Nós avaliamos a utilidade de um painel de anticorpos constituído por CD5, CD10, CD23, CD43, bcl-2 e ciclina D1 na classificação de 134 linfomas de pequenas células B. O CD10, positivo nos linfomas foliculares, o CD23, positivo nos linfomas linfocíticos/LLC, e a ciclina D1, expressa nos linfoma do manto, foram os que mais contribuíram na diferenciação destes linfomas, firmando o diagnóstico em 88,1% dos casos. A ausência de aspecto nodular e de células dendríticas, e a presença de centros de proliferação diferencia o linfoma linfocítico/LLC dos outros tipos. A expressão de proteína p53 e de antígeno Ki-67 > 20% foi associada com tempo de sobrevida menor, principalmente no linfoma do manto / We evaluated the usefulness of a panel of antibodies comprising CD5, CD10, CD23, CD43, bcl-2 and cyclin D1 in the classification of 134 small B-cell lymphomas. CD10, positive in follicular lymphomas, CD23, positive in lymphocytic lymphoma/CLL and cyclin D1 expressed in mantle cell lymphoma were the ones that contributed the most in the differentiation of these lymphomas, confirming the diagnosis in 88.1% of the cases. The absence of nodular aspect and dendritic cells and the presence of proliferation centers differentiate the lymphocytic lymphoma/CLL from the other types. The expression of p53 protein and Ki-67 > 20% was associated to a shorter survival, especially in mantle cell lymphoma

Topoisomerases são enzimas nucleares que participam na regulação da estrutura do DNA nas células eucarióticas. A topoisomerase III é o mais novo membro da família das topoisomerases. Seu papel no desenvolvimento dos tumores mamários ainda necessita ser investigado. O objetivo do presente estudo foi avaliar a imunoexpressão da topoisomerase III nos carcinomas mamários, e comparar sua expressão com dados clinicopatológicos e marcadores imunohistoquímicos clássicos de importância prognóstica nos carcinomas mamários. Utilizando-se tissue microarrays contendo 171 casos de carcinomas ductais mamários primários, foi analisada a expressão imunohistoquímica de topoisomerase III, receptor de estrógeno, receptor de progesterona, HER-2, Ki67, p53 e BRCA-1. Positividade para topoisomerase III foi encontrada em 33,9% dos casos, e sua expressão relacionou-se com metástases à distância (p=0.036) e óbito (p=0.006). Negatividade para topoisomerase III relacionou-se com negatividade para HER=2 (p<0.001), p53 (p<0.001) e BRCA-1 (p=0.001), e com baixa expressão de Ki-67 (p<0.001). Na Análise de Riscos Múltiplos de Cox, a expressão de topoisomerase III foi um significante preditor de sobrevida [razão de risco 3.006 (intervalo de confiança a 95%: 1.582-5.715); p=0.001]. Concluindo, a topoisomerase III pode ser útil na avaliação do prognóstico de pacientes com câncer de mama, além de ser um fator independente de predição da sobrevida. / Topoisomerases are ubiquitous nuclear enzymes that regulate DNA structure in eukaryotic cells. The role of topoisomerase III, the newest member of the topoisomerase family, in the clinical outcome of breast cancer is still poorly understood. This study aims to investigate the immunoexpression of topoisomerase III in breast cancer and its relationships with clinicopathological features and immunohistochemical markers of prognostic significance in breast pathology. Using tissue microarrays containing 171 cases of primary invasive breast cancer, we analyzed the immunoexpression of topoisomerase III, estrogen receptor, progesterone receptor, HER-2, Ki67, p53 and BRCA-1. Immunostaining for topoisomerase III was found in 33.9% of breast carcinomas, and immunopositivity was related with distant metastasis (p=0.036) and death (p=0.006). Decreased expression of topoisomerase III was related with negativity with HER-2 (p<0.001), p53 (p<0.001) and BRCA1 (p=0.001) and low expression of Ki67 (p<0.001). In the multivariate analysis, topoisomerase III expression was a significant predictor of survival [hazard ratio 3.006 (95% confidence interval 1.582-5.715); p=0.001]. In conclusion, topoisomerase III expression can be a useful marker in assessing the prognosis of patients with breast cancer and is an independent predictor of survival.

