Orientador: Silvia Regina Brandalise / Dissertação (mestrado) - Universidade Estadual de Campinas, Faculdade de Ciencias Medicas / Made available in DSpace on 2018-08-14T10:29:48Z (GMT). No. of bitstreams: 1 Rizzatti_Marcelo.pdf: 1017352 bytes, checksum: fe168887c2451c5f8aa8394d87ffa50b (MD5) Previous issue date: 2009 / Resumo: Introdução: O aumento da sobrevida dos pacientes pediátricos portadores de câncer se deve aos avanços no diagnóstico, nas técnicas cirúrgicas e radioterápicas, na terapia de suporte e, entre outros fatores, aos regimes quimioterápicos intensivos. Estes procedimentos tornam tais pacientes mais vulneráveis às intercorrências infecciosas, principalmente decorrentes de graus variáveis de mielotoxicidade. Dentre as infecções com elevada morbimortalidade se destaca a enterocolite. Além das complicações inerentes a esta patologia, interrupções e alterações do esquema quimioterápico, diferentes graus de desnutrição e óbito não raramente ocorrem. Poucas são as publicações na literatura sobre esta entidade na pediatria oncológica, principalmente com foco na complexidade da definição dos critérios diagnósticos da enterocolite e os diagnósticos diferenciais com outras patologias abdominais, que podem ocorrer ao longo da terapia do câncer. Objetivos: 1. Estudar o valor prognóstico dos sintomas e sinais clínicos em pacientes pediátricos com o diagnóstico de enterocolite, na vigência de tratamento oncológico. 2. Estudar o valor prognóstico dos achados ultrassonográficos abdominais com o quadro clínico e evolução destes pacientes. Material e Métodos: Estudo retrospectivo realizado em 188 pacientes portadores de câncer abaixo de 25 anos de idade, consecutivamente diagnosticados e tratados no Centro Infantil Boldrini, acompanhados no período de 2003 a 2007, com o diagnóstico clínico presuntivo de colite. O diagnóstico confirmatório de enterocolite foi baseado na espessura da parede intestinal igual ou superior a 3 milímetros, verificada ao exame ultrassonográfico abdominal, dos pacientes com a queixa de um ou mais sintomas relacionados (dor ou tensão abdominal, vômitos, diarréia, associados ou não a febre). A espessura da parede intestinal foi dividida em 3 grupos: 3 a 5 mm, 5,1 a 10 mm e acima de 10 mm. Análise estratificada foi realizada de acordo com a intensidade da granulocitopenia no momento da suspeita do diagnóstico de enterocolite, idade e sexo dos pacientes, tipo histológico do câncer, número dos segmentos intestinais envolvidos, quimioterápicos utilizados, tratamento cirúrgico instituído e ocorrência de septicemia. Resultados: No período do estudo, 1159 crianças e adolescentes com idade até 25 anos e portadores de câncer, foram admitidos no Centro Infantil Boldrini. Destes, 188 pacientes (16,5%) tiveram um ou mais episódios de enterocolite, totalizando 231 eventos. 118 episódios ocorreram no sexo masculino e 113 episódios ocorreram no sexo feminino. A maior freqüência, de acordo com a faixa etária dos pacientes, foi de 120 a 240 meses (44,6%). 87% da população de estudo apresentavam, ao diagnóstico de enterocolite, granulócitos =500/mm3. Os dados demográficos (idade, sexo, peso e estatura), sinais/sintomas, tipo do câncer, terapia e achados ultrassonográficos foram retrospectivamente coletados. 27,3% dos episódios de enterocolite apresentaram espessura de alça intestinal > 3 = 5 mm, 55% de > 5 = 10 mm e 17,7% > 10 mm. 27 pacientes com enterocolite faleceram (11,7%). A espessura da parede intestinal > 10 mm e a ocorrência de mais de 4 sintomas ao diagnóstico da enterocolite, estiveram associados a maior taxa de óbito. O uso concomitante de opióides foi registrado em 101 episódios de enterocolite (43,7%). A distensão abdominal teve valor prognóstico associado ao óbito (p = 0,0018). Dentre os quimioterápicos, a citarabina teve associação significativa nos casos que evoluíram para óbito (p = 0,0261). Conclusões: A presença de 4 ou mais sinais/sintomas ao diagnóstico da enterocolite, utilização prévia do quimioterápico citarabina e a presença de distensão abdominal foram associados maior letalidade nos pacientes