Thesis (Ph. D.)--State University of New York at Buffalo, 1971. / eContent provider-neutral record in process. Description based on print version record. Includes bibliographical references (leaves 181-194).

Orientadores: Luiz Paulo Kowalski, Oslei Paes de Almeida / Dissertação (mestrado) - Universidade Estadual de Campinas, Faculdade de Odontologia de Piracicaba / Made available in DSpace on 2018-08-09T14:07:50Z (GMT). No. of bitstreams: 1 Silva_KeniaRegina_M.pdf: 1402143 bytes, checksum: 385a4aeaced1369767478ecb4c8dd53b (MD5) Previous issue date: 2007 / Resumo: As neoplasias benignas e malignas que acometem glândulas salivares constituem cerca de 1 a 4% de todas as neoplasias do organismo humano. As glândulas parótidas são as mais frequentemente envolvidas, seguidas das glândulas salivares menores e submandibulares, sendo raramente acometidas as glândulas sublinguais. A presença de metástases regionais, extensão do tumor, dor na apresentação e idade maior que 55 anos têm sido considerados como indicadores de pior prognóstico. O objetivo deste estudo foi avaliar as características clínicas, histopatológicas e imunohistoquímicas de 293 tumores malignos das glândulas salivares tratados no Departamento de Cirurgia de Cabeça e Pescoço do Hospital A.C. Camargo, São Paulo, a fim de identificar fatores de riscos associados ao desenvolvimento de metástases linfonodais e sua importância prognóstica. Os dados clínicos dos pacientes foram obtidos por meio dos prontuários médicos e transferidos para uma ficha clínica padronizada especialmente para o estudo. Os diagnósticos histopatológicos foram confirmados, através da revisão dos preparados histológicos. As reações imunoistoquímicas foram feitas através da técnica da estreptavidina-biotina-peroxidase, utilizando-se anticorpos contra proteína p53, antígeno carcinoembrionário (CEA), Ki-67, c-erbB-2 e bcl-2. Dos pacientes que participaram do estudo, 150 eram homens (51,2%) e 143 (48,8%) mulheres, com idade média de 48 anos, variando de 5 a 91 anos. Cento e cinqüenta dois casos (51,9%) eram tumores primários das glândulas salivares maiores, sendo desses 120 em parótida. O tipo histológico mais comum foi Carcinoma Mucoepidermóide seguido pelo Carcinoma Adenóide Cístico, que juntos corresponderam a 70,3% dos casos. Cirurgia foi o tratamento mais realizado e 119 pacientes foram submetidos a esvaziamento cervical. Cento e quatro pacientes (35,5%) apresentaram recidivas locais, regionais e ou à distância. Metástases linfonodais foram observadas em 25% dos casos com idade superior a 65 anos (p=0,020) e em 23% dos pacientes que foram a óbito pela doença (p=0,004). A sobrevida global em 5 anos foi de 65,6% e em 10 anos 54,6%. Reações imunoistoquímica para p53, bcl-2, Ki-67, CEA, c-erbB-2 foram positivas em 31,2%, 46,6%, 27,1%, 19,2% e 41,0% respectivamente. Após a análise dos dados, observou-se que os fatores de riscos para presença de metástases linfonodais incluíam a idade maior que 40 anos, linfonodos clinicamente comprometidos, p53 positivo e C-erb-2 negativo. Os fatores prognósticos independentes para óbito foram idade acima dos 40 anos, linfonodos clinicamente comprometidos, diâmetro do tumor maior que 4 cm e tumores com marcação positiva para Ki-67. Conclusão: Metástases linfonodais estão associadas a idade, achado clinico de presença de metástases e imunoexpressão de p53 (positivo) e C-erbB-2 (negativo). A metástase linfonodal é um fator prognóstico independente em carcinomas de glândulas salivares / Abstract: Benign and malignant salivary gland neoplasias comprises 4¿10% of all the neoplasias affecting humans. The parotid glands are the most commonly affected, followed by minor salivary and submandibular glands. Regional metastasis, tumor extension, presence of pain, and age older than 55 years have been considered poor prognostic indicators. The aim of this study was to analyze the clinical, histological and immunohistochemical characteristics of malignant salivary gland tumors treated at the Department of Head and Neck Surgery, A.C. Camargo Hospital, São Paulo, and to identify the risk factors associated with lymph node metastasis and its prognostic relevance. Clinical data