External validation of a Brazilian predictive nomogram for pathologic outcomes following radical prostatectomy in tertiary teaching institutions: the USP nomograms.

PURPOSES: (a) To externally validate the Crippa and colleagues' nomograms combining PSA, percentage of positive biopsy cores (PPBC) and biopsy Gleason score to predict organ-confined disease (OCD) in a contemporary sample of patients treated at a tertiary teaching institution. (b) To adjust such variables, resulting in predictive nomograms for OCD and seminal vesicle invasion (SVI): the USP nomograms. MATERIALS AND METHODS: The accuracy of Crippa and colleagues' nomograms for OCD prediction was examined in 1002 men submitted to radical prostatectomy between 2005 and 2010 at the University of São Paulo (USP). ROC-derived area under the curve (AUC) and Brier scores were used to assess the discriminant properties of nomograms for OCD. Nomograms performance was explored graphically with LOESS smoothing plots. Furthermore, univariate analysis and logistic regression models targeted OCD and SVI. Variables consisted of PSA, PPBC, biopsy Gleason score and clinical stage. The resulted predictive nomograms for OCD and SVI were internally validated with bootstrapping and the same abovementioned procedures. RESULTS: Crippa and colleagues' nomograms for OCD showed ROC AUC = 0.68 (CI: 0.65-0.70), Brier score = 0.17 and overestimation in LOESS plots. USP nomograms for OCDand SVI showed ROC AUC of 0.73 (CI: 0.70-0.76) and 0.77 (CI: 0.73-0.79), respectively, and Brier scores of 0.16 and 0.08, respectively. The LOESS plots showed excellent calibration for OCD and underestimation for SVI. CONCLUSIONS: Crippa and colleagues' nomograms showed moderate discrimination and considerable OCD overestimation. USP nomograms showed good discrimination for OCD and SVI, as well as excellent calibration for OCD and SVI underestimation.

External validation of a brazilian predictive nomogram for pathologic outcomes following radical prostatectomy in tertiary teaching institutions: the USP nomograms

Purposes(a) To externally validate the Crippa and colleagues’ nomograms combining PSA, percentage of positive biopsy cores (PPBC) and biopsy Gleason score to predict organ-confined disease (OCD) in a contemporary sample of patients treated at a tertiary teaching institution. (b) To adjust such variables, resulting in predictive nomograms for OCD and seminal vesicle invasion (SVI): the USP nomograms.Materials and MethodsThe accuracy of Crippa and colleagues’ nomograms for OCD prediction was examined in 1002 men submitted to radical prostatectomy between 2005 and 2010 at the University of São Paulo (USP). ROC-derived area under the curve (AUC) and Brier scores were used to assess the discriminant properties of nomograms for OCD. Nomograms performance was explored graphically with LOESS smoothing plots. Furthermore, univariate analysis and logistic regression models targeted OCD and SVI. Variables consisted of PSA, PPBC, biopsy Gleason score and clinical stage. The resulted predictive nomograms for OCD and SVI were internally validated with bootstrapping and the same abovementioned procedures.ResultsCrippa and colleagues’ nomograms for OCD showed ROC AUC = 0.68 (CI: 0.65-0.70), Brier score = 0.17 and overestimation in LOESS plots. USP nomograms for OCD and SVI showed ROC AUC of 0.73 (CI: 0.70-0.76) and 0.77 (CI: 0.73-0.79), respectively, and Brier scores of 0.16 and 0.08, respectively. The LOESS plots showed excellent calibration for OCD and underestimation for SVI.ConclusionsCrippa and colleagues’ nomograms showed moderate discrimination and considerable OCD overestimation. USP nomograms showed good discrimination for OCD and SVI, as well as excellent calibration for OCD and SVI underestimation.

Increased expression of MMP-9 and IL-8 are correlated with poor prognosis of Bladder Cancer.

BACKGROUND: Extracellular matrix homeostasis is strictly maintained by a coordinated balance between the expression of metalloproteinases (MMPs) and their inhibitors. The purpose of this study was to investigate whether the expression of MMP-9, MMP-2 and its specific inhibitors, are expressed in a reproducible, specific pattern and if the profiles are related to prognosis in Bladder Cancer (BC). METHODS: MMP-9, MMP-2 and its specific inhibitors expression levels were analyzed by quantitative real-time polymerase chain reaction (qRT-PCR) in fresh-frozen malignant tissue collected from 40 patients with BC submitted to transurethral resection of bladder. The control group consisted of normal bladder tissue from five patients who had undergone retropubic prostatectomy to treat benign prostatic hyperplasia. RESULTS: MMP-9 was overexpressed in 59.0 % of patients, and MMP-2, TIMP-1, TIMP-2, MMP-14, RECK and IL-8 was underexpressed in most of the patients. Regarding prognostic parameters we observed that high-grade tumors exhibited significantly higher levels of MMP-9 and IL-8 (p = 0.012, p = 0.003). Invasive tumors (pT1-pT2) had higher expression levels of MMP-9 than superficial tumors (pTa) (p = 0.026). The same was noted for IL-8 that was more expressed by invasive tumors (p = 0.015, p = 0.048). Most importantly tumor recurrence was related with higher levels of both MMP-9 (p = 0.003) and IL-8 (p = 0.005). CONCLUSION: We have demonstrated that the overexpression of MMP-9 and higher expression of IL-8 are related to unfavorable prognostic factors of urothelial bladder cancer and tumor recurrence and may be useful in the follow up of the patients.

