Liver cancer is a major cause of death worldwide and the impact that it has is set to increase in the coming decades. More than half a million cases are diagnosed each year and it is likely many more sufferers are dying unidentified in parts of the world with poor healthcare. Survival rates for untreated cases after diagnosis are low with few patients living beyond one year. A key cause for low survival rates being that the standard treatment is surgical resection; fewer than one quarter of patients are suitable for invasive surgery and five year survival rates rarely exceeds 66 %. RadioFrequency Ablation (RFA) is a minimally invasive technique which utilises the electrically resistive property of tissue to deposit heat energy locally in the vicinity of the tips of an RFA needle. Heat is transferred away through the tissue by conduction, convection of large blood vessels, and bulk flow of blood in smaller vessels. Liver cells, both cancerous and benign, when exposed to the resultant abnormally high temperatures die considerably more rapidly than in cases of natural hyperthermia. It is thus the radiotherapist’s objective to place the RFA needle in a position that maximises destruction of tumour cells, but minimises the collateral damage of surrounding healthy cells. The learning curve of this nontrivial task is reflected unfavourably in the statistics that relate patient survival rate to clinician experience. In this thesis two mathematical models are presented that could be combined into a ‘global’ model of the effects of RFA. To predict cell death in these conditions under RFA, the O’NeillModel is presented in which cells are accounted for by one of three states: alive, vulnerable, and dead. A mechanistic interpretation of the O’Neill Model is attained through comparison to a model from the literature. A known, but little investigated occurrence of tissue swelling in the annular region peripheral to the ablation volume is modelled in a novel way through equations from the literature that track ion transport across the cell membrane; the O’Neill Model for cell death is also incorporated into this model of oedema.

INTRODUÇÃO: Os tumores renais pequenos e localizados são hoje diagnosticados mais frequentemente graças ao uso mais intenso dos métodos de imagem, o que favorece técnicas de tratamento menos traumáticas e igualmente eficazes. Dentre as técnicas minimamente invasivas, uma alternativa atraente é a radiofrequência (RF) por ser eficiente, de baixo custo e fácil aplicação. OBJETIVO: Avaliar métodos de aprimoramento da aplicação da RF para promover lesão celular renal de forma mais eficiente, obtendo lesões maiores, utilizando diferentes temperaturas e, em seguida, administrar drogas vasoativas para comparar o tamanho das lesões. Objetivou-se avaliar também se há remanescência de células viáveis na área abrangida pela lesão. MATERIAL E MÉTODO: O estudo foi realizado na Divisão de Clínica Urológica do Hospital das Clínicas da Faculdade de Medicina da Universidade de São Paulo entre janeiro de 2005 e dezembro de 2008. Inicialmente, 16 cães (Grupo A) foram submetidos a RF no parênquima renal com diferentes temperaturas: 80, 90 e 100 graus centígrados. Para comparar os resultados, foi analisado o tamanho das lesões nas diferentes temperaturas por medida da profundidade e da largura, correlacionadas com a impedância. Em seguida, usando a temperatura de 90 oC, 14 cães foram submetidos a RF com injeção dos dois diferentes agentes vasoativos: como vasoconstritor, a adrenalina (Grupo B), versus a prostaglandina E1 (Grupo C) como vasodilatador. Após 14 dias, os animais foram submetidos a nefrectomia para avaliação das lesões e a sacrifício. RESULTADOS: Houve diferença estatisticamente significante na profundidade (p < 0,001) e largura (p < 0,001) da lesão entre as três temperaturas (80, 90 e 100 oC), sendo que há um pico no tamanho das lesões renais na temperatura de 90 oC. Foi observada diferença estatisticamente significante da impedância entre as três temperaturas estudadas (p < 0,001), e se observou resultado mais favorável a 90 oC (menor impedância) e similar entre as temperaturas de 80 e 100 oC. A segunda etapa do estudo demonstrou que o uso da prostaglandina E1 resultou em lesões significativamente mais profundas e mais largas que o uso da adrenalina e também que a resistência tecidual foi menor com a prostaglandina E1. CONCLUSÕES: A temperatura de 90 oC foi mais eficiente para provocar destruição celular com a RF por produzir lesões mais extensas na largura e profundidade, quando comparada com as temperaturas de 80o e 100 oC (p < 0,001). A impedância