A forte expressão do fator de crescimento endotelial vascular do tipo -C (VEGF-C) tem sido correlacionada com a presença de metástases linfonodais em carcinomas espinocelulares (CECs) de boca. O objetivo deste estudo consistiu em avaliar a expressão imuno-histoquímica do anticorpo anti-VEGF-C, nas células malignas de pacientes com CEC de boca em estádios iniciais, correlacionando-a com a ocorrência de metástases ocultas nos linfonodos cervicais e com o prognóstico dos pacientes. Um total de 87 pacientes com CEC de língua e assoalho de boca, estadiamento clínico I e II, tratados no Departamento de Cirurgia de Cabeça e Pescoço, do Hospital do Câncer A.C. Camargo, São Paulo, no período de 1968 a 2001, foram analisados quanto as características demográficas, clínicas, classificação pelo sistema TNM, tratamento e evolução clínica. Avaliou-se também o índice de malignidade tumoral histopatológico e a expressão imuno-histoquímica de VEGF-C foi comparada entre os CECs de boca sem (pN0) e com (pN+) comprometimento linfonodal (metástases ocultas). As probabilidades de sobrevidas global, livre de doença e específica por câncer dos pacientes com CEC, acumuladas nos períodos de cinco e dez anos, em relação a expressão tumoral de VEGF-C, foram calculadas pelo método de Kaplan-Meier. De sessenta e quatro pacientes submetidos ao esvaziamento cervical eletivo, quatorze deles (21,9%) apresentaram comprometimento linfonodal cervical histopatológico (metástase oculta). De acordo com os resultados, não houve correlação estatisticamente significativa entre a expressão de VEGF-C e as principais variáveis demográficas, clínicas, microscópicas e o índice histopatológico de malignidade tumoral (p=0,406), bem como com relação a ocorrência de metástases ocultas nos linfonodos cervicais (p=0,876). O único fator de prognóstico significativo para a sobrevida global (p=0,030) foi a ocorrência de metástase oculta comprovada por exame histopatológico. Concluiu-se que a expressão imuno-histoquímica isolada de VEGF-C nas células malignas não influenciou a evolução clínica e o prognóstico dos pacientes com CEC de língua e assoalho de boca nos estádios iniciais (I e II) e, portanto, o esvaziamento cervical eletivo permanece como uma intervenção terapêutica recomendada no tratamento destes pacientes. / The high expression of vascular endothelial growth factor-C (VEGF-C) has been correlated with the presence of lymph node metastasis from oral squamous cell carcinoma (OSCC). The purpose of this study was to evaluate the immunoexpression of VEGF-C antibody in malignant cells of patients in early stages of OSCC, and to correlate it with occult cervical lymph node metastasis and patients prognosis. Eighty seven patients with OSCC of tongue and floor of the mouth, clinical stage I and II, treated at the Department of Head and Neck Surgery and Otorhinolaryngology of Cancer Hospital A. C. Camargo, São Paulo, from 1968 to 2001, were included in this study. It was evaluated the demographical and clinical characteristics, TNM classification, treatment and clinical outcome. The histopathological malignancy index and immunoexpression of VEGF-C and their correlation with OSCC with (pN+) and without (pN0) positive lymph node (occult metastasis) were also evaluated. The overall and disease-free survival for OSCC patients for five and ten years related to VEGF-C tumor expression were calculated by Kaplan-Meier method. Among 64 patients that were submitted to elective neck dissection, 14 (21,9%) showed positive histopathological lymph node (occult metastasis). Our results did not show statistically significant difference for VEGF-C expression and main demographical, clinical, microscopical characteristics and histopathological malignancy index (p=0,406), as well as to occult neck metastasis (p=0,876). The occult lymph node metastasis was a prognostic factor for overall survival of patients with OSCC (p=0,030). In conclusion, the immunoexpression of VEGF-C in malignant cells per se did not influence the clinical outcome and prognosis of patients with OSCC of tongue and floor of the mouth in early stages (I and II). Therefore, elective neck dissection seems to be a therapeutical recommendation for the treatment of these patients.

