Une grossesse extra-utérine est une grossesse implantée en dehors de la cavité utérine. Il existe quatre thérapeutiques pour leur prise en charge : l’expectative, le traitement médical par méthotrexate, le traitement chirurgical conservateur (salpingotomie) et le traitement chirurgical radical (salpingectomie). Le choix entre ces 4 traitements repose tout d’abord sur des critères de faisabilité (traitement médical et expectative sont par exemple exclus en cas de rupture tubaire). Ces critères de faisabilité peuvent être résumés par la notion d’activité de la GEU. Cette notion permet de différencier les grossesses extra-utérines peu actives pouvant bénéficier d’un traitement médical des grossesses extra-utérines actives requérant un traitement chirurgical.Chaque traitement présente des avantages et des inconvénients et la principale question toujours en suspens concerne la fertilité après prise en charge d’une GEU. L’essai randomisé DEMETER a donc été conçu pour évaluer l’existence éventuelle d’une différence de fertilité de plus de 20% entre traitement médical et traitement chirurgical conservateur d’une part pour les GEU peu actives et entre traitement chirurgical conservateur et radical d’autre part pour les GEU actives.Il n’y a pas de différence significative de plus de 20% de fertilité deux ans après la prise en charge d’une grossesse extra-utérine que ce soit pour les grossesses peu actives entre traitement médical et traitement chirurgical conservateur ou pour les grossesses actives entre traitement chirurgical conservateur et radical. Par ailleurs, cet essai a aussi permis de conclure à la supériorité, en terme d’échec immédiat, du traitement chirurgical conservateur avec injection postopératoire de méthotrexate par rapport au traitement médical pour la prise en charge des GEU peu actives. La plus grande efficacité du traitement chirurgical conservateur est probablement majorée par l’injection postopératoire de méthotrexate. Le taux de conversion d’un traitement chirurgical conservateur vers un traitement chirurgical radical est important : 10% dans le groupe des GEU peu actives et 21% (significativement plus élevé) dans le groupe des GEU actives. Enfin, Le délai de guérison est plus court après traitement chirurgical conservateur qu’après traitement médical.Ces résultats couplés aux données de la littérature permettent d’élaborer des recommandations sur la prise en charge des grossesses extra-utérines. Notamment, pour les GEU peu actives avec un taux d’hCG inférieur à 5000UI/ml sans signe de rupture tubaire ou de défaillance hémodynamique, un traitement médical par méthotrexate doit être proposé sous réserve d’une bonne compliance de la patiente pour le suivi. Une prise en charge par chirurgie conservatrice reste une option valide. Dans ce cas, une injection postopératoire de méthotrexate sera réalisée systématiquement dans les 24 heures suivant l’intervention. Le traitement des GEU actives est chirurgical et la décision entre conservateur et radical a lieu en peropératoire. Enfin, une information aux patientes pourra être délivrée sur l’absence de différence de fertilité 2 ans après le traitement d’une GEU. / An ectopic pregnancy is a pregnancy implanted outside uterine cavity. There are four different treatments to manage tubal ectopic pregnancy: expectation, medical treatment (methotrexate), conservative surgery (salpingotomy) and radical surgery (salpingectomy). The choice between these different treatments is based on feasibility criteria (medical treatment and expectation are not feasible in case of tubal rupture). These feasibility criteria can be summarized by activity of ectopic pregnancy. This activity allowed differentiating less active ectopic pregnancies that can be supported by medical treatment and active ectopic pregnancies that required surgery.All of these treatments present advantages and disadvantages and the major unresolved issue concerns subsequent fertility after management of ectopic pregnancy. Randomized trial DEMETER has thus been designed to evaluate a difference of 20% between medical management and conservative surgery for less active ectopic pregnancy and between conservative and radical surgery for active ectopic pregnancy. Differences for two years subsequent fertility after management of ectopic pregnancy were not more than 20% between medical management and conservative surgery for less active ectopic pregnancy as between conservative and radical surgery for active ectopic pregnancy. This trial also allowed concluding to the superiority of conservative surgery with a systematic postoperative injection of methotrexate compared to medical treatment for management of less active ectopic pregnancy. This superiority might be enhanced by postoperative methotrexate injection. The conversion rate to radical surgery when a conservative surgery is decided is important: 10% for less active ectopic pregnancy and 21% (significantly higher) for active ectopic pregnancy. Recovery time is shorter after conservative surgery compared to medical management.Results of DEMETER trial and literature review allowed giving guidelines for management of ectopic pregnancy. Less active ectopic pregnancy with hCG rate less than 5.000UI/l without tubal rupture or hemodynamic failure can be managed in first intention by medical treatment (methotrexate) if the women is assiduous to a close check. However, conservative surgery for less active ectopic pregnancy is a good option. A systematic postoperative injection of methotrexate in the 24 first hours after surgery should be recommended. Active ectopic pregnancy has to be managed surgically and decision between conservative and radical surgery should be done in the operative room. Finally, women have to be informed about the absence of difference between treatments for subsequent fertility.

