Introdução: o status dos linfonodos axilares permanece um dos mais importantes fatores prognósticos no carcinoma de mama em estágios iniciais, além de definir o uso de terapias complementares. A biópsia de linfonodo sentinela (BLNS) surgiu com a finalidade de estadiar a axila com o mínimo de morbidade, tendo como objetivo a identificação e o estudo patológico do primeiro linfonodo axilar proveniente da drenagem linfática da mama. Pacientes com axila clinicamente negativa têm indicação de biópsia de linfonodo sentinela como método de estadiamento da axila, e quando o resultado era positivo para metástase recomendava-se o esvaziamento axilar. Por recomendação do ACOSOG Z0011, o esvaziamento axilar (EA) após uma biópsia de linfonodo sentinela positivo não é necessário. Esse estudo demonstrou não haver benefício em realizar o EA na presença de LNS positivo na sobrevida global ou na sobrevida livre de doença. Objetivos: Avaliar a taxa de recidiva e morte em pacientes submetidas à cirurgia conservadora de mama e BLNS positiva com posterior esvaziamento axilar no Hospital de Clínicas de Porto Alegre; e, como objetivo secundário, avaliar as características clínicas e patológicas dessa população. Método: foi realizado um estudo de coorte retrospectiva, incluindo pacientes com diagnóstico de carcinoma de mama invasor submetidas à cirurgia conservadora da mama e BLNS, cujo resultado foi positivo para presença de metástases, e foram submetidas ao EA o período de janeiro de 2004 a dezembro de 2008. Resultados: foram incluídas 144 pacientes submetidas à biópsia de linfonodo sentinela e CCM; 33 tiveram o achado de biópsia de linfonodo sentinela positivo para metástase, e dessas 33 pacientes restaram 27 para análise dos dados. A taxa de sucesso na identificação do LNS foi de 0,96. A idade média das pacientes foi de 53,8 anos, o número de LNS ressecados foi de 1,6 por paciente; a média do tamanho tumoral foi de 2,3 cm. Seis pacientes apresentaram doença axilar residual correspondendo a 22,2% da amostra e tiveram um risco relativo de morte de 3 vezes mais para aquelas sem doença axilar residual e 50% a mais de desenvolvimento de metástases. Conclusão: O comprometimento axilar é importante fator no prognóstico das pacientes com câncer de mama, quanto maior o comprometimento da axilar pior será o desfecho de sobrevida livre de doença e de morte. Acreditamos que se pode aplicar a conduta do ACOSOG Z0011 também nas pacientes do HCPA devido à alta sensibilidade do método no nosso meio. / Introduction: The status of axillary lymph nodes remains one of the most important prognostic factors in breast carcinoma in the early stages, in addition it helps to defining the use of complementary therapies. Sentinel lymph node biopsy (SLNB) was developed with the purpose of staging the axilla with minimal morbidity, aiming at the identification and pathological study of the first axillary lymph node from the lymphatic drainage of the breast. Patients with clinically negative lymph node have indication of SLNB as a method of axillary staging, and with a positive finde for metastasis the axilar clereance was performed. Nowadays, due to the ACOSOG Z0011 Study, the axillary dissection (AD) after a positive SLNB for metastasis was put in check. This estudy have as a result no difference in global survive ou disease free survive if ALND was not performed in a positive SLNB. In the present study, we intend to evaluate the clinical and histopathological characteristics of patients submitted to breast conservative surgery and sentinel lymph node biopsy with a positive result for metastasis. Main objective: Evaluate the rate of recurrence and death in patients submitted to conservative breast surgery and BLNS with posterior axillary emptying at Hospital de Clínicas, Porto Alegre. It is a secondary objective to evaluate the clinical and pathological characteristics of this population. Material and Methods: A retrospective cohort study was performed, including 144 patients diagnosed with invasive breast carcinoma submitted to conservative breast surgery and SLNB, whose results were positive for metastases, and were submitted to AD, at the Mastology Unit of the Hospital de Clinicas de Porto Alegre (HCPA), from January 2004 to December 2008. Results: Of 144 patients submitted to SLNB and BCS, 33 had SLNB positive for metastasis, of these 33 patients remained 27 for data analysis. The success rate in LNS identification was 0.96. The mean age of the patients was 53.8 years, the number of resected SLN was 1.6 per patient; The mean tumor size was 2.3 cm. Six patients had residual axillary disease corresponding to 22.2% of the sample and had a relative risk of death of 3 times more for those without residual axillary disease and 50% more for the development of metastases. Conclusion: Axillary involvement is an important factor in the prognosis of patients with breast cancer, and the greater the axillary impairment, the worse the diseasefree survival outcome and death. We believe that the ACOSOG Z0011 trial can also be applied to HCPA patients who meet the inclusion criteria for this purpose, due to the high sensitivity of the method in our environment.

