Optimizing treatment for non muscle-invasive bladder cancer with an app.

OBJECTIVES: To evaluate overall and recurrence-progression rate-adjusted concordance of treatment prescription in non-muscle-invasive bladder cancer (NMIBC) of an app based on the best available scientific evidence and the urologist's opinion. METHODS: Development of an app (APPv) specifically designed for the treatment and follow-up of NMIBC and validation of the proposed APPv treatment endpoint by means of a prospective double-blind observational concordance study of related samples in 100 patients with initial or successive histological diagnosis of NMIBC. RESULTS: The treatment prescribed by the urologist agrees with that proposed by the APPv in 64% of cases (kappa index 0.55, P < 0.0001). Regarding low risk, the agreement is 77% (kappa 0.55, P = 0.002), 63% (kappa 0.52, P < 0.0001) for intermediate risk, 17% (kappa 0.143, P = 0.014) in high risk and 66% (kappa 0.71, P = 0.01) for very high risk. Of patients receiving adjuvant intravesical treatment according to APPv, 89.1% remain free of recurrence vs. 61.1% of those with disagreement (P = 0.0004), with a RR 0.46 (95%CI: 0.25-0.86) vs. RR 2.4 (95%CI: 1.5-3.8, P = 0.001). In the APPv-urologist agreement group, 100% of patients are free of progression and 88.9% in the disagreement group (P = 0.004) with a RR 1 vs. RR 1.125 (95%CI: 1-1.26, P = 0.004). CONCLUSIONS: APPv can improve adherence to treatment recommendations according to clinical practice guidelines and health outcomes at NMIBC.

Vesical Imaging-Reporting and Data System (VI-RADS): experiencia inicial en la clasificación del cáncer de vejiga músculo-infiltrante / Vesical Imaging-Reporting and Data System (VI-RADS): Initial experience in the classification of muscle-invasive bladder cancer

Objetivo: Analizar la precisión diagnóstica del sistema VI-RADS® en radiólogos sin experiencia previa en su uso para diferenciar tumores de vejiga no músculo-infiltrantes de tumores de vejiga músculo-infiltrantes (TVMI) en lesiones sospechosas de malignidad en cistoscopia sin resección transuretral previa (RTU).Material y métodosEstudio retrospectivo en el que se incluyó a 18 pacientes con lesiones sospechosas en cistoscopia a los que se les realizó una RM de vejiga. Dos radiólogos sin experiencia previa en el sistema VI-RADS® evaluaron los estudios. Tras la RM, a los pacientes se les realizó una RTU de las lesiones sospechosas. Se analizaron la sensibilidad y la especificidad del sistema para valores VI-RADS® ≥3 o VI-RADS® ≥ 4, así como el índice kappa de Cohen, entre ambos radiólogos.ResultadosLos valores medios de sensibilidad y especificidad de ambos radiólogos considerando tanto los estudios VI-RADS® ≥ 3 o VI-RADS® ≥ 4 fueron del 91,7% y el 87,5, respectivamente. El índice kappa, considerando los estudios VI-RADS® ≥ 3 positivos fue de 0,551 (p<0,05) y considerando positivos los estudios VI-RADS® ≥ 4 de 0,571 (p<0,05).ConclusiónEl sistema VI-RADS® presenta unos excelentes valores de sensibilidad (91,7%) y especificidad (87,5%) en la clasificación de los TVMI cuando lo utilizan radiólogos sin experiencia previa en su uso con una moderada concordancia interobservador. (AU)

Objective: to analyze the diagnostic accuracy of the VI-RADS® system in the differentiation of non-muscle-invasive bladder tumors (NMIBT from muscle-invasive bladder tumors (MIBT in suspicious cystoscopic findings without prior transurethral resection (TUR evaluated by radiologists with no prior experience in its use.Material and methodsretrospective study carried out with 18 patients with suspicious lesions in cystoscopy. All of them underwent MRI of the bladder. Two radiologists with no prior experience in the use of the VI-RADS® system evaluated the results. All patients underwent TUR of the suspicious lesions after MRI. The sensitivity and specificity of the system were analyzed for VI-RADS® values ≥ 3 or VI-RADS® ≥ 4, as well as the Cohen's kappa coefficient between both radiologists.Resultsthe mean values of sensitivity and specificity of both radiologists considering both the VI-RADS® ≥ 3 or VI-RADS® ≥ 4 values were 91.7% and 87.5%, respectively. The kappa coefficient considering the VI-RADS® ≥ 3 as positive, was 0.551 (P<.05), while considering the VI-RADS® ≥ 4 as positive, it was 0.571 (P<.05).ConclusionThe VI--RADS® system presents excellent sensitivity (91.7% and specificity (87.5% values in the classification of MIBT performed by radiologists with no prior experience in its use, with a moderate interobserver agreement. (AU)

Vesical Imaging-Reporting and Data System (VI-RADS®): Initial experience in the classification of muscle-invasive bladder cancer. / Vesical Imaging-Reporting and Data System (VI-RADS®): experiencia inicial en la clasificación del cáncer de vejiga músculo-infiltrante.

