RESUMO
INTRODUCTION AND OBJECTIVE: Overexpression of MMPs has been related to biochemical recurrence after radical prostatectomy. TIMP1 and TIMP2 are controllers of MMPs and the aim of this study is to evaluate the expression levels of MMPs and their regulators using immunohistochemistry in tissue microarray of localized prostate cancer (PC). MATERIALS AND METHODS: Immune-expression of MMP-9, MMP-2, TIMP1, TIMP-2, MMP-14 and IL8, were analyzed by immunohistochemistry in radical prostatectomy specimens of 40 patients with localized PC who underwent surgery between September 1997 and February 2000. Protein expression was considered as categorical variables, negative or positive. The results of the immune-expression were correlated to Gleason score (GS), pathological stage (TNM), pre-operatory PSA serum levels and biochemical recurrence in a mean follow up period of 92.5 months. RESULTS: The loss of TIMP1 immune-expression was related to biochemical recurrence. When TIMP1 was negative, 56.3% patients recurred versus 22.2% of those whose TIMP1 was positive (p=0.042). MMP-9, MMP-2, IL8 and MMP-14 were positive in the majority of PC. TIMP-2 was negative in all cases. CONCLUSION: Negative immune-expression of TIMP1 is correlated with biochemical recurrence in patients with PC possibly by failing to control MMP-9, an important MMP related to cancer progression.
Assuntos
Metaloproteinases da Matriz/análise , Recidiva Local de Neoplasia/patologia , Neoplasias da Próstata/patologia , Inibidor Tecidual de Metaloproteinase-1/análise , Inibidor Tecidual de Metaloproteinase-2/análise , Adulto , Idoso , Biomarcadores Tumorais/análise , Progressão da Doença , Humanos , Imuno-Histoquímica , Interleucina-8/análise , Estimativa de Kaplan-Meier , Masculino , Pessoa de Meia-Idade , Gradação de Tumores , Recidiva Local de Neoplasia/química , Estadiamento de Neoplasias , Antígeno Prostático Específico/sangue , Prostatectomia , Neoplasias da Próstata/química , Neoplasias da Próstata/cirurgia , Estatísticas não ParamétricasRESUMO
PURPOSE: To ensure patient safety and surgical efficiency, much emphasis has been placed on the training of laparoscopic skills using virtual reality simulators. The purpose of this study was to determine whether laparoscopic skills can be objectively quantified by measuring specific skill parameters during training in a virtual reality surgical simulator (VRSS). MATERIALS AND METHODS: Ten medical students (with no laparoscopic experience) and ten urology residents (PGY3-5 with limited laparoscopic experience) were recruited to participate in a ten-week training course in basic laparoscopic skills (camera, cutting, peg transfer and clipping skills) on a VRSS. Data were collected from the training sessions. The time that individuals took to complete each task and the errors that they made were analyzed independently. RESULTS: The mean time that individuals took to complete tasks was significantly different between the groups (p < 0.05), with the residents being faster than the medical students. The residents' group also completed the tasks with fewer errors. The majority of the subjects in both groups exhibited a significant improvement in their task completion time and error rate. CONCLUSION: The findings in this study demonstrate that laparoscopic skills can be objectively measured in a VRSS based on quantified skill parameters, including the time spent to complete skill tasks and the associated error rate. We conclude that a VRSS is a feasible tool for training and assessing basic laparoscopic skills.