A fluorescência é uma técnica amplamente empregada na área de diagnóstico médico, com aplicações distintas. Uma de suas aplicações é a detecção de um determinado marcador que pode ser injetado no paciente. A indocianina verde (ICG) é um exemplo de marcador fluorescente que pode ser empregado para auxiliar na identificação do linfonodo sentinela. A excitação é realizada em 780 nm e a emissão detectada ao redor de 850 nm. Tais comprimentos de onda são muito favoráveis para aplicação médica por apresentarem pouca absorção por tecidos biológicos. O objetivo deste trabalho foi desenvolver um sistema de imagens por fluorescência de ICG. Este sistema é basicamente constituído por um dispositivo de iluminação e de aquisição e tratamento de imagem. Dois protótipos foram construídos e testados, um com excitação Laser e o segundo a LED. O dispositivo de iluminação oferece uma iluminação uniforme em uma área de 10 por 15 cm a uma distância de 30 cm. A fluorescência é captada por um sistema composto por duas câmeras perpendiculares uma à outra e um espelho dicroico angulado 45° a ambas, cuja função é separar a imagem por bandas. Uma das câmeras capta a imagem refletida do espelho no espectro visível e a outra capta a imagem transmitida pelo espelho no infravermelho. As imagens obtidas pelas câmeras recebem tratamento em uma rotina desenvolvida em plataforma LabVIEW® para destacar a região com fluorescência sobreposta na imagem sob iluminação branca em tempo real, sendo possível salvar figuras ou vídeos, dependendo da necessidade do operador. O equipamento foi testado no Hospital de Câncer de Barretos em pacientes para ressecção cirúrgica de tumores de cabeça e pescoço e de melanoma e apresentou resultados promissores. / Fluorescence is a widely used technique in medical diagnostic, with several applications. One of its applications is the screening of a particular marker that can be injected into the patient. The indocyanine green (ICG) is an example of fluorescent marker that can be used to assist the identification of the sentinel lymph node. The excitation is performed at 780 nm and the emission is detected around 850 nm. Such wavelengths are very suitable for medical applications due to their little absorption by biological tissues. The objective of this study was to develop a system of fluorescence imaging of ICG. This system is basically constituted by an irradiation and image acquisition device and a routine for image processing. Two prototypes were built and tested, the first one with Laser excitation and the second with LED. The lighting device provides uniform illumination in an area of 10 by 15 cm at a distance of 30 cm. The fluorescence is collected by a system with two cameras orthogonal to each other and a dichroic mirror angled 45 ° to both, whose function is to separate the image in bands. One of the cameras captures the image reflected from the mirror in the visible spectrum and the other captures the image absorbed by the mirror in the infrared. The images obtained by the cameras receive treatment on a routine developed in LabVIEW® platform to highlight the fluorescent region overlapping the image under white light in real time, making it possible to save pictures or videos, depending on the needs of the operator. The equipment was tested in Barretos\' Cancer Hospital in patients for surgical resection of head and neck tumors and melanoma tumors and presented promising results.