A proteína catiônica eosinofílica (ECP) presente nos grânulos específicos dos eosinófilos apresenta atividade citotóxica, particularmente para células tumorais, entretanto a função exata dos eosinófilos e de seus produtos nas neoplasias malignas continua obscura. O objetivo desse trabalho foi investigar a prevalência do polimorfismo 434(G>C) do gene ECP em pacientes com carcinoma espinocelular (CEC) de boca e sua correlação com a eosinofilia tecidual associada aos tumores (TATE), bem como com as características demográficas, clínicas e microscópicas. O genótipo 434 do gene ECP em 165 pacientes saudáveis e em 157 pacientes com CEC de boca, tratados no Hospital do Câncer A.C. Camargo entre 1984 a 2002, foi detectado pela clivagem da seqüência específica de DNA amplificada com a enzima de restrição PstI e análise dos produtos de clivagem pela eletroforese em gel de agarose. A TATE foi determinada por análise morfométrica. A associação entre os genótipos, a intensidade da TATE e as variáveis demográficas, clínicas e microscópicas foi avaliada pelo teste qui-quadrado ou teste exato de Fisher. As análises das sobrevidas global, livre de doença e específica por câncer foram feitas pelo estimador limite de Kaplan-Meier e a comparação das curvas de sobrevida foi realizada utilizando-se o teste log-rank. Notou-se uma predominância dos indivíduos heterozigotos para o polimorfismo 434(G>C) do gene ECP. Nenhuma diferença estatística significativa foi obtida entre os diferentes genótipos, a intensidade da TATE e as variáveis demográficas, clínicas e microscópicas. Uma maior freqüência de esvaziamento cervical bilateral, recidiva local, embolização vascular, comprometimento das margens cirúrgicas e realização de radioterapia pós-operatória foi observada nos pacientes com CEC de boca, TATE intensa e genótipos 434GC/CC. Não houve correlação estatística significativa entre os diferentes genótipos 434 do gene ECP e as sobrevidas global, livre de doença e específica por câncer. Baseados em nossos resultados, concluímos que houve uma tendência de os pacientes com CEC de boca, intensa eosinofilia tecidual e genótipos 434GC/CC do gene ECP apresentarem uma evolução clínica desfavorável, quando comparados aos indivíduos com genótipo 434GG, provavelmente pela presença de uma variante genética dessa proteína com propriedades citotóxicas alteradas. / Eosinophil cationic protein (ECP), found in secretory granules of human eosinophils, presents cytotoxic activity, particularly against cancer cells. The specific functional role of eosinophils in solid malignant tumors remains unclear. The aim of this study was to investigate the prevalence of the ECP-gene polymorphism 434(G>C) in oral squamous cell carcinoma (OSCC) patients and its association with tumor-associated tissue eosinophilia (TATE), as well as demographic, clinical and microscopic variables. The 434 genotypes in the ECP-gene of 165 healthy individuals and 157 OSCC patients, submitted to surgical treatment at the Hospital A.C. Camargo from 1984 to 2002, were detected by cleavage of the amplified DNA sequence with restriction enzyme PstI and analyses of the cleaved product by agarose gel electrophoresis. TATE, in OSCC, was obtained by morphometric analysis. Chisquare test or Fishers exact test was used to analyze the association among ECP-gene polymorphism 434(G>C), TATE, demographic, clinical and microscopic variables. Diseasefree survival and overall survival were calculated by the Kaplan-Meier product-limit actuarial method and the comparison of the survival curves were performed using log rank test. Most of healthy individuals and OSCC patients showed the genotype 434GC. There was no statistical association among 434 genotypes, TATE intensity and demographic, clinical or microscopic variables of OSCC patients. Higher frequency of bilateral neck dissection, local recurrence, vascular embolization, involved resection margins and postoperative radiotherapy was detected in OSCC patients with intense TATE and 434GC/CC genotypes. No statistically significant differences on survival rates were found among 434 genotypes. In conclusion, these results suggest a tendency of worse clinical outcome in OSCC patients with intense TATE and 434GC/CC genotypes, probably due an ECP genetic variant with altered cytotoxic activity.

Das neoplasias malignas que ocorrem na boca, 95% são representados pelo Carcinoma Epidermóide Bucal. Esta é uma doença usualmente agressiva, com comportamento biológico imprevisível e prognóstico desfavorável sendo a infiltração local e consequente emissão de metástases a principal causa de morte dos pacientes. A identificação de marcadores moleculares que possam predizer o curso clínico da doença, orientar a determinação do tratamento, bem como conduzir o desenvolvimento de novas terapias que melhorem os índices de sobrevida, tem sido o objetivo de inúmeras pesquisas. O presente estudo procurou determinar a correlação da expressão imunoistoquímica da c-erbB-2 e vimentina com características clínicas da neoplasia e o prognóstico dos pacientes a partir da análise retrospectiva de 65 casos de Carcinoma Epidermóide Bucal. c-erbB-2 e vimentina estavam expressos em 61,54% e 70,8% das amostras analisadas, respectivamente. Não foi observada correlação estatisticamente significante entre a expressão destes marcadores e as características clínicas avaliadas, porém houve uma tendência à expressão imunoistoquímica da vimentina em relação ao índice N. Quanto à sobrevida dos pacientes, esta foi influenciada pelo gênero dos pacientes, hábito de fumar cigarro, estádio clínico da doença, índice N e modalidade de tratamento submetido, sendo o gênero o único fator prognóstico independente detectado. A expressão imunoistoquimica da c-erbB-2 e vimentina não se demonstraram preditivos de sobrevida em carcinomas epidermóides de boca. / About of malignancies in oral mucosa, 95% are represented by oral squamous cell carcinoma (OSCC). This disease is usually aggressive, with unpredictable biological behavior and poor prognosis and the local infiltration and consequent metastases the main cause of death of patients. The identification of molecular markers that may predict the clinical course of disease, guide the treatment as well as lead the development of new therapies that improve the rates of survival, has been the goal of many studies. This study examined the correlation of immunohistochemical expression of c-erbB-2 and vimentin with clinical features and prognosis of OSCC patients from the retrospective analysis of 65 cases. c-erbB-2 and vimentin were expressed in 61.54% and 70.8% of samples, respectively. There was no statistically significant correlation between the expression of these markers and clinical characteristics, but a tendency to vimentin expression in the lymph node status. The patients survival, was influenced by their gender, smoking habits the, clinical stage of disease, N index and modalities of treatment. The gender was the only independent prognostic factor detected. The immunohistochemical expression of c-erbB-2 and vimentin did not show up predictive of survival in oral cavity squamous cell carcinoma.

INTRODUÇÃO: Existe uma dúvida na literatura médica se a monitorização respiratória do paciente crítico internado na Unidade de Terapia Intensiva contribuiria para melhora de seu prognóstico. OBJETIVO: Avaliar de maneira prospectiva se a mensuração de parâmetros respiratórios na admissão dos pacientes em ventilação espontânea na Unidade de Terapia Intensiva estaria relacionada com a necessidade de suporte ventilatório, duração da internação dos pacientes na UTI e com a mortalidade hospitalar. MÉTODOS: Foram avaliados prospectivamente 195 pacientes admitidos respirando espontaneamente (37,4% do total das admissões no período do estudo) na Unidade de Terapia Intensiva Adultos do Hospital Israelita Albert Einstein. No momento da admissão, foram medidos o VC espontâneo, a FR, a Pimax, a Pemax, FiO2, SpO2 , FC e foi investigado se o paciente apresentava causa pulmonar para a insuficiência respiratória. Os pacientes foram acompanhados até a alta hospitalar ou óbito. Um modelo de regressão logística por etapas progressivas e um modelo de regressão linear múltipla foram aplicados para avaliação das associações entre os parâmetros mensurados à entrada dos pacientes na UTI e a necessidade de suporte ventilatório, tempo de internação na UTI e mortalidade intrahospitalar. RESULTADOS: A média de idade dos 195 pacientes foi de 