Made available in DSpace on 2016-08-10T10:39:19Z (GMT). No. of bitstreams: 1 DEIDIMAR CASSIA BATISTA ABREU.pdf: 2392648 bytes, checksum: 56abc80b014df4ae449910b6f18afeae (MD5) Previous issue date: 2008-05-28 / In Brazil, breast cancer is the most incident tumor in the female population, and its natural history demonstrates variable clinical courses and different survival rates, according to each patient. Since the systemic therapy has an essential role in the treatment of breast cancer patients, the selection of those that will relapse became an important issue. Identification of significant prognostic factors is essential in therapeutic programs. Because it has been extensively reported that mutated p53 proteins are more stable its wild type counterpart, immunodetection of nuclear p53 protein in tumor cells became an indirect method used to analyze TP53 mutations. Immunodetection of nuclear p53 protein is considered a bad prognostic factor in a long list of human malignant tumors. This study analyze the imunodetection of p53 nuclear protein and its possible association with recognized prognostic factors in a group of 214 patients with breast cancer assisted at Hospital Araujo Jorge, in Brazil. In our study any association was demonstrated between p53 immunodetection and recognized clinical factors including: age over than 60 years old, clinical stage, tumor microscopic grade, immunodetection of estrogen and progesterone receptor, c-erbB-2, tumor size and nodal involvement. p53 immunodetection did not significantly influenced five years survival rates in the patients analyzed in our series. Similar results have been reported by different groups. We concluded that the more sensitive molecular methods must be evaluated, in order to validate the prognostic value of TP53 mutations in breast cancer. / No Brasil, o câncer de mama constitui-se na patologia maligna mais incidente na população feminina e a sua história natural demonstra um curso clínico e sobrevida variáveis. Desde que a terapia sistêmica tornou-se parte integrante do tratamento, a necessidade de saber se uma paciente terá maior ou menor probabilidade de recidiva loco-regional ou à distância tornou-se fundamental. O conhecimento de fatores prognósticos é de suma importância na determinação e eficácia dos programas terapêuticos. A imunodetecção da proteína p53 representa um método indireto de avaliar mutações no gene TP53 e tem sido descrita como fator prognóstico para inúmeras neoplasias malignas humanas e tem sido associada a um pior prognóstico das pacientes. Este estudo avaliou a imunodetecção nuclear da proteína p53 e sua associação com os fatores clínicopatológicos relativos ao paciente e ao tumor, em uma série de 214 pacientes portadoras de carcinoma de mama e atendidas no Hospital Araújo Jorge em Goiânia, no período de 1997-2001. Em nossa casuística a imunodetecção positiva de p53 nas células tumorais não demonstrou nenhuma associação com os parâmetros clínicopatológicos convencionais, incluindo: idade superior a 60 anos, estadiamento clínico, grau de anaplasia, expressão de receptores de estrogênio e/ou progesterona, c-erbB-2, comprometimento linfonodal e tamanho tumoral. A imunodetecção da proteína p53 não influenciou significativamente a sobrevida das pacientes analisadas em nossa série. Resultados semelhantes foram obtidos por outros estudos. Assim, concluímos que métodos moleculares mais sensíveis à detecção de mutações sejam testados, a fim de validar o papel prognóstico das mutações em TP53 no câncer de mama.

