INTRODUÇÃO: A Doença de Fabry (DF) é uma doença lisossomal de herança ligada ao X, causada pela deficiência da enzima alfa-galactosidase A (alfa-Gal A), que leva ao acúmulo gradual de glicoesfingolipídeos, em especial a globotriaosilceramida, nos lisossomos do endotélio vascular de tecidos cardíaco, renal, cerebral, olhos e pele. Os principais sintomas iniciais são: dores neuropáticas de extremidades, hipoidrose, dores abdominais recorrentes, angioqueratomas e córnea verticillata. As complicações, que aparecem a partir da terceira década de vida, incluem morte prematura por insuficiência renal, cardíaca e alterações cerebrovasculares. Angioqueratomas são uma das manifestações mais precoces da DF. OBJETIVOS: detectar os portadores da DF a partir de casos de angioqueratoma diagnosticados através de exames anatomopatológicos de biópsia cutânea; descrever o quadro clínico dos afetados e portadoras heterozigotas; realizar aconselhamento genético. MÉTODOS: Uma revisão sistemática de biópsias de pele de 2003 a 2012 foi feita em quatro hospitais universitários. Os pacientes foram convocados para anamnese, exame físico e coleta de história familial. A dosagem enzimática de alfa-Gal A por papel filtro e em leucócitos em homens e a análise molecular por PCR e sequenciamento do gene GLA em homens e mulheres foram realizados naqueles com suspeita de DF. RESULTADOS: Foram localizados 125 registros de angioqueratomas, sendo possível convocar 52 pacientes. Destes, 45 (M:21 e F:24) compareceram para serem examinados. O diagnóstico de DF foi confirmado 3/45 (6,6%), todos do sexo masculino, pela baixa atividade enzimática da alfa-Gal A. A idade dos pacientes eram 16, 21 e 32 anos. Foram identificados outros 13 familiares (cinco homens e oito mulheres) destas 3 famílias. Os principais achados clínicos nos oito homens afetados foram: dores de extremidades (62,5%), angioqueratomas (87,5%), alterações renais (87,5%), cardíacas (12,5%) e presença de córnea verticillata(37,5%) Nas oito mulheres os achados clínicos foram: dores de extremidades (75%), angioqueratomas (12,5%), alterações renais (37,5%) cardíacas (12,5%) e presença de córnea verticillata(0%). A frequência desses achados mostrou-se semelhante à descrita na literatura. As mutações patogênicas no gene GLA, herdadas da mãe, foram identificadas nas 3 famílias e já haviam sido descritas anteriormente. CONCLUSÕES: A DF foi identificada em 3/45 pacientes (6,6%) pelos registros histopatológicos. Portanto, o angioqueratoma é um marcador útil para a detecção da doença. A dosagem enzimática de alfa-Gal A e/ou estudo molecular foram fundamentais para a confirmação diagnóstica da DF. Foi possível identificar outros 13 familiares afetados (5 homens, 8 mulheres), o que reforça a importância do aconselhamento genético. Todos os pacientes apresentavam outros achados clínicos da DF além dos angioqueratomas, os quais, no entanto, não haviam sido diagnosticados. O diagnóstico da DF ainda é tardio e há necessidade de reconhecimento dos médicos sobre as manifestações dessa doença para possibilitar um diagnóstico precoce / INTRODUTION: Fabry disease (FD) is an X-linked lysosomal disorder, caused by the deficiency of the enzyme alfa-galactosidase A (alfa-Gal A), which leads to gradual accumulation of glycosphingolipids, especially globotriaosylceramide, in lysosomes of the vascular endothelium of the cardiac tissue, kidney, brain, eyes and skin. The main initial symptoms are: neuropathic pain in the extremities, hypohidrosis, recurrent abdominal pain, angiokeratomas and cornea verticillata. Complications, which appear from the third decade of life on, include premature death from renal, cardiac and cerebrovascular abnormalities. Angiokeratomas are one of the earliest manifestations of FD. OBJECTIVES: to identify relatives with FD from cases of angiokeratoma diagnosed by pathological examinations of skin biopsy; to describe the clinical features of the affected individuals and heterozygotes; to perform genetic counseling. METHODS: A systematic review of skin biopsies from 2003 to 2012 was done in four university hospitals. Patients were submitted to anamnesis, physical examination and family history collection. The enzymatic assay of alfa-Gal A using dried blood spot in filter paper and leukocytes in men and molecular analysis by PCR and sequencing of the GLA gene in men and women were performed in patients with suspected FD. RESULTS: We found 125 biopsy records of angiokeratomas, and were able to contact 52 patients. Of these, 45 (M: 21 and F: 24) were evaluated. The diagnosis of FD was confirmed in 3/45 (6.6%), all male, with low enzymatic activity of alfa-Gal A. The patients\' ages were 16, 21 and 32 years. We identified 13 other family members (five men and eight women) of these three families. The main clinical findings in the eight affected men were pain in the extremities (62,5%), angiokeratomas (87,5%), renal abnormalities (87,5%), cardiac abnormalities (12,5%) and cornea verticillata (37,5%). In the eight female patients the clinical findings were: pain in the extremities (75%), angiokeratomas (12,5%), renal abnormalities (37,5%) cardiac abnormalities (12,5%) and cornea verticillata (0%). The frequency of these findings was similar to that described in the literature. The pathogenic mutations in the GLA gene, maternally inherited, were identified in three families and had been described previously. CONCLUSIONS: FD was identified in 3/45 patients (6.6%) by histopathologic records. Therefore, angiokeratoma is a useful marker for the detection of disease. The enzymatic measurement of alfa-Gal A and / or molecular studies were essential to confirm the diagnosis of FD. It was possible to identify 13 other affected family members (5 men, 8 women), which reinforces the importance of genetic counseling. All patients, in addition to angiokeratomas, had other clinical manifestations of FD; however these had not been diagnosed before. The diagnosis of FD is still late and doctors need to be aware of the manifestations of this disease to enable early diagnosis