com enterocolite (p = 0,0255, p=0,0018 e p = 0,0195, respectivamente), sendo que as últimas duas variáveis elevaram a chance de óbito em até três vezes mais. As demais variáveis estudadas não apresentaram diferença estatisticamente significativa em associação ao óbito. / Abstract: Introduction: Increased survival rates for patients with oncological diseases are among other factors, due to intensive chemotherapy regimens, which turn such patients vulnerable to infectious complications secondary to severe myelotoxicity. Among these, it is worth to mention the necrotizing enterocolitis (or typhlitis), exposing the patient to therapy interruptions, chemotherapy regimen changes, delayed treatment, weight loss and eventually death. Few published studies and nonconsensus criteria for diagnostic confirmation of colitis, among other abdominal diseases along cancer therapy in children and adolescents, justify this study. Objectives: 1. To study the prognostic value of clinical signs and symptoms in pediatric patients with enterocolitis diagnosis. 2. To study the prognostic value of abdominal ultrasound findings, related to clinical features and survival of these patients. Methods: A retrospective study with pediatric cancer patients that clinically presented the diagnosis of colitis treated at the Centro Infantil Boldrini, from January/2003 to December/2007. Confirmatory diagnosis was defined by the bowell wall thickness equal or greater than 3 millimeters (at ultrasound), together or associated with the presence of one or more related symptoms (abdominal pain or tension pain, vomiting, diarrhea or fever). For prognostic association, the bowell wall thickness was stratified as 3 to 5 mm, 5.1 to 10 mm and above 10.1 mm. The variables granulocytopenia intensity, chemotherapy, surgical treatment and sepsis occurence were also analyzed. Results: From January/2003 to December/2007 1159 pediatric patients were admitted to Boldrini's Center with a cancer diagnosis. 188 patients had one or mor colitis episodes (incidence of 16,5%). A total of 231 episodes were retrospectively analised. 118 cases were in males and 113 cases were in females. According to the patient's age with enterocolitis, the prevalente group was with ages between 120 to 240 months (44.6%). 87% of the study population with, the diagnosis of enterocolitis, had granulocyte = 500/mm3. The demographic data (age, sex, weight and height), signs/symptoms, type of cancer, therapy and ultrasound findings were retrospectively collected for all patients. 27.3% of episodes of enterocolitis detected thickness of the intestinal wall > 3 = 5 mm, 55% of > 5 = 10 mm and 17.7% > 10 mm. 27 patients with enterocolitis died (11.7%). The thickness of the intestinal wall > 10 mm and the occurrence of more than 4 symptoms to diagnosis of enterocolitis, were associated with higher rates of death. The previous use of opioids occurred in 101 episodes of enterocolitis (43.7%). The abdominal distension had prognostic value in mortality (p = 0.0018). Among the chemotherapy, cytarabine had significant influence in the cases who died (p = 0.0261). Death rate due to enterocolitis was 11.7%. Conclusions: The presence of 4 or more signs/symptoms to the diagnosis of enterocolitis, prior use of cytarabine chemotherapy and the presence of abdominal distension were associated with higher mortality in patients with enterocolitis (p= 0.0255, p = 0.0018 and p = 0.0195, respectively), whereas the latter two variables increased the odds of death in up to three times more. The other variables showed no statistically significant difference in association with death. / Universidade Estadual de Campi / Saude da Criança e do Adolescente / Mestre em Saude da Criança e do Adolescente