Background: Whiplash associated disorders (WAD) account for a large proportion of the overall impairment and disability from traffic injuries and causes substantial bio psychosocial consequences for some individuals. Aims: To increase the knowledge about factors described in terms of either function /impairment, activity/disability and life satisfaction in acute and chronic WAD as well as possible implications for rehabilitation. Within this aim the incidence and recovery rate of whiplash injury and prognostic factors of interest for early rehabilitation have been studied. Subjects and Methods: Fifty-five healthy controls and 34 WAD subjects were analysed within and between groups concerning a) biomechanical out put, endurance, fatigue and muscle tension (EMG activity of trapezius, infraspinatus and deltoideus) during repetitive shoulder forward flexion b) impairments and activity/disability and life satisfaction.356 subjects seeking medical attention due to whiplash trauma, 296 were available at follow up, mean 16 months post injury. Incidence and odds ratio of accident and other background factors on disability were determined. Thirty-four out of 43 patients with whiplash injury were investigated through quantitative sensory tests at six weeks and 71 months after injury. 62 WAD participated in an interdisciplinary rehabilitation program (a pilot study) designed to evaluate such rehabilitation program for patients with chronic (in relatively early stage) WAD. Program evaluation of impairment, disability and life satisfaction (prospective and retrospective) was carried out before and after program and at 6 months. Results: No significant effects of sex or age on the ability to relax between repetitive r muscle contractions (SAR) were found in healthy subjects (study I). Significantly higher inability to relax between contractions was found for the two portions of trapezius and infraspinatus in the WAD group compared to the healthy group (study II). Significantly lower levels of activity preferences were noted for three out of five indices in females with WAD The WAD group had significantly higher prevalence of neropsychological and emotional symptoms. Both pain related symptoms and neropsychological symptoms were of significant importance for aspects of disability and life satisfaction in this group (study IV). Sensory disturbances over the trigeminal skin area persisted over the years. At follow-up a significant correlation was found between the sensory disturbances and the symptoms related to the central nervous system while no significant relationship was found with the musculoskeletal symptoms (study HI) .The annual incidence according to the grading of the Quebec Task Force on Whiplash-Associated Disorders (WAD 1-3) was 3.2/1000 and 4.2/1000 when WAD 0 was included. Sixty-eight percent of the patients recovered during the follow-up Pre-traumatic neck pain, low educational level, female gender and WAD grade E-Ill were significantly associated with a poor prognosis (study IV). . Participants in the rehabilitation program reported increased coping ability. Stress reactions seemed rather frequent (32 %). Pain intensity in the neck and upper back were significantly decreased at 6 months follow-up. However, for most of the functional and psychological markers, no significant changes were found (study V). Conclusion: The higher prevalence of musculoskeletal complaints of the neck shoulder region in females cannot be explained by higher muscle tension and clinical assumption of increased muscle tension seems correct in whiplash patients Results indicate heterogeneity among WAD subjects. Females are at risk after a whiplash trauma but the severity of initial symptoms and signs also affect outcome as well as low education. High levels of neuropsychological symptoms and pain, signs of posttraumatic stress, fear and avoidance, loss of control, anxiety, bio-mechanical and psychosocial factors at work (studies) and social support are potential factors to be aware of. Extensive and costly investigations are in most cases not necessary. However most persons will recover a whiplash injury. Multidisciplinary/interdisciplinary assessment should be considered at three months if substantial negative effect on the person’s ability to function and health situation exists. / <p>Diss. (sammanfattning) Umeå : Umeå universitet, 2001, härtill 6 uppsatser.</p> / digitalisering@umu

The aim of this thesis was to investigate the prognostic role of the proliferation markers cyclin B1 and Phosphorylated Histone 3 (PPH3) in breast cancer (BC). In paper I we used an experimental study design, we compared women dying early from their BC with women free from relapse more than eight years after initial diagnosis. All women had stage I, node-negative and hormone receptor positive disease. None had received adjuvant chemotherapy. We found that low-risk node negative patients with high expression of cyclin B1 had a significantly worse outcome than patients with low expression of cyclin B1. In paper II a population-based case control study was performed to further investigate the prognostic value of cyclin B1. One hundred and ninety women who died from BC were defined as cases and 190 women alive at the time for the corresponding case’s death were defined as controls. Inclusion criteria were tumor size 50 mm, no lymph node metastases, and no adjuvant chemotherapy. Two investigators evaluated the stainings independently. Cyclin B1 was found to be a prognostic factor for BC death that could identify high-risk patients with a good to very good reproducibility. Paper III aimed to investigate the role of proliferation in male breast cancer (MBC). One hundred and ninety-seven MBC tumors were stained for cyclin A, B1, D1 and Ki67. Overexpression of cyclin A and B1 and elevated mitotic count were predictive of breast cancer death. Ki67 was re-evaluated and different cut-offs were used, but no prognostic value could be demonstrated. On the other hand high levels of cyclin D1 were associated with better outcome in MBC. In paper IV we applied the immunohistochemichal panel suggested from international guidelines to the same patient material as in paper II, to discriminate luminal A from luminal B BC. We wanted to evaluate if different cut-off values of Ki67, cyclin A or B1 could more clearly separate luminal A from B. Cyclin A, B1 and Ki67 (cut-off 20%) could detect difference in outcome between these subtypes with cyclin A showing greater prognostic value. The aim of paper V was to examine the prognostic role of PPH3 compared to the proliferation markers Ki67, cyclin A and cyclin B1 with focus on ER positive disease. PPH3 was found to be a prognostic factor for breast cancer death but in the multivariate analysis including all proliferation markers, only cyclin A remained a prognostic factor. Finally, we conclude that both cyclin B1 and PPH3 are prognostic factors for breast cancer death, but are outperformed by cyclin A in ER positive patients. In male breast cancer prognostic factors need to be further studied.