Linfadenopatia pode estar presente em qualquer fase da infecção pelo HIV a apresenta uma variedade de diagnósticos diferenciais possíveis, desde manifestações secundárias ao próprio HIV até doenças oportunistas ou neoplasias. Foi realizado um estudo de corte transversal de pacientes que realizaram biópsias de linfonodo periférico no Hospital de Clínicas de Porto Alegre entre Janeiro de 2004 a Dezembro de 2008. Foram realizadas 210 biópsias, 131 (61,9%) pacientes eram do sexo masculino, a mediana da idade foi 36 (18-74) anos e da contagem de CD4 149 (1-756) cels/mm3. Cento e seis (50,5%) biópsias foram realizadas na região cervical. Os diagnósticos mais prevalentes incluíram micobacteriose 105 casos (50,2%) sendo que mais de 90% dos casos foram tuberculose; hiperplasia reacional (HR) 48 casos (22,7%), linfoma 19 casos (9,0%) e micoses sistêmicas 12 casos (5,7%) que incluíram a histoplasmose, paracoccidioidomicose e criptococose. Esse estudo demonstra que a biópsia de linfonodos periféricos em pacientes com infecção pelo HIV é uma importante ferramenta no diagnóstico de doenças oportunistas no nosso meio. / Peripheral lymphadenopathy is commonly present in HIV- infected patients and has a wide spectrum of differential diagnoses. We performed a cross-sectional study of peripheral lymph node biopsies performed from 2004 to 2008 in HIV patients assisted in a public hospital in Southern Brazil. Two hundred and ten biopsies were performed, 131(61.9%) patients were male, median of age was 36 years old with a mean of lymphocyte CD4 count of 149 (1-756) cells/mm3. Most of biopsies were performed in the cervical site 106 (50.5%). The most prevalent diagnosis were mycobacteriosis 105 (50.2%), more than 90% was tuberculosis; reactive follicular hyperplasia 48 (22.7%); lymphoma 19 (9.0%); systemic mycosis 12 (5.7%), including histoplasmosis, paracoccidioidomycosis and cryptococcosis. Peripheral lymph node biopsy is a useful tool to diagnose opportunistic diseases such as mycobacteriosis, HIV related malignancies and invasive fungal infections in HIV-infected patients.

CoordenaÃÃo de AperfeiÃoamento de Pessoal de NÃvel Superior / estudar o linfonodo sentinela em pacientes portadoras de cÃncer na mama localmente avanÃado e que foram submetidos a quimioterapia neoadjuvante, compararando-o com os linfonodos axilares nÃo-sentinelas. Verificar a taxa de identificaÃÃo do linfonodo sentinela nestas pacientes, assim como estimar a sensibilidade, especificidade, falso-negativo, valor preditivo negativo e acurÃcia do mÃtodo. Metodologia: estudo transversal de validaÃÃo de teste diagnÃstico, envolvendo 34 pacientes oriundas do AmbulatÃrio da Maternidade-Escola Assis Chateaubriand. As pacientes portadoras de cÃncer na mama localmente avanÃado foram submetidas a quimioterapia neoadjuvante e aquelas que apresentaram axila clinicamente negativa para metÃstase de cÃncer de mama foram submetidas a biopsia do linfonodo sentinela e linfadenectomia axilar, utilizando administraÃÃo subareolar de azul patente, e este, apÃs sua identificaÃÃo, foi estudado mediante o exame de citologia de contato e parafina e comparado com conteÃdo linfÃtico axilar nÃo-sentinela. Realizada anÃlise descritiva e anÃlise dos testes utilizando teste t de Student, as proporÃÃes dos testes foram consideradas significativamente diferentes quando a probabilidade de estas serem semelhantes foi menor ou igual a 0,05. Resultados: Quando foi testada a citologia de contato intra-operatÃrio e parafina linfonodo sentinela e padrÃo-ouro os linfonodos sentinelas e nÃo-sentinelas, a taxa de identificaÃÃo do linfonodo sentinela foi de 85,3%. A sensibilidade foi de 84,62% e a especificidade de 100%. O valor preditivo negativo de 87,99% e taxa de falso-negativo de 12,01%. A acurÃcia foi de 92,77%. Dado observado na amostra foi a diferenÃa significativa do nÃmero mÃdio do total de linfonodos observados entre o grupo de pacientes com tempo de intervenÃÃo cirÃrgica Ãtimo p=0,037. Quando foi testada apenas a citologia de contato intraoperatÃria do linfonodo sentinela e padrÃo-ouro, a parafina dos linfonodos sentinelas e nÃo-sentinelas a sensibilidade foi de 62,50%, a especificidade de 100%, valor preditivo negativo de 75,04%, falso-negativo de 24,96% e acurÃcia de 82,38%. ConclusÃo: a citologia de contato intraoperatÃrio do linfonodo sentinela para pacientes com cÃncer de mama localmente avanÃados com axila clinicamente negativa apÃs quimoterapia neoadjuvante apresenta baixa sensibilidade e taxa de falso-negativo elevada. / Aims: investigating sentinel lymph node in patients with locally advanced