INTRODUÇÃO: O aprimoramento dos métodos de rastreamento e a conscientização da população geral contribuíram para o diagnóstico cada vez mais precoce do câncer de mama e proporcionou, juntamente com o avanço na terapêutica, altas taxas de sobrevida. O estado do acometimento axilar por metástase é um dos principais fatores prognósticos em pacientes com câncer de mama, particularmente naquelas com diagnóstico em estádio inicial. Na última década, esforços científicos foram direcionados para simplificar a amostragem dos linfonodos axilares, diminuindo a morbidade, mas respeitando os princípios oncológicos. Nesse sentindo, a biópsia do linfonodo sentinela foi considerada o avanço mais importante. Ao se obter um método preditor do estado axilar, que apresente os benefícios da abordagem padrão dissecção axilar e biópsia de linfonodo sentinela porém sem seus efeitos colaterais e que seja facilmente reproduzível, realizaremos um grande avanço na avaliação e terapêutica do câncer de mama inicial. MÉTODOS: Foi realizado estudo transversal retrospectivo com base nos prontuários de pacientes com câncer de mama invasivo, não metastático, com qualquer idade, atendidas entre 1999 e 2007 no Setor de Mastologia da Disciplina de Ginecologia do Departamento de Obstetrícia e Ginecologia da Faculdade de Medicina da Universidade de São Paulo e Clínica Professor José Aristodemo Pinotti, cujo estudo histopatológico e imunoistoquímico foi supervisionado por um único médico patologista. Realizamos uma subdivisão imunoistoquímica dos tumores, sendo considerado luminal A os tumores com receptores hormonais positivos e HER 2 negativo; luminal B os com receptores hormonais positivos e HER 2 positivo; HER 2 as pacientes com receptores hormonais negativos e HER 2 positivo e triplo negativo aquelas com receptores hormonais e HER 2 negativos. Correlacionamos esses subtipos com as variáveis clínicas idade e tamanho tumoral para predizer a probabilidade de acometimento linfonodal axilar. RESULTADOS: Duzentos e trinta e nove casos foram analisados. No subtipo luminal A, a possibilidade de metástase foi maior quanto menor a idade da paciente e maior o tamanho do tumor. Essa foi a única associação que apresentou diferença estatisticamente significante. As pacientes que possuíam tumores triplo negativo tiveram, aproximadamente, 90% menos chance de metástase linfonodal que as pacientes com tumor luminal A. CONCLUSÕES: As pacientes com tumor luminal A apresentaram, significativamente, maior probabilidade de metástase linfonodal axilar. As pacientes com de tumores triplo negativo, com idade superior a 55 anos ou tumores menores que 2 cm, revelaram menor probabilidade de metástase axilar / INTRODUTION: The improvement of screening methods and awareness of general population contributed to the increasingly early diagnosis of breast cancer and provided, together with advances in therapy, high survival rates. The status of axillary involvement is a major prognostic factor in patients with breast cancer, particularly those with early stage. In the last decade, research efforts were directed to simplify the sampling of axillary lymph nodes, decreasing the morbidity, but respecting the oncological principles. In this sense, the sentinel lymph node biopsy was considered the most important advance. If we obtain a method to predict the axillary status, with the benefits of the standard approach - axillary dissection and sentinel lymph node biopsy - without its side effects and easily reproducible, we will hold a major advance in the assessment and treatment of early breast cancer. METHODS: We conducted a retrospective cross-sectional study based on records of patients with invasive breast cancer, non metastatic, with any age, treated between 1999 and 2007 in the breast cancer Sector of the Gynecology Discilpine of the Department of Obstetrics and Gynecology, Faculty of Medicine, University of São Paulo and Private Clinic of Professor José Aristodemo Pinotti, whose histopathological studies were supervised by a single pathologist. We performed an immunohistochemical subdivision of the tumors, and considered luminal A tumors with positive hormonal receptors and negative HER 2, luminal B with positive hormonal receptors and positive HER 2, HER 2 patients with negative hormonal receptors and positive HER 2 and the triple-negative those with negative hormonal receptors and HER 2. Those subtypes were correlated with the clinical variables age and tumor size in predicting the likelihood of axillary lymph node involvement. RESULTS: Two hundred and nine cases were analyzed. In the luminal A, the possibility of axillary metastasis was higher in the younger patients and larger tumors. That was the only combination that showed statistically significant difference. The patients who had triplenegative tumors had approximately 90% less chance of lymph node metastasis than patients with tumors luminal A. CONCLUSIONS: The patients with luminal A tumors showed a significantly association with greater likelihood of axillary lymph node metastasis. The patients with triple negative tumors, age over 55 years or tumors smaller than 2 cm showed a lower likelihood of axillary lymph node metastasis

Introdução e objetivo: A avaliação da gravidade da neoplasia em pacientes com câncer de próstata tem como propósito identificar e tratar somente os pacientes com doença clinicamente significativa. Os parâmetros clínicos e histopatológicos tradicionalmente utilizados na estratificação de risco classificam erroneamente uma parcela importante dos pacientes. O objetivo deste estudo foi avaliar o papel da ressonância nuclear multiparamétrica de próstata (RNMMP) e da biópsia transretal realizada com fusão de imagem e estimativa visual na estratificação precoce dos pacientes em vigilância ativa. Métodos: Foram incluídos prospectivamente pacientes com câncer de próstata de baixo risco candidatos a vigilância ativa: biópsia inicial convencional com no mínimo 12 fragmentos; escore de Gleason <= 6; PSA sérico <= 10,0; <= 3 fragmentos positivos; <= 50% de acometimento de cada fragmento; toque T1c ou T2a. Todos os pacientes foram submetidos à RNMMP e biópsia confirmatória: biópsia aleatória sistemática e biópsia guiada com fusão de imagem (ultrassom e RNMMP) e analisada por método cognitivo de estimativa visual. As regiões suspeitas para câncer foram definidas e classificadas utilizando-se a escala PI-RADS (Prostate Imaging Reporting and Data System). Definimos reclassificação na biópsia confirmatória como aparecimento de escore de Gleason >= 7, > 3 fragmentos positivos ou >= 50% de envolvimento de qualquer fragmento. A performance da RNMMP em prever os resultados da biópsia confirmatória foi estudada. Análise uni e multivariada mediante regressão logística avaliou a relação entre idade, PSA, densidade de PSA, número de fragmentos positivos na biópsia inicial e o escore da RNMMP e a chance de reclassificação na biópsia confirmatória. Resultados: Cento e cinco pacientes estiveram disponíveis para análise final. Quarenta e dois (40%) pacientes apresentaram PI-RADS 1,2 ou 3 e 63 (60%) PI-RADS 4 ou 5. No geral, 87 pacientes foram submetidos à biópsia guiada com fusão. A taxa de reclassificação entre pacientes com PI-RADS 1,2,3,4 e 5 foi de 0%, 23.1%, 9.1%, 74.5% e 100%, respectivamente. No geral, a sensibilidade, especificidade, valor preditivo positivo (VPP) e valor preditivos negativo (VPN) da RNMMP para predição de reclassificação foi de 92.5%, 76%, 81% e 90.5%, respectivamente. Daqueles reclassificados, 47 (44.8%) tinham escore de Gleason >= 7 e 11 apresentavam (10.4%) >= 3 fragmentos positivos e >= 