62,36±18,67, 77 mulheres. Trinta dos 195 pacientes necessitaram de suporte ventilatório (15,38%) e 20 pacientes morreram durante sua internação no hospital (10,25%). O tempo médio de internação na UTI foi de 5,1±5,8 dias. O modelo de regressão logística selecionou a Pimax (OR=1,04, p=0,018), doença respiratória primária (OR=2,8, p=0,036), FC (OR=1,03, p=0,022) e FiO2 (OR=1,04, p=0,043) como as variáveis relacionadas à necessidade de suporte ventilatório e o volume corrente espontâneo inicial (OR=0,92, p=0,000) como a variável relacionada à mortalidade intrahospitalar. O modelo de regressão linear múltipla selecionou a FC (Coeficiente=0,005, p=0,000), FR (Coeficiente =0,009, p=0,004), VC (Coeficiente = - 0,006, p=0,000) e sexo (Coeficiente =0,128, p=0,009) como as variáveis relacionadas ao tempo de internação na UTI. CONCLUSÃO: Em pacientes admitidos na UTI respirando espontaneamente, uma FC aumentada, necessidade de altas FiO2, Pimax diminuída e a presença de doença respiratória primária estiveram relacionadas com necessidade de suporte ventilatório. Pacientes do sexo masculino, com uma FC aumentada, FR aumentada e um baixo VC espontâneo apresentaram tempo de internação prolongado na UTI. A mensuração de VC espontâneo diminuído à admissão na UTI esteve fortemente relacionada a um aumento da mortalidade hospitalar. / INTRODUCTION: There is a doubt in the medical literature if the patients respiratory monitoring at ICU admission could improve their prognosis. OBJECTIVE: To measure respiratory parameters in patients admitted at ICU in spontaneous ventilation and relate them to the necessity of ventilatory support, length of ICU stay and hospital mortality. METHODS: We prospectively evaluated 195 patients admitted to the Adult ICU of the Albert Einstein Hospital in spontaneous ventilation (37.4% of total study period admissions). At ICU entry, we measured tidal volume (TV), respiratory rate (RR), maximal inspiratory pressure (MIP), maximal expiratory pressure (MEP), FiO2, SpO2, heart rate (HR) and we verified if the patient had a primary pulmonary disease. The patients were followed till hospital discharge or death. A stepwise logistic regression and multiple linear regression models were built to evaluate the relation of the respiratory parameters at ICU entry and the necessity of ventilatory support, ICU length of stay and intra-hospital mortality. RESULTS: The 195 patients mean age was 62.36±18.67, 77 females. Thirty of 195 patients needed ventilatory support (15.38%) and 20 died in the hospital (10.25%). The mean ICU length of stay was 5.1±5.8 days. The logistic regression model selected MIP (OR=1.04, p=0.018), primary respiratory disease (OR=2.8, p=0.036), HR (OR=1.03, p=0.022) and FiO2 (OR=1.04, p=0.043) as the variables related to the necessity of ventilatory support and the initial TV (OR=0.92, p=0.000) as the variable related to intra-hospital mortality. The multiple linear regression model selected the HR (Coefficient=0.005, p=0.000), RR (Coefficient =0.009, p=0.004), VT (Coefficient = - 0.006, p=0.000) and sex (Coefficient =0.128, p=0.009) as the variables related to the ICU length of stay. CONCLUSION: In spontaneous ventilated patients at ICU admission, a higher HR, higher FiO2, a lower MIP and a primary respiratory diagnosis were related to the necessity of ventilatory support. Male patients with a higher HR, higher RR and lower TV had a prolonged ICU length of stay. The initial measurement of a low spontaneous TV was strongly related to an increase in hospital mortality.

Introdução: Os anticorpos antiproteína P ribossomal (anti-P) são considerados marcadores sorológicos específicos do Lúpus Eritematoso Sistêmico (LES) e estão associados a acometimento hepático nesta doença. As semelhanças entre a hepatite autoimune (HAI) e a hepatite associada ao LES levou ao questionamento se o anticorpo anti-P também estaria presente na HAI. Objetivo: Avaliar a frequência e significância clínica do anticorpo anti-P em uma grande coorte de pacientes com HAI. Métodos: Foram analisados os soros de 96 pacientes com HAI, coletados no diagnóstico e comparados com 82 soros de indivíduos saudáveis. Todos os soros foram testados para