breast cancer whom were administered neoadjuvant chemotherapy, by contrast to non-sentinel axillary lymph nodes. Verifying the identification of sentinel lymph node rate in these patients, as well as estimating methodâs sensibility, specificity, false-negative and accuracy. Methodology: transversal study for validation of a diagnostic test, with 34 patients from Maternidade-Escola Assis Chateaubriandâs ambulatory. The locally advanced breast cancer patients were treated with neoadjuvant chemotherapy, and the ones with cancer metastasis clinically negative axilla were submitted to sentinel lymph node biopsy and axillary lymphadenectomy, using subareolar patent blue, and, after its identification, it was studied with contact cytology and paraffin and it was compared with non-sentinel axillary lymph content. The descriptive analysis of tests used Studentâs t-test, and tests proportions were considered significantly different when their similarity possibility was less or equal to 0.05. Results: When intraoperatory contact cytology study, paraffin sentinel lymph node and gold standar, sentinel and non-sentinel lymph nodes, the sentinel lymph node identification rate was 85.3%. Sensibility was 84.62%, and specificity was 100%. The predictive negative value was 87.99%, and the false-negative rate was 12.01%. Accuracy rate was 92.77%. The study points the significant difference of total lymph nodes mean number observed among the group with optimal time of surgical intervention p=0.037. When only the intraoperatory contact cytology of sentinel lymph node and gold pattern, the paraffin of sentinel and non-sentinel lymph nodes, sensibility was 62.50%, specificity 100%, predictive negative value 75.04%, false-negative 24.96%, and accuracy 82.38%. Conclusion: intraoperatory contact cytology of sentinel lymph node to locally advanced breast cancer patients with clinically negative axilla after neoadjuvant chemotherapy presents low sensibility and high false-negative rates.

INTRODUÇÃO: Asma é uma doença inflamatória crônica das vias aéreas que envolve diversos tipos de células, especialmente eosinófilos, células T, macrófagos, células epiteliais e células dendríticas. Durante a exposição alérgica, células dendríticas migram para os linfonodos broncopulmonares e iniciam a resposta imune na asma. Em asma humana, poucas informações sobre células dendríticas, células B, células T, eosinófilos, VCAM em linfonodos broncopulmonares são conhecidas. Poucos estudos também descrevem a interação celular entre linfonodos e vias aéreas na asma durante exacerbações. MÉTODOS: Foram analisados por método histoquímico, imuno-histoquímico e análise de imagens as expressões de Vermelho Congo, FatorXIIIa+, CD83+, CD207+, CD1a+, CD23+, CD20+, CD4+, CD8+, VCAM, em vias aéreas grandes e linfonodos broncopulmonares de 11 indivíduosnão asmáticos falecidos por asma e 8 controles não asmáticos. A análise dos marcadores foi realizada na região cortical dos linfonodos e em três regiões das vias aéreas: camadas interna, muscular e externa. RESULTADOS: Os indivíduos asmáticos apresentaram maior expressão de eosinófilos nos lifonodos broncopulmonares e nas três camadas das vias aéreas. Os marcadores FatorXIIIa+, CD23+, CD20+, CD4+ e CD8+ apresentaram aumento na camada externa das vias aéreas dos indivíduos asmáticos. CONCLUSÕES: Os eosinófilos estão aumentados nos linfonodos broncopulmonares e nas vias aéreas dos asmáticos. Alguns marcadores como o FatorXIIIa+, CD20+, CD4+, CD8+ e CD23+ estão aumentados apenas na camada externa das vias aéreas dos asmáticos. VCAM, CD83+, CD207+, CD1a+ não apresentaram aumento nos asmáticos. Este resultado sugere que esses marcadores não estão relacionados ao evento da asma fatal nos indivíduos estudados. As correlações encontradas entre vias aéreas e linfonodos nos asmáticos sugerem que na asma fatal ocorra um fluxo celular direcionado. Nossos resultados fornecem novas evidências para a participação do linfonodo broncopulmonar na exacerbação da asma / INTRODUCTION: Asthma is a chronic inflammatory disease of the airways that involves many different cells, specially mast cells, eosinophils, T cells, macrophages, epithelial cells and dendritic cells (DCs). During allergen exposure, pulmonary DCs migrate to bronchopulmonary lymph nodes (LNs) and prime the immune cells that will characterize the immune response in asthma. In human asthma, there is no information about the composition of DCs, B cells, T cells, and vessels in the regional LNs involved in the immune responses to inhaled antigens. Also, there is little information about the lung - LN cells trafficking occurring in asthma during exacerbations. METHODS: Using histochemistry, immunohistochemistry and image analysis, we investigated the expression of Congo Red+ (eosinophil), factor XIIIa+, CD23+, CD4+, CD8+, CD20+, CD207+, CD83+, CD1a+ cells and VCAM-1+ in the large airways and bronchopulmonary lymph nodes of 11 non-smoker patients that died due to an asthma exacerbation and compared with 8 deceased non-asthmatic controls. The analysis of the markers was carried out in the cortical área of the lymph nodes and three layers of the airways: internal, airway smooth muscle and outer layer. RESULTS: The LNs of asthmatics had increased expression of eosinophils when compared to controls. The large airways of asthmatics had increased expression of eosinophils in all the layers and factor XIIIa+, CD4+, CD8+, CD20+ and CD23+ had increased in the outer layer. CONCLUSIONS: A fatal asthma episode is associated with an altered expression of eosinophils in LNs and large airways.Factor XIIIa+ monocyte dendritic cel, CD4+, CD8+, CD20+, CD23+ cells had increased in the large airways without a concomitant increase in the expression of these cells in bronchopulmonary LNs.However, some DC cell trafficking between the airway mucosa and LNs seems occurs in this severe fatal asthma exacerbation

Introdução: o carcinoma de endométrio é uma das neoplasias ginecológicas mais comuns nos países industrializados. O tratamento desta doença é primariamente cirúrgico. Segundo a normatização da Federação Internacional de Ginecologia e Obstetrícia (FIGO), a cirurgia ideal consiste na realização de histerectomia total, anexectomia bilateral, linfadenectomia retroperitonial e coleta de citologia peritoneal. No entanto, a realização sistemática da linfadenectomia tem sido contestada. Alguns centros de referência acreditam que deva ser realizada apenas em um grupo de pacientes com alto risco para disseminação linfática da doença. O desafio é encontrar marcadores pré-operatórios que possam ser preditivos da presença de doença linfonodal e, assim , virem a ser utilizados para a definição da necessidade da linfadenectomia. Objetivos: verificar se a expressão imuno-histoquímica (IMH) positiva da p53 na amostra endometrial diagnóstica e, se o valor sérico do CA 125 obtido no tempo pré-operatório, podem ser efetivos para prever a presença de doença linfonodal. Métodos: um estudo transversal restrospectivo foi realizado. Foram incluídas 111 pacientes com carcinoma de endométrio submetidas a histerectomia com anexectomia bilateral e linfadenectomia com ou sem citologia peritoneal. Noventa pacientes apresentavam CA 125 pré-operatório e 73, a avaliação da p53. Cinquenta e quatro pacientes apresentavam as duas variáveis em combinação. Foram estabelecidas as associações entre o valor de CA 125 e da expressão IMH da p53 com o envolvimento linfonodal. Uma curva ROC foi construída para identificar o valor de CA 125 com melhor Sensibilidade (S) e Especificidade (E) para doença linfonodal. / Introduction: endometrial carcinoma is one of the most common gynecological malignancies in industrialized countries. The treatment of this disease is primarily surgical. According to the International Federation of Gynecology and Obstetrics surgery ideal consists in performing total hysterectomy, bilateral adnexectomy, retroperitoneal lymphadenectomy and peritoneal cytology. However, the systematic lymphadenectomy has been disputed, and should only be performed in a group of patients at high risk of lymphatic spread of the disease. The challenge is to find preoperative markers that may be predictive of the presence of lymph node disease and thus come to be used to determine the necessity of lymphadenectomy. Objectives: to determine whether the positive immunohistochemical expression (IMH) of p53 in diagnostic endometrial sample and, if the value of serum CA 125, obtained during pre-operative, can be effective to predict the presence of lymph node disease. Methods: a cross-sectional study was conducted. The final sample consisted of 111 patients with endometrial carcinoma undergoing hysterectomy with bilateral adnexectomy and lymphadenectomy with or without peritoneal cytology. Ninety two patients had preoperative CA 125 and 73, evaluation of p53. Fifty four patients had both variables in combination. Associations have been established between the value of CA 125 and IMH expression of p53 with lymph node involvement. A ROC curve was constructed to identify the value of CA 125 with better sensitivity (S) and specificity (E) for lymph node disease.

Le récepteur activateur de NF-κB (RANK), membre de la famille des récepteurs au TNF, est connu pour son rôle dans l’homéostasie de l’os, mais joue aussi un rôle important dans le système immunitaire. J’ai tout d’abord étudié des outils permettant de cibler RANK/RANKL. J’ai caractérisé et comparé l’activité biologique de deux anticorps anti-RANK. J’ai également criblé une librairie de petites molécules pour identifier des inhibiteurs de l’interaction RANK/RANKL. Dans une deuxième partie, je me suis intéressée au rôle du ligand de RANK (RANKL) dans l’homéostasie du ganglion lymphatique. RANKL joue un rôle dans la différenciation des ostéoclastes mais son rôle dans la différenciation d’autres macrophages n’a pas été étudié. Nous avons étudié des souris déficientes pour RANKL dans les cellules marginales réticulaires (MRC) qui expriment RANKL de manière constitutive dans le ganglion adulte. Nous avons observé une diminution de la population de macrophages sous-capsulaires (SSM). Nous avons également montré que les cellules endothéliales lymphatiques (LEC) expriment l’intégrine alpha 2b (ITGA2b) et que cette expression est sensible à la présence de RANKL. / The TNF-family member Receptor Activator of NF-κB (RANK) is known for its role in bone homeostasis and is increasingly recognized as a central player in immune regulation. Firstly I looked for new molecular tools to target RANK/RANKL axis. I characterized and compared the biological activity of two anti-RANK antibodies. Moreover, I screened the Prestwick Chemical Library® of small molecules in order to identify inhibitors of RANK/RANKL interaction. Secondly, I studied the effect of the RANK/RANKL axis in lymph node homeostasis. RANKL is known to promote osteoclast differentiation but whether it also plays a role in the differentiation of other macrophage subsets is not known. We addressed this question by conditionally deleting RANKL from marginal reticular stromal cells (MRCs) that constitutively express RANKL in the lymph node. We observed impaired differentiation of the subcapsular sinus macrophages (SSMs). We also studied lymph node lymphatic endothelial cells (LECs) and showed that integrin alpha 2b (ITGA2b) is expressed by a lymph node subset of LECs and its expression is sensitive to RANKL.

<p>The main objective of radiation therapy is to obtain the highest possible probability of tumor cure while minimizing adverse reactions in healthy tissues. A crucial step in the treatment process is to determine the location and extent of the primary tumor and its loco regional lymphatic spread in relation to adjacent radiosensitive anatomical structures and organs at risk. These volumes must also be accurately delineated with respect to external anatomic reference points, preferably on surrounding bony structures. At the same time, it is essential to have the best possible physical and radiobiological knowledge about the radiation responsiveness of the target tissues and organs at risk in order to achieve a more accurate optimization of the treatment outcome.</p><p>A computerized whole body Atlas has therefore been developed to serve as a dynamic database, with systematically integrated knowledge, comprising all necessary physical and radiobiological information about common target volumes and normal tissues. The Atlas also contains a database of segmented organs and a lymph node topography, which was based on the Visible Human dataset, to form standard reference geometry of organ systems. The reference knowledgebase and the standard organ dataset can be utilized for Atlas-based image processing and analysis in radiation therapy planning and for biological optimization of the treatment outcome. Atlas-based segmentation procedures were utilized to transform the reference organ dataset of the Atlas into the geometry of individual patients. The anatomic organs and target volumes of the database can be converted by elastic transformation into those of the individual patient for final treatment planning. Furthermore, a database of reference treatment plans was started by implementing state-of-the-art biologically based radiation therapy planning techniques such as conformal, intensity modulated, and radiobiologically optimized treatment planning.</p><p>The computerized Atlas can be viewed as a central framework that contains different forms of optimal treatment plans linked to all the essential information needed in treatment planning, which can be adapted to a given patient, in order to speed up treatment plan convergence. The Atlas also offers a platform to synthesize the results of imaging studies through its advanced geometric transformation and segmentation procedures. The whole body Atlas is anticipated to become a physical and biological knowledgebase that can facilitate, speed up and increase the accuracy in radiation therapy planning and treatment optimization.</p>

<p>Breast cancer is the most common malignancy among females in Sweden. Axillary lymph-node dissection is a standard procedure in the management of breast cancer, aiming at obtaining prognostic information for adjuvant therapy decisions. Axillary dissection entails considerable morbidity. The aims of this study were to establish more selective surgical approaches and to investigate angiogenesis, a potential predictor for lymph-node metastases and prognosis.</p><p>Clinical nodal status, tumour size and S-phase were associated with nodal metastases in cohort of 1145 women. The proportion of nodal metastases was 13% in the subgroup with the lowest risk.</p><p>In a study from two registries, 675 and 1035 breast cancers ≤10 mm diagnosed by screening mammography had nodal metastases in 6,5% and 7%, respectively. Clinically detected cancers had a risk of 16% and 14%, respectively.</p><p>In a study on 415 women, a 5-node biopsy of the axilla had a sensitivity of 97,3% and a false negative rate of 2,7% in comparison with axillary dissection.</p><p>Six sections from 21 breast cancers were analysed for microvessel density (MVD). The inter-section variation contributed more to the total variance than inter-tumour variation, 45,0% and 37,3%, respectively.</p><p>In a cohort of 315 women, breast cancers with high MVD more frequently had p53 mutations (27,1%) compared with cases with low MVD (18,4%). This difference was not statistically significant (p=0,075). p53 mutations were associated with a worse outcome, whereas MVD was not.</p><p>In conclusion, women with screening detected ≤10 mm breast cancers have a low risk of lymph node metastases and some may not need axillary dissection in the future. The 5-node biopsy could be an alternative to axillary dissection. MVD is associated with methodological weaknesses and routine use is not recommended.</p>

Breast cancer is the most common malignancy among females in Sweden. Axillary lymph-node dissection is a standard procedure in the management of breast cancer, aiming at obtaining prognostic information for adjuvant therapy decisions. Axillary dissection entails considerable morbidity. The aims of this study were to establish more selective surgical approaches and to investigate angiogenesis, a potential predictor for lymph-node metastases and prognosis. Clinical nodal status, tumour size and S-phase were associated with nodal metastases in cohort of 1145 women. The proportion of nodal metastases was 13% in the subgroup with the lowest risk. In a study from two registries, 675 and 1035 breast cancers ≤10 mm diagnosed by screening mammography had nodal metastases in 6,5% and 7%, respectively. Clinically detected cancers had a risk of 16% and 14%, respectively. In a study on 415 women, a 5-node biopsy of the axilla had a sensitivity of 97,3% and a false negative rate of 2,7% in comparison with axillary dissection. Six sections from 21 breast cancers were analysed for microvessel density (MVD). The inter-section variation contributed more to the total variance than inter-tumour variation, 45,0% and 37,3%, respectively. In a cohort of 315 women, breast cancers with high MVD more frequently had p53 mutations (27,1%) compared with cases with low MVD (18,4%). This difference was not statistically significant (p=0,075). p53 mutations were associated with a worse outcome, whereas MVD was not. In conclusion, women with screening detected ≤10 mm breast cancers have a low risk of lymph node metastases and some may not need axillary dissection in the future. The 5-node biopsy could be an alternative to axillary dissection. MVD is associated with methodological weaknesses and routine use is not recommended.