RESUMO
BACKGROUND: Renal cell carcinoma (RCC) is the most common neoplasm of the adult kidney. Metastatic RCC is difficult to treat. The 5-year survival rate for metastatic RCC is ≤10%. Recently, microRNAs (miRNAs) have been shown to have a role in cancer metastasis and potential as prognostic biomarkers in cancer. METHOD: We performed a miRNA microarray to identify a miRNA signature characteristic of metastatic compared with primary RCCs. We validated our results by quantitative real-time PCR. We performed experimental and bioinformatic analyses to explore the involvement of miR-215 in RCC progression and metastasis. RESULTS: We identified 65 miRNAs that were significantly altered in metastatic compared with primary RCCs. We validated our results by examining the expression of miR-10b, miR-126, miR-196a, miR-204 and miR-215, in two independent cohorts of patients. We showed that overexpression of miR-215 decreased cellular migration and invasion in an RCC cell line model. In addition, through gene expression profiling, we identified direct and indirect targets of miR-215 that can contribute to tumour metastasis. CONCLUSION: Our analysis showed that miRNAs are altered in metastatic RCCs and can contribute to kidney cancer metastasis through different biological processes. Dysregulated miRNAs represent potential prognostic biomarkers and may have therapeutic applications in kidney cancer.
Assuntos
Carcinoma de Células Renais/genética , Carcinoma de Células Renais/patologia , Genes Supressores de Tumor , Neoplasias Renais/genética , Neoplasias Renais/patologia , MicroRNAs/genética , Biomarcadores Tumorais/genética , Carcinoma de Células Renais/metabolismo , Processos de Crescimento Celular/genética , Linhagem Celular Tumoral , Movimento Celular/genética , Progressão da Doença , Perfilação da Expressão Gênica , Regulação Neoplásica da Expressão Gênica , Testes Genéticos/métodos , Proteínas de Homeodomínio/metabolismo , Humanos , Neoplasias Renais/metabolismo , Análise em Microsséries/métodos , Invasividade Neoplásica , Metástase Neoplásica , Proteínas do Tecido Nervoso/metabolismo , Prognóstico , Proteínas de Ligação a RNA/metabolismo , Reação em Cadeia da Polimerase em Tempo Real/métodos , Proteínas Repressoras/metabolismo , Reação em Cadeia da Polimerase Via Transcriptase Reversa/métodos , Taxa de Sobrevida , Homeobox 2 de Ligação a E-box com Dedos de ZincoRESUMO
PURPOSE: Recent evidence demonstrates that decreasing shock wave frequency from the previous standard of 120 to 60 shocks per minute results in improved fragmentation of stones located within the renal collecting system. We report the first randomized trial to our knowledge to examine the effect of a slower shock wave frequency for shock wave lithotripsy on stones located in the proximal ureter. MATERIALS AND METHODS: A total of 163 patients with a previously untreated radiopaque calculus in the upper ureter measuring at least 5 mm underwent stratified block randomization according to stone size, and shock wave lithotripsy at 60 or 120 shocks per minute. Stone-free status at 3 months was confirmed with noncontrast computerized tomography or a plain abdominal x-ray and ultrasound study. RESULTS: Of the patients 77 were randomized to 60 shocks per minute and 86 were randomized to 120 shocks per minute. The groups were similar in gender, age, body mass index and initial stone area. At 3 months the 60 shocks per minute group had a higher overall stone-free rate (64.9% vs 48.8%, p = 0.039). Significantly fewer shocks were administered to patients treated at 60 shocks per minute (mean 2,680 vs 2,940, p <0.001). However, mean treatment times were longer (44.3 vs 24.5 minutes, p <0.001). Patients treated with 60 shocks per minute required fewer auxiliary procedures (29.9% vs 45.4%) (p = 0.031). CONCLUSIONS: Decreasing the rate of shock wave administration from 120 to 60 shocks per minute results in improved stone-free rates. A slower treatment rate of proximal ureteral stones reduces the need for additional shock wave lithotripsy or more invasive treatments to render patients stone-free, without any increase in morbidity, and with an acceptable increase in treatment time.
Assuntos
Litotripsia/métodos , Cálculos Ureterais/terapia , Método Duplo-Cego , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Estudos Prospectivos , Cálculos Ureterais/patologiaRESUMO
BACKGROUND: Laparoscopic colorectal surgery has clear advantages over open surgery; however, the effectiveness of the approach depends on the conversion rate. The objective of this work was to prospectively validate a model that would predict conversion in laparoscopic colorectal surgery. METHODS: A simple clinical model for predicting conversion in laparoscopic colorectal surgery was previously developed based on a multivariable logistic regression analysis of 367 procedures. This model was applied prospectively to a follow-up group of 248 procedures by the same team, including 54 procedures performed by one new fellowship-trained surgeon. RESULTS: Patients in the follow-up group were more likely to have cancer (56% vs 44%, p = 0.007) and were more obese (median, 71.0 vs 66.0 kg; p < 0.001). The rate of conversion in the follow-up group was unchanged (8.9% vs 9.0%, p > 0.05). Despite expected trends toward increasing risk of conversion with weight level (<60 kg, 6.8%; 60-<90 kg, 9.0%; >90 kg, 12.1%; p > 0.05) and malignancy (10.1% vs 7.3%, p > 0.05), the model did not distinguish well between groups at risk for conversion. Contrary to the model, however, the fellowship-trained surgeon had a conversion rate that was not higher than that of the other, more experienced surgeons (7.3% vs 9.3%, p > 0.05) even though he was less experienced, and operating on patients who were more obese (median, 75.0 vs 70 kg; p = 0.02) and more likely to have cancer (59% vs 55%, p > 0.05). Recalculated conversion scores that excluded the inexperience point for the fellowship-trained surgeon showed a good fit for the model. Considering the original and follow-up experience together (615 cases), the model clearly stratifies patients into low (0 points), medium (1-2 points), and high risk (3-4 points) for conversion, with respective rates of 2.9%, 8.1%, and 20% ( p = 0.001). CONCLUSION: This model appears to be a valid predictor of conversion to open surgery. Fellowship training may provide sufficient experience so that learning curve issues are redundant in early practice. This model now requires validation by other centers.
Assuntos
Doenças do Colo/cirurgia , Bolsas de Estudo , Cirurgia Geral/educação , Laparoscopia/estatística & dados numéricos , Doenças Retais/cirurgia , Peso Corporal , Neoplasias Colorretais/epidemiologia , Neoplasias Colorretais/cirurgia , Feminino , Seguimentos , Humanos , Aprendizagem , Modelos Logísticos , Masculino , Modelos Teóricos , Obesidade/complicações , Estudos Prospectivos , Resultado do TratamentoRESUMO
BACKGROUND: As compared with open donor nephrectomy (OpenDN), laparoscopic donor nephrectomy (LapDN) offers donors more rapid recovery and recipients equivalent graft function, but LapDN costs remain greater. This study compared LapDN and OpenDN with cost-utility analysis. METHODS: Utilities were assessed with time trade-off, probabilities derived from systematic review of the literature and the costs derived from 27 OpenDN and 34 LapDN patients treated contemporaneously. A societal perspective was taken. Lost employment costs were included. An incremental cost-effectiveness ratio (ICER) was calculated with best- and worst-case scenarios for confidence intervals. Sensitivity analyses assessed robustness. RESULTS: LapDN costs are lower (11,170.71 dollars vs 12,631.91 dollars), whereas quality of life (QOL) is superior (0.7247 vs 0.6585 quality-adjusted life years [QALY], rendering LapDN a dominant strategy. The model was robust to all variables, and LapDN remained dominant from a payer perspective. In a worst-case scenario, the ICER for LapDN was at most 2,231.61 dollars per QALY. CONCLUSIONS: LapDN offers improved QOL at lower costs, despite the fact that this analysis included patients treated during the learning curve of LapDN at our institution. By potentially increasing organ donor rates, LapDN may be further cost saving by decreasing the number of patients receiving dialysis.
Assuntos
Transplante de Rim/economia , Laparoscopia/economia , Nefrectomia/economia , Nefrectomia/métodos , Estudos de Coortes , Intervalos de Confiança , Controle de Custos , Custos de Cuidados de Saúde , Humanos , Transplante de Rim/métodos , Ontário , Estudos Prospectivos , Anos de Vida Ajustados por Qualidade de Vida , Sensibilidade e Especificidade , Doadores de TecidosRESUMO
BACKGROUND: Postoperative recovery often is assessed with parameters (pain and return to work) susceptible to bias. This study sought objectively to compare postoperative health-related quality of life (HRQL) after laparoscopic and open nephrectomy with the Postoperative Recovery (PRS) (a validated questionnaire designed to assess pain), activities of daily living (ADL), and HRQL in postoperative patients. METHODS: Patients undergoing contemporaneous laparoscopic and open nephrectomy received the PRS pre- and postoperatively. The results were analyzed with analysis of covariance (ANCOV) and survival analysis. RESULTS: The 33 open nephrectomy and 38 laparoscopic patients in this study were comparable in age, gender, body mass index (BMI) and employment. Laparoscopic operative time was longer (p = 0.015), and the hospital stay was shorter (p<0.001). Laparoscopic patients had higher HRQL scores from postoperative days 3 to 365 (p<0.001), and they returned to preoperative HRQL faster (p<0.001). CONCLUSIONS: An objective HRQL instrument confirms that laparoscopic nephrectomy patients recover faster and with a higher HRQL than open surgery patients. The PRS can be modified for use after other abdominal procedures, and may prove useful for comparisons of other minimally invasive surgical techniques.
Assuntos
Laparoscopia/estatística & dados numéricos , Nefrectomia/estatística & dados numéricos , Qualidade de Vida , Inquéritos e Questionários , Atividades Cotidianas , Adulto , Análise de Variância , Índice de Massa Corporal , Feminino , Humanos , Obstrução Intestinal/etiologia , Nefropatias/cirurgia , Neoplasias Renais/cirurgia , Laparoscopia/efeitos adversos , Tempo de Internação/estatística & dados numéricos , Masculino , Nefrectomia/efeitos adversos , Ontário , Medição da Dor , Satisfação do Paciente/estatística & dados numéricos , Estudos Prospectivos , Reoperação , Reprodutibilidade dos Testes , Infecção da Ferida Cirúrgica/etiologia , Resultado do Tratamento , Retenção Urinária/etiologiaRESUMO
OBJECTIVE: To address the issues of work-force planning and modelling in the 21st century for the specialty of urology in the Province of Ontario. DESIGN: Data (from 1991 to 1995) regarding urology physician resources were gathered from Health Canada, the Royal College of Physicians and Surgeons of Canada, the Ontario Physician Human Resources Data Centre, the Canadian Post-M.D. Education Registry, the System for Health Area Resource Planning (SHARP) database, the Canadian Institute for Health Information and the National Physician Database. Specifically, the age and gender breakdown of currently active Ontario urologists, measures of urologist clinical activity (from Ontario Hospital Insurance Plan billings and questionnaires), inputs into and exits from the active urologist population were gathered, and estimates of future needs for urologist services, based on current population and demographic models, were made. A model to predict the balance between future needs for urology services and future supply of urologists was then created and validated against data drawn from the SHARP database. RESULTS: The model revealed that there will be a significant shortage of urologists in Ontario in the immediate and long-term future; by the year 2010 there will be a shortfall of 101 urologists in Ontario, or 51% of the total needed. CONCLUSIONS: Enlarging the urology training programs in Ontario would help to minimize the estimated shortfall. Systematic modelling of physician work-force needs for the future is necessary for the optimal allocation of health care resources. The methodology of the urology work-force model is generalizable to physician work-force planning for other specialty groups on a provincial or national basis.
Assuntos
Necessidades e Demandas de Serviços de Saúde/tendências , Urologia , Simulação por Computador , Humanos , Modelos Estatísticos , Ontário , Crescimento Demográfico , Urologia/economia , Recursos HumanosRESUMO
PURPOSE: We determined the number of shock wave lithotripsy treatments that should be given for a single ureteral stone before alternate modalities are used. MATERIALS AND METHODS: We compared the stone-free rate of initial shock wave lithotripsy for ureteral calculi with that of subsequent treatments. We evaluated 1,593 ureteral stones treated with the Dornier MFL 5000 lithotriptor* from January 1, 1994 to September 1, 1999 using various parameters associated with treatment outcome. RESULTS: The stone-free rate after initial treatment was 68% (1,086 of 1,593 stones), which decreased to 46% (126 of 273) after re-treatment 1. We observed a further decrease in the stone-free rate after re-treatment 2 to 31% (19 of 61 stones, p = 0.001). The cumulative stone-free rate increased to 76% (1,212 of 1,593 stones) after 2 treatments and to 77% (1,231 of 1593) after 3. The stone-free rate for stones 10 mm. or less was significantly better than that of stones 11 to 20 mm. initially (64% versus 43%) and after re-treatment (49% versus 37%). A ureteral stent decreased the stone-free rate of initial treatment and re-treatment 1 by 12% and 14%, respectively (p = 0.001). After initial treatment the stone-free rate of the upper and mid ureter was significantly higher than that of the lower ureter. Patient weight had no significant impact on success in either group. CONCLUSIONS: The stone-free rate of re-treating ureteral calculi with shock wave lithotripsy decreases significantly after the initial treatment. These findings imply that ureteroscopic management of ureteral stones may be better than shock wave lithotripsy after initial shock wave lithotripsy fails.
Assuntos
Litotripsia , Cálculos Ureterais/terapia , Adolescente , Adulto , Idoso , Idoso de 80 Anos ou mais , Criança , Pré-Escolar , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Retratamento , Falha de TratamentoRESUMO
OBJECTIVE: To standardise infundibular width (IFW) measurement, to determine patient variability, and to determine inter-rater variability on intravenous pyelography (IVP). PATIENTS AND METHODS: Fifty outpatient IVP films were randomly drawn from two hospitals between 1 July 1998 and 31 August 1999, and examined to measure the lower calyceal IFW on the 5, 10 and 20 min films with compression, and after voiding. Kidneys with previous renal surgery, hydronephrosis or renal anatomical anomalies were excluded; in all, 81 kidneys from 50 patients were examined. The IFW was measured at the narrowest point along the infundibulum. All 50 films were then reviewed by two urologists unaware of their origin, to determine the inter-rater reliability of the infundibular measurements. RESULTS: Analysis of variance (anova) with posthoc analysis showed a significant difference in IFW at each phase of the IVP (repeated measures anova, P < 0.001). The mean (95% confidence interval) IFW was greatest on the compression film, at 4.4 (2.6) mm, and least on the postvoid film, at 1.6 (2.1) mm. Overall inter-rater reliability was 0.9780 (intraclass correlation coefficient), and the Pearson correlation between each rater for the IFW at each phase of the IVP was >/= 0.886. CONCLUSIONS: There is wide variability in lower calyceal IFW among the various IVP films in a given study. Thus any predictive value of the IFW must be standardized for the timing and IVP film type (compression, postvoid, etc.). The inter-rater reliability of IFW is high, suggesting that if used correctly it may be more useful in predicting the outcome after shock wave lithotripsy.
Assuntos
Pelve Renal/diagnóstico por imagem , Adolescente , Adulto , Idoso , Idoso de 80 Anos ou mais , Análise de Variância , Humanos , Cálculos Renais/diagnóstico por imagem , Cálculos Renais/patologia , Pessoa de Meia-Idade , Variações Dependentes do Observador , Prognóstico , Sensibilidade e Especificidade , Urografia/normasRESUMO
PURPOSE: We compare the effectiveness of mechanical percussion and inversion with observation for eliminating lower caliceal fragments 3 months after shock wave lithotripsy. MATERIALS AND METHODS: At 3 months after shock wave lithotripsy 69 patients with residual lower caliceal fragments 4 mm. or less were randomized to receive either mechanical percussion and inversion or observation for 1 month. The observation group then received crossover mechanical percussion and inversion if fragments persisted. All patients were followed with plain film of the kidneys, ureters and bladder to assess the stone area and stone-free status, and renal tomography or noncontrast spiral computerized tomography to confirm stone-free status. A blinded radiologist reviewed all films. Patients were treated with a mechanical chest percussor applied to the flank while inverted to greater than 60 degrees after receiving 20 mg. furosemide. RESULTS: A total of 35 patients were randomized to receive immediate mechanical percussion and inversion therapy and 34 observation. Of the patients in the observation group 28 subsequently received mechanical percussion and inversion after completing the observation period. The groups were not different in gender, body mass index, side affected, stone location or renal anatomical features. The mechanical percussion and inversion group had a substantially higher stone-free rate than the observation group (40% versus 3%, respectively, p <0.001). The mechanical percussion and inversion group also had a greater improvement in total stone area than controls (-63.3% versus +2.7%, respectively, p <0.001). No significant adverse effects were noted in the mechanical percussion and inversion group. CONCLUSIONS: Mechanical percussion and inversion is a safe and effective treatment option for residual lower caliceal fragments 3 months after shock wave lithotripsy. Nearly 50% of patients become stone-free, and stone burden is decreased by 50% in the remainder.