a presença do anticorpo anti-P pelo método de ELISA, do anticorpo anti-DNA de dupla fita pelo método de imunofluorescência indireta usando Crithidia luciliae e do anticorpo anti-Sm pelo método de ELISA. Os critérios de exclusão adotados foram a presença de outros anticorpos específicos de LES como o anti-DNA de dupla fita (n=1) e o anti-Sm (n=2) ou se o paciente apresentasse o diagnóstico de LES definido pelo Colégio Americano de Reumatologia (n=0). Os prontuários médicos foram revisados para dados demográficos, clínicos e resultados de exames laboratoriais relacionados a hepatopatia e anticorpos específicos de HAI. Resultado: Títulos moderados ou alto (> 40 U) de anti-P foram encontrados em 9,7% (9/93) dos pacientes com HAI e em nenhum dos controles (p = 0,003). No diagnóstico, os pacientes com anti-P positivo ou negativo apresentavam características demográficas/clínicas semelhantes, como a frequência de cirrose (44,4% vs 28,5%, p = 0,44) e exames laboratoriais relacionados a hepatite (p > 0,05). Entretanto, ao final do seguimento destes pacientes (média de 10,2 ± 4,9 anos), os pacientes positivos para anticorpos anti-P apresentaram uma maior frequência de cirrose quando comparados a pacientes negativos para anti-P (100% vs 60%, p = 0,04). Conclusão: a demonstração da presença do anticorpo anti-P em pacientes com HAI sem evidência de LES sugere um mecanismo comum de acometimento hepático nestas duas doenças. Além disso, a presença deste anticorpo parece predizer um pior prognóstico nos pacientes com HAI / Background: Autoantibodies to ribosomal P proteins (anti-rib P) are specific serological markers for systemic lupus erythematosus (SLE) and are associated with liver involvement in this disease. The similarity in autoimmune background between autoimmune hepatitis (AIH) and SLE- associated hepatitis raises the possibility that anti-rib P antibodies might also have relevance in AIH. Aims: To evaluate the frequency and clinical significance of anti-rib P antibodies in a large AIH cohort. Methods: Sera obtained at diagnosis of 96 AIH patients and of 82 healthy controls were tested for IgG anti-ribosomal P protein by ELISA. All of the sera were also screened for other lupus-specific autoantibodies, three patients with the presence of anti-dsDNA (n=1) and anti-Sm (n = 2) were excluded. Results: Moderate to high titers (> 40 U) of anti-rib P antibody were found in 9.7% (9/93) of the AIH patients and none of the controls (P = 0.003). At presentation, AIH patients with and without anti-rib P antibodies had similar demographic/clinical features, including the frequency of cirrhosis (44.4% vs. 28.5%, P = 0.44), hepatic laboratorial findings (p > 0.05). Importantly, at the final observation (follow-up period 10.2 ± 4.9 years), the AIH patients with anti-rib P had a significantly higher frequency of cirrhosis compared to the negative group (100% vs. 60%, P = 0.04). Conclusion: The novel demonstration of anti-rib P in AIH patients without clinical or laboratory evidence of SLE suggests a common underlying mechanism targeting the liver in these two diseases. In addition, this antibody appears to predict the patients with worse AIH prognoses

Made available in DSpace on 2016-08-19T18:16:06Z (GMT). No. of bitstreams: 1 DISSERTACAO KARLA.pdf: 550872 bytes, checksum: a1efbaeab3d76483b6e7b53d97cc5a68 (MD5) Previous issue date: 2012-09-28 / The acute lymphoblastic leukemia (ALL) is characterized by abnormal proliferation of immature lymphoid cells and represents the most common cancer in children. The evaluation of prognostic factors in patients with ALL enables the implantation of different therapeutic approaches. The aberrant expression of markers CD56, CD57 and CD16 may be a way to assess this prognosis. The objective of this study was to characterize patients with ALL and to evaluate the prognostic influence of aberrant expression of markers CD56, CD16 and CD57 in ALL. 44 patients treated at the Maranhense Oncology Institute Aldenora Bello in Sao Luis - MA were evaluated, from March 2010 to October 2011. Patients were diagnosed with ALL according to the morpho-cytochemical and immunophenotype criteria. The expression of markers