Orientadores: Marcio Ajudarte Lopes, Ana Lúcia Carrinho Ayroza Rangel / Tese (doutorado) - Universidade Estadual de Campinas, Faculdade de Odontologia de Piracicaba / Made available in DSpace on 2018-08-26T15:42:38Z (GMT). No. of bitstreams: 1 Frare_JulianaCristina_D.pdf: 1500588 bytes, checksum: a3865c52c3a98f44b6f09c260fd6cdca (MD5) Previous issue date: 2015 / Resumo: O carcinoma espinocelular (CEC) é considerado uma doença relativamente incomum em pacientes com idade inferior a 40 anos e existem especulações que este tumor apresenta um comportamento biológico mais agressivo neste grupo. Sendo assim, o objetivo deste estudo foi analisar o perfil clinicopatológico de pacientes jovens (? 40 anos) com CEC oral e correlacioná-lo com o de um grupo controle (? 50 anos) através de quatro sistemas de gradação histopatológica ¿ (1) Sistema da Organização Mundial de Saúde ¿ Sistema OMS, (2) Sistema de Gradação de Malignidade de Margens Invasivas Profundas ¿ Sistema MG, (3) Modelo de Risco Histológico ¿ Sistema HR e (4) Escore de risco BD. Foram selecionados 14 pacientes jovens e 14 pacientes controle com similar estadiamento clínico e localização do tumor. Dados demográficos e clínicos foram obtidos de prontuários de pacientes e os cortes histológicos das peças cirúrgicas emblocadas em parafina foram avaliados de acordo com os quatro sistemas de gradação. As associações entre as categorias foram realizadas através do teste de Qui-quadrado ou teste Exato de Fischer. As análises de sobrevida foram realizadas de acordo com o método de Kaplan-Meier. A comparação entre os grupos mostrou maior associação de modalidades de tratamento em pacientes jovens (p=0.022) e que estes apresentaram maior taxa de recidiva local e metástase regional (p=0.018 / OR= 3.998). Pacientes jovens tiveram menor sobrevida livre de doença em 5 anos (p=0.069). Não houve diferença na sobrevida global em 5 anos entre grupos estudados (p=0.376). Não houve diferença na gradação histológica entre os grupos estudados de acordo com os quatro sistemas utilizados (OMS, MG, HR e BD). Nos sistemas HR e BD mais tumores foram classificados como de alto risco prognóstico que nos sistemas OMS e MG. Este estudo mostrou que, apesar de o grau de diferenciação histológica dos tumores ter sido semelhante entre os grupos e terem sido utilizadas mais modalidades terapêuticas (cirurgia, radioterapia e quimioterapia adjuvantes) no grupo jovem, maior incidência de recidivas e metástases foi observado em pacientes jovens, mostrando uma tendência de um comportamento mais agressivo / Abstract: Squamous cell carcinoma (SCC) is considered a relatively uncommon disease in patients younger than 40 years old and there are speculations that this tumor has a more aggressive biological behavior in this group. Thus, the aim of this study was to analyze the clinicopathologic profile of young patients (? 40 years) with oral squamous cell carcinoma and correlate with a control group (? 50 years) by means of four histopathological grading systems - (1) World Health Organization System - WHO System (2) Deep Invasive Margins Deep Malignancy Grading System - MG System, (3) Histologic Risk Model - HR System, and (4) BD Risk Score. Fourteen young patients and 14 control patients with similar clinical stage and tumor location were selected. Demographic and clinical data were obtained from patient's records and histological sections of the paraffin-embedded blocks of surgical specimens were evaluated according to four histopathological grading systems. Associations between categories were performed through Chi-square test and Exact Fisher test. The survival analyzes were performed according to Kaplan-Meier method. The comparison between groups showed that a greater association of treatment modalities in younger patients (p = 0.022) and these had a higher incidence of local recurrence and regional metastasis (p = 0.018 / OR=3.998). Younger patients had lower disease-free survival in 5 years (p = 0.069). There was no difference in overall 5-year survival between the studied groups (p=0.376). There was no difference in histological grading between groups according to the four used systems (WHO, MG, HR and BD). In HR and BD systems more tumors were classified as high risk prognosis than in WHO and MG systems. This study showed that, despite tumors histologic grade was similar between groups and more therapeutic modalities (surgery, adjuvant radiotherapy and chemotherapy) were used in the young group, higher incidence of recurrence and metastasis were observed in young patients, showing a tendency to a more aggressive behavior / Doutorado / Patologia / Doutora em Estomatopatologia

