Objetivo: Determinar a correlação entre os níveis de PSA, escore Gleason e a estimativa de volume tumoral em fragmentos de biópsia de próstata em pacientes portadores de CaP. Material e Métodos: No período de 26 de abril a 15 de setembro de 2000 foram avaliados 64 pacientes submetidos à dosagem do PSA sérico e com biópsia transretal da próstata compatível com carcinoma. Os fragmentos biopsiados foram analisados quanto ao diagnóstico anatomo-patológico, graduação histológica pelo sistema Gleason e estimativa de volume tumoral através da determinação da proporção de carcinoma nos fragmentos obtidos na biópsia e medida do maior eixo tumoral. Resultados: Este estudo demonstrou a associação positiva entre estimativa de volume tumoral e níveis séricos de PSA. Entre as medidas de volume tumoral a correlação foi de maior magnitude quando se considera a proporção objetiva de carcinoma na amostra. Em relação ao escore Gleason, foi demonstrada associação significativa com níveis séricos de PSA (p<0,01) e com as medidas de volume tumoral (p<0,05). Conclusão:Existe correlação entre níveis séricos de PSA, escore Gleason e estimativa de volume tumoral em fragmentos de biópsia da próstata de pacientes com adenocarcinoma da próstata, porém o impacto dessa associação na determinação prognóstica desses pacientes permanece indeterminada. / Purpose: To determine the correlation between serum prostate specific antigen (PSA) levels, Gleason score and tumor volume in prostate needle biopsy cores in patients with prostate cancer. Materials and Methods: A total of 64 patients who underwent prostate biopsy between april 26th and September 15th 2000 had the histologic diagnosis of prostate cancer. Prostate needle biopsy specimens where examined for histologic diagnosis, Gleason score and tumor volume measure through the determination of the cancer ratio in the biopsy cores and by the linear measurement of the biggest tumor axle . Serum PSA levels obtained previously to the biopsy were also determined. Results: We found a positive correlation between tumor volume estimative and PSA serum levels. Considering the tumor volume measures, the cancer ratio in the biopsy cores was the independt measure wich had the strongest correlation. Considering Gleason score, a significant association with PSA serum levels was demonstrated (p<0,01) as well when associated to tumor volume measures, Gleason (p<0,05). Conclusions: There is correlation between PSA serum levels, Gleason score and tumor volume measures in prostate needle biopsy cores in men with prostate cancer, however the impact of this association in the prognostic determination of these patients remains unclear.

Objetivo: Determinar a correlação entre os níveis de PSA, escore Gleason e a estimativa de volume tumoral em fragmentos de biópsia de próstata em pacientes portadores de CaP. Material e Métodos: No período de 26 de abril a 15 de setembro de 2000 foram avaliados 64 pacientes submetidos à dosagem do PSA sérico e com biópsia transretal da próstata compatível com carcinoma. Os fragmentos biopsiados foram analisados quanto ao diagnóstico anatomo-patológico, graduação histológica pelo sistema Gleason e estimativa de volume tumoral através da determinação da proporção de carcinoma nos fragmentos obtidos na biópsia e medida do maior eixo tumoral. Resultados: Este estudo demonstrou a associação positiva entre estimativa de volume tumoral e níveis séricos de PSA. Entre as medidas de volume tumoral a correlação foi de maior magnitude quando se considera a proporção objetiva de carcinoma na amostra. Em relação ao escore Gleason, foi demonstrada associação significativa com níveis séricos de PSA (p<0,01) e com as medidas de volume tumoral (p<0,05). Conclusão:Existe correlação entre níveis séricos de PSA, escore Gleason e estimativa de volume tumoral em fragmentos de biópsia da próstata de pacientes com adenocarcinoma da próstata, porém o impacto dessa associação na determinação prognóstica desses pacientes permanece indeterminada. / Purpose: To determine the correlation between serum prostate specific antigen (PSA) levels, Gleason score and tumor volume in prostate needle biopsy cores in patients with prostate cancer. Materials and Methods: A total of 64 patients who underwent prostate biopsy between april 26th and September 15th 2000 had the histologic diagnosis of prostate cancer. Prostate needle biopsy specimens where examined for histologic diagnosis, Gleason score and tumor volume measure through the determination of the cancer ratio in the biopsy cores and by the linear measurement of the biggest tumor axle . Serum PSA levels obtained previously to the biopsy were also determined. Results: We found a positive correlation between tumor volume estimative and PSA serum levels. Considering the tumor volume measures, the cancer ratio in the biopsy cores was the independt measure wich had the strongest correlation. Considering Gleason score, a significant association with PSA serum levels was demonstrated (p<0,01) as well when associated to tumor volume measures, Gleason (p<0,05). Conclusions: There is correlation between PSA serum levels, Gleason score and tumor volume measures in prostate needle biopsy cores in men with prostate cancer, however the impact of this association in the prognostic determination of these patients remains unclear.