Assuntos
Simulação por Computador , Internato e Residência , Laparoscopia/educação , Estudantes de Medicina , Urologia/educação , Interface Usuário-Computador , Competência Clínica , Feminino , Humanos , Curva de Aprendizado , Masculino , Estudos Prospectivos , Reprodutibilidade dos Testes , Análise e Desempenho de Tarefas , Fatores de TempoRESUMO
INTRODUCTION: Cell adhesion molecules (CAM) are required for maintaining a normal epithelial phenotype, and abnormalities in CAM expression have been related to cancer progression, including bladder urothelial carcinomas. There is only one study that correlates E-cadherin and Α-, Β- and y-catenin expression with prognosis of upper tract urothelial carcinomas. Our aim is to study the pattern of immune expression of these CAMs in urothelial carcinomas from the renal pelvis and ureter in patients who have been treated surgically. Our goal is to correlate these expression levels and characteristics with well-known prognostic parameters for disease-free survival. MATERIALS AND METHODS: We evaluated specimens from 20 patients with urothelial carcinomas of the renal pelvis and ureter who were treated with nephroureterectomy or ureterectomy between June 1997 and January 2007. CAM expression was evaluated by immunohistochemistry in a tissue microarray and correlated with histopathological characteristics and patient outcomes after a mean follow-up of 55 months. RESULTS: We observed a relationship between E-cadherin expression and disease recurrence. Disease recurrence occurred in 87.5% of patients with strong E-cadherin expression. Only 50.0% of patients with moderate expression and 0% of patients with weak or no expression of E-cadherin had disease recurrence (p = 0.014). There was also a difference in disease-free survival. Patients with strong E-cadherin expression had a mean disease-free survival rate of 49.1 months, compared to 83.9 months for patients with moderate expression (p = 0.011). Additionally, an absence of Α-catenin expression was associated with tumors that were larger than 3 cm (p = 0.003). CONCLUSIONS: We demonstrated for the first time that immune expression of E-cadherin is related to tumor recurrence and disease-free survival rates, and the absence of Α-catenin expression is related to tumor size in upper tract urothelial carcinomas.
Assuntos
Biomarcadores Tumorais/análise , Caderinas/análise , Carcinoma/química , Cateninas/análise , Neoplasias Ureterais/química , Sistema Urinário/química , Idoso , Idoso de 80 Anos ou mais , Carcinoma/patologia , Moléculas de Adesão Celular/análise , Métodos Epidemiológicos , Feminino , Humanos , Imuno-Histoquímica , Masculino , Pessoa de Meia-Idade , Prognóstico , Distribuição por Sexo , Fatores de Tempo , Análise Serial de Tecidos , Neoplasias Ureterais/patologia , Sistema Urinário/patologia , alfa Catenina/análise , beta Catenina/análise , gama Catenina/análiseRESUMO
PURPOSE: To evaluate whether the use of the physical surgical simulator may benefit the development of laparoscopic skills. METHODS: Ten medical students were divided into two groups: the first one performed ten weekly training sessions with a physical surgical simulator - ETX A2 LAP and, afterwards, one laparoscopic cholecystectomy in a porcine model, while the second group performed only a laparoscopic cholecystectomy. Both groups were compared regarding bleeding, total surgical time, time to perform each surgical step and qualitative parameters, based on a previously validated tool. RESULTS: There was no difference in any of the evaluated parameters. CONCLUSION: We did not find any evidence of benefit in the use of the physical simulator for surgical performance in medical students.
Assuntos
Educação de Graduação em Medicina/métodos , Laparoscopia/educação , Treinamento por Simulação/métodos , Adulto , Animais , Competência Clínica , Avaliação Educacional , Desenho de Equipamento , Feminino , Humanos , Laparoscopia/métodos , Masculino , Duração da Cirurgia , Reprodutibilidade dos Testes , Estatísticas não Paramétricas , Estudantes de Medicina , Suínos , Fatores de Tempo , Adulto JovemRESUMO
Abstract Purpose: To evaluate whether the use of the physical surgical simulator may benefit the development of laparoscopic skills. Methods: Ten medical students were divided into two groups: the first one performed ten weekly training sessions with a physical surgical simulator - ETX A2 LAP and, afterwards, one laparoscopic cholecystectomy in a porcine model, while the second group performed only a laparoscopic cholecystectomy. Both groups were compared regarding bleeding, total surgical time, time to perform each surgical step and qualitative parameters, based on a previously validated tool. Results: There was no difference in any of the evaluated parameters. Conclusion: We did not find any evidence of benefit in the use of the physical simulator for surgical performance in medical students.