50% de envolvimento de qualquer fragmento individualmente. Na análise multivariada, somente a densidade de PSA e a RNMMP permaneceram como fatores preditivos significativos para reclassificação (p < 0,05). Na tabulação cruzada a biópsia aleatória sistemática teria deixado de classificar corretamente 15 pacientes com câncer significativo detectados pela biópsia com fusão de imagem. Por outro lado, a biópsia aleatória sistemática detectou cinco casos de câncer significante que não teriam sido identificados pela biopsia de fusão de imagem isoladamente. Conclusões: A RNMMP é uma ferramenta importante na predição da taxa de reclassificação da gravidade da neoplasia de próstata em pacientes candidatos à vigilância ativa submetidos à biopsia confirmatória. A taxa de reclassificação na biopsia confirmatória é particularmente alta no grupo de pacientes com lesões PI-RADS grau 4-5. Apesar da utilidade da biópsia com fusão de imagem, recomenda-se a manutenção da prática de se retirar fragmentos sistemáticos aleatórios quando da realização da biópsia confirmatória para maximizar a detecção de neoplasia de comportamento agressivo / Introduction and objective: The goal of prostate cancer (PCa) risk stratification is to identify and treat only men with clinically significant disease. Clinical and pathologic parameters currently used to stratify PCa risk misclassify a significant amount of patients. The objective of this study was to evaluate the role of multiparametric magnetic resonance imaging of the prostate (mpMRI) and transrectal guided biopsy with visual estimation (TRUS-Bx) in early risk stratification of patients with prostate cancer on active surveillance. Methods: Study subjects were prospectively enrolled including patients with low risk, low-grade, localized PCa: Gleason <= 6, T1c-T2a, PSA <=10 ng/ml, no more than 3 positive cores and <= 50% involvement of single cores. They were followed with subsequent mp-MRI and confirmatory biopsy (CB): standard biopsy (SB) and visual estimation-guided TRUS-Bx. Cancer-suspicious regions (CSRs) were defined using Prostate Imaging Reporting And Data System (PIRADS) scores. Reclassification occurred if CB confirmed Gleason >= 7, > 3 positive fragments or >= 50% involvement of any core. The performance of mp- MRI on predicting CB results was assessed. Univariate and multivariate logistic regression were performed to study relationships between age, PSA, PSA density, number of positive cores in the initial biopsy and mpMRI grade on CB reclassification. Results: 105 patients were available for analysis. 42 (40%) patients had PIRADS 1,2 or 3 lesions and 63 (60%) had only grades 4 or 5 lesions. Overall, 87 patients underwent visual estimation TRUS-Bx. Reclassification among patients with PI-RADS 1,2,3,4 and 5 was 0%, 23.1%, 9.1%, 74.5% and 100%, respectively. Overall, mpMRI sensitivity, specificity, PPV and NPV for disease reclassification were 92.5%, 76%, 81% and 90.5%, respectively. Of men reclassified 47 (44.8%) were upstaged because of Gleason >= 7, 11 (10.4%) because of >= 3 positive fragments plus >= 50% involvement. On multivariate analysis, only PSA density and mpMRI remained significant for reclassification (p < 0,05). On cross-tabulation SB would have missed 15 significant cases detected by targeted biopsy. On the other hand SB detected 5 cases of significant cancer not detected by targeted biopsy alone. Conclusions: Multiparametric magnetic resonance imaging is a significant tool for predicting cancer severity reclassification on CBx among AS candidates. The reclassification rate on CBx is particularly high in the group of patients who have PI-RADS grades 4 or 5 lesions. Despite the usefulness of visual-guided biopsy, it still remains highly recommended to retrieve standard fragments during CBx in order to avoid missing significant tumors

Magnetic Resonance Imaging (MRI) provides unique advantages such as superior soft tissue contrast, true multiplanar imaging, variable contrast mechanisms, measurement of temperature changes, perfusion and diffusion, and no ionizing radiation. Despite considerable research efforts in the field of interventional MRI, numerous challenges remain including restricted access to the patient, high acoustic noise and a shortage of MRI-safe devices. Novel methods and devices are presented in this thesis with the primary objective of enabling effective MRI-guided interventions, particularly abdominal needle and common catheter-based endovascular interventions. Firstly, a set of MRI-safe devices (guidewires, micro guidewires, catheters and micro catheters) were developed with passive or inductively coupling resonant markers for MRI visualisation. Secondly, a method was implemented for wireless tracking and dynamic guidance of instruments. Thirdly, a framework of technologies was developed for in-room display, wireless MRI remote control and multi-user communication along with a dedicated user interface and imaging protocol. These implementations were assessed in regards to MRI-safety, performance and usability and evaluated for MRI-guided liver biopsies, balloon angioplasty procedures and also for mechanical thrombolysis. Flow phantoms, Thiel soft-embalmed human cadavers with partially re-established perfusion and a porcine model were used for in vitro, ex vivo and in vivo validation, respectively. The results demonstrate that these interventions are experimentally feasible and practical when using the presented developments: automated device tracking and equipment designed for MRI-guided interventions streamlined procedural workflow. Specifically, it was shown that fast and accurate needle placements along complex trajectories were feasible using a wireless interactive display and control device with a dedicated user interface for interventions. Moreover, safe and efficacious balloon angioplasties of the iliac artery were practical using the described framework of technologies along with a dedicated MRI protocol. Finally, it was demonstrated that these developments could be adapted and applied to MRI-guided endovascular mechanical thrombolysis of the middle cerebral artery. The technologies, described in this thesis have been shown to overcome many of the present limitations and should therefore be useful for enabling MRI-guided interventions while not further constraining the operating physician in an already complex environment. Nevertheless, it is acknowledged that many crucial issues remain to be solved in the field of iMRI and in the context of the presented research. In particular further device optimisations, improvements of the tracking implementation along with further in vivo evaluations are required before moving towards clinical evaluation. This thesis sets the groundwork for moving ahead with the eventual clinical realisation of optimised MRI-guided interventions.