京都大学 / 0048 / 新制・課程博士 / 博士(医学) / 甲第22316号 / 医博第4557号 / 新制||医||1040(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 松田 秀一, 教授 安達 泰治 / 学位規則第4条第1項該当 / Doctor of Medical Science / Kyoto University / DFAM

京都大学 / 新制・課程博士 / 博士(医学) / 甲第23073号 / 医博第4700号 / 新制||医||1049(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 黒田 知宏, 教授 増永 慎一郎 / 学位規則第4条第1項該当 / Doctor of Medical Science / Kyoto University / DGAM

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<p><strong>Abstract</strong></p> <p><strong>Purpose: </strong>While most children diagnosed with cancer survive their initial disease, the intensive treatments they receive place them at risk for late effects. Long-term follow-up (LTFU) care is recommended for cancer survivors for surveillance and early detection of late effects. Knowledge, or lack thereof, regarding diagnosis, treatment and late effects is an important barrier and/or facilitator for attending LTFU care in adolescent and young adult (AYA) cancer survivors. The purpose of our study was to examine the extent of knowledge in Canadian AYA survivors of childhood and adolescent cancer, and identify factors associated with such knowledge.</p> <p><strong>Methods: </strong>Survivors of childhood and adolescent cancer, between the ages of 15 and 26 years, were recruited from three pediatric oncology centres. Patients were invited to participate in the study through mail and clinic recruitment. A questionnaire booklet, including the Cancer Knowledge Survey that asked questions about cancer, treatment and late effects, was administered to collect necessary information. Clinical data was extracted from hospital records to validate participants’ answers.</p> <p><strong>Results: </strong>250 (response rate= 75.5 percent) out of 331 patients invited to participate completed the questionnaire booklet. 18 (7.2 percent) participants lacked information regarding their type of cancer, whereas 25 (10.3 percent) participants were ‘not knowledgeable’ of their treatment. Lack of knowledge regarding treatment was associated with being non-white [odds ratio= 0.3 (0.2-0.6)] compared with white. Also, 83 (33.5 percent) participants were unaware of their late effects. Lack of knowledge regarding late effects was associated with younger age [odds ratio= 1.2 (1.1-1.3)], and having leukemia compared with embryonal tumour [odds ratio= 3.41 (1.10-10.6)].</p> <p><strong>Conclusion:</strong> Results from this study highlights important knowledge deficits, especially in terms of understanding risk of late effects from cancer treatments. Findings from this study can be used to design programs and interventions aimed at increasing cancer knowledge in AYA cancer survivors.</p> / Master of Science (MSc)

Bakgrund:Bröstcancer är den vanligaste cancerdiagnosen hos kvinnor i Sverige. En behandling går ut på att operera bort hela eller delar av det sjuka bröstet. Behandlingen har många gånger sekundär verkan på individens sexuella hälsa.  Syfte:Att beskriva bröstcancerdrabbade kvinnors sexuella hälsa efter utförd mastektomi. Metod:En litteraturöversikt av åtta kvalitativa artiklar genomfördes. Analysen skede enligt Fribergs trestegsmodell.  Resultat:Det finns variationer i den upplevda sexuella hälsan hos kvinnor efter utförd mastektomi. Vissa kvinnor känner nedsatt sexuella hälsa på grund av att det är svårt att acceptera de kroppsfärändringar mastektomin inneburit. Andra upplever inte att kroppsförändringen har påverkat den sexuella hälsan. Erfarenheter av ett förändrat sexuellt självförtroende uppkommer, det är efter genomgången mastektomi mer av betydelse med närhet, kyssar och kramar som i sig ger tillfredsställelse. Andra har svårt att känna lust och är rädda för att bli avisade vid sexuell kontakt. Kvinnor som uppger att de tappat bort sin sexuella identitet i samband med mastektomin uppgav en sämre sexuell hälsa än de tidigare haft. God information från vårdpersonal och ett gott stöd från partner bidrog till god sexuell hälsa.  