INTRODUÇÃO: O câncer de próstata é responsável por 15% dos casos novos de câncer que acometem os homens e pela 5ª causa de morte. As técnicas minimamente invasivas, sobretudo a cirurgia robótica tornou-se a técnica comumente empregada nos Estados Unidos. Muitos artigos tentam demonstrar a curva de aprendizado necessária para a estabilização dos resultados, mas a implementação de novas tecnologias passa por diversos desafios, além da avaliação de seus resultados e dos custos, o que em países em desenvolvimento pode ter um importante impacto no sistema de saúde. OBJETIVO: Avaliar a curva de aprendizado da prostatectomia radical laparoscópica robótica assistida (PRRA) para o tratamento do câncer de próstata, de acordo com a continência urinária, a potência sexual, o tempo cirúrgico e o controle oncológico. MÉTODOS: Duzentos pacientes com neoplasia de próstata localizada submetidos à PRRA por um único cirurgião foram divididos em quatro grupos de acordo com a sequência das cirurgias. Foram avaliados os dados intra-operatórios, como: tempo cirúrgico, perda sanguínea estimada e as margens cirúrgicas. Também durante o pósoperatório foram avaliadas a potência (IIEF) e a continência (ICIQ). RESULTADOS: Os pacientes apresentaram idade média de 60,6 anos (59,72-61,61), volume prostático ao toque retal de 40 gramas e valor do PSA 6,95 ng/ml (5,79-8,10) semelhantes em todos os grupos (p > 0,05). A biópsia prostática pré-operatória mostrou diferença no escore de Gleason e no tamanho da próstata, sendo que o escore 6 foi menos frequente no grupo 4, representado por 23 pacientes (46%) e no grupo 1, com 39 pacientes (78%) (p < 0,01). Já o tamanho prostático avaliado pelo USTR foi de 39,6 gramas (29,75-48,7) no grupo 4 e 30,5 gramas (23,0-38,15) no grupo 2. A curva de aprendizado estabelecida demonstrou uma diminuição no tempo cirúrgico de 157 minutos (145-170) no grupo 1, para 132 minutos (119-140) no grupo 2 (p < 0,01). A perda sanguínea estimada também se reduziu aproximadamente pela metade: de 395 ml (250-500) no grupo 1, para 200 ml (150-250) no grupo 3 (p < 0,01). As margens positivas reduziram de 16% para apenas 8%, mas se mostraram estatisticamente semelhantes (p=0,236). A capacidade de penetração com doze meses praticamente dobrou de 38% (19 pacientes) no grupo 1 para 80% (40 pacientes) no grupo 4 (p=0,003). A continência avaliada com um ano mostrou-se melhor no grupo 4 (98%) quando comparado aos pacientes do grupo 1 (94%) (p=0,001). As complicações foram estatisticamente semelhantes entre os quatro grupos (p = 0,668). A análise da recidiva bioquímica não demonstrou diferença (p > 0,05). CONCLUSÕES: A curva de aprendizado da PRRA é variável de acordo com o parâmetro a ser avaliado, e apesar do equipamento e da tecnologia, à medida que se aumenta a experiência do cirurgião, melhores resultados são obtidos. O tempo de cirurgia e o sangramento estabilizaram-se, respectivamente, após 50 e 100 PRRA. A potência e a continência, por