was determined by flow cytometry and clinical data were obtained through chart review. Two groups were divided as the expression or not of these markers and compared in relation to prognostic variables. The average of age in the sample was 6,28 years, with a predominance of males (60,0%). The average of blasts counted in bone marrow (BM) and peripheral blood (PB) was 77,0 and 39,6, respectively. The L1 morphology of the blasts from BM was the most frequent (80,0%). The profile of the blood count at diagnosis indicated: 24.061 leukocytes/mm3; 56.510 platelets/mm3 and 8,0 g/dL hemoglobin. According to the classification GBTLI-99, 60,0% of the patients were in low risk of recurrence group and in the end of the induction phase of treatment (D29), 70,0% of the patients had remission. The patients with ALL T had mean of age (10,6 years; p = 0,0204) and leukometry (48.200/mm3; p = 0,0167) significantly higher than patients with ALL B. 80,0% of the patients expressed the CD56 marker and no patient expressed CD16 and/or CD57 markers. Patients who did not express the marker CD56 had age significantly higher those who expressed (9,3 years; p = 0,0353). For patients with ALL B, the average of blasts from PB of patients who expressed the CD56 marker was higher than those not expressed (41,1; p = 0,0226). It is concluded that CD56 expression characterizes a worse prognosis for patients with ALL B, due to a significantly higher average of blasts counted in PB found in our study. However, a greater number of cases and a longer observation time would be needed to better emphasize this evidence. / A Leucemia linfóide aguda (LLA) é caracterizada pela proliferação anormal de células linfóides imaturas e representa a neoplasia mais comum em crianças. A avaliação de fatores prognósticos em pacientes com LLA possibilita a implantação de abordagens terapêuticas diferenciadas. A expressão aberrante dos marcadores CD56, CD57 e CD16 pode ser uma forma de avaliar tal prognóstico. O objetivo deste trabalho foi caracterizar os pacientes com LLA e avaliar a influência prognóstica da expressão aberrante dos marcadores CD56, CD16 e CD57 na LLA. Foram avaliados 40 pacientes, atendidos no Instituto Maranhense de Oncologia Aldenora Bello (IMOAB), em São Luís MA, no período de março de 2010 a outubro de 2011. Os pacientes foram diagnosticados com LLA, segundo os critérios morfo-citoquímicos e imunofenotípicos. A expressão dos marcadores foi determinada através da citometria de fluxo e os dados clínicos foram obtidos através da revisão de prontuários. Dois grupos foram divididos quanto à expressão ou não dos referidos marcadores e comparados em relação às variáveis prognósticas. A média de idade na amostra foi de 6,28 anos, sendo o sexo masculino predominante (60,0%). A média de blastos contados na medula óssea (MO) e sangue periférico (SP) foram de 77,0 e 39,6, respectivamente. A morfologia L1 dos blastos da MO foi a mais frequente (80,0%). O perfil do hemograma, ao diagnóstico, indicou: 24.061 leucócitos/mm3, 56.510 plaquetas/mm3 e 8,0 g/dL de hemoglobina. De acordo com a classificação GBTLI-99, 60,0% dos pacientes se encontravam no grupo de baixo risco de recidiva e ao final da fase de indução do tratamento (D29), 70,0% dos pacientes alcançaram a remissão. Os pacientes portadores de LLA T apresentaram média de idade (10,6 anos; p= 0,0204) e leucometria (48.200/mm3; p= 0,0167) significativamente mais altas do que os pacientes com LLA B. 80,0% dos pacientes expressaram o marcador CD56 e nenhum paciente expressou o CD16 e/ou o CD57. Os pacientes que não expressaram o marcador CD56 tinham idade significativamente maior daqueles que o expressaram (9,3 anos; p= 0,0353). Para os pacientes portadores de LLA B, a média de blastos do SP dos pacientes que expressaram o marcador CD56 foi maior do que a média dos que não o expressaram (41,1; p= 0,0226). Conclui-se que a expressão do CD56 sugere um pior prognóstico para os pacientes com LLA B, em virtude de uma média significativamente maior de blastos contados no SP encontrada no nosso estudo, contudo, um maior número de casos e um maior tempo de observação seriam necessários para enfatizar melhor esta evidência.