Os nódulos de tireoide são frequentemente encontrados na prática clínica e, com o auxílio de ultrassonografia de alta resolução, podem ser identificados em 17 a 67% da população. A alta prevalência desses nódulos causa preocupação frequente aos pacientes e aos clínicos devido ao risco de malignidade, o que, por sua vez, leva a investigações laboratoriais de alto custo, invasivas e, eventualmente, a cirurgias desnecessárias. A punção aspirativa com agulha fina (PAAF) é o método diagnóstico pré-operatório mais preciso para identificação de um nódulo maligno de tireoide, mas não consegue excluir malignidade nos casos de citologia inadequada, nódulos com diagnóstico citológico de lesão folicular ou atipia de significado indeterminado e nas citologias sugestivas de neoplasia folicular. O objetivo deste estudo foi analisar as características clínicas, laboratoriais, ultrassonográficas e citológicas de uma população de pacientes com nódulos de tireoide submetidos a tireoidectomia e a relação entre estes achados e o risco de malignidade. Além disto, em relação aos nódulos malignos, verificar se o valor de TSH esteve associado a um estadiamento mais avançado da doença. Foram avaliados prontuários de 353 pacientes submetidos a tireoidectomia, acompanhados no Hospital das Clínicas da FMUSP de São Paulo, no período de fevereiro de 2002 a abril de 2010. O número total de nódulos nestes pacientes foi 392. As características clínicas e laboratoriais analisadas em cada paciente foram idade, sexo, valores séricos de TSH e T4 livre, presença de anticorpo anti-tireoperoxidase (anti- TPO) e anti-tireoglobulina (anti-TG). Foram avaliadas a presença de características ultrassonográficas sugestivas de benignidade (presença de halo periférico hipoecoico, aparência espongiforme, aspecto isoecóico ou hiperecoico) e de malignidade (nódulo sólido hipoecoico, contornos irregulares, presença de microcalcificações). Baseados nestas características, os nódulos foram classificados em benignos, indeterminados e suspeitos para malignidade. O diagnóstico citológico foi classificado em benigno, indeterminado, suspeito e maligno, e a análise combinada das características ultrassonográficas e citológicas também foi avaliada. Ao exame histopatológico, 200 nódulos eram malignos e 192 nódulos eram benignos. Os nossos resultados mostraram que sexo, idade, valores séricos de TSH e T4 livre e presença de anticorpo anti-TPO e anti-TG não estiveram associados a uma maior chance de malignidade. O valor de TSH sérico também não esteve associado a maior risco de recorrência ou estadiamento mais avançado nos pacientes com câncer Os nódulos maiores estiveram mais associados a benignidade quando avaliamos toda amostra. Na análise multivariada de toda amostra, após regressão logística, apenas a citologia maligna, hipoecogenicidade e presença de microcalcificações foram associados a malignidade. Já, a classificação ultrassonográfica que não se baseia em apenas uma característica mas em um conjunto de características, apresentou um alto valor preditivo de benignidade e foi útil na identificação de nódulos com citologia indeterminada. A classificação ultrassonográfica tem o potencial de reduzir o número de cirurgias para nódulos com citologia indeterminada / Thyroid nodules are often encountered in clinical practice, and with the use of high-resolution ultrasound may be identified in 17 to 67% of the population. The high prevalence of these nodules cause frequent concern to patients and clinicians due to the risk of malignancy, wich in turn leads on costly investigations, use of invasive diagnostic methods and sometimes unnecessary surgeries. Fine needle aspiration biopsy (FNAB) is the most accurate preoperative diagnostic method to identify a malignant thyroid nodule. However, FNAB cannot rule out malignancy in cases of inadequate cytology, follicular lesions, atypia of undetermined significance, and in cytology suggestive of follicular neoplasm. The aim of this study was to analyze clinical, laboratory, ultrasound and cytopathologic characteristics of a group of patients with thyroid nodules undergoing thyroidectomy and the relationship between serum levels of TSH and the risk of malignancy. In nodules found to be malignant in this cohort, we analyzed the association of TSH levels with advanced disease stage and risk of recurrence. We analyzed the records of 353 patients who were followed at Hospital das Clínicas - São Paulo Medical School, between February 2002 and April 2010, and who subsequently underwent thyroidectomy. The total number of nodules in these patients was 392. The clinical and laboratory characteristics included in the analysis were age, gender, serum levels of TSH and free T4, and presence of serum thyroid anti-peroxidase (anti-TPO) and anti-thyroglobulin (anti-TG) antibodies. We evaluated the presence of ultrasonographic features suggestive of benignity (isoechoic or hyperechoic appearance, presence of hypoechoic peripheral halo, spongiform appearance) and malignancy (hypoechoic appearance, irregular border, presence