transcranial direct current stimulation is a noninvasive brain stimulation technique that allows the modulation of neuronal membranes. This therapy can enhance or inhibit action potential generation in cortical neurons. In some instances, medications acting in the central nervous system may be helpful despite their adverse side effects. It is important to determine if cathodal transcranial direct current stimulation over the dorsolateral prefrontal cortex, an area that modulates emotion and motor cortex excitability, has an analgesic effect on chronic temporomandibular disorders pain. METHOD/DESIGN: The investigators will run a randomized, controlled crossover double blind study with 15 chronic muscular temporomandibular disorder subjects. Each subject will undergo active (1 mA and 2 mA) and sham transcranial direct current stimulation. Inclusion criteria will be determined by the Research Diagnostic Criteria for Temporomandibular Disorders questionnaire, with subjects who have a pain visual analogic scale score of greater than 4/10 and whose pain has been present for the previous 6 months, and with a State-Trait Anxiety Inventory score of more than 42. The influence of transcranial direct current stimulation will be assessed through a visual analogic scale, quantitative sensory testing, quantitative electroencephalogram, and the State-Trait Anxiety Inventory score. DISCUSSION: Some studies have demonstrated a strong association between anxiety/depression and chronic pain, where one may be the cause of the other. This is especially true in chronic temporomandibular disorders, and breaking this cycle may have an effect over the symptoms and associated dysfunction. We believe that by inhibiting activity of the dorsolateral prefrontal cortex though cathodal transcranial direct current stimulation, there may be a change in both anxiety/depression and pain level. Transcranial direct current stimulation may emerge as a new tool to be considered for managing these patients. We envision that the information obtained from this study will provide a better understanding of the management of chronic temporomandibular disorders. TRIAL REGISTRATION: This trial was registered at clinicaltrials.gov on 24 May 2014 (Identifier: NCT02152267 )

Diagnóstico diferencial no melanoma primário e metastático por espectroscopia FT-Raman

PURPOSE: To qualify the FT-Raman spectral data of primary and metastatic cutaneous melanoma in order to obtain a differential diagnosis. METHODS: Ten normal human skin samples without any clinical or histopathological alterations, ten cutaneous melanoma fragments, and nine lymph node metastasis samples were used; 105, 140 and 126 spectra were obtained respectively. Each sample was divided into 2 or 3 fragments of approximately 2 mm³ and positioned in the Raman spectrometer sample holder in order to obtain the spectra; a monochrome laser light Nd:YAG at 1064 nm was used to excite the inelastic effect. RESULTS: To differentiate the three histopathological groups according to their characteristics extracted from the spectra, data discriminative analysis was undertaken. Phenylalanine, DNA, and Amide-I spectral variables stood out in the differentiation of the three groups. The percentages of correctly classified groups based on Phenylalanine, DNA, and Amide-I spectral features was 93.1%. CONCLUSION: FT-Raman spectroscopy is capable of differentiating melanoma from its metastasis, as well as from normal skin.OBJETIVO: Qualificar os dados espectrais FT-Raman do melanoma cutâneo primário e metastático e assim realizar o diagnóstico diferencial. MÉTODOS: Foram utilizadas amostras de 10 fragmentos de pele sem alterações clínicas ou histopatológicas, 10 de melanomas cutâneos e 9 de metástases linfonodais; 105, 140 and 126 espectros foram obtidos respectivamente. Cada amostra foi dividida em 2 ou 3 frações de 2 mm³ e posicionada no porta amostras do espectrômetro Raman para obtenção dos espectros, por meio da excitação do espalhamento inelástico pelo laser de Nd:YAG em 1064 nm incididos na amostra. RESULTADOS: Para diferenciar os três grupos formados de acordo com as características fornecidas pelos espectros, realizamos a análise discriminante dos dados. As variáveis espectrais Fenilalanina, DNA e Amida-I se destacaram na capacidade de diferenciação dos três grupos histológicos. A porcentagem de classificação correta utilizando estes critérios foi de 93,1%; o que mostra a eficiência da análise realizada. CONCLUSÃO: A espectroscopia FT-Raman é capaz de diferenciar o melanoma de sua metástase, assim como da pele normal.UNIFESPUniversidade Federal de São Paulo (UNIFESP) Department of SurgeryPathology DepartmentPathology Department Federal University of ABC Head of Center for Human and Natural Sciences (CCNH)UNIVAP Institute of Research and Development Head of Biomedical Vibrational Spectroscopy LaboratoryUniversidade Federal de São Paulo (UNIFESP) Department of Surgery Head of Division of Plastic SurgeryUNIFESP, Department of SurgeryUNIFESP, Department of Surgery Head of Division of Plastic SurgerySciEL

Gastric non-Hodgkin Lymphoma

Extranodal lymphomas account for about 30% of all non-Hodgkin lymphomas (NHL), and although they can originate in any tissue, the gastrointestinal tract is the most commonly affected structure with the stomach being the most common subtype. Diffuse Large B cell lymphoma (DLBCL) and MALT (mucosa associated lymphoid tissue) lymphoma account for more than 95% of the cases of gastric lymphoma. The indolent development of MALT lymphoma stands out as it is a type of cancer subject to chronic antigen stimulation by the Helicobacter pylori bacteria. Conversely, diffuse large B cell lymphomas, whose pathogenesis is uncertain, can be a transformation from MALT NHL or perhaps a new type of lymphoma. In this study we carried out a review of the literature, stressing the key aspects of these lymphomas in the clinical practice.Os linfomas extralinfonodais representam aproximadamente 1/3 de todos os linfomas não Hodgkin (LNH) e, embora possam ter início em qualquer tecido, mais frequentemente acometem o trato gastrointestinal, sendo o estômago o órgão responsável pela grande maioria dos casos. Os linfomas primários gástricos são comumente LNH, sendo representados em mais de 95% dos casos pelo linfoma difuso de grandes células B e pelo linfoma MALT (mucosa associated lymphoid tissue). De evolução indolente, o linfoma MALT destaca-se por ser um modelo de câncer secundário à estimulação antigênica crônica exercida por uma bactéria denominada Helicobacter pylori (HP). No outro polo, situa-se o linfoma difuso de células B (LDGCB), que, de patogênese duvidosa, pode tratar-se de uma transformação de LNH MALT ou ainda se caracterizar por um linfoma "de novo". Neste estudo, revisamos a literatura, enfatizando aspectos importantes à prática clínica destes linfomas