Objectives: Ductal carcinoma in situ (DCIS) is a non-invasive lesion of an increasing clinical importance. Individual risk assessment is essential for an optimal treatment. Our objective was to identify clinical and molecular characteristics of a subgroup of DCIS with an unfavorable prognosis. Methods: In a population study, we analyzed women with DCIS diagnosed within one mammography screening unit. In the experimental part of this work, we conducted a comparative analysis of five biological markers in normal tissue, DCIS and invasive breast cancer by means of gene expression analysis and analysis of loss of heterozygosity (LOH). Results: We demonstrated a high proportion of pure (no invasive component) DCIS (14.41%) of all breast lesions described as malignant. In our sample, we saw a homogeneous distribution of risk factors without noting a clear pattern identifying high-risk subtypes. We noted significant differences in clinical management of tumors with similar characteristics, which demonstrates the present state of limited use of clinical predictors. In the laboratory experiment, we showed differences in loss of heterozygosity (LOH) between DCIS and invasive breast cancer for BRCA1 (8.69% vs. 44.74%) and BRCA2 (9.52% vs. 45.0%). In contrast, we did not find any differences for p53 (31.82%...

Objectives: Ductal carcinoma in situ (DCIS) is a non-invasive lesion of an increasing clinical importance. Individual risk assessment is essential for an optimal treatment. Our objective was to identify clinical and molecular characteristics of a subgroup of DCIS with an unfavorable prognosis. Methods: In a population study, we analyzed women with DCIS diagnosed within one mammography screening unit. In the experimental part of this work, we conducted a comparative analysis of five biological markers in normal tissue, DCIS and invasive breast cancer by means of gene expression analysis and analysis of loss of heterozygosity (LOH). Results: We demonstrated a high proportion of pure (no invasive component) DCIS (14.41%) of all breast lesions described as malignant. In our sample, we saw a homogeneous distribution of risk factors without noting a clear pattern identifying high-risk subtypes. We noted significant differences in clinical management of tumors with similar characteristics, which demonstrates the present state of limited use of clinical predictors. In the laboratory experiment, we showed differences in loss of heterozygosity (LOH) between DCIS and invasive breast cancer for BRCA1 (8.69% vs. 44.74%) and BRCA2 (9.52% vs. 45.0%). In contrast, we did not find any differences for p53 (31.82%...

This is a non-final version of an article published in final form in International Journal of Gynecological Cancer. Final publication is available at http://journals.lww.com/ijgc/Pages/default.aspx / 京都大学 / 0048 / 新制・課程博士 / 博士(医学) / 甲第19557号 / 医博第4064号 / 新制||医||1013(附属図書館) / 32593 / 京都大学大学院医学研究科医学専攻 / (主査)教授 武藤 学, 教授 平岡 眞寛, 教授 古川 壽亮 / 学位規則第4条第1項該当 / Doctor of Medical Science / Kyoto University / DFAM

京都大学 / 0048 / 新制・課程博士 / 博士(医学) / 甲第21628号 / 医博第4434号 / 新制||医||1033(附属図書館) / 京都大学大学院医学研究科医学専攻 / (主査)教授 溝脇 尚志, 教授 平井 豊博, 教授 森田 智視 / 学位規則第4条第1項該当 / Doctor of Medical Science / Kyoto University / DFAM

Die ERC ist der diagnostisch Goldstandard bei Patienten mit Klatskintumor und kann auch zur palliativen Stenttherapie eingesetzt werden. Wir konnten die Morbidität und Mortalität der post-ERC-Cholangitis bei Patienten mit Klatskintumor deutlich reduzieren, in dem wir nach MRCP-gestützter Bestimmung des Drainageziels nur eine unilaterale Kontrastierung und Stenteinlage durchführten. Die DNA-Zytometrie war der beste Prognosefaktore für das postoperative Überleben von resezierten Patienten mit Klatskintumor. Im Gegensatz zu diploiden und polyploiden Klatskintumoren hatten Patienten mit aneuploiden Tumoren trotz kurativer Resektion eine sehr schlechte Prognose infolge früher Mikrometastasierung. Bei einigen Patienten mit Klatskintumor liegt eine Billroth II-Gastro-Jejunostomie vor. Trotz der erschwerten Endokoppassage gelang es uns meistens, sowohl die Majorpapille zu erreichen, als auch trotz der inversen Endoskopposition eine sichere Papillotomie durchzuführen. Die perkutane Drainagetherapie mittels PTCD ist eine wertvolle Alternative zur transpapillären Stenttherapie. Als kurative Therapie bei nicht-resezierbaren Cholangiokarzinomen werden Lebertransplantationen durchgeführt. Damit assoziierte biliäre Komplikationen konnten bei uns in den meisten Fällen erfolgreich durch endoskopische Therapie behandelt werden. / ERC is considered as the diagnostic gold standard for patients with Klatskin tumor and can be also used for palliative stenting. We could reduce morbidity as well as mortality due to post-ERC-cholangitis performing MRCP-guided identification of the drainage target and subsequently unilateral contrasting and stenting. DNA-cytomtery was the best prognostic factor predicting the postoperative survival propability of patients with cholangiocarinoma. In contrast to patients resected due to diploid or polyploid Klatskin tumors patients with aneuploid tumors suffered from a bad prognosis due to early micrometastasis. Some patients afflicted from Klatskin tumors have a Billroth II gastro-jejunostomy. In spite of the more difficult endoscopic passage we were mostly able to advance the endoscope to the major papille and to perform a save papillotomy. The percutaneous drainage therapy by means of PTCD is an important alternative to transpapillary stenting. Liver transplantation is performed to cure patients with unresectable Klatskin tumor. Biliary complications which occur after transplantations can be successfully treated in most cases by means of endoscopic therapy.