of microcalcifications). Based on these ultrasonographic characteristics, we classified the nodules as benign, indeterminate or suspicious for malignancy. According to the FNAB cytology, we also subdivided the nodules into benign, indeterminate, suspicious and malignant. The combined analysis of ultrasonographic features and cytopathology was also evaluated. On histopathology, 200 nodules were malignant and 192 were benign. Our results showed that gender, age, serum levels of TSH and free T4, as well as the presence of anti-TPO and anti-TG were not associated with increased risk of malignancy. Similarly, serum TSH value was not associated with increased risk of recurrence or more advanced stage in patients with thyroid cancer. A large nodule size was associated with benignity. In multivariate analysis, after logistic regression, only malignant cytology, hypoechoic appearance and presence of microcalcifications were associated with malignancy. Furthermore, the ultrasonographic classification, wich was not based in only one feature but in a set of characteristics, showed a high predictive value for benignity and seems to be useful in identifying nodules with indeterminate cytology at risk for malignancy. The use of ultrassonographic classification has the potential to reduce the number of surgeries for nodules with indeterminate cytology

NTRODUÇÃO: Embora haja cada vez mais provas de que a co-infecção pelo HCV piora a evolução da hepatotoxicidade relacionada ao HIV, as influências dos diferentes fatores associados a este permanecem mal compreendidas. Este estudo está destinado a avaliar os dados epidemiológicos, laboratoriais e HAART e sua associação com a evolução da taxa de progressão da fibrose (FPR), em doentes co-infectados acompanhados em centros de referência para o tratamento de HIV/VHC na cidade de São Paulo, Brasil. MÉTODOS: 938 prontuários de patientes coinfectados foram revisados para este estudo e 102 preencheram os critérios de inclusão. Um estudo transversal, avaliando os aspectos sócioepidemiológicos, laboratoriais e biópsia hepática foi realizado e correlacionado o grau de fibrose hepática e a FPR encontrada. RESULTADOS: A população foi caracterizada por indivíduos homens (83,3%), de meia-idade (42,9 anos), brancos (53,9%), com o principal fator de risco de aquisição de ambas as infecções foi através da utilização de drogas ilícitas (72,5%), principalmente intravenosa e presença de consumo de álcool (75,5%), com predominância do genótipo 1 de HCV (56,9%) e tempo médio de uso de antirretrovirals de 7,9 anos (DP = 3,6 a). A avaliação histológica não mostrou qualquer relação entre maior grau de fibrose na biópsia hepática relacionados com a exposição da antirretrovirals ou mesmo na FPR. Abuso de drogas ilícitas, incluindo cocaína inalada e intravenosa relacionam-se com taxas mais elevadas fibrose hepática e FPR. CONCLUSÃO: Os resultados enfatizam a necessidade de incentivar a retirada do consumo de drogas ilícitas da população de pacientes coinfectados HIV/VHC em uso de qualquer regime antirretroviral. O nosso estudo não encontrou nenhuma relação entre a utilização de regimes baseados em IP ou NNRTI e um pior prognóstico da fibrose hepática ou FPR na população avaliada. / BACKGROUND: Although there\'s growing evidence that the co-infection with HCV worsens the evolution of the HIV-related hepatotoxicity, the influence of the different factors associated to this remains poorly understood.This study intended to evaluate the epidemiological, laboratorial and HAART associated to the evolution of the fibrose progression rate (FPR) in co-infected patients followed in reference centers for the treatment of HIV/HCV in the city of São Paulo, Brazil. METHODS: 938 medical charts of co-infected patientes were reviewed for this study.and 102 fullfilled the inclusion and exclusion criteria to participate. A cross-sectional study evaluating socio-epidemiological aspects, laboratorial assesment and liver biopsy was performed and correlated with the fibrosis rate and the fibrosis progression rate (FPR). RESULTS: The population was characterized by male (83,3%), middle-age (42,9 years), white (53,9%) individuals, with a main risk factor of adquisition of both the infections trough illicit drugs-use (72,5%), mainly intravenous and alcohol consumption (75,5%), with predominance of HCV genotype 1 (56,9%) with a medium time of use of antiretrovirals of 7,9 years (SD=3,6 y). Histologic evaluation showed no relation between higher fibrosis degree in the liver biopsy related to the exposure of the antiretrovirals or even in the fibrosis progression rate (FPR). Illicit drugs abuse, including inaled and intravenous cocaine , were related to higher liver fibrosis rates and FPR. CONCLUSION: Our results emphasize the necessity of encourage the withdraw of ilicit drugs consumption in the HIV/HCV co-infected population in use of any antiretroviral regimen. Our study does no find any relation between the use of IP or NNRTI-based regimens and the poor prognosis of the liver fibrosis in this population.