Assuntos
Humanos , Animais , Masculino , Feminino , Adulto , Adulto Jovem , Laparoscopia/educação , Educação de Graduação em Medicina/métodos , Treinamento por Simulação/métodos , Estudantes de Medicina , Suínos , Fatores de Tempo , Reprodutibilidade dos Testes , Competência Clínica , Laparoscopia/métodos , Estatísticas não Paramétricas , Avaliação Educacional , Desenho de Equipamento , Duração da CirurgiaRESUMO
BACKGROUND AND PURPOSE: Becoming proficient in laparoscopic surgery is dependent on the acquisition of specialized skills that can only be obtained from specific training. This training could be achieved in various ways using inanimate models, animal models, or live patient surgery--each with its own pros and cons. Currently, there are substantial data that support the benefits of animal model training in the initial learning of laparoscopy. Nevertheless, whether these benefits extent themselves to moderately experienced surgeons is uncertain. The purpose of this study was to determine if training using a porcine model results in a quantifiable gain in laparoscopic skills for moderately experienced laparoscopic surgeons. MATERIALS AND METHODS: Six urologists with some laparoscopic experience were asked to perform a radical nephrectomy weekly for 10 weeks in a porcine model. The procedures were recorded, and surgical performance was assessed by two experienced laparoscopic surgeons using a previously published surgical performance assessment tool. The obtained data were then submitted to statistical analysis. RESULTS: With training, blood loss was reduced approximately 45% when comparing the averages of the first and last surgical procedures (P=0.006). Depth perception showed an improvement close to 35% (P=0.041), and dexterity showed an improvement close to 25% (P=0.011). Total operative time showed trends of improvement, although it was not significant (P=0.158). Autonomy, efficiency, and tissue handling were the only aspects that did not show any noteworthy change (P=0.202, P=0.677, and P=0.456, respectively). CONCLUSIONS: These findings suggest that there are quantifiable gains in laparoscopic skills obtained from training in an animal model. Our results suggest that these benefits also extend to more advanced stages of the learning curve, but it is unclear how far along the learning curve training with animal models provides a clear benefit for the performance of laparoscopic procedures. Future studies are necessary to confirm these findings and better understand the impact of this learning tool on surgical practice.
Assuntos
Laparoscopia/educação , Laparoscopia/métodos , Modelos Animais , Nefrectomia/educação , Nefrectomia/métodos , Competência Profissional , Sus scrofa/cirurgia , Animais , Perda Sanguínea Cirúrgica , Percepção de Profundidade , Laparoscopia/efeitos adversos , Nefrectomia/efeitos adversos , Fatores de TempoRESUMO
OBJECTIVE: To evaluate the correlation between transforming growth factor beta (TGF-ß1) expression and prognosis in prostate cancer. PATIENTS AND METHODS: TGF-ß1 expression levels were analyzed using the quantitative real-time polymerase chain reaction to amplify RNA that had been isolated from fresh-frozen malignant and benign tissue specimens collected from 89 patients who had clinically localized prostate cancer and had been treated with radical prostatectomy. The control group consisted of li patients with benign prostate hyperplasia. The expression levels of TGF-ß1 were compared between the groups in terms of Gleason scores, pathological staging, and prostate-specific antigen serum levels. RESULTS: In the majority of the tumor samples, TGF-ß1 was underexpressed 67.0% of PCa patients. The same expression pattern was identified in benign tissues of patients with prostate cancer. Although most cases exhibited underexpression of TGF-ß1, a higher expression level was found in patients with Gleason scores ≥ 7 when compared to patients with Gleason scores < 7(p = 0.002). Among the 26 cases of TGF-ß1 overexpression, 92.3% had poor prognostic features. CONCLUSIONS: TGF-ß1 was underexpressed in prostate cancers; however, higher expression was observed in tumors with higher Gleason scores, which suggests that TGF-ß1 expression may be a useful prognostic marker for prostate cancer. Further studies of clinical specimens are needed to clarify the role of TGF-ß1 in prostate carcinogenesis.