No description available.

This study aimed to describe the prognostic and predictive factors of breast cancer and the correlation between them with the clinical outcomes observed in patients surgically treated at the University Hospital of Santa Maria, from 1999 to 2009. The study was retrospective, observational , transversal and analytical. The data was obtained by reviewing the medical records of patients with the Medical Records and Statistics Service sector (SAME). Female patients with malignant pathology of the breast, without distant metastases at diagnosis, and treated surgically in HUSM were included in the sample. Patients with a diagnosis of carcinoma in situ of the breast, male patients, patients with metastases at the time of surgery, patients with other concomitant cancer, patients who had surgical treatment before 1999, patients less than 60 months of follow-up, patients transferred after treatment and patients diagnosed with malignant phyllodes tumor. In the period, 411 cases were identified, 136 of them being excluded. In total, 275 cases were included in the study, and the classification of molecular subtypes was performed in 185 cases. The results were: mean age at diagnosis of 53.13 years; average tumor size in pathology assessment of 2.91 cm; 86.18% type invasive ductal carcinoma; 57.45% histologic grade 2; 60 cases of pure luminal tumors and 196 patients in stages I and II (pathological staging); 205 patients presented with disease without activity; It was reported 45 deaths, and in 33 of them the cause was breast cancer. It was not possible to compare the most variables between the groups. Difference was observed between the groups in histological grade and KI-67. The development of a prospective study is suggested, with its own protocol, for proper description of these factors, which will analyze them and compare them among subgroups of patients. The effort to acknowledge the profile and development of malignant neoplasm of the breast can help individualize treatment, adjusting it for each case. / O presente estudo teve como objetivo descrever os fatores prognósticos e preditivos do câncer mama e a correlação destes com os desfechos clínicos observados, em pacientes tratadas cirurgicamente, no Hospital Universitário de Santa Maria, no período de 1999 a 2009. O estudo foi retrospectivo, observacional, transversal e analítico. Os dados foram obtidos por meio da revisão dos prontuários das pacientes junto ao setor de Serviço de Arquivo Médico e Estatística (SAME). Foram incluídas na amostra pacientes com diagnóstico de patologia maligna da mama, do sexo feminino, sem metástases à distância no momento do diagnóstico e tratadas cirurgicamente no HUSM. Foram excluídos pacientes com diagnóstico de carcinoma in situ da mama, pacientes do sexo masculino, pacientes com metástases no momento da cirurgia, pacientes com outro câncer concomitante, pacientes com tratamento cirúrgico antes de 1999, pacientes com menos de 60 meses de seguimento, pacientes transferidos após o tratamento e pacientes com diagnóstico de tumor phyllodes maligno. No período, identificaram-se 411 casos, sendo 136 deles excluídos. No total, 275 casos foram incluídos no estudo, sendo que a classificação em subtipos moleculares foi possível em 185 casos. Os resultados encontrados foram: média de idade ao diagnóstico de 53,13 anos; média de tamanho tumoral na avaliação da patologia de 2,91 cm; 86,18% do tipo carcinoma ductal invasivo; 57,45% grau histológico 2; 60 casos de tumores luminais puros e 196 pacientes nos estádios I e II (estadiamento patológico); 205 pacientes apresentavam-se com doença sem atividade; foram relatados 45 óbitos, sendo que em 33 deles a causa foi o câncer de mama. Não foi possível a comparação da maioria das variáveis entre os grupos. Foi observada diferença entre os grupos no grau histológico e no KI-67. Sugere-se a elaboração de estudo prospectivo, com protocolo próprio, para adequada descrição destes fatores, o que permitirá analisálos e compará-los entre os subgrupos de pacientes. O esforço para o conhecimento do perfil e da evolução da neoplasia maligna da mama pode auxiliar na individualização do tratamento, ajustando-o para cada caso.