INTRODUÇÃO: O aprimoramento dos métodos de rastreamento e a conscientização da população geral contribuíram para o diagnóstico cada vez mais precoce do câncer de mama e proporcionou, juntamente com o avanço na terapêutica, altas taxas de sobrevida. O estado do acometimento axilar por metástase é um dos principais fatores prognósticos em pacientes com câncer de mama, particularmente naquelas com diagnóstico em estádio inicial. Na última década, esforços científicos foram direcionados para simplificar a amostragem dos linfonodos axilares, diminuindo a morbidade, mas respeitando os princípios oncológicos. Nesse sentindo, a biópsia do linfonodo sentinela foi considerada o avanço mais importante. Ao se obter um método preditor do estado axilar, que apresente os benefícios da abordagem padrão dissecção axilar e biópsia de linfonodo sentinela porém sem seus efeitos colaterais e que seja facilmente reproduzível, realizaremos um grande avanço na avaliação e terapêutica do câncer de mama inicial. MÉTODOS: Foi realizado estudo transversal retrospectivo com base nos prontuários de pacientes com câncer de mama invasivo, não metastático, com qualquer idade, atendidas entre 1999 e 2007 no Setor de Mastologia da Disciplina de Ginecologia do Departamento de Obstetrícia e Ginecologia da Faculdade de Medicina da Universidade de São Paulo e Clínica Professor José Aristodemo Pinotti, cujo estudo histopatológico e imunoistoquímico foi supervisionado por um único médico patologista. Realizamos uma subdivisão imunoistoquímica dos tumores, sendo considerado luminal A os tumores com receptores hormonais positivos e HER 2 negativo; luminal B os com receptores hormonais positivos e HER 2 positivo; HER 2 as pacientes com receptores hormonais negativos e HER 2 positivo e triplo negativo aquelas com receptores hormonais e HER 2 negativos. Correlacionamos esses subtipos com as variáveis clínicas idade e tamanho tumoral para predizer a probabilidade de acometimento linfonodal axilar. RESULTADOS: Duzentos e trinta e nove casos foram analisados. No subtipo luminal A, a possibilidade de metástase foi maior quanto menor a idade da paciente e maior o tamanho do tumor. Essa foi a única associação que apresentou diferença estatisticamente significante. As pacientes que possuíam tumores triplo negativo tiveram, aproximadamente, 90% menos chance de metástase linfonodal que as pacientes com tumor luminal A. CONCLUSÕES: As pacientes com tumor luminal A apresentaram, significativamente, maior probabilidade de metástase linfonodal axilar. As pacientes com de tumores triplo negativo, com idade superior a 55 anos ou tumores menores que 2 cm, revelaram menor probabilidade de metástase axilar / INTRODUTION: The improvement of screening methods and awareness of general population contributed to the increasingly early diagnosis of breast cancer and provided, together with advances in therapy, high survival rates. The status of axillary involvement is a major prognostic factor in patients with breast cancer, particularly those with early stage. In the last decade, research efforts were directed to simplify the sampling of axillary lymph nodes, decreasing the morbidity, but respecting the oncological principles. In this sense, the sentinel lymph node biopsy was considered the most important advance. If we obtain a method to predict the axillary status, with the benefits of the standard approach - axillary dissection and sentinel lymph node biopsy - without its side effects and easily reproducible, we will hold a major advance in the assessment and treatment of early breast cancer. METHODS: We conducted a retrospective cross-sectional study based on records of patients with invasive breast cancer, non metastatic, with any age, treated between 1999 and 2007 in the breast cancer Sector of the Gynecology Discilpine of the Department of Obstetrics and Gynecology, Faculty of Medicine, University of São Paulo and Private Clinic of Professor José Aristodemo Pinotti, whose histopathological studies were supervised by a single pathologist. We performed an immunohistochemical subdivision of the tumors, and considered luminal A tumors with positive hormonal receptors and negative HER 2, luminal B with positive hormonal receptors and positive HER 2, HER 2 patients with negative hormonal receptors and positive HER 2 and the triple-negative those with negative hormonal receptors and HER 2. Those subtypes were correlated with the clinical variables age and tumor size in predicting the likelihood of axillary lymph node involvement. RESULTS: Two hundred and nine cases were analyzed. In the luminal A, the possibility of axillary metastasis was higher in the younger patients and larger tumors. That was the only combination that showed statistically significant difference. The patients who had triplenegative tumors had approximately 90% less chance of lymph node metastasis than patients with tumors luminal A. CONCLUSIONS: The patients with luminal A tumors showed a significantly association with greater likelihood of axillary lymph node metastasis. The patients with triple negative tumors, age over 55 years or tumors smaller than 2 cm showed a lower likelihood of axillary lymph node metastasis

Στις αρχές της δεκαετίας του 80 μια νέα εποχή ξεκινά για την Μαστογραφία και τον καρκίνο του Μαστού, με τη χρήση της τεχνικής "χαμηλής δόσης Μαστογραφίας", τη σωστή ενημέρωση των γυναικών για την πρόληψη του καρκίνου του μαστού και την εφαρμογή του πληθυσμιακού ελέγχου σε ασυμπτωματικές γυναίκες, με συνέπεια να αυξήσουν τον αριθμό των μη-ψηλαφητών και μη ψηλαφητών καρκίνων μαστού που διαγιγνώσκονται σε πρώιμα στάδια (0, Ι, ΙΙ, ΙΙΙΑ κλπ) με καλλίτερη πρόγνωση και θεραπεία. Προηγούμενες κλινικές μελέτες προσπάθησαν να συσχετίσουν τα ακτινολογικά με τα ιστολογικά χαρακτηριστικά του καρκίνου του μαστού αλλά δεν κατάφεραν να αναδείξουν σημαντικές διαφορές όσον αφορά τα ιστολογικά και βιολογικά χαρακτηριστικά μεταξύ των συμπωματικών και των μαστογραφικά εντοπιζόμενων μη ψηλαφητών καρκινωμάτων του μαστού . Επιπλέον, αρκετοί ερευνητές φαίνεται να καταλήγουν στο συμπέρασμα ότι τα καλά προγνωστικά χαρακτηριστικά των καρκινωμάτων του μαστού που αναδεικνύονται με την προληπτική μαστογραφία σχετίζονται άμεσα ή έμμεσα με την επίδραση βιολογικών παραγόντων. Σκοπός της παρούσας