Slutsatser:God information och rimliga förväntningar preoperativt i kombination med delaktig partner har god effekt på sexuell hälsa efter utförd mastektomi. / Background: Breast cancer is the most common cancer diagnosis in women in Sweden. One treatment method involves eliminating all or part of the diseased breast. The treatment often has secondary effects on the individual's sexual health. Aim: To describe women affected by breast cancer’s sexual health after performing mastectomy. Method: A literature review of eight qualitative studies was performed. The analysis was conducted according to Friberg ́s three-step model. Result: There are variations in the perceived sexual health of women after performed mastectomy. Some women experience impaired sexual health because of difficulty to accept the bodily changes their mastectomy has led to. Others do not experience that their bodily changes have affected their sexual health. Experiences of a changed sexual self-confidence arise; it is more important with closeness, kissing and hugging after the mastectomy, which gives satisfaction. Others have difficulty experiencing feelings of desire and are afraid of rejection at sexual contact. Women who stated that they have lost their sexual identity in connection with mastectomy reported a worse sexual health than they had previously. Good information from healthcare professionals and good support from partners contributed to good sexual health. Conclusions: Good information and reasonable expectations pre-surgery in combination with a participant partner have a good effect on sexual health after performing a mastectomy.

Glioblastoma multiforme (GBM) tumors are highly malignant in nature and despite an aggressive therapy regimen, long–term survival for glioma patients is uncommon as cells with intrinsic or acquired resistance to treatment repopulate the tumor. This creates the need to investigate new therapies for enhancing GBM treatment outside of the standard of care, which includes Temozolomide (TMZ). Our lab focused on two novel strategies to overcome resistance in GBMs. In our first approach, the cellular responses of GBM cell lines to two new TMZ analogues, DP68 and DP86, are reported. The efficacy of these compounds was independent of DNA repair mediated by Methyl Guanine Methyl Transferase (MGMT) and the mismatch repair (MMR) pathway. DP68 or DP86 treated cells do not give rise to secondary spheres, demonstrating that they are no longer capable of self-renewal. DP68-induced damage includes interstrand DNA crosslinks and exhibits a distinct S-phase accumulation before G2/M arrest; a profile that is not observed for TMZ-treated cells. DP68 induces a strong DNA damage response and suppression of FANCD2 expression or ATR expression/kinase activity enhanced the anti-GBM effects of DP68. Collectively, these data demonstrate that DP68, and to a lesser extent DP86, are potent anti-GBM compounds that circumvent TMZ resistance and inhibit recovery of cultures. Our second approach stems from a previous discovery in our lab which demonstrated that the combination of TMZ with Notch inhibition, using a gamma secretase inhibitor (GSI), enhances GBM therapy. Efficacy of TMZ + GSI treatment is partially due to GBM cells shifting into a permanent senescent state. We sought to identify a miR signature that mimics the effects of TMZ + GSI as an alternative vi approach to enhance GBM therapy. MiR-34a expression was highly upregulated in response to TMZ or TMZ + GSI treatment. Exogenous expression of miR-34a revealed that it functions as a tumor suppressor and mimicked the in vitro effects of TMZ + GSI treatment. Additionaly, miR-34a overexpression leads to the downregulation of Notch family members. Together these two studies contribute to our understanding of the complex mechanisms driving resistance in GBM tumors and suggest strategies to develop more effective therapies.

Diss. (sammanfattning) Umeå : Umeå universitet, 2010.