O Tumor Odontogênico Queratocístico (TOQC) é considerado uma entidade com alta taxa de recidiva e agressividade local, apresentando também frequente associação com a Síndrome do Carcinoma Basocelular Neviode (SCBCN), por isso a patogêneses de este tumor tem sido intensamente estudada. A transformação e proliferação de células neoplásicas normalmente envolvem a desregulação de vias de sinalização que participam do desenvolvimento embrionário normal, principalmente a via Sonic Hedgehog (Shh). A expressão de certas proteínas presentes nesta via foi detectada em vários tumores odontogênicos, sugerindo que desempenha um papel importante nas interações epiteliais e na proliferação de células tumorais. Embora o papel da via de sinalização Shh não esteja bem estabelecida no desenvolvimento de TOQCs, sugere-se que sua ativação pode ser correlacionada com o comportamento clínico agressivo destas lesões. O objetivo deste estudo foi avaliar a expressão imunoistoquímica das proteínas da via de sinalização Shh em TOQCs esporádicos e associados a SCBCN, além de comparar a sua expressão entre lesões recorrentes e não recorrentes. Para isso foi realizado um estudo retrospectivo onde as características clinicopatológicas de 62 pacientes foram avaliadas, a expressão imunoistoquímica das proteínas Shh, Ptch1, Ptch2, Smo, Gli1, Gli2 e Gli3 foi analisada em todas as amostras, comparando TOQCs sindrômicos (29 lesões) e TOQCs esporádicos (57 lesões), assim como sua respectiva recorrência. Com este estudo foi possível observar que as proteínas Shh, Smo e Gli1 revelaram aumento da expressão em TOQCs associados a SCBCN, em comparação com tumores esporádicos. Shh mostrou expressão citoplasmática intermédia dentro da camada basal em tumores sindrômicos, Smo por sua vez revelou forte expressão nuclear e citoplasmática nas camada basal e suprabasal de tumores sindrômicos, enquanto que a expressão de Gli1 foi mais elevada apenas no citoplasma de TOQCs associados a síndrome em comparação com tumores esporádicos. No que diz respeito a sua recorrência, as proteínas Ptch1 e Gli2 mostraram maior expressão em TOQCs esporádicos e recorrentes, enquanto que a expressão Gli1 foi mais relevante nos tumores recorrentes e associados a SCBCN. Os nossos resultados sugerem que a maior expressão das proteínas Shh, Smo e Gli1 em TOQCs pode contribuir para o diagnóstico precoce de lesões associadas com a SCBCN. Da mesma forma, as proteínas Ptch1 e Gli2 pode predizer o risco de recorrência de TOQCs esporádicos, enquanto Gli1 sugere uma potencial associação de recorrência em tumores sindrômicos. / Keratocystic Odontogenic Tumor (KCOT) is considered an entity of high recurrence rates and local aggressiveness, also often presenting association with Nevoid basal cell carcinoma syndrome (NBCCS), and the pathogenesis of this tumor has been therefore intensively studied. The transformation and proliferation of neoplastic cells usually involve deregulation of signaling pathways participating in normal embryonic development, mainly via Sonic Hedgehog (Shh). The expression of certain proteins of this pathway has been detected in several odontogenic tumors, suggesting that plays an important role in epithelial interactions and proliferation of tumor cells. Although the role of Shh signaling pathway is not well established in the development of KCOTs it has been suggested that its activation can be correlated to the aggressive clinical behavior of these lesions. The aim of this study is therefore to evaluate the immunohistochemical expression of proteins of Shh signaling pathway in sporadic KCOTs and associated with NBCCS and to compare their expression between recurring and non-recurring lesions.thus, a retrospective study was performed where the clinicopathological features of 62 patients were evaluated, the immunohistochemical expression of the Shh, Ptch1, Ptch2, Smo, Gli1, Gli2 and Gli3 protein, was analyzed in all samples, comparing syndromic KCOTs ( 29 lesions) and sporadic KCOTs (57 lesions), and also their respective recurrence. The results showed that the expression of Shh, Smo and Gli1 proteins was increased in KCOTs associated with NBCCS compared to sporadic tumors. Shh showed intermediate cytoplasmic expression within the basal layer syndromic tumors, Smo in turn showed strong nuclear expression and cytoplasmic in basal and suprabasal layers of syndromic tumors, while Gli1 cytoplasm expression was higher only in KCOTs associated syndrome compared with sporadic tumors. Regarding recurrent tumors, Ptch1 and Gli2 proteins showed higher expression in sporadic and recurrent KCOTs, while Gli1 expression was more significant in recurrent tumors and associated NBCCS. Our results suggest that increased expression of Shh, Smo and Gli1 proteins in KCOTs can contribute to early diagnosis of KCOTs associated with the NBCCS. Likewise, Ptch1 and Gli2 proteins can predict the risk of recurrence of sporadic KCOTs, while Gli1 suggest a potential association to recurrence into syndromic tumors.

Introdução: O carcinoma epidermóide de cabeça e pescoço tem na cirurgia e na radioterapia, as principais modalidades terapêuticas iniciais. Nas recidivas loco-regionais, a cirurgia é a escolha padrão de tratamento. Objetivos: Identificação de fatores prognósticos clínicos, histopatológicos e biomoleculares e a avaliação da sobrevida após cirurgia de resgate. Casuística e Métodos: Estudo retrospectivo de pacientes submetidos a tratamento cirúrgico inicial, com revisão de variáveis histopatológicas e expressão imunohistoquímica de VEGF, ciclina d1 e EGF-R no tumor inicial e no resgate. Das recidivas, 10 eram de estádio clínico precoce (I e II) e 18, avançado (III e IV). O período de seguimento médio foi de 33,4 meses. Resultados: A comparação das variáveis histológicas e dos marcadores moleculares no tumor inicial e na recidiva não apresentou alterações estatisticamente significantes. A sobrevida global após cirurgia de resgate foi superior nas recidivas com diagnóstico após seis meses (p=0,02). Conclusões: Os achados sugerem que a expressão de VEGF superior a 75% é fator preditivo para controle da doença após a recidiva. A sobrevida entre o tempo decorrido do tratamento inicial e a recidiva foi estatisticamente significante / Introduction: The usual management of squamous cell carcinoma (SCC) head and neck is the surgery associated or not to post surgical radiotherapy. Salvage surgery is the first therapeutic option for recurrent tumors. Objective: The identification of prognostic factors and to assess survival interval after salvage surgery for SCC. Methods: Retrospective analysis of patients treated with surgery and review of histopathological variables and immunohistochemical expression of VEGF, EGF-R and Ciclina in the initial tumor and salvage surgery. Twenty eight patients were submitted salvage surgery with 10 were staged as early tumors (I and II) and 18 as advanced ones (III and IV). The average follow-up was 33.4 months. Results: The comparison of histopathologicals variables in the initial tumor and loco regional recurrence no statistically significant changes. Survival after salvage surgery was 70% in cases with recurrences diagnosed after six months of follow-up (p=0.02). Conclusions: The findings suggest that variables immunohistopathologicals in loco regional recurrence were of minor importance in prognosis. The time between the initial treatment and recurrence loco regional was independent variable of survival