Assuntos
Biomarcadores Tumorais/metabolismo , Neoplasias da Próstata/metabolismo , Fator de Crescimento Transformador beta1/metabolismo , Adulto , Idoso , Carcinógenos/metabolismo , Expressão Gênica , Humanos , Masculino , Pessoa de Meia-Idade , Gradação de Tumores , Prognóstico , Antígeno Prostático Específico/sangue , Prostatectomia , Neoplasias da Próstata/patologia , Neoplasias da Próstata/cirurgia , Reação em Cadeia da Polimerase em Tempo Real , Estatísticas não Paramétricas , Fator de Crescimento Transformador beta1/genéticaRESUMO
Introduction and objective: Overexpression of MMPs has been related to biochemical recurrence after radical prostatectomy. TIMP1 and TIMP2 are controllers of MMPs and the aim of this study is to evaluate the expression levels of MMPs and their regulators using immunohistochemistry in tissue microarray of localized prostate cancer (PC). Materials and Methods: Immune-expression of MMP-9, MMP-2, TIMP1, TIMP-2, MMP-14 and IL8, were analyzed by immunohistochemistry in radical prostatectomy specimens of 40 patients with localized PC who underwent surgery between September 1997 and February 2000. Protein expression was considered as categorical variables, negative or positive. The results of the immune-expression were correlated to Gleason score (GS), pathological stage (TNM), pre-operatory PSA serum levels and biochemical recurrence in a mean follow up period of 92.5 months. Results: The loss of TIMP1 immune-expression was related to biochemical recurrence. When TIMP1 was negative, 56.3% patients recurred versus 22.2% of those whose TIMP1 was positive (p=0.042). MMP-9, MMP-2, IL8 and MMP-14 were positive in the majority of PC. TIMP-2 was negative in all cases. Conclusion: Negative immune-expression of TIMP1 is correlated with biochemical recurrence in patients with PC possibly by failing to control MMP-9, an important MMP related to cancer progression.
Assuntos
Adulto , Idoso , Humanos , Masculino , Pessoa de Meia-Idade , Metaloproteinases da Matriz/análise , Recidiva Local de Neoplasia/patologia , Neoplasias da Próstata/patologia , Inibidor Tecidual de Metaloproteinase-1/análise , /análise , Biomarcadores Tumorais/análise , Progressão da Doença , Imuno-Histoquímica , /análise , Estimativa de Kaplan-Meier , Gradação de Tumores , Estadiamento de Neoplasias , Recidiva Local de Neoplasia/química , Prostatectomia , Antígeno Prostático Específico/sangue , Neoplasias da Próstata/química , Neoplasias da Próstata/cirurgia , Estatísticas não ParamétricasRESUMO
Purpose To ensure patient safety and surgical efficiency, much emphasis has been placed on the training of laparoscopic skills using virtual reality simulators. The purpose of this study was to determine whether laparoscopic skills can be objectively quantified by measuring specific skill parameters during training in a virtual reality surgical simulator (VRSS). Materials and Methods Ten medical students (with no laparoscopic experience) and ten urology residents (PGY3-5 with limited laparoscopic experience) were recruited to participate in a ten-week training course in basic laparoscopic skills (camera, cutting, peg transfer and clipping skills) on a VRSS. Data were collected from the training sessions. The time that individuals took to complete each task and the errors that they made were analyzed independently. Results The mean time that individuals took to complete tasks was significantly different between the groups (p < 0.05), with the residents being faster than the medical students. The residents' group also completed the tasks with fewer errors. The majority of the subjects in both groups exhibited a significant improvement in their task completion time and error rate. Conclusion The findings in this study demonstrate that laparoscopic skills can be objectively measured in a VRSS based on quantified skill parameters, including the time spent to complete skill tasks and the associated error rate. We conclude that a VRSS is a feasible tool for training and assessing basic laparoscopic skills. .