também foi menor com 90 oC (p < 0,001). Observou-se que as lesões produzidas sem drogas não apresentaram diferença significante comparado com o uso de prostaglandina E1. Porém, o uso de adrenalina promoveu lesões menores (p < 0,001) quando comparada com os dois outros grupos. Não foram observadas células viáveis na análise microscópica dentro dos limites atingidos pela RF em ambos os experimentos / INTRODUCTION: Small, localized renal tumors are diagnosed more frequently nowadays due to the more intense use of imaging methods, which favor less traumatic but equally efficacious treatment techniques. Among the minimally invasive techniques, an attractive alternative is that of radiofrequency (RF), as it is efficient, and easily applicable. OBJECTIVE: To assess methods for the improvement of the application of RF, for the more efficient promotion of the renal cell lesion, to obtain larger lesions, making use of various temperatures and then administering vasoactive drugs to compare the size of the lesions produced, and also to assess the existence of remaining viable cells in the area affected by the lesion. MATERIAL AND METHOD: The study was undertaken at the Urological Clinical Division of the Hospital das Clínicas of the Medical School of the University of São Paulo, between January 2005 and December 2008. Initially, 16 dogs (Group A) underwent RF of the renal parenchyma at various temperatures: 80, 90 and 100 degrees centigrade. For the comparison of the results, the size of the lesions at the various temperatures was analyzed by the measurement of their depth and width, correlated with the impedance. Then, using a temperature of 90 oC, 14 dogs were submitted to RF with an injection of one of the two different vasoactive agents: adrenaline, vasoconstrictor (Group B), versus with E1 prostaglandin, vasodilator (Group C). After 14 days, the animals underwent nephrectomy for the assessment of the lesions, and then were sacrificed. RESULTS: It was observed that, with the application of RF at the temperatures of 80, 90 and 100 oC, there was a statistically significant difference in the depth (p < 0.001) and width (p < 0.001) of the lesions as between the three temperatures, with a peak in the size of the renal lesions at 90 oC. A statistically significant difference in impedance was observed as between the three temperatures studied (p < 0.001), the most favorable result occurring at 90 oC (least impedance) and similar ones occurring between the temperatures of 80 and 100 oC. The second phase of the study demonstrated that the use of the prostaglandin E1 gave rise to significantly deeper and wider lesions than did the use of adrenaline and also that the tissue resistance was less than with the prostaglandin E1. CONCLUSIONS: It was observed that the temperature of 90oC was more efficient in provoking cell destruction with RF as it produced more extensive lesions both in width and depth than those at the temperatures of 80o and 100 oC (p < 0.001). The impedance was also less at 90 oC (p < 0.001). It was observed that the lesions produced without drugs presented no significant difference with the use of prostaglandin. However, the use of adrenaline provoked smaller lesions (p < 0.001) than did the other two (technical) groups. No viable cells were observed by microscopic analysis within the limits attained by the RF, in either of the experiments

INTRODUÇÃO: Os tumores renais pequenos e localizados são hoje diagnosticados mais frequentemente graças ao uso mais intenso dos métodos de imagem, o que favorece técnicas de tratamento menos traumáticas e igualmente eficazes. Dentre as técnicas minimamente invasivas, uma alternativa atraente é a radiofrequência (RF) por ser eficiente, de baixo custo e fácil aplicação. OBJETIVO: Avaliar métodos de aprimoramento da aplicação da RF para promover lesão celular renal de forma mais eficiente, obtendo lesões maiores, utilizando diferentes temperaturas e, em seguida, administrar drogas vasoativas para comparar o tamanho das lesões. Objetivou-se avaliar também se há remanescência de células viáveis na área abrangida pela lesão. MATERIAL E MÉTODO: O estudo foi realizado na Divisão de Clínica Urológica do Hospital das Clínicas da Faculdade de Medicina da Universidade de São Paulo entre janeiro de 2005 e dezembro de 2008. Inicialmente, 16 cães (Grupo A) foram submetidos a RF no parênquima renal com diferentes temperaturas: 80, 90 e 100 graus centígrados. Para comparar os resultados, foi analisado o tamanho das lesões nas diferentes temperaturas por medida da profundidade e da largura, correlacionadas com a impedância. Em seguida, usando