Introdução: O carcinoma basocelular (CBC) é o tipo mais comum de câncer da pele não-melanoma na população mundial. A elevada prevalência do acometimento da face determina elevada morbidade, a despeito da baixa taxa de mortalidade. Localização, dimensão, subtipo histológico, recidiva e delimitação imprecisa relacionam-se ao risco de invasão e destruição local, sendo critérios de indicação da cirurgia micrográfica de Mohs (CMM), padrão ouro para tratamento do CBC, por elevadas taxas de cura e preservação de tecido sadio. Objetivo: Analisar possíveis preditores da extensão subclínica e do número de fases da CMM para o CBC, em conjunto com o emprego de imuno-histoquímica (IHQ). Métodos: Amostra de 101 casos de CBC excisados por CMM, delimitados previamente por dermatoscopia, foi analisada quanto ao perfil demográfico, características e possíveis relações entre as variáveis determinantes do risco para realização de duas ou mais e três ou mais fases na CMM. Marcação por IHQ dos anticorpos Ber-EP4, MNF-116, E-Caderina e VGEF foi realizada em onze casos de diferentes subtipos do CBC. Resultados: Na amostra, com 49,5% de tumores recidivados, predominou o sexo feminino (58,4%), com idade média de 60,2 anos e localização no segmento cefálico, sendo 52,5% dos tumores na região nasal. Subtipo histológico de alto risco em 69,3%, sendo 64,7% entre os primários e 74% entre os recidivados. Em 46,5% evidenciou-se mais de um tipo histológico, coexistindo baixo e alto risco em 33,7%; 97% apresentou mais de um critério de risco para indicação de CMM, predominando a localização em 91,1%, sendo baixas aquelas por delimitação imprecisa (12,9%) e margens comprometidas (6,9%); 60,4% dos tumores foram removidos por uma fase cirúrgica, 39,6% por duas ou mais e 10,9% por três ou mais. Recidiva elevou as chances de 2 fases para remoção completa (OR=2,40 I.C.95% 1,06 5,44; teste do X2 = 4,47, p= 0,03), assim como localização na região nasal e zona H (p = 0,04 e p = 0,056, respectivamente). O maior número de critérios elevou as chances de 2 fases e 3 fases (p = 0,02 e p = 0,03, respectivamente). As intensidades de marcação com Ber-EP4 e E-Caderina foram mais acentuadas no subtipo micronodular comparadas ao esclerodermiforme. Todos os marcadores evidenciaram os ninhos neoplásicos multifocais dispersos e em meio ao intenso processo infamatório. O VEGF, mostrou marcação mais intensa e evidente no infiltrado inflamatório perineoplásico. Conclusões: A coexistência de padrões e predomínio do alto risco nos CBC primários e recorrentes evidenciam potenciais causas de recidiva, invasão e destruição, e da indicação da CMM. Localização cefálica e recorrência são critérios que corroboraram tal indicação e, o maior número de critérios presentes, a predição da extensão subclínica. A dermatoscopia auxiliou na delimitação pré-cirurgica do CBC. Idade avançada pode exigir mais fases para remoção do CBC. Marcadores imunohistoquímicos podem ser úteis para evidenciar a neoplasia nos tecidos ou em meio a processo infamatório. O reconhecimento de fatores preditivos é auxiliar na decisão terapêutica, no planejamento cirúrgico e na obtenção das altas taxas de cura por meio da CMM. / Introduction: Basal cell carcinoma (BCC) is the most common type of non-melanoma skin cancer and the most frequently occurring form of cancer worldwide. BCC occurs mostly on the face, and despite low mortality rate, it generates high morbidity. Some features such as size, histological subtype, location, recurrence, poor delimitation and others are predictors of recurrence. Mohs micrographic surgery (MMS) is the gold-standard treatment for BCC. It has the highest cure rates and causes less damage to healthy tissue than other options. Objective: This study aims to analyze predictors of subclinical spread and number of stages in MMS for removing BCC and the use of immunohistochemistry (IHC). Methods: We selected 101 patients with BCC and indication for MMS. Analyzed the demographic profile of the patients and relations between the characteristics of tumor risk and number of surgical stages (one, two or more and three or more stages). Immunostaining (Ber-EP4 antibodies, MNF-116, E-Cadherin and VGEF) was performed in 11 BCC with different histological subtypes. Results: Among 101 BCC, 49,5% was recurrent. There was a female predominance (58.4%) with mean age of 60.2. There was also a predominance on the face, most of them located on the nose (52,5%). Histological types with high risk of recurrence predominated (69.3%), 64,7% among primary and 74% among recurrent ones. 46.5% tumors had more than one histological type, with low and high risk in the same lesion in 33.7%. Most BCC (97%) had more than one criteria to be treated by MMS and location was the most frequent (91,1%). Poorly defined (12.9%) and positive margins (6.9%) occurred only in a few cases. 60,4% were removed by one surgical stage; 39,6% by 2 and 10,9% needed 3 stages. Among recurrent BCC, the chance of 2 surgical stages was 2,4 times compared to primary tumors (p= 0,03). BCC located on nasal region and mask areas of the face were also associated with 2 stages (p = 0.04 and p = 0.056, respectively). The number of criteria was also associated with 2 and 3 stages (p = 0.02 and p = 0.03, respectively). Intensity of Ber-EP4 and E-Cadherin were more pronounced in micronodular subtype compared to morpheaform. In areas with intense inflammatory cell infiltrate, anti-Ber-EP4, anti-MNF116 and anti-E-Cadherin were useful to highlight the neoplastic cells. Anti-VEGF showed up clearly in the inflammatory infiltrate around tumor. Conclusion: Mixed histopathological pattern observed in many tumors and predominance of high-risk histology in primary and recurrent BCC highlight potential causes of recurrence, invasion, destruction, and indication for MMS. Location and recurrence stood out as a criterion for MMS and a greater number of criteria was associated with subclinical extension of the BCC. Age was also associated with an increased number of stages. Dermoscopy helped in the demarcation of surgical margins. As for the IHC, it would be useful to highlight BCC in areas with intense inflammation. Recognition of predictive factors is important in therapeutic decision, surgical planning and to obtain the highest cure rates by MMS.