Introduction: Research suggests that patients with head and neck cancer from poorer backgrounds are more likely to have recurrences or die earlier than similar patients from affluent backgrounds. Survival is influenced by tumour characteristics on presentation and a range of individual factors such as socioeconomic status and comorbidity. Deprived patients of more advanced age have a higher likelihood of having comorbidity; this may be due to high-risk lifestyle behaviours such as smoking and drinking. Therefore, it seems reasonable to assume that survival will be lower in these deprived patients which can be attributed to comorbidity compared to index diseases such as the head and neck cancer itself. Survival rates for head and neck cancer patients are approximately 50% in the first five years in Scotland. This is dependent on a range of individual and tumour-related factors such as head and neck cancer sub-type and stage at diagnosis. The risk of head and neck cancer developing in deprived patients has been likened to that of developing head and neck cancer in heavy smokers. While the relationship between deprivation and comorbidity in head and neck cancer has been established, how both factors affect survival is yet to be explored. Reviewing these two factors individually has demonstrated the need to assess how both interact with each other in determining clinical presentation and survival. Aim: The aims of this thesis are:- 1. To investigate the roles and interrelationship between comorbidity and deprivation on the survival of HNC patients. 2. To investigate whether there are differences in HNC presentation based on comorbidity and deprivation. 3. To ascertain whether patients from deprived backgrounds with comorbidity present with more advanced cancers. Methods: In order to answer the research questions, this project began by describing the index disease, HNC and how comorbidity and deprivation are placed within the epidemiology of this disease using systematic review methods. The rationale for embarking upon this study was highlighted. Data linkage of administrative datasets We used anonymised patient data that was accessed through an encrypted repository held by the Health Informatics Centre. The data that was used in the retrospective cohort analysis was obtained from a prospective dataset collected by the Fife Head and Neck cancer Specialist Nurse (Fife data) and a retrospective case note review from the Tayside oncology records held by the Ear Nose and Throat Department and the Oral and Maxillofacial Surgery team. Thereafter we matched the patient data with that from routine medical datasets such the Scottish Morbidity Records, SMR01- inpatient discharges and SMR06 – Cancer Registry data. We conducted survival analysis methods with the intent of assessing the impact of both comorbidity and deprivation in determining survival. Results: The systematic review found that worsening levels of comorbidity were linked to reduced survival whereas patients with low incomes and poor educational attainment also had poor survival outcomes. Being young and having severe comorbidity appeared to also be associated with poorer survival. In the retrospective cohort analysis, the level of association between risk of death with comorbidity and deprivation could not be clearly ascertained in the patients from Fife. The Tayside data to a larger extent supported the systematic review findings particularly for the comorbidity measures with clearly defined measures of association for the Scottish Index of Multiple Deprivation income and education domains. Conclusions: This thesis was able to use evidence triangulation by way of a systematic review of the literature followed by a retrospective cohort analysis to investigate what influence on prognosis both comorbidity and deprivation posed in patients with head and neck cancer. There was substantiation of both factors interacting with head and neck cancer to cause a significantly reduced impact on survival. The inherent difficulties of measuring socioeconomic status and comorbidity encountered in this thesis may go some way towards illustrating the complexity and multifaceted nature of both comorbidity and socioeconomic status; particularly the quite complex interplay between socioeconomic status, comorbidity, stage at diagnosis, and access to care in head and neck cancer, and these factors’ ultimate impact on survival. We found that socioeconomic status i.e. deprivation, comorbidity, stage at diagnosis, access to care, and survival are all potentially causally related. Future work directed at using administrative data linked to medical records would not be sufficient; there is need for epidemiological and clinical studies to unravel the survival disadvantage. To this end clinical cohorts could be nested within larger registry based studies which would allow for uniform interventions based on clinical practice guidelines, uniform SES measurement and ascertainment of comorbidity using a head and neck cancer comorbidity index, i.e. the Washington University Head and Neck Cancer Index.

L’accident vasculaire cérébral, est une pathologie aigüe et grave, qui peut conduire au décès rapide du patient ou à un handicap neurologique sévère, moteur et/ou cognitif. Dans les situations les plus sévères, l’action médicale amène à envisager des limitations ou arrêt de certains traitements si le pronostic s’avère « catastrophique », signifiant le plus souvent le risque d’un handicap « inacceptable ».L’action médicale dans ces situations est particulièrement complexe. Elle pose la question de la finalité de l’acte médical au regard de la qualité de vie future du patient, qui suppose l’estimation délicate de la valeur de la vie, prédiction par essence incertaine. Mais si le pronostic tient une place centrale dans cette action, d’autres facteurs jouent également un rôle déterminant, comme celui du contexte. Ce travail de thèse propose une exploration des notions de pronostic et de « proportionnalité des soins » et une approche éthique reposant sur la prise en compte de la complexité et la délibération aristotélicienne. / Stroke is an acute and severe pathology, which can lead to rapid death or severe neurological motor and / or cognitive disability. In the most severe situations, medical action leads to consider withholding or withdrawal of treatments, if the prognosis appears to be "catastrophic", meaning most often the risk of "unacceptable" disability.The medical action in these situations is particularly complex. It raises the question of the purpose of the medical act in relation to the future quality of life of the patient, which involves the delicate estimate of the value of life, prediction inherently uncertain. But if the prognosis holds a central place in this action, other factors also play a role, such as the context. This thesis offers an exploration of the concepts of prognosis and “proportionality care” and an ethical approach based on taking into account the complexity and Aristotelian deliberation.