Análise da expressão das metaloproteinases 2 e 9 e seus reguladores no câncer de bexiga / Expression of metalloproteinases 2 and 9 and their regulator genes in bladder cancer

Introdução: O Carcinoma Urotelial de Bexiga (CUB) é o segundo tumor urológico mais prevalente no Brasil. Devido ao elevado custo médico no processo que envolve seu diagnóstico, tratamento e seguimento, o CUB é um dos tipos de tumores mais caros para os sistemas de saúde. Embora existam fatores prognósticos definidos, como o estadiamento patológico, a diferenciação histológica e a presença de invasão angiolinfática (IAL), os mesmos demonstram-se insuficientes para uma acurada definição de comportamento da doença. Com a evolução da pesquisa molecular um grande número de potenciais novos marcadores de agressividade tem surgido. As Metaloproteinases da matriz (MMP) sao proteínas teciduais, pertencentes à família das endoproteinases, que degradam vários componentes da matriz extracelular. A expressão de diversas MMPs, especialmente MMP-2 e MMP-9 (gelatinases), bem como seus ativadores e inibidores, tem sido estudada como potencial marcador de comportamento tumoral em várias neoplasias. Objetivos: Avaliarmos os níveis de expressão dos genes das gelatinases MMP-2 e MMP-9 no CUB, assim como proteínas envolvidas em suas vias de ativação e inibição (MMP-14, IL-8, TIMP-1, TIMP-2, RECK e TGF-! ). Material e Método: Estudamos pela técnica de qRT-PCR a expressão dos 8 genes em amostras de CUB de 40 pacientes submetidos a RTUb, tendo como grupo controle amostras de urotélio sem câncer de 6 pacientes submetidos a prostatectomia aberta por HPB, bem como sua relação com marcadores prognósticos clássicos (estádio, grau e IAL). Resultados: Houve uma superexpressão de MMP-9 na maioria das amostras de CUB, bem como subexpressão de MMP-2, TIMP-1, TIMP-2, MMP-14, IL-8, TGF-! e RECK. Comparando os níveis de expressão dos genes com o estádio patológico, houve uma superexpressão de MMP-9 nos tumores pT1-2, quando comparados com pTa (p=0,026), bem como maior expressão de IL-8 nos tumores pT1 e pT2 (p=0,015 e p=0,048, respectivamente). Embora estatisticamente nao significativa, houve uma...

Introduction: Bladder cancer (BC) is the second most common urological tumor in Brazil. Because its high cost on diagnosis, treatment and follow-up, BC is one of the most expensive malignancies for health care providers. Although we have well-known prognostic factors, like pathological stage, histologic grade and lymphovascular invasion, they are insufficient to figure more accurate tumor aggressiveness. Recent molecular biology helped us to discover a huge amount of potential markers. Matrix metalloproteinases (MMP) are tissue endopeptidases that degrade components of extracellular matrix. Expression of several MMP, specially MMP-2 and MMP-9 (gelatinases), and their activators and inhibitors, are investigated as potential behavior markers in many neoplasms. Objectives: The aim of this study was to evaluate expression levels of gelatinases MMP-2 and MMP-9 genes by quantitative real-time polymerase chain reaction (qRT-PCR) in BC, as well as other proteins evolved in the activation and inhibition pathways (MMP-14, IL-8, TIMP-1, TIMP-2, RECK e TGF-b). Material and Method: Present study analyzed tissue expression of 8 genes in BC samples of transutethral resection of 40 patients by qRT-PCR, as well as their relation with current prognostic factors (stage, grade and LVI). The control group was composed of utothelial tissue from 6 patients with benign prostatic hyperplasia (BPH) treated surgically with retropubic prostatectomy. Results: In the tumor samples, MMP-9 presented an overexpression and MMP-2, TIMP-1, TIMP-2, MMP-14, RECK, IL-8, and TGF-b were underexpressed in BC tissue compared to control. Comparing gene level expression to pathologic stage, there was MMP-9 overexpression in pT1-2 tumors compared to pTa (p=0.026), as wall as IL-8 overexpression in pT1 and pT2 tumors (p=0.015 e p=0.048, respectively). Although not statiscally significant, there was MMP-14 overexpression in pT2 tumors in comparison to pTa-1 (p=0.087). About grade, there was MMP-9...

Percutaneous nephroscopic management of upper urinary tract transitional cell carcinoma: recurrence and long-term followup.

PURPOSE: We present long-term results of the percutaneous approach and resection of upper urinary tract transitional cell carcinoma, and we evaluate the prognostic factors related to recurrence. MATERIALS AND METHODS: A total of 34 patients underwent primary percutaneous resection of an upper urothelial tumor. We treated the patients with a superficial tumor that was completely resected macroscopically. Adjuvant topical chemotherapy or immunotherapy was administered. Patients were followed with excretory urography. Ureteroscopy and computerized tomography were obtained when clinically indicated. RESULTS: With a mean followup of 51 months ipsilateral recurrence developed in 41.2%. Median time to recurrence was 24 months. The rate of kidney preservation was 73.5%. Two patients died of the disease. There was a trend of recurrence in patients with multifocal tumors (OR 2.66, 95% CI 0.07-1.92), history of bladder carcinoma in situ (OR 2.4, 95% CI 1.61-3.74), tumor in renal pelvis (OR 6.45, 95% CI 0.01-1.46) and multiple tumor locations (OR 6.53, 95% CI 0.01-1.54). CONCLUSIONS: The percutaneous approach to renal urothelial tumor should be considered a valid option with a good long-term outcome. Recurrence is not uncommon and, as transitional cell carcinoma superficial bladder cancer it may be treated with endourological maneuvers or radical surgery, but with the obligation to a long lasting, strict surveillance.