Introdução: O tratamento para o derrame pleural maligno recidivado tem caráter paliativo, sendo a pleurodese o método mais utilizado. Contudo, nem todos os procedimentos são efetivos, em parte por um encarceramento do pulmão pela pleura visceral espessada que impede o contato entre os folhetos pleurais e subsequente pleurodese efetiva. A elastância pleural reflete o grau de encarceramento da pleura visceral, contudo sua correlação com a efetividade da pleurodese não é bem conhecido. Objetivo: Analisar a correlação entre a elastância pleural e a efetividade radiológica (quantificada por tomografia de tórax) da pleurodese realizada através de cateteres pleurais. Os objetivos secundários deste estudo são: correlacionar a elastância pleural com a qualidade de vida, graus de dispneia e dor após o procedimento, efetividade clínica, complicações e mortalidade. Correlacionar a posição da extremidade do cateter pleural com o sucesso radiológico e clínico da pleurodese. Métodos: Estudo prospectivo com 131 pacientes candidatos a pleurodese por instilação de nitrato de prata ou talco mineral por cateter pleural. As pressões pleurais foram aferidas através de manômetro hidrostático ou de transdutor eletrônico de pressão vascular durante o esvaziamento do líquido e usadas para calcular a elastância pleural, em cm H2O/L. A efetividade radiológica foi avaliada pelos volumes pleurais medidos por tomografias computadorizadas de tórax logo após a drenagem e 30 dias após a pleurodese. A efetividade clínica foi avaliada conforme a necessidade de procedimentos adicionais para controle de sintomas. A qualidade de vida foi avaliada através do questionário geral da OMS. A avaliação da dor foi feita pela quantificação na Escala Visual Analógica de Dor. A análise da dispneia foi realizada através da quantificação da funcionalidade na escala de dispneia do British Medical Research Council. Todos esses questionários foram aplicados antes da drenagem, 30 dias após pleurodese e, então, trimestralmente. Para a análise da segurança dos procedimentos foram considerados os tempos de internação e de drenagem e a ocorrência de complicações. Todos os pacientes foram seguidos até o óbito ou até o término do estudo, em novembro de 2014, registrando as complicações e as datas do óbito para a construção da curva de sobrevida. Resultados: Avaliamos 87 pacientes de um total de 131 recrutados. Não houve diferença entre os volumes pleurais nas duas tomografias realizadas. A efetividade clínica foi observada em 86,20% dos pacientes. Não houve diferença em nenhum dos domínios da qualidade de vida. Encontramos diferenças entre a dispneia e a dor aferidas 30 dias após a pleurodese e antes da drenagem. Complicações ocorreram em 14,94% dos casos. A mediana da sobrevida global foi de 16 meses. Não foram encontradas correlações entre as elastâncias pleurais em 400 ml, 800 ml e total com nenhum dos desfechos radiológicos, clínicos (efetividade clínica, qualidade de vida, dispneia, dor e complicações) ou com a sobrevida dos pacientes. A posição da ponta do cateter pleural não se correlacionou com o sucesso radiológico ou clínico da pleurodese. Conclusões: A elastância pleural não se mostrou, até o presente momento, capaz de predizer os defechos radiológicos, clínicos e a sobrevida em pacientes submetidos a pleurodese / Background: The treatment of recurrent malignant pleural effusion has a palliative purpose. Pleurodesis is the most used method. However, not all the procedures are effective, in part because of the lung entrapment by the visceral pleura, preventing the contact between the pleural surfaces and subsequente effective pleurodesis. The pleural elastance reflects the degree of entrapment of the visceral pleura, but its correlation with the effectiveness of pleurodesis is not well known. Objetive: To evaluate the correlation between pleural elastance and radiological effectiveness (measured by tomography) of bedside pleurodesis. The secondary objectives of this study are: correlating the pleural elastance with quality of life, degree of dyspnea and pain after the procedure, clinical effectiveness, complications and mortality. Evaluate the role of intrapleural position of the pleural catheter in early lung expansion and success of pleurodesis. Methods: Prospective study including 131 patients with recurrent malignant pleural effusion candidates for treatment with bedside pleurodesis with silver nitrate or mineral talc. Pleural pressures were measured through hydrostatic gauge or electronic pressure transducer during emptying of effusion and used to calculate the pleural elastance in cm H2O/L. Pleural volumes measured by CT scans of the chest after drainage and 30 days after pleurodesis were assess the radiological effectiveness. The clinical effectiveness was evaluated as the need for additional procedures to control symptoms. The quality of life was assessed using the WHO general questionnaire. Quantifying the Visual Analog Scale of Pain did pain assessment. Measuring the functionality in the British Medical Research Council dyspnea scale made the analysis of dyspnea. All these questionnaires were applied prior to drainage, 30 days after pleurodesis and then quarterly. Results: We evaluated 87 patients of a total of 131 recruited. There was no difference between the two pleural volumes CT scans performed. The clinical effectiveness was observed in 86.20% of patients. There was no difference in any of the domains of quality of life. We found differences between dyspnea and pain measured 30 days after pleurodesis and before draining. Complications occurred in 14.94% of cases. The median overall survival was 16 months. No correlations between pleural elastance in 400 ml, 800 ml and complete were found with all the imaging, clinical (clinical effectiveness, quality of life, dyspnea, pain and complications) or with patient survival outcomes. The tip of the pleural catheter was not correlated with the radiological or clinical success of pleurodesis. Conclusions: The pleural elastance was not, so far, able to predict the radiological outcomes, clinical outcomes and survival in patients undergoing bedside pleurodesis

Introdução: A reinfecção pelo Helicobacter pylori em países em desenvolvimento parece ser maior do que nos países desenvolvidos. O retratamento da bactéria e o controle periódico de cura são necessários, quando elevadas taxas de reinfecção são verificadas. O objetivo do trabalho foi determinar a taxa anual de reinfecção, em pacientes brasileiros com úlcera péptica, num seguimento de cinco anos. Métodos: Pacientes com úlcera péptica, diagnosticada por endoscopia digestiva alta e infecção pelo Helicobacter pylori documentada por histologia, teste da urease, reação em cadeia da polimerase e teste respiratório, foram tratados para erradicação da bactéria. A cura da infecção foi verificada com os mesmos exames, três meses após o término do tratamento. Avaliação clínica e teste respiratório foram realizados aos seis e nove meses. Com um ano de seguimento, endoscopia, exame histológico, teste da urease, reação em cadeia da polimerase e teste respiratório foram novamente realizados. Até o quinto ano de seguimento, foram feitas consultas semestrais e testes respiratórios anuais. Na inclusão dos pacientes e nos reinfectados foram estudados 15 diferentes genes da bactéria. Resultados; Cento e quarenta e sete pacientes foram seguidos: 19 por um ano, oito por dois anos, quatro por três anos, cinco por quatro anos e 98 por cinco anos, num total de 557 pacientes/ano. Não ocorreu reinfecção no primeiro ano. No segundo ano, dois pacientes se reinfectaram, no terceiro quatro pacientes, no quarto três pacientes e no quinto um paciente, num total de 10 reinfecções. A taxa anual de reinfecção por pacientes/ano foi de 1,8%. Conclusão: O Brasil, um país em desenvolvimento com alta prevalência da infecção pelo Helicobacter pylori, apresenta uma taxa de reinfecção semelhante à dos países desenvolvidos / Introduction: The Helicobacter pylori reinfection rate seems to be higher in developing countries, than in developed ones. If a high reinfection rate is verified, periodical exams and bacterial retreatment would be necessary. The objective of this study was to determine the annual reinfection rate of Helicobacter pylori, in Brazilian patients with peptic ulcer disease, in a five year follow-up. Methods: Patients, with peptic ulcer disease diagnosed by upper digestive endoscopy and Helicobacter pylori infection verified by histological examination, rapid urease test, polymerase chain reaction and urea breath test, were treated for bacterial eradication. The infection cure was determined by the same proceedings, three months after the treatments end. Clinical evaluation and urea breath test were performed at sixth and ninth months of the follow-up. At one year of the follow-up, upper digestive endoscopy, histological examination, rapid urea test, polymerase chain reaction and urea breath test were repeated. Up to the fifth year of follow-up semester clinical evaluation and annual urea breath test were performed. All the patients included in the study and all the reinfected patients were tested for fifteen different genes of the Helicobacter pylori. Results: One hundred and forty-seven patients were followed: nineteen patients for one year, eight patients for two years, four patients for three years, five patients for four years and ninety-eight patients for five years. The total of patients/years follow-up was 557. Reinfection did not occur in the first year of the follow-up. In the second year, two patients became reinfected; in the third year, four patients; in the fourth, three and in the fifth, one patient. The total of reinfected patients was 10. The annual reinfection rate was 1,8%. Conclusion: Brazil, a developing country, presents a high prevalence of Helicobacter pylori infection. Nonetheless, the reinfection rate is similar to the developed countries.