Assuntos
Feminino , Humanos , Masculino , Simulação por Computador , Internato e Residência , Laparoscopia/educação , Estudantes de Medicina , Interface Usuário-Computador , Urologia/educação , Competência Clínica , Curva de Aprendizado , Estudos Prospectivos , Reprodutibilidade dos Testes , Análise e Desempenho de Tarefas , Fatores de TempoRESUMO
INTRODUCTION: Cell adhesion molecules (CAM) are required for maintaining a normal epithelial phenotype, and abnormalities in CAM expression have been related to cancer progression, including bladder urothelial carcinomas. There is only one study that correlates E-cadherin and α-, β- and γ-catenin expression with prognosis of upper tract urothelial carcinomas. Our aim is to study the pattern of immune expression of these CAMs in urothelial carcinomas from the renal pelvis and ureter in patients who have been treated surgically. Our goal is to correlate these expression levels and characteristics with well-known prognostic parameters for disease-free survival. MATERIALS AND METHODS: We evaluated specimens from 20 patients with urothelial carcinomas of the renal pelvis and ureter who were treated with nephroureterectomy or ureterectomy between June 1997 and January 2007. CAM expression was evaluated by immunohistochemistry in a tissue microarray and correlated with histopathological characteristics and patient outcomes after a mean follow-up of 55 months. RESULTS: We observed a relationship between E-cadherin expression and disease recurrence. Disease recurrence occurred in 87.5% of patients with strong E-cadherin expression. Only 50.0% of patients with moderate expression and 0% of patients with weak or no expression of E-cadherin had disease recurrence (p = 0.014). There was also a difference in disease-free survival. Patients with strong E-cadherin expression had a mean disease-free survival rate of 49.1 months, compared to 83.9 months for patients with moderate expression (p = 0.011). Additionally, an absence of α-catenin expression was associated with tumors that were larger than 3 cm (p = 0.003). CONCLUSIONS: We demonstrated for the first time that immune expression of E-cadherin is related to tumor recurrence and disease-free survival rates, and the absence of α-catenin expression is related to tumor size in upper tract urothelial carcinomas.
Assuntos
Idoso , Idoso de 80 Anos ou mais , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Caderinas/análise , Carcinoma/química , Cateninas/análise , Biomarcadores Tumorais/análise , Neoplasias Ureterais/química , Sistema Urinário/química , Carcinoma/patologia , Moléculas de Adesão Celular/análise , Métodos Epidemiológicos , Imuno-Histoquímica , Prognóstico , Distribuição por Sexo , Fatores de Tempo , Análise Serial de Tecidos , Neoplasias Ureterais/patologia , Sistema Urinário/patologia , alfa Catenina/análise , beta Catenina/análise , gama Catenina/análiseRESUMO
OBJECTIVE: To evaluate the correlation between transforming growth factor beta (TGF-β1) expression and prognosis in prostate cancer. PATIENTS AND METHODS: TGF-β1 expression levels were analyzed using the quantitative real-time polymerase chain reaction to amplify RNA that had been isolated from fresh-frozen malignant and benign tissue specimens collected from 89 patients who had clinically localized prostate cancer and had been treated with radical prostatectomy. The control group consisted of li patients with benign prostate hyperplasia. The expression levels of TGF-β1 were compared between the groups in terms of Gleason scores, pathological staging, and prostate-specific antigen serum levels. RESULTS: In the majority of the tumor samples, TGF-β1 was underexpressed 67.0 percent of PCa patients. The same expression pattern was identified in benign tissues of patients with prostate cancer. Although most cases exhibited underexpression of TGF-β1, a higher expression level was found in patients with Gleason scores >7 when compared to patients with Gleason scores <7(p = 0.002). Among the 26 cases of TGF-β1 overexpression, 92.3 percent had poor prognostic features. CONCLUSIONS: TGF-β1 was underexpressed in prostate cancers; however, higher expression was observed in tumors with higher Gleason scores, which suggests that TGF-β1 expression may be a useful prognostic marker for prostate cancer. Further studies of clinical specimens are needed to clarify the role of TGF-β1 in prostate carcinogenesis.