sua vez, estabilizaram-se após 150 PRRA. É importante ressaltar que o controle oncológico necessita de um período de acompanhamento mais longo para ser avaliado / BACKGROUND: Prostate cancer is responsible for 15% of new cases of male cancer and is the fifth leading cause of death. Minimally invasive and mainly, robotic surgery technique became the technique most widely utilized in the United States. Many articles have tried to demonstrate the required learning curve to achieve the plateau. Although, new techniques implementation go through many challenges besides the evaluation of its results, costs also became an issue, which may impact in developing countries health system. OBJECTIVE: We aim to evaluate the learning curve of robot-assisted radical prostatectomy (RARP) for the treatment of prostate cancer, according to continence, potency, surgical time and oncologic control. METHODS: Two hundred patients with localized prostate cancer that underwent RARP by a single surgeon were divided into four groups according to its surgical sequence. Intraoperative data, such as surgical time, estimated blood loss and margins were recorded. Also postoperative functional parameters as continence and potency were gathered using validated questionnaires (ICIQ and IIEF). RESULTS: Patients mean age were 60.6 years (59.72- 61.61), mean prostate volume at digital rectal examination was 40 grams and PSA value 6.95 ng/ml (5.79-8.10) were similar in all groups (p > 0.05). Pre-operative prostate biopsy showed difference in Gleason score and prostate size. Gleason score 6 was less frequent in group 4, 23 patients (46%), than group 1, 39 patients (78%)(p <0.01) and prostate size at TRUS was 39.6 grams (29.75- 48.7) in group 4 and 30.5 grams (23.0- 38.15) in group 2. The established learning curve showed a reduction on surgical time from 157 minutes (145-170) in group 1 to 132 minutes (119-140 min) in group 2 (p < 0.01). The estimated blood loss also decreased almost to half, from 395 ml (250-500) in group 1 to 200 ml (150-250) in group 3 (p < 0.01). Positive margins decreased from 16% to only 8 %, but were statistically similar (p=0.236). Nineteen patients (38%) could have sexual intercourse at an year after the surgery, in the first group but latest, in the fouth group, it doubled to 40 patients (80%) (p=0.003). Also continence improved in group 4(98%) when compared with group 1 (94%) (p=0.001). Complications were similar between groups (p=0.668). Biochemical recurrence also showed no difference (p > 0.05). CONCLUSIONS: Therefore, the learning curve of the RARP is variable according to the evaluated parameter and obviously, despite the equipment and technology, the increase of surgical experience the best the outcome. Surgery time plateau were achieved at 50 RARP, estimated blood loss stabilized after 100 surgeries, sexual function and urinary continence after 150 RARP. Cancer control requires a longer follow-up period for review