Estudamos nesta dissertação o tempo de recorrência em sistemas dinâmicos, concentrando-nos na estatística do tempo de retorno. Calculamos numericamente a distribuição de tempo de retorno a uma região específica do espaço de fases de sistemas caóticos e comparamos com a distribuição binomial, deduzida para um processo aleatório. Os principais resultados obtidos foram: surgimento do efeito que denominamos memória de curto alcance, típico de sistemas determinísticos e associado à distribuição das órbitas periódicas instáveis; a distribuição de tempo de retorno caracteriza as principais propriedades temporais no caso de sistemas intermitentes. As conexões do tempo de retorno com regimes de transporte anômalo foram apresentadas, ressaltando suas limitações. O tempo de retorno foi utilizado ainda para analisar séries temporais, obtidas tanto de um modelo de mistura de um contaminante escalar passivo, como experimentalmente no plasma confinado magnéticamente. No primeiro caso constatamos que os retornos da série temporal assemelham-se às recorrências no espaço de fases do sistema dinâmico responsável pela mistura do contaminante: o mapa padrão com fase aleatória. Constatamos o surgimento de caudas de lei de potência na distribuição de tempo de retorno e calculamos sua dependência com o aumento da não linearidade e da aleatoriedade do sistema. Destacamos o efeito de múltiplas caudas de lei de potência, ausente no caso das distribuições obtidas no espaço de fases. Às séries obtidas em Tokamaks aplicamos o modelo de cascata log-normal para explicar sua função densidade de probabilidade. A distribuição de tempo de retorno destas séries mostrou estar diretamente relacionada com a correlação de curto e longo alcance presente na série. / We study the recurrence time in dynamical systems. The statistics of the recurrence time to a specific region of the phase space of chaotic dynamical systems were obtained numerically and compared with the binomial-like distribution, deduced for a random process. The main results are: the presence of the so called short time memory effect, typical for deterministic systems and related to the distribution of the unstable periodic orbits; the return time distribution captures the main temporal properties of intermittent systems. The possible connections of the recurrence time statistics to the anomalous transport were presented, with special attention to their limitations. The return time statistics was applied to analyze time series obtained from an Hamiltonian model and from magnetically confined plasma. In the first case we noticed that the recurrences of the series were similar to the recurrences obtained in the phase space of the Hamiltonian dynamical system: the standard map with a random phase. We analyze the dependence of the power-law tails of the distributions with the non-linearity and with the randomness of the system. One effect that appears only in the time series case is the multiple power law tails. We apply the log-normal cascade model to explain the probability density function of the series obtained in Tokamaks. The recurrence time statistics of the series is closely related to the short and long time correlation present on the series.

Background: At the time of diagnosis, approximately 75% of all bladder cancers are Non-Muscle Invasive Bladder Cancers (NMIBC) - the standard treatment for these cancers is a Transurethral Resection of the Bladder Tumour (TURBT). Although, the vast majority of these cancers are not life-threatening, they have a high risk of recurrence (and progression, particularly in higher risk NMIBC), despite the use of adjuvant intravesical chemotherapy. Consequently, patients are kept on long term cystoscopic surveillance with endoscopic removal if recurrences are detected - this impacts on patients' quality of life and contributes to the high cost for the healthcare provider. Aims: The fundamental aim of this series of clinical studies, spanning 12 years, was to identify and implement, means of improving the efficiency in both processing and operating on patients with NMIBC to not only reduce recurrence, but also to reduce the duration of follow up and repeat operations. It was an evolutionary process where the findings in the preceding studies formed the basis of the subsequent one - while the aim of the individual studies were different, there was a clear link to the essential principles, thus forming a coherent collection of studies. Methods and results: The project was carried out in 3 phases (with 2 or 3 main studies in each phase, augmented by 1 to 2 linked studies - making the entire submission for PhD by publications a series of 12 studies, to date): Phase 1 (5 studies in this phase): The aim was to demonstrate the natural history of non-invasive bladder cancer and identify sub-categories of patients who could be discharged from surveillance at 5 years. This was initially achieved by evaluating a prospectively maintained cohort of non-invasive bladder cancer patients diagnosed between 1978 and 1984 at the Western General Hospital, Edinburgh. This study identified the importance of the recurrence rate at the first follow up cystoscopy (RRFFC) as an essential prognostic marker. This finding was further validated using 2 separate cohorts from a different Centre (the Royal Infirmary, Edinburgh) managed in the 80s and the 90s, respectively. The data confirmed that over the decades, recurrence patterns do change, possibly as a result of differing techniques and improvements in optics and instruments; however, what remained the same was the prognostic value of the RRFFC. Phase 2 (3 studies in this phase): The early recurrence was deemed to be the result of missed and tumours left behind at the initial TURBT, i.e. a marker of quality. However, RRFFC was only known 3 months after the initial surgery. Since the RRFFC was such an important prognostic factor, the aim of this phase was to determine the surgical factors contributing to the quality of TURBT and subsequently implement changes to the principles in carrying out the surgery to improve this quality. This was achieved by prospective collection of information regarding all patients undergoing TURBT for new bladder cancers, recording the tumour features, surgeon experience, if the resection was deemed to have been complete or not, and the pathological results. We identified that the detrusor muscle in the resected specimen and the experience of the surgeon were independent determinants of TURBT quality. This finding was validated in a further study using cohorts from another time period and another Centre - this allowed me to develop the concept of Good Quality White Light TURBT (GQWLTURBT) as the benchmark for the white light TURBT. Phase 3 (4 studies in this phase): Photodynamic Diagnosis assisted TURBT (PDDTURBT) was demonstrated in randomised controlled trials as a technique that reduces the recurrences in NMIBC. In the absence of evidence with this technique in the 'real life' setting nor comparisons with standardised, benchmarked white light TURBT technique, we performed a prospective controlled study comparing PDD-TURBT and GQ-WLTURBT, evaluating early and delayed recurrence rates in 2 separate studies. I also performed a multicentre UK study on the outcomes with PDD-TURBT and collaborated with other experts in Europe in producing a review article around Photodynamic Diagnosis and the cost effectiveness of this technique. Summary: This coherent series of studies has contributed to knowledge in bladder cancer surgery by, among others: (a) mapping the individual patient natural history of non-invasive bladder cancer; (b) confirming the importance of early recurrence as a strong prognostic indicator; (c) identifying predictors of this early recurrence and the quality of TURBT; (d) introducing the concept of the benchmark Good Quality White Light TURBT and (e) demonstrating the benefits of photodynamic diagnosis within a 'real life' setting.