were obtained from the medical records. Histopathological slides were reviewed and immunohistochemical reactions against p53 protein, carcinoembryonic antigen (CEA), Ki-67, c-erbB-2 and bcl-2 performed using the streptavidin-biotin-peroxidase method. Results revealed that 150 patients were men (51.2%) and 143 women (48.8%), with a mean age of 48 years, varying from 5 to 91 years. Primary tumors involving the major salivary glands were observed in 152 cases (51.9%), 120 of which affected the parotid glands. Histological analysis revealed Mucoepidermoid Carcinoma (41.6%) followed by Adenoid Cystic Carcinoma (28.7%) totaling 70.3% of the cases. Surgery was needed in most of the cases and 119 patients were submitted to neck dissection. Recurrence was observed for 104 patients (35.5%). Survival rate was 65.6% at 5 years and 54.6% at 10 years. Immunohistochemical reactions for p53, bcl-2, Ki-67, CEA, c-erbB-2 were positive in 31.2%, 46.6%, 27.1%, 19.2% and 41.0% of the cases, respectively. Clinically affected lymph nodes, p53 positive and C-erb-2 negative tumor cells, and age older than 40 years were regarded as risk factors for lymph node metastasis. Clinically affected lymph nodes, tumors 4 cm or greater in diameter, tumors with Ki-67 positive cells, and age older than 40 years were considered independent prognostic factors for death. Conclusion: limph node metastasis are associated with age, clinical identification of metastatic limph nodes and immunoexpression of p53 (positive) and C-erbB-2 (negative). Limph node metastasis is a significant and independent prognostic factor in salivary gland carcinomas / Mestrado / Patologia / Mestre em Estomatopatologia

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Objetivo: Comparar os resultados obtidos com a sialoendoscopia na melhora do fluxo salivar aferido através cintilografia em pacientes com síndrome de Sjögren primária. Material e método: Pacientes provenientes do Ambulatório de Reumatologia do HCPA com diagnóstico de Síndrome de Sjögren Primária foram submetidos a cintilografia de parótidas previamente ao procedimento de sialoendoscopia. Durante o procedimento de sialoendoscopia, uma das glândulas parótida foi lavada com solução fisiológica e a outra com solução de corticóide, escolha esta predeterminado por randomização. Após completo um mês do procedimento, um novo exame de cintilografia de glândulas parótidas foi realizado visando observar o fluxo salivar para comparação. Resultados: Participaram e completaram a pesquisa 13 pacientes, todas do sexo feminino, com idade média de 53,38 anos (27 - 76 anos). Houve melhora dos resultados de excreção salivar com radiofármaco no exame de cintilografia, após a realização da sialoendoscopia, em 10 pacientes, perfazendo 76,92% da amostra. Analisando cada glândula tratada separadamente (26 glândulas), houve melhora após a sialoendoscopia em 18 glândulas (69,23%), 8 destas utilizaram dexametasona e 10 utilizaram solução fisiológica na lavagem. Não houve melhora em 8 glândulas (30,77%). Conclusão: Este estudo mostra a sialoendoscopia como importante ferramenta na melhora do fluxo salivar aferido por cintilografia em pacientes com Síndrome de Sjögren Primária, aumentando a excreção salivar através da dilatação e consequente desobstrução dos ductos. Sugere que não há diferença estatisticamente significativa entre as soluções de lavagem intraductal solução fisiológica e solução com dexametasona. / Objective: To compare the results utilizing sialendoscopy to improve salivary flow mensured by scintigraphy in Primary Sjögren’ Syndrome. Material and method: Patients from Rheumatology clinic of Porto Alegre’s Clinic Hospital with diagnose of Primary Sjögren' Syndrome were submitted to parotid’s scintigraphy previous to sialendoscopy of both parotid. During the perform of sialendoscopy, one of the parotid gland was wash down with saline solution and the other with dexamethasone solution. Previous determination of the sides was achieved by randomization. After one month of procedure, a new scintigraphy of parotid’s glands was performed to observe the salivary flow for further comparison. Results: Participated and completed the study 13 patients, all female, with average age of 53,38 years (17 - 76 years old). The improve of salivary excretion on scintigraphy was achieved in 10 patients, performing 76,92% of the sample. Analyzing each gland in separate (26 glands), the improve after sialendoscopy was achieved in 18 glands (69,23%), 8 of these used dexamethasone and 10 used saline solution in washing. There was no improve in 8 glands (30,77%). Conclusion: This study demonstrate the use of sialedoscopy as an important tool to improve salivary flow mensured by scintipraphy in Primary Sjögren’ Syndrome patients, increasing the salivary excretion due to the dilatation and consequently clearing of ducts. It suggests that is no statistically difference between the solutions saline versus dexamethasone.

Thesis (Ph. D.)--University of Washington, 1997. / eContent provider-neutral record in process. Description based on print version record. Includes bibliographical references.

Objetivo: Comparar os resultados obtidos com a sialoendoscopia na melhora do fluxo salivar aferido através cintilografia em pacientes com síndrome de Sjögren primária. Material e método: Pacientes provenientes do Ambulatório de Reumatologia do HCPA com diagnóstico de Síndrome de Sjögren Primária foram submetidos a cintilografia de parótidas previamente ao procedimento de sialoendoscopia. Durante o procedimento de sialoendoscopia, uma das glândulas parótida foi lavada com solução fisiológica e a outra com solução de corticóide, escolha esta predeterminado por randomização. Após completo um mês do procedimento, um novo exame de cintilografia de glândulas parótidas foi realizado visando observar o fluxo salivar para comparação. Resultados: Participaram e completaram a pesquisa 13 pacientes, todas do sexo feminino, com idade média de 53,38 anos (27 - 76 anos). Houve melhora dos resultados de excreção salivar com radiofármaco no exame de cintilografia, após a realização da sialoendoscopia, em 10 pacientes, perfazendo 76,92% da amostra. Analisando cada glândula tratada separadamente (26 glândulas), houve melhora após a sialoendoscopia em 18 glândulas (69,23%), 8 destas utilizaram dexametasona e 10 utilizaram solução fisiológica na lavagem. Não houve melhora em 8 glândulas (30,77%). Conclusão: Este estudo mostra a sialoendoscopia como importante ferramenta na melhora do fluxo salivar aferido por cintilografia em pacientes com Síndrome de Sjögren Primária, aumentando a excreção salivar através da dilatação e consequente desobstrução dos ductos. Sugere que não há diferença estatisticamente significativa entre as soluções de lavagem intraductal solução fisiológica e solução com dexametasona. / Objective: To compare the results utilizing sialendoscopy to improve salivary flow mensured by scintigraphy in Primary Sjögren’ Syndrome. Material and method: Patients from Rheumatology clinic of Porto Alegre’s Clinic Hospital with diagnose of Primary Sjögren' Syndrome were submitted to parotid’s scintigraphy previous to sialendoscopy of both parotid. During the perform of sialendoscopy, one of the parotid gland was wash down with saline solution and the other with dexamethasone solution. Previous determination of the sides was achieved by randomization. After one month of procedure, a new scintigraphy of parotid’s glands was performed to observe the salivary flow for further comparison. Results: Participated and completed the study 13 patients, all female, with average age of 53,38 years (17 - 76 years old). The improve of salivary excretion on scintigraphy was achieved in 10 patients, performing 76,92% of the sample. Analyzing each gland in separate (26 glands), the improve after sialendoscopy was achieved in 18 glands (69,23%), 8 of these used dexamethasone and 10 used saline solution in washing. There was no improve in 8 glands (30,77%). Conclusion: This study demonstrate the use of sialedoscopy as an important tool to improve salivary flow mensured by scintipraphy in Primary Sjögren’ Syndrome patients, increasing the salivary excretion due to the dilatation and consequently clearing of ducts. It suggests that is no statistically difference between the solutions saline versus dexamethasone.

Objetivo: Comparar os resultados obtidos com a sialoendoscopia na melhora do fluxo salivar aferido através cintilografia em pacientes com síndrome de Sjögren primária. Material e método: Pacientes provenientes do Ambulatório de Reumatologia do HCPA com diagnóstico de Síndrome de Sjögren Primária foram submetidos a cintilografia de parótidas previamente ao procedimento de sialoendoscopia. Durante o procedimento de sialoendoscopia, uma das glândulas parótida foi lavada com solução fisiológica e a outra com solução de corticóide, escolha esta predeterminado por randomização. Após completo um mês do procedimento, um novo exame de cintilografia de glândulas parótidas foi realizado visando observar o fluxo salivar para comparação. Resultados: Participaram e completaram a pesquisa 13 pacientes, todas do sexo feminino, com idade média de 53,38 anos (27 - 76 anos). Houve melhora dos resultados de excreção salivar com radiofármaco no exame de cintilografia, após a realização da sialoendoscopia, em 10 pacientes, perfazendo 76,92% da amostra. Analisando cada glândula tratada separadamente (26 glândulas), houve melhora após a sialoendoscopia em 18 glândulas (69,23%), 8 destas utilizaram dexametasona e 10 utilizaram solução fisiológica na lavagem. Não houve melhora em 8 glândulas (30,77%). Conclusão: Este estudo mostra a sialoendoscopia como importante ferramenta na melhora do fluxo salivar aferido por cintilografia em pacientes com Síndrome de Sjögren Primária, aumentando a excreção salivar através da dilatação e consequente desobstrução dos ductos. Sugere que não há diferença estatisticamente significativa entre as soluções de lavagem intraductal solução fisiológica e solução com dexametasona. / Objective: To compare the results utilizing sialendoscopy to improve salivary flow mensured by scintigraphy in Primary Sjögren’ Syndrome. Material and method: Patients from Rheumatology clinic of Porto Alegre’s Clinic Hospital with diagnose of Primary Sjögren' Syndrome were submitted to parotid’s scintigraphy previous to sialendoscopy of both parotid. During the perform of sialendoscopy, one of the parotid gland was wash down with saline solution and the other with dexamethasone solution. Previous determination of the sides was achieved by randomization. After one month of procedure, a new scintigraphy of parotid’s glands was performed to observe the salivary flow for further comparison. Results: Participated and completed the study 13 patients, all female, with average age of 53,38 years (17 - 76 years old). The improve of salivary excretion on scintigraphy was achieved in 10 patients, performing 76,92% of the sample. Analyzing each gland in separate (26 glands), the improve after sialendoscopy was achieved in 18 glands (69,23%), 8 of these used dexamethasone and 10 used saline solution in washing. There was no improve in 8 glands (30,77%). Conclusion: This study demonstrate the use of sialedoscopy as an important tool to improve salivary flow mensured by scintipraphy in Primary Sjögren’ Syndrome patients, increasing the salivary excretion due to the dilatation and consequently clearing of ducts. It suggests that is no statistically difference between the solutions saline versus dexamethasone.

Objectifs : Notre travail avait pour objectifs (i) d’évaluer le bénéfice dosimétrique et de prédire le bénéfice clinique d’une radiothérapie adaptative pour des cancers des voies aéro‐digestives supérieures, à la fois en termes de toxicité et de contrôle local, (ii) d’identifier les patients bons candidats à une stratégie de radiothérapie adaptative, et (iii) d’identifier le meilleur schéma de radiothérapie adaptative pour épargner les parotides. Matériels et méthodes : Le bénéfice dosimétrique a été évalué en utilisant les données de patients inclus dans une étude de phase III évaluant le bénéfice clinique d’une radiothérapie adaptative. La dose cumulée sans et avec radiothérapie adaptative a été estimée par des méthodes de recalage élastique. Une évaluation des différents algorithmes de recalage a été faite à la fois en termes de précision spatiale et d’impact sur la dose estimée. Des modèles de prédiction du risque de surdosage ont été développés en utilisant des modèles linéaires généralisées mixtes et une validation croisée par leave‐one‐out. L’évaluation de différents schémas de radiothérapie adaptative (en termes de fréquence et de nombre) a été réalisée en se basant sur l’épargne des parotides. La valeur prédictive de paramètres quantitatifs issus de la TEP a été évaluée à travers une revue systématique de la littérature. La valeur prédictive de paramètres intensité issue de la TEP a été analysée dans 2 cohortes indépendantes. Résultats : Nos travaux ont confirmé qu’en l’absence de radiothérapie adaptative pour des cancers des VADS, il existe un risque de surdosage des parotides de plus de 2 Gy pour les 2/3 des patients. Il s’y associe un risque de sous dosage de la tumeur de plus de 1 Gy pour 50 % des patients. Une radiothérapie adaptative permet de corriger à la fois le surdosage des parotides (bénéfice clinique estimée de 10 % de diminution du risque de xérostomie) et le sous dosage de la tumeur. Basés sur des paramètres issus de la planification et de la première semaine de traitement, des modèles de prédiction du risque de sur dosage des parotides ou de sous dosage de la tumeur ont été développés. Les paramètres TEP prédictifs du risque de récidive ont été identifiés. Un nomogramme a pu être développé et validé dans une 2nd cohorte de patients. Conclusion : Nos travaux confirment le bénéfice d’une radiothérapie adaptative pour épargner les parotides et maintenir la couverture tumorale. Ce bénéfice dosimétrique devrait permettre une diminution de la toxicité et une amélioration du contrôle local. Des paramètres anatomiques et dosimétriques simples permettent l’identification des patients à risque de surdosage des parotides ou de sous dosage de la tumeur. L’utilisation de la TEP permet d’identifier précocement les patients à haut risque de récidive, candidats potentiels à une intensification thérapeutique. Ces résultats justifient la poursuite des travaux sur une cohorte de patients plus importante, idéalement dans le cadre d’études cliniques de phase III. / Objectifs: The aims of this work were (i) to evaluate the dosimetric benefit and to predict the clinical benefit of adaptive radiotherapy for head and neck cancer, regarding both toxicities and local control, (ii) to identify patients whose good candidate for an adaptive strategy, and (iii) to identify the best adaptive strategy to spare the parotid glands. Materials and methods: The dosimetric benefit was assessed using data from a phase III study evaluating the clinical benefit of an adaptive radiotherapy. Cumulated dose with and without adaptive was estimated using deformable image registration. Different methods of deformable image registration were evaluated regarding both spatial and dose estimation accuracy. Predictive model of the risk of parotid gland overdose was computed using generalized linear mixed model and cross validation by leave‐one‐out. The dosimetric benefit of numerous replanning strategies, defined by various numbers and timing of replanning, with regard to parotid gland sparing, was quantified. We performed a systematic review to evaluate the predictive value of quantitative PET parameters. The predictive value of PET intensity parameters was assessed using two independent cohorts of patients. Résultats: Without adaptive radiotherapy, 65% of the patients had a PG overdose of more than 2 Gy and 50% of the patients had a tumor underdose of more than 1 Gy. Adaptive radiotherapy allows to correct both parotid gland overdose and tumor underdose. Based on parameters calculated at the planning and at the first week of treatment, predictive models of PG overdose and tumor underdose were computed. PET parameters correlated with overall survival were identified. Using two independent cohorts of patients, a nomogram to predict survival was build and externally validated. Conclusion: Our studies showed the benefit of adaptive radiotherapy to spare the parotid glands while increasing tumor coverage. These benefits should allow to decrease the toxicities while increasing local control. Early anatomical and dosimetric parameters allow identifying patients at risk of tumor underdose or parotid gland overdose. PET performed before the treatment allows identifying patients with a high‐risk of locoregional failure and death, potentially candidates for treatment. These results justify further studies on a larger cohort of patients, ideally in phase III clinical trials.

SAMMANFATTNING Bakgrund: Vid hjärnundersökningar finns även andra strukturer utanför hjärnan som är innerverade av nervsystemet. Det är möjligt att sjukdomen i hjärnan avspeglas där också. Det finns många sjukdomar och tillstånd med liknande symptom och att ställa rätt diagnos kan vara svårt. Många sjukdomar påverkar det autonoma nervsystemet och ett sätt att hitta rätt diagnos kan vara att undersöka hur det fungerar.  Syfte: Att se vilka variationer av radioaktivitetsupptag som fanns i parotiskörtlarna mellan patienterna som avbildades med 11C-PE2I PET/DT. Samt att kunna se om denna information kan utnyttjas till att identifiera dysfunktion av autonoma nervsystemet (MRT-bilder är även en tillhjälps verktyg). Metod: Studiedesignen var en retrospektiv kvantitativ studie. Hundra (konsekutiva) patienter indelades i grupper så som: normal, Parkinsons, Parkinsons sjukdom med kombination av vaskulära förändringar och atypisk Parkinson sjukdom. Isotopupptag i basala ganglier och parotiskörtlar har mätts. Några patienters MRT- bilder var tillgängligt till kvantifiering.   Resultat: kombinerade gruppen med Parkinsons sjukdom, atypisk Parkinsons sjukdom och vaskulära förändringar har en uppreglering av antalet fria dopaminreceptorer i parotis jämfört med friska (även i bara PSP samt bara vaskulära grupper) med (p <0.05).   Slutsats: Det finns variation av upptaget mellan en del av grupper därmed kan sjukdomen i hjärnan avspeglas i körtlar också.   Nyckelord: Neurodegenerativa sjukdomar, Autonom dysfunktion, 11CPE2I-PET/DT, parotiskörtlar, basala ganglier / ABSTRACT Background: At brain examination, there are also other structures outside the brain that are innervated by the nervous system. It is possible that the disease of the brain is reflected there as well. There are many diseases and conditions with similar symptoms and making the right diagnosis can be difficult. Many diseases affect the autonomic nervous system and one way to find the right diagnosis may be to investigate how it works.     Purpose: to see what variations in radioactivity uptake were found in the parotic glands between the patients depicted with the 11C-PE2I PET/CT. As well as being able to see how valuable this information is in being used to identify dysfunction of the autonomic nervous system (MRT- images are also an aids tool).   Method: The study design was a retrospective quantitative study. One hundred (consecutive) patients were divided in groups such as normal, Parkinson's, Parkinson's disease with combination of vascular changes and atypical Parkinson's disease. Isotope uptake in basal ganglia and parotic glands has been measured. Some patients' MRT images were available for quantification.     Result: the results show that the combined group of Parkinson's disease, atypical Parkinson's disease and vascular changes has an upregulation of the number of free dopamine receptors in parotid compared to healthy ones (also in PSP only and only vascular groups) with (p <0.05).    Conclusion: There is variation of uptake between some of the groups thus the disease in the brain can be reflected in glands as well.     Keywords: Neurodegenerative Diseases, Autonomic Dysfunction, 11CPE2I-PET/CT, Parotid Glands, Basal Ganglia