Assuntos
Adulto , Idoso , Humanos , Masculino , Pessoa de Meia-Idade , Neoplasias da Próstata/metabolismo , Fator de Crescimento Transformador beta1/metabolismo , Biomarcadores Tumorais/metabolismo , Carcinógenos/metabolismo , Expressão Gênica , Gradação de Tumores , Prognóstico , Prostatectomia , Antígeno Prostático Específico/sangue , Neoplasias da Próstata/patologia , Neoplasias da Próstata/cirurgia , Reação em Cadeia da Polimerase em Tempo Real , Estatísticas não Paramétricas , Fator de Crescimento Transformador beta1/genéticaRESUMO
Introdução: O câncer de próstata (CaP) é o tumor mais freqüente do homem no Brasil tendo sido estimados mais de 52.350 novos casos em 2010, sendo a segunda causa de óbito por câncer em homens. O prognóstico depende fundamentalmente dos níveis séricos de Prostatic Specific Antigen (PSA) estádio tumoral (TNM) e grau de diferenciação histológica (Gleason). Porém esses têm sido insuficientes na definição do prognóstico da neoplasia. Por isso pesquisas têm sido direcionadas para a identificação de alterações moleculares que possam prever o potencial de agressividade do câncer de próstata. Metaloproteinases da matriz (MMP) são proteínas pertencentes a uma família de aproximadamente 30 enzimas proteolíticas ou endoproteinases que degradam vários componentes da matriz extracelular. A detecção de sua expressão tem sido estudada como marcador sensível e específico de vários tumores, principalmente as MMP pertencentes ao grupo das gelatinases MMP-2 e MMP-9. Objetivo: o objetivo deste nosso trabalho foi avaliarmos pela técnica de qRT-PCR e imuno-histoquímica os níveis de expressão dos genes das MMP pertencentes ao grupo das gelatinases, MMP-2 e MMP-9, bem como outros sabidamente envolvidos em suas vias de ativação (MMP-14, IL-8) e inibição (TIMP-1, TIMP-2, RECK e TGF-) no câncer localizado de próstata. Material e Métodos: O estudo consistiu na análise de espécimes de 79 pacientes com câncer da próstata submetidos a prostatectomia radical entre setembro de 1997 e fevereiro de 2000. Esses oito genes foram então testados quanto a seu valor prognóstico no câncer da próstata através da técnica de reação em cadeia da polimerase quantitativa com transcriptase reversa (qRT-PCR). Análise proteica foi feita a partir de 40 pacientes deste pool. O grupo controle foi composto de tecido de 11 pacientes com hiperplasia benigna da próstata (HPB) tratados cirurgicamente com prostatectomia retropúbica. Resultados: MMP-9 esteve superexpressa e MMP-2, TIMP-1, TIMP-2, MMP 14, IL-8, TGF-...
Introduction: Currently, Prostate cancer (PCa) is the most common tumor in men in Brazil. It was estimated that more than 52,350 new cases were diagnosed in 2010, being the second cause of death by cancer in man. The prognosis depends mainly on Prostate Specific Antigen (PSA) serum levels, tumor stage (TNM) and histological grade (Gleason), but these parameters, even combined, are insufficient to define the correct prognosis of PCa. Therefore research has been directed towards the identification of molecular alterations that may predict potential aggressiveness of PCa. Matrix metalloproteinases (MMPs) are proteins that belong to a family of about 30 proteolytic enzymes that degrade various components of the extracellular matrix. The analysis of MMPs expression has been studied as a sensitive and specific marker of prognosis of several tumors, and special attention was focused in the group of gelatinases, MMP-2 and MMP-9.Objective: The aim of this study was to evaluate the expression levels of MMP-2 and MMP-9 genes and proteins by quantitative real-time polymerase chain reaction (qRT-PCR) and immunohistochemistry in localized PCa. We also evaluated the expression of genes that are involved in the control of MMP-2 and MMP as activators (MMP- 14, IL-8) or inhibitors (TIMP-1, TIMP-2, RECK and TGF-).Materials and Methods: The casuistic consisted of 79 surgical specimens from patients with localized PCa who underwent radical prostatectomy between September 1997 and February 2000. The control group was composed of specimens from 11 patients with benign prostatic hyperplasia (BPH) treated surgically with retropubic prostatectomy. The results of the 8 genes expression, through qRTPCR and immunohistochemistry, were correlated to the diagnosis and prognosis of PCa. The protein expression analysis was carried out in 40 patients of the casuistic. Results: The MMP-9 was overexpressed, while MMP-2, TIMP-1, TIMP-2, MMP-14, RECK, IL-8, and TGF- were underexpressed...