OBJETIVO: Descrever prospectivamente o curso da doença de Vogt-Koyanagi-Harada (DVKH) com integração de parâmetros de atividades clínicos, estruturais e funcionais. MÉTODOS: Foram incluídos pacientes com diagnóstico da DVKH na fase aguda (parte I) e não aguda (tempo de doença maior que 12 meses; parte II). Os pacientes na fase aguda receberam tratamento inicial padronizado com pulsoterapia de metilprednisolona seguido de corticoterapia oral em doses lentamente regressivas, pelo período de 15 meses. As avaliações consistiram em exame clínico, retinografia, angiografias com fluoresceína (AGF) e indocianina verde (AIV) e tomografia de coerência óptica (TCO). Foram realizadas nos seguintes momentos: parte I, no diagnóstico e meses 1, 2, 4, 6, 9 e 12; parte II, na inclusão e a cada três meses. Eletrorretinograma campo total (ERGct) e eletrorretinograma multifocal (ERGmf) foram realizados na parte I, no 1.o mês e a cada seis meses e, na parte II, na inclusão e com 12 meses. A leitura dos exames, na parte I, foi efetuada por duas leitoras, não mascaradas; na parte II, foi realizada por três leitores mascarados e treinados, sendo considerada a leitura concordante entre, pelo menos, dois examinadores. As angiografias e TCO foram realizadas no aparelho Spectralis® (HRA+OCT, Heidelberg Engineering). Tratamento adicional com corticoterapia em doses imunossupressoras ou intensificação da imunossupressão sistêmica foi indicado nos casos com recidivas clínicas, na presença de sinais de atividade à AGF ou duas pioras consecutivas >= 30% no ERGct. Os sinais de atividade detectados na AGF, AIV e TCO foram denominados sinais subclínicos. RESULTADOS: Na parte I, foram incluídos nove pacientes (7F/2M) com idade mediana de 33 anos e intervalo mediano entre início dos sintomas e tratamento de 13 dias. Na apresentação inicial, sinais clínicos característicos da doença (coroidite difusa com hiperemia do disco óptico, descolamento seroso de retina e uveíte anterior acompanhados de sinais extraoculares) melhoraram dentro dos primeiros 30 dias em todos os casos. Os principais sinais subclínicos variaram no tempo de melhora ou desaparecimento: espessura de coroide (EC) subfoveal diminuiu para o valor mediano de 347u m aos 30 dias; dark dots diminuíram ao longo do seguimento, porém ainda estavam presentes aos 12 meses. Piora da inflamação foi observada em 17 de 18 olhos no tempo mediano de sete meses quando a redução do corticoide oral atingiu a dose média de 0,3mg/kg/d. Os sinais subclínicos mais frequentemente observados foram dark dots, fuzzy vessels e aumento da EC. Em 10 destes 17 olhos a piora foi acompanhada de queda da função pelo ERG. Três padrões de evolução puderam ser caracterizados: sem recidivas clínicas ou subclínicas (padrão A, 1 olho), com recidivas subclínicas somente (padrão B, 11 olhos) e com recidivas clínicas (padrão C, 6 olhos). Identificou-se que a EC aos 30 dias após início do tratamento >= 506u m teve sensibilidade e especificidade > 80% na detecção dos casos com recidivas clínicas (padrão C). A função pelo ERGct e ERGmf permaneceu alterada em relação ao grupo controle com 24 meses, apesar da melhora progressiva observada desde o início do tratamento. Na análise longitudinal dos pacientes, a função entre 12 e 24 meses permaneceu estável no grupo de doentes que recebeu tratamento adicional (8 olhos), enquanto no grupo que não o recebeu (4 olhos) houve deterioração da função ( < 0,001). Na análise dos grupos segundo padrão de recidiva, observou-se que os olhos com padrão B sem tratamento adicional tinham piora funcional maior em relação àqueles com padrão C ou B tratados (p < 0,001). Na parte II, foram incluídos 20 pacientes (17F/3M), com idade mediana ao diagnóstico de 31 anos, intervalo mediano entre início de sintomas e tratamento de 19 dias e tempo mediano de doença à inclusão de 55 meses. Na avaliação da concordância interobservador na leitura dos sinais subclínicos, EC teve concordância substancial (kappa=0,8), enquanto sinais angiográficos tiveram concordância sutil (kappa < 0,2). O curso da doença em 85% dos pacientes foi com recidiva clínica (padrão C, 11 casos) ou recidiva subclínica (padrão B, 6 casos). Nas 11 avaliações com detecção de células na câmara anterior (CA), sinais subclínicos de inflamação de segmento posterior foram concomitantemente observados em 64% dos olhos. Esta mesma concomitância de sinais subclínicos de inflamação de segmento posterior na presença de células na CA foi observada na parte I do estudo. Nos pacientes com padrão B, a variação da EC foi o principal sinal subclínico observado. A função pelo ERG foi realizada sequencialmente em 13 casos. Olhos com padrão C (7 pacientes), com grande comprometimento funcional desde a inclusão, evoluíram com piora mais acentuada do que aqueles com padrão B (5 pacientes). Ao se individualizar os olhos com padrão B, observou-se que esse diferencial (padrão B melhor que C) devia-se ao grupo padrão B com tratamento (p < 0,001). CONCLUSÕES: Neste estudo prospectivo de pacientes com DVKH em seguimento mínimo de 12 meses, desde as fases aguda e não aguda, três padrões de evolução foram observados, sendo que 94% (parte I) e 85% (parte II) dos pacientes apresentaram recidiva/piora clínica (padrão C) e/ou subclínica (padrão B). Na parte I do estudo, a piora da inflamação foi detectada aos sete meses de evolução durante dose regressiva do corticoide equivalente a 0,3mg/kg/d, apesar do tratamento inicial com corticoides em altas doses lentamente regressivo. A EC aferida 30 dias após o início do tratamento acima de 506 ?m mostrou-se um fator com sensibilidade e especificidade acima de 80% na identificação dos casos que evoluíram com recidivas clínicas. Dentre os sinais para detecção de inflamação subclínica, as alterações na EC são confiáveis, enquanto que sinais angiográficos devem ser interpretados com cautela. Exames sequenciais tornam a leitura mais