OBJECTIVE: to analyze the diagnostic accuracy of the VI-RADS® system in the differentiation of non-muscle-invasive bladder tumors (NMIBT from muscle-invasive bladder tumors (MIBT in suspicious cystoscopic findings without prior transurethral resection (TUR evaluated by radiologists with no prior experience in its use. MATERIAL AND METHODS: retrospective study carried out with 18 patients with suspicious lesions in cystoscopy. All of them underwent MRI of the bladder. Two radiologists with no prior experience in the use of the VI-RADS® system evaluated the results. All patients underwent TUR of the suspicious lesions after MRI. The sensitivity and specificity of the system were analyzed for VI-RADS® values ≥ 3 or VI-RADS® ≥ 4, as well as the Cohen's kappa coefficient between both radiologists. RESULTS: the mean values of sensitivity and specificity of both radiologists considering both the VI-RADS® ≥ 3 or VI-RADS® ≥ 4 values were 91.7% and 87.5%, respectively. The kappa coefficient considering the VI-RADS® ≥ 3 as positive, was 0.551 (P<.05), while considering the VI-RADS® ≥ 4 as positive, it was 0.571 (P<.05). CONCLUSION: The VI--RADS® system presents excellent sensitivity (91.7% and specificity (87.5% values in the classification of MIBT performed by radiologists with no prior experience in its use, with a moderate interobserver agreement.

Myopodin methylation is a prognostic biomarker and predicts antiangiogenic response in advanced kidney cancer.

Myopodin is a cytoskeleton protein that shuttles to the nucleus depending on the cellular differentiation and stress. It has shown tumor suppressor functions. Myopodin methylation status was useful for staging bladder and colon tumors and predicting clinical outcome. To our knowledge, myopodin has not been tested in kidney cancer to date. The purpose of this study was to evaluate whether myopodin methylation status could be clinically useful in renal cancer (1) as a prognostic biomarker and 2) as a predictive factor of response to antiangiogenic therapy in patients with metastatic disease. Methylation-specific polymerase chain reactions (MS-PCR) were used to evaluate myopodin methylation in 88 kidney tumors. These belonged to patients with localized disease and no evidence of disease during follow-up (n = 25) (group 1), and 63 patients under antiangiogenic therapy (sunitinib, sorafenib, pazopanib, and temsirolimus), from which group 2 had non-metastatic disease at diagnosis (n = 32), and group 3 showed metastatic disease at diagnosis (n = 31). Univariate and multivariate Cox analyses were utilized to assess outcome and response to antiangiogenic agents taking progression, disease-specific survival, and overall survival as clinical endpoints. Myopodin was methylated in 50 out of the 88 kidney tumors (56.8 %). Among the 88 cases analyzed, 10 of them recurred (11.4 %), 51 progressed (57.9 %), and 40 died of disease (45.4 %). Myopodin methylation status correlated to MSKCC Risk score (p = 0.050) and the presence of distant metastasis (p = 0.039). Taking all patients, an unmethylated myopodin identified patients with shorter progression-free survival, disease-specific survival, and overall survival. Using also in univariate and multivariate models, an unmethylated myopodin predicted response to antiangiogenic therapy (groups 2 and 3) using progression-free survival, disease-specific, and overall survival as clinical endpoints. Myopodin was revealed hypermethylated in kidney cancer. Myopodin methylation status identified which patients showed a more aggressive clinical behavior and predicted antiangiogenic response. These observations support the clinical utility of an unmethylated myopodin as a prognostic and predictive biomarker in kidney cancer.

[Interaction between sildenafil and calcineurin inhibitors in renal transplant recipients with erectile dysfunction]. / Interacción entre sildenafilo y los inhibidores de la calcineurina en trasplantados renales con disfunción eréctil.

AIM: Hepatic metabolism of sildenafil uses the same metabolic pathway as the calcineurin inhibitors (cyclosporine/tacrolimus), through the CYP3A4 isoenzyme. The aim of this pilot study was to evaluate the potential interaction between sildenafil therapy and circulating levels of cyclosporine and tacrolimus in a group of steady-state renal transplant recipients with erectile dysfunction. MATERIAL AND METHODