Factors involved in the pathogenesis of human uveal melanoma

Trabalho final de mestrado integrado em Medicina (Otorrinolaringologia), apresentado à Faculdade de Medicina da Universidade de Coimbra.Introdução: A presbiacusia é a causa mais comum de défice auditivo em adultos e está na origem de muitas outras alterações que comprometem a qualidade de vida dos doentes, entre as quais se destaca a maior incidência de patologia do foro depressivo e a correlação com perda de funções cognitivas que pode vir a culminar em quadros demenciais. No entanto, a maior parte dos indivíduos desvaloriza a situação e são poucos os que procuram ajuda médica. A vida social do indivíduo desempenha um papel essencial neste processo e na decisão de utilizar ou não uma prótese auditiva. Objetivos: Precisar o número de doentes seguidos no Centro Hospitalar e Universitário de Coimbra (CHUC) por presbiacusia e qual a percentagem destes que utiliza prótese auditiva. Simultaneamente, pretendemos apreciar o impacto que esta patologia tem na vertente social destes doentes. Materiais e métodos: Foram analisados todos os processos clínicos do serviço de Otorrinolaringologia (ORL) do CHUC que datassem do ano civil de 2010 em diante. Paralelamente, foi aplicado um questionário a 50 destes doentes. As perguntas em causa foram selecionadas a partir do Hearing Handicap Inventory for the Elderly (HHIE) Portuguese short version. Resultados: Este estudo revelou um total de 2643 indivíduos com diagnóstico de presbiacusia corroborado por audiograma tonal típico. Apenas 3,14% utilizam prótese auditiva, dos quais 67,45% são do sexo feminino. A análise dos questionários mostrou que 74% dos indivíduos apresenta scores que indicam que a patologia em causa prejudica a sua qualidade de vida. Conclusões: Perante um elevado número de pacientes com queixas de hipoacusia, só uma pequena fração recorre a medidas de reabilitação auditiva, sendo a utilização de próteses substancialmente superior no sexo feminino. A perda auditiva da maior parte dos indivíduos em estudo tem repercussões na sua vida social. A gravidade dessas repercussões é maior no sexo feminino, principalmente para idades inferiores a 75 anos.Introduction: Presbycusis is the most common cause of auditory deficit in adults and it’s also the root of many other pathological processes that compromise the patient’s quality of life, such as the augmented incidence of depression and the connection to the loss of cognitive functions that may culminate in dementia. However, the majority of these individuals devalues the situation and only a few seek medical help. The social life of the individual plays an essential role in this process and in the decision to use or not a hearing aid. Objectives: Specify the number of patients followed at the Centro Hospitalar e Universitário de Coimbra (CHUC) due to presbycusis and the percentage of those who use hearing aids. Simultaneously, we aim to assess the impact that this disease has on the social life of these patients. Methods: All clinical files present in the department of Otorhinolaryngology (ORL) dating from 2010 onwards were analyzed. Simultaneously, a questionnaire was administered to 50 of these patients. The questions composing this questionnaire were selected from the Hearing Handicap Inventory for the Elderly (HHIE) Portuguese short version. Results: This study revealed a total of 2643 individuals diagnosed with presbycusis corroborated by a typical tonal audiogram. Only 3.14% use hearing aids, of which 67.45% are female. Analysis of the questionnaires showed that 74% of the individuals present scores that indicate this pathology adversely affects their quality of life. Conclusions: Given the large number of patients with complaints of hearing loss, only a small fraction uses measures of auditory rehabilitation, with the use of hearing aids being substantially higher in females. The hearing loss of most of the individuals in this study has repercussions in their social life. The severity of these effects is higher in females, especially for the age group ‘younger than 75 years’

Genetics of Uveal Melanoma

Non

Aspects of dose, dose rate and radioisotopes in brachytherapy of uveal melanoma

Uveal melanomas constitute melanomas arising from the choroid, the ciliary body or the iris, and in adults stands for the most common primary malignant intraocular tumor. It has a high risk of metastatic spread followed by inevitable death, and unfortunately the prognosis has not improved over the last decades. In the beginning the only considerable treatment was enucleation, i.e. removal of the entire eye. However, brachytherapy has since the 70’s become the primary treatment for medium sized tumors, and the survival rate has been shown to be equal compared to primary enucleation. The aim of our studies included in this thesis was to investigate the efficacy of today’s brachytherapy treatment regime and if any differences in ocular or patient survival could be found considering different brachytherapy aspects. When investigating only ruthenium-106 brachytherapy, no association was found between high or low dose rate and the risk of secondary enucleation, i.e. enucleation due to extensive unwanted side effects, insufficient treatment effect on the tumor or tumor relapse. In further analysis with both ruthenium-106 and iodine-125 brachytherapy included in the study and the risk of tumor related mortality considered, there was no statistical difference in outcome related to either dose or dose rate applied and we found no negative consequences for patients that received lower dose and dose rates than intended. As there is a gender difference in survival outcome for some cancers, we investigated this issue regarding uveal melanoma, but no differences could be found indicating this should be a factor to consider when planning treatment. Ruthenium-106 brachytherapy is generally used throughout Europe. In Sweden, iodine-125 for larger medium sized tumors became available 20 years after ruthenium-106 brachytherapy had begun. We therefore had a great opportunity to analyze the larger tumors treated with ruthenium-106 in the earlier years and compare them to same size tumors treated with iodine-125. There was no difference in survival between matched groups, but ruthenium-106-treated patients had a significantly higher risk of needing retreatment, thus making iodine-125 the preferred nuclide for thicker tumors. In conclusion gender is not a factor that needs considering when planning treatment for uveal melanoma. Treatment with brachytherapy is both safe and effective within the current recommended doses and dose rates. Our findings suggest that lower doses and dose rates still would be adequate, and this should be investigated further. The current protocol for radioisotope selection based on tumor thickness also seems adequate for the best possible ocular and survival outcome

Prognostic value of specific chromosome imbalances, mutation profile, and BAP1 expression in uveal melanoma

Valore prognostico di specifiche aberrazioni cromosomiche, profilo mutazionale e espressione di BAP1 nel melanoma uveal

Cancer Immunology

The past decade has seen immunotherapy rise to the forefront of cancer treatment. This Special Issue of Cancers aims to elaborate on the latest developments, cutting-edge technologies, and prospects in cancer immunology and immunotherapy. Seventeen exceptional studies, including original contributions and review articles, written by international scientists and physicians, primarily concerning the fields of tumor biology, cancer immunology, therapeutics, and drug development, comprise the main body of this Special Issue