confiável. A presença de células na CA comportou-se como a \"ponta do iceberg\" de uma inflamação mais difusa. O estudo eletrorretinográfico demonstrou resultado subnormal mesmo após 24 meses de seguimento na parte I; tratamento adicional pode evitar piora funcional nos pacientes com sinais subclínicos de inflamação. A pior função da retina em pacientes com inflamação clínica (padrão C) da parte II e dos pacientes com inflamação subclínica (padrão B) de ambas as partes do estudo sugerem que o tratamento ideal das recidivas inflamatórias ainda deve ser alvo de futuros estudos / OBJECTIVES: To describe the course of Vogt-Koyanagi-Harada disease (VKHD) prospectively, integrating clinical, structural and functional parameters. METHODS: Patients with VKHD in the acute (part I) and non-acute (more than 12 months from diagnosis) phases (part II) were included. Patients in the acute phase received a standard treatment with methylprednisolone pulsetherapy followed by high-dose oral corticosteroids with slow tapering during 15 months. Evaluations included clinical exams, fluorescein (FA) and indocyanine green (ICGA) angiographies and optical coherence tomography (OCT). In part I, they were performed at inclusion, then after 1,2,4,6,9,and 12 months; in part II, they were performed at inclusion then every 3 months for up to 12 months. Functional evaluation using electroretinography (ERG) was performed at inclusion and every 6 months in part I and at inclusion and at 12 months in part II. Two non-blinded readers analyzed the imaging exams in part I. In part II, three trained and blinded-readers performed the imaging exams analysis. For study`s purpose, at least two concordant readings were considered. Imaging exams utilized the Spectralis® (HRA+OCT, Heidelberg engineering). Inflammatory signs detected on FA, ICGA and OCT were denominated as subclinical signs. Additional treatment with high doses of corticosteroids or more intensive systemic immunosuppression was indicated in cases with clinical signs of inflammation, with subclinical signs on FA or with two consecutive worsening > 30% on ERG. RESULTS: Nine patients (7F/2M) were included in part I; median age was 33 years old and median time elapsed from onset of symptoms to treatment was 13 days. At disease presentation, classic signs (choroiditis, anterior uveitis, serous retinal detachment, optic disc hyperemia and extraocular manifestations) were observed; they improved in 30 days after treatment. Subclinical signs improved in variable periods of time: subfoveal choroidal thickness (CT) decreased to a median value of 347 ?m, 30 days after the beginning of treatment, dark dots diminished during the follow-up but they were still observed at 12 months. Relapse (worsening of inflammation) was noticed in 17 of 18 eyes at a median follow up time of seven months, when tapering schedule corticosteroid dosage reached the mean dose of 0.3mg/kg/d of prednisone. Dark dots, fuzzy vessels and choroid thickening were the most frequent subclinical signs. Relapses in 10 of 17 eyes were concomitant with worsening on ERG. Three patterns of evolution could be delineated: no signs of inflammation (pattern A, 1 eye), only subclinical signs of inflammation (pattern B, 11 eyes) and clinical signs of inflammation (pattern C, 6 eyes). CT>=506 ?m 30 days after the beginning of treatment was more than 80% sensitive and specific to detect more severe cases (pattern C). ERG parameters at 24 months were subnormal as compared to the control group, despite improvement during follow-up. Further long-term results after 24 month demonstrated stabilization of ERG parameters in patients that had received additional treatment, whereas there was worsening in those patients who had not received additional treatment (p<0.001). Moreover, pattern B patients without additional treatment had a further decrease on ERG values compared to results observed in pattern C or B patients with additional treatment (p<0.001). In Part II, 20 patients (17F/3M) were included; median age at diagnosis was 31 years old, median lag time from onset of symptoms and treatment was 19 days and median time after diagnosis was 55 months. The interobserver agreement for CT reading was substantial (kappa 0.8), whereas for angiographic signs was slight (kappa < 0.2). Recurrences, clinically (pattern C, 11 cases) or subclinically (pattern B, 6 cases) detected, were observed in 85% of cases. Concomitant inflammation of posterior segment detected by subclinical signs was present in 64% of cases with cells in anterior chamber. Simultaneous signs of subclinical inflammation of posterior segment and anterior uveitis were also observed in part I. CT change was the main subclinical sign observed in pattern B patients. ERG evaluation was performed in 13 cases. Pattern C cases (7 patients) presented worse results than pattern B cases (5 patients). Further analysis depicted that pattern B patients who had an additional treatment had better results than pattern B non-treated and pattern C (p<0.001). CONCLUSION: Three patterns of evolution were observed in VKHD patients during this prospective study, 94% (part I) and 85% (part II) presented recurrence/worsening with clinical (pattern C) or subclinical (Pattern B) signs of inflammation. In part I, worsening was observed at seven months after treatment start when reaching mean dose of 0.3mg/Kg/d of prednisone even after initial high-dose of corticosteroids followed by slow tapering. At day 30 after treatment, CT >= 506 ?m had a greater than 80% sensitivity and specificity to detect cases with pattern C evolution. Considering subclinical signs, CT increase reliably detected recurrence, whereas angiographic signs required cautious interpretation. Sequential analysis was more conclusive than an isolated exam. Anterior chamber cells seemed to be the \"tip of the iceberg\" of a more diffuse inflammation. ERG analysis was subnormal even after 24 months of follow up since disease onset; additional treatment could prevent functional worsening in patients with subclinical signs of inflammation. Worse retinal function in patients with clinical recurrences (pattern C) in part II and subclinical recurrences (pattern B) in parts I and II suggest that ideal treatment of recurrences should be further pursued

Submitted by Carvalho Dias João Paulo (joao.dias@famerp.br) on 2018-04-04T14:21:17Z No. of bitstreams: 1 leandrofreitascolturato_dissert.pdf: 2059005 bytes, checksum: 00cf44fb001e34750da28245f55440a6 (MD5) / Made available in DSpace on 2018-04-04T14:21:17Z (GMT). No. of bitstreams: 1 leandrofreitascolturato_dissert.pdf: 2059005 bytes, checksum: 00cf44fb001e34750da28245f55440a6 (MD5) Previous issue date: 2016-06-20 / Introduction: Ten to 15% of cervical cancer patients have had tumor recurrence in early stage (FIGO IB1 - IIA). They have presented negative lymph nodes to hematoxylin-eosin (HE) staining technique. Objectives: In patients with cervical cancer in stage IB1 - IIA (FIGO): 1) to assess the prevalence of pelvic lymph node micrometastasis (MI) through the immunoreactivity of antibody anti pan - cytokeratin AE1/AE3 in lymph node tissue and its correlation with tumor recurrence and overall survival; 2) to describe, in the primary tumor of patients with recurrence tumor and/or lymph node micrometastasis, the immunohistochemical expression (IHC) of the lymphatic endothelial marker D2-40 and their correlation with histopathologic findings by conventional hematoxylin-eosin staining. Material and Method: We studied 83 medical records of patients admitted at Centro de Referência da Saúde da Mulher do Estado de São Paulo (Hospital Pérola Byington) in clinical stages IB1, IB2, and IIA. They were submitted exclusively to primary surgical treatment with hysterectomy Querleu C1 and had no lymph node metastases in the presence of Hematoxylin-Eosin. We collected data from the patients’ medical records. We studied variables, such as sociodemographic, reproductive, and histopathological characteristics, as well as the therapeutic follow-up of these patients. The histological sections of the tumors were reviewed systematically. Each lymph node was analyzed by IHC with AE1/AE3 antibody with six histological sections of three micrometers thick. The patients were divided into groups with recurrence (GCR) and without recurrence (GSR). The patients were also separated according to the presence or absence of lymph node micrometastasis or isolated tumor cells. Qualitative and quantitative variables between groups were compared using chi-square test and parametric Student's t-test. Results: Fifteen patients (18.07%) have had recurrence. At a significance level of 5%, there was significant difference between the GCR and GSR and the variables: pregnancies, size of the major axis of the tumor (cm), lymph node micrometastasis, clinical stage IB2 or IIA, and the mean number of negative lymph nodes. The direct analysis with lymph node micrometastasis or isolated tumor cells showed a significant difference among the variables clinical stage IB2 or IIA, and a stromal invasion depth greater than 2/3. Conclusions: The presence of lymph node micrometastasis is an important risk factor to tumor recurrence. These patients should be considered eligible for radiochemotherapy adjuvant treatment. / Introdução: Dez a 15% das pacientes com câncer do colo do útero em estádio clínico inicial (FIGO IB1 – IIA), com linfonodos negativos à técnica de Hematoxilina-eosina (HE), apresentam recidiva tumoral. Objetivos: Em pacientes com câncer de colo do útero nos estádios IB1 – IIA (FIGO): 1) Avaliar a prevalência de micrometástase (MI) linfonodal pélvica por meio da imunoexpressão do anticorpo anti-pan – citoqueratina AE1/AE3 no tecido linfonodal e sua correlação com recidiva tumoral e sobrevida global; 2) Descrever, no tumor primário de pacientes com recidiva tumoral e/ou MI linfonodal, a expressão imuno-histoquímica (IHQ) do marcador endotelial linfático D2-40 e sua concordância com achados histopatológicos convencionais, por meio da coloração HE. Material e Método: Estudaram-se 83 prontuários de pacientes admitidas no Centro de Referência da Saúde da Mulher do Estado de São Paulo – Hospital Pérola Byington nos estádios clínicos IB1, IB2 e IIA, submetidas ao tratamento cirúrgico primário com histerectomia Querleu C1 exclusivamente e que apresentavam ausência de metástases linfonodais à HE. A coleta de dados foi realizada nos prontuários e realizou-se levantamento das características sociodemográficas, reprodutivas, histopatológicas, terapêuticas e de seguimento dessas pacientes. Os cortes histológicos dos tumores foram revisados de forma sistemática e cada linfonodo analisado por IHQ com anticorpo AE1/AE3, com seis cortes histológicos de três micrometros de espessura. As pacientes foram divididas em grupos com recidiva (GCR) e sem recidiva do tumor (GSR). Foram também divididas de acordo com a variável presença ou ausência de MI linfonodal ou células tumorais isoladas. Para comparar os grupos em relação às variáveis qualitativas e quantitativas foi utilizado o teste Qui-quadrado e o teste paramétrico t de Student, respectivamente. Resultados: Quinze pacientes (18,07%) apresentaram recidiva tumoral. Com significância de 5%, houve diferença significante entre os GCR e GSR e as variáveis: gestações, tamanho do maior eixo do tumor (cm), MI linfonodal, estadiamento clínico IB2 ou IIA e número médio de linfonodos negativos. Na análise direta, com MI linfonodal ou CTI, houve diferença significante com as variáveis estadiamento clínico IB2 ou IIA e profundidade de invasão estromal maior do que 2/3. Conclusões: A presença de MI linfonodal é fator de risco importante para recidiva tumoral. Essas pacientes devem ser consideradas elegíveis para tratamento radioquimioterápico adjuvante.