a temperatura de 90 oC, 14 cães foram submetidos a RF com injeção dos dois diferentes agentes vasoativos: como vasoconstritor, a adrenalina (Grupo B), versus a prostaglandina E1 (Grupo C) como vasodilatador. Após 14 dias, os animais foram submetidos a nefrectomia para avaliação das lesões e a sacrifício. RESULTADOS: Houve diferença estatisticamente significante na profundidade (p < 0,001) e largura (p < 0,001) da lesão entre as três temperaturas (80, 90 e 100 oC), sendo que há um pico no tamanho das lesões renais na temperatura de 90 oC. Foi observada diferença estatisticamente significante da impedância entre as três temperaturas estudadas (p < 0,001), e se observou resultado mais favorável a 90 oC (menor impedância) e similar entre as temperaturas de 80 e 100 oC. A segunda etapa do estudo demonstrou que o uso da prostaglandina E1 resultou em lesões significativamente mais profundas e mais largas que o uso da adrenalina e também que a resistência tecidual foi menor com a prostaglandina E1. CONCLUSÕES: A temperatura de 90 oC foi mais eficiente para provocar destruição celular com a RF por produzir lesões mais extensas na largura e profundidade, quando comparada com as temperaturas de 80o e 100 oC (p < 0,001). A impedância também foi menor com 90 oC (p < 0,001). Observou-se que as lesões produzidas sem drogas não apresentaram diferença significante comparado com o uso de prostaglandina E1. Porém, o uso de adrenalina promoveu lesões menores (p < 0,001) quando comparada com os dois outros grupos. Não foram observadas células viáveis na análise microscópica dentro dos limites atingidos pela RF em ambos os experimentos / INTRODUCTION: Small, localized renal tumors are diagnosed more frequently nowadays due to the more intense use of imaging methods, which favor less traumatic but equally efficacious treatment techniques. Among the minimally invasive techniques, an attractive alternative is that of radiofrequency (RF), as it is efficient, and easily applicable. OBJECTIVE: To assess methods for the improvement of the application of RF, for the more efficient promotion of the renal cell lesion, to obtain larger lesions, making use of various temperatures and then administering vasoactive drugs to compare the size of the lesions produced, and also to assess the existence of remaining viable cells in the area affected by the lesion. MATERIAL AND METHOD: The study was undertaken at the Urological Clinical Division of the Hospital das Clínicas of the Medical School of the University of São Paulo, between January 2005 and December 2008. Initially, 16 dogs (Group A) underwent RF of the renal parenchyma at various temperatures: 80, 90 and 100 degrees centigrade. For the comparison of the results, the size of the lesions at the various temperatures was analyzed by the measurement of their depth and width, correlated with the impedance. Then, using a temperature of 90 oC, 14 dogs were submitted to RF with an injection of one of the two different vasoactive agents: adrenaline, vasoconstrictor (Group B), versus with E1 prostaglandin, vasodilator (Group C). After 14 days, the animals underwent nephrectomy for the assessment of the lesions, and then were sacrificed. RESULTS: It was observed that, with the application of RF at the temperatures of 80, 90 and 100 oC, there was a statistically significant difference in the depth (p < 0.001) and width (p < 0.001) of the lesions as between the three temperatures, with a peak in the size of the renal lesions at 90 oC. A statistically significant difference in impedance was observed as between the three temperatures studied (p < 0.001), the most favorable result occurring at 90 oC (least impedance) and similar ones occurring between the temperatures of 80 and 100 oC. The second phase of the study demonstrated that the use of the prostaglandin E1 gave rise to significantly deeper and wider lesions than did the use of adrenaline and also that the tissue resistance was less than with the prostaglandin E1. CONCLUSIONS: It was observed that the temperature of 90oC was more efficient in provoking cell destruction with RF as it produced more extensive lesions both in width and depth than those at the temperatures of 80o and 100 oC (p < 0.001). The impedance was also less at 90 oC (p < 0.001). It was observed that the lesions produced without drugs presented no significant difference with the use of prostaglandin. However, the use of adrenaline provoked smaller lesions (p < 0.001) than did the other two (technical) groups. No viable cells were observed by microscopic analysis within the limits attained by the RF, in either of the experiments