Jusqu'à ce jour, très peu de travaux empiriques ont évalué les aspects psychologiques associés au cancer de la prostate. Cette étude transversale vise donc à comparer la prévalence des difficultés psychologiques (i.e., anxiété et dépression), psychophysiologiques (i.e., insomnie, fatigue) et des difficultés sexuelles en fonction de trois modalités de traitement pour le cancer de la prostate (radiothérapie, curiethérapie et prostatectomie radicale) et du temps écoulé depuis le diagnostic. L'échantillon est composé de 861 hommes ayant complété une batterie de questionnaires. Les résultats démontrent que les difficultés sexuelles constituent le problème le plus fréquent suivies de l'insomnie et de l'anxiété. De plus, les symptômes psychologiques et psychophysiologiques restent relativement stables dans le temps alors que les symptômes physiques tendent à se résorber. Enfin, les patients ayant reçu de la radiothérapie ont un risque plus élevé de souffrir d'humeur dépressive, de détresse psychologique globale et de fatigue comparativement aux patients n'ayant pas reçu ce traitement.

No description available.

No description available.

Thesis (MSc)--Stellenbosch University, 2015. / ENGLISH ABSTRACT: Targeted therapy for prostate cancer may offer potential improvement over current conventional therapies because of its specificity. Although conventional treatments are effective, they are not curative and have several limitations. In prostate cancer, activation of both the epidermal growth factor receptor (EGFR) and the phosphatidylinositol 3 – kinase (PI3K)/Akt/mammalian target of rapamycin (mTOR) pathway have been implicated in tumorigenesis and resistance to both conventional and targeted anticancer therapies. Having a better understanding of the molecular mechanisms involved in PCa development, progression and resistance to therapy, could assist in the design of novel therapeutic strategies. The objective of this study was to inhibit key molecular targets of the human epidermal growth factor receptor signalling pathway and expose prostate cell lines to doses of radiation, so as to establish potential therapeutic targets that may be amenable to combined modality therapy, and formulate a cocktail of inhibitors to evaluate its radiosensitising capability. The EGFR/PI3K/mTOR pathway plays an important role in the radiosensitivity of the human prostate carcinoma cell line (DU145) and the normal cell line (1542N). In our study we have shown that AG-1478, an EGFR inhibitor, and BEZ-235, a dual inhibitor of the PI3K/mTOR pathway, singly or in combination, at low and relatively high radiation doses, resulted in radiosensitisation of DU145 cells. Radio-protection was achieved in 1542N cells. AG-1478 had no effect on radiosensitivity. / AFRIKAANSE OPSOMMING: Geteikende terapies wens hul spesifisiteit teenoor konvensionele terapies vir prostaat kanker, mag potensieel verbetering offer. Konvensionele behandeling is wel effektief maar nie genesend nie wens ‘n aantal beperkings, sowel as die toksisiteit vir normale selle. In prostaat kanker is die aktivering van beide die epidermiese groei faktor reseptor (EGFR) en fosfatidielinositol 3-kinase/Akt/soogdier teiken vir rapamisien (mTOR) seingewing baan sterk betrek by tumor groeisel en weerstand teen konvensionele en geteikende anti-kanker terapies. Beter begrip van die molekulêre meganismes betrokke by prostaat kanker ontwikkeling, bevordering en weerstand teen terapie, kan die ontwerp van nuwe terapeutiese strategies ondersteun. Die doelwit van hierdie studie was om sleutel molekulêre teikens van die epidermiese groei faktor reseptor seingewing baan te inhibeer en om prostaat selle bloot te stel aan dosisse bestraling, om potensiële terapeutiese teikens te vestig wat vatbaar is vir gekombineerde modaliteit terapie, om ‘n mengsel van stremmiddels te formuleer, en om die straling gevoeligmaking bekwaamheid daarvan te evalueer. Die EGFR/PI3K/mTOR seingewingbaan speel ‘n belangrike rol in the radiosensitiwiteit van die menslike prostaat kanker sellyn (DU145) en die normale prostaat sellyn (1542N). Die studie bevind dat AG-1478, ‘n EGFR stremmer, en BEZ-235, ‘n tweevoudige beperker van die fosforinositied 3-kinase (PI3K) en soogdier teiken vir rapamisien (mTOR) seingewingbaan, enkel of in kombinasie die DU145 selle radiosensitiseer vir straling dosisse van 2 en 6 Gy. Stralings beskerming was verkry met die 1542N sellyn. AG-1478 het geen effek getoon op radiosensitiwiteit nie.

published_or_final_version / Anatomy / Doctoral / Doctor of Philosophy

published_or_final_version / abstract / Anatomy / Master / Master of Philosophy

published_or_final_version / abstract / Anatomy / Doctoral / Doctor of Philosophy