μελέτης είναι η ανάδειξη των δεικτών που σχετίζονται με την μαστογραφική απεικόνιση της κακοήθων ογκόμορφων αλλοιώσεων ψηλαφητών και μη και της επιθετικότητας της νόσου. Μελετήθηκαν συνολικά πεντακόσιες εβδομήντα τέσσερεις ογκόμορφες αλλοιώσεις ψηλαφητές ή μη του μαστού σε πεντακόσιες εβδομήντα ασθενείς που εντοπίστηκαν κατά τη διάρκεια του μαστογραφικού ελέγχου στο εργαστήριο μας κατά την περίοδο 1994- 2004. Όλοι οι ασθενείς υποβλήθηκαν σε βιοψία δια λεπτής βελόνης (FNA) ή κατευθυνόμενη από με μαστογραφία χειρουργική βιοψία. Η ιστολογική εξέταση ανέδειξε 410/574 (71,4%) κακοήθεις ογκόμορφες αλλοιώσεις και 164/574 (28,5%) καλοήθεις. Ανοσοϊστοχημεία πραγματοποιήθηκε σε τομές παραφίνης σε 390 από τις 410 κακοήθεις αλλοιώσεις χρησιμοποιώντας μία ποικιλία μονοκλωνικών και πολυκλωνικών αντισωμάτων ενάντια στις εξής πρωτεϊνες: ER, PR, p53, HER-2,Ki 67 και KATH D. Οι κακοήθεις ογκόμορφες αλλοιώσεις ταξινομήθηκα από την Μαστογραφική τους απεικόνιση (σύμφωνα Breast Imaging Reporting and Dada System BI RADS) σε τρείς κατηγορίες : στην κατηγορία Β (οι αστεροειδείς κακοήθεις ογκόμορφες αλλοιώσεις) ήταν το (44,8%), στην κατηγορία Α (οι άτονες με ασαφή ή εν μέρει ασαφή όρια) το 36% και στην κατηγορία Γ (σκιάσεις και αποτιτανώσεις) που ήταν 18,2% όλων των κακοήθων ογκόμορφων αλλοιώσεων. Η ανάλυση των αποτελεσμάτων μεταξύ της μαστογραφικής απεικόνισης των κακοήθων ογκόμορφων αλλοιώσεων και των ιστολογικών και βιολογικών χαρακτηριστικών των ανέδειξε : Σημαντική συσχέτιση της μαστογραφικής απεικόνισης με το μέγεθος των ογκόμορφων αλλοιώσεων (p=0.01<0.05). Σημαντική συσχέτιση με το βαθμό διαφοροποιήσεως της κακοήθειας (p=0.005<0.05). Σημαντική συσχέτιση με την έκφραση των πρωτεϊνών p53 (p=0.015) και Ki -67( p=0.02). Δεν παρατηρήθηκε σημαντική συσχέτιση της απεικόνισης των ογκόμορφων αλλοιώσεων με την ηλικία των ασθενών (p=0.08>0.05), με την ανίχνευση πυρηνικής θετικότητας για τους οιστρογονικούς (ER) και τους προγεστερονικούς(PR) υποδοχείς (p =0.4>0.05) καθώς και με τις πρωτεΐνες HER-2. και KATH D. Επίσης παρατηρήθηκε οριακή συσχέτιση στην απεικόνιση των κακοήθων ογκόμορφων αλλοιώσεων και των λεμφαδένων. Συμπερασματικά βρήκαμε ότι η κατηγορία Β με τις αστεροειδείς ογκόμορφες αλλοιώσεις είχε ευνοϊκότερη επίδραση από τ η κατηγορία Α με τις άτονες με ασαφή ή εν μέρει ασαφή όρια και με τις ογκομορφές αλλοιώσεις και αποτιτανώσεις (κατηγορία Γ). Οι άτονες με ασαφή ή με εν μέρει ασαφή όρια κακοήθεις ογκόμορφες αλλοιώσεις(κατηγορία Α) σχετίζονται με χαμηλής διαφοροποίηση κακοήθεια (grade 3) με υπερέκφραση του p53 και Ki -67 και με αρνητικούς υποδοχείς (PR και ER). Οι όγκοι αυτοί είναι μεγάλοι όγκοι με ίδια πολλές φορές μαστογραφική απεικόνιση με εκείνη των καλοηθών ογκόμορφων αλλοιώσεων. / At the beginning of 80 a new era for the Mammography and the breast cancer started with the use of the technique "low dose Mammography", with the correct information of women for the prevention of the breast cancer and the application of mass screening in asymptomatic women, with the result to increase the number of palpable and no- palpable breast cancers diagnosed in early stages (0,I,II,IIIA etr) with better prognosis and therapy. Previous clinical studies have attempted to correlate the radiological with the histological characteristics of breast cancer but did not succeed to show significant differences as for us the histological and biological characteristics among the symptomatic and the mammographically localized non- palpable breast cancers. Furthermore, many investigators see to conclude that the best prognostic characteristics of breast cancers that are identified with the preventive mammography are directly or indirectly related by the effect of biological factors. The aim of the present study is to mark out indicators that are related with the mammographic appearance of malignant palpable and no- palpable lesions and the aggressiveness of disease. In total five hundred seventy four palpable and no- palpable breast lesions have been studied in five hundred seventy patients that were localized during the mammographic screening in our department, between 1994 to 2004. All the patients were subjered to line needle biopsy (FNA) or mammographically guided open surgical biopsy. Histological examination showed 410/574 (71.4%) malignant lesions and 164/574 (28.5%) benign lesions. Immunohistochemistry was performed in paraffin sections in 390 of 410 malignant lesions using a variety of monoclonal and polyclonal antibodies against the following proteins ER,PR, P53, HER-2, Ki67and KATH D. The malignant lesions were classified from their mammographic appearance (according to Breast Imaging Reporting and Dada System BI RADS) in three categories: category A (lesions with poorly defined or partially poorly defined margins)were 36%, category B (speculated malignant lesions) were 44.8% and category C (lesions wih calcifications) were 18.2% of all malignant lesions. The analysis of our results between the mammographic appearance of the malignant lesions and their histological and biological characteristic showed the following: 1) Significant correlation existed between the mammographic appearance and the size of the lesions (p=0.01<0.05). 2) Significant correlation existed with the degree of differentiaton of malignancy (p=0.005<0.05). 3) Significant correlation existed with over expression of proteins P53 (p=0.015). and Ki- 67 (p=0.02). No significant correlation was observed between the appearance of lesins with the age of the patients (p=0.08>0.05), with the detection of nuclear positivity of the estrogens (ER) and progesterone (PR) receptors (p=0.4>0.05) and also with the proteins HER-2 and KATH D. Furthermore a bode line correlation was observed between the appearance of the malignant lesions and lymph notes. In summary, it was found that the category B patients with the speculated lesions had a more favorable effect than category A with the poorly defined or partially poorly defined limits, and the category C lesions with calcifications. The poorly defined or partially poorly defined limits malignant lesions (category A) are related with low grade malignancy (grade 3, with over expression of P53 and Ki-67 and with negative receptors (PR and ER). These are large size lesions and are difficulty diagnosed from benign lesions.

No description available.

Ziel der vorliegenden Arbeit war es, 1. die Einflüsse von Alter bzw. Parität auf Prävalenz und Entwicklung endometrialer Alterationen beim Rind zu untersuchen, 2. einen repräsentativen Überblick über die mittels Endometriumbiopsie erfassbaren Erkrankungen bei klinisch gesunden Kühen zu schaffen 3. die Entwicklung der histopathologischen Befunde nach einer weiteren Trächtigkeit zu dokumentieren. Grundlage dieser Arbeit sind sechs Endometriumbioptate von klinisch (inklusive rektaler Untersuchung) gesunden Färsen (Gruppe A), 165 Bioptate von klinisch gesunden Kühen (Gruppe B) sowie Bioptat-Paare (Gruppe C) von 46 Tieren, die im Abstand einer Trächtigkeit entnommen wurden. Die Proben der Gruppe A dienten als Kontrollgruppe, wobei die Gefäße als Grundlage für die Normalstruktur vor der ersten Trächtigkeit herangezogen wurden. Innerhalb der Endometriumbioptate der Färsen (Gruppe A) waren keine pathologischen Veränderungen (Endometritis, Endometrose, Angiosklerose) und keine Lymphfollikel nachweisbar. Bezüglich der Endometritis-Prävalenz, die bei 23,6 % lag, ließ sich in Gruppe B keine Abhängigkeit von der Parität oder dem Entnahmezeitpunkt nachweisen. Eine Endometrose trat überwiegend bei Erstkalbinnen (24,4 %) und Tieren mit fünf Abkalbungen (41,6 %) auf. Eine Korrelation mit dem Alter lag nicht vor. Auffällig war die signifikant höhere Endometrose-Prävalenz innerhalb der ersten acht Wochen p.p. (20,1 %), im Vergleich zu später entnommenen Proben (3,2 %). Für das Auftreten von Lymphfollikel, die im Mittel bei 53,3 % der Kühe auftraten, konnten keine Korrelationen mit der Parität oder dem Zeitpunkt der Bioptatentnahme ermittelt werden. Auch scheint weder das Vorliegen einer Endometritis die Entwicklung von Lymphfollikeln zu begünstigen, noch schützen Lymphfollikel im Endometrium vor einer Entzündung des Uterus. Mit steigender Parität war eine Zunahme der Angiosklerose-Prävalenz zu verzeichnen, allerdings konnte keine statistisch signifikante Korrelation zum Grad der Gefäßveränderungen (anhand der H.E.-Färbung) nachgewiesen werden. Innerhalb der Karunkel lagen signifikant höhergradige Veränderungen vor als in interkarunkulären Gefäßen. Da das Alter der Tiere eng mit der Anzahl der Abkalbungen korreliert, war eine gesonderte Betrachtung der altersassoziierten Einflüsse anhand des untersuchten Materials nicht möglich. Mittels der durchgeführten Untersuchungen ließ sich kein negativer Einfluss der vorwiegend geringgradigen histopathologischen Veränderungen im Endometrium (Endometritis, Endometrose, Angiosklerose, Lymphfollikel) auf die Fertilität (Erstbesamungserfolg, Rastzeit, Güstzeit, Gesamtträchtigkeitsrate) nachweisen. Innerhalb der Gruppe C konnte nach einer weiteren Trächtigkeit ein signifikanter Anstieg der Endometrose-Prävalenz von 7,0 % auf 25,6 % nachgewiesen werden, während der Anteil der Tiere mit einer Endometritis bzw. Angioskerose nahezu unverändert blieb. Bei einigen Tieren wurde allerdings in der ersten Probe, jedoch nicht im Folgebioptat, eine Endometrose diagnostiziert. Bei einer Kuh lag dabei sogar zuerst eine mittelgradige periglanduläre Fibrose vor, die im zweiten Bioptat nicht mehr nachweisbar war. Im Hinblick auf die Entwicklung vaskulärer Alterationen konnte nach einer weiteren Trächtigkeit eine signifikante Zunahme der Faserzubildungen (Pikrosiriusrot-Färbung) in der Tunica media interkarunkulärer arterieller Gefäße und karunkulärer Arterien sowie in der Tunica adventitia von interkarunkulären Arteriolen nachgewiesen werden. Weiterhin wurden im Zweitbioptat anhand der Pikrosiriusrot-Färbung signifikant höhergradigere Veränderungen (Gesamtschädigung) der karunkulären Arterien und Arteriolen diagnostiziert. Für alle übrigen Gefäßtypen lag zwar eine Zunahme der Gesamtschädigung im zweiten Bioptat vor, diese war jedoch nicht statistisch signifikant. Zu beiden Untersuchungszeitpunkten konnten innerhalb des untersuchten Materials vor allem Elastosen und Elastofibrosen nachgewiesen werden. Dabei lagen bezüglich der Art der zugebildeten Fasern keine signifikanten Unterschiede zwischen beiden Proben vor. Insgesamt konnten anhand des untersuchten Materials von klinisch gesunden Kühen zahlreiche pathologische Befunde im Endometrium diagnostiziert werden. Allerdings ist die Interpretation der Befunde bislang schwierig, da keine Einflüsse auf die Fertilität nachweisbar waren. Jedoch lagen besonders im Hinblick auf die Endometritis und Endometrose meist nur geringgradige Veränderungen vor, so dass sich diese vermutlich nicht negativ auf die Fruchtbarkeit auswirken. Weiterhin ist anhand der vorliegenden Ergebnisse fraglich, ob eine Endometrose beim Rind als irreversible Erkrankung angesehen werden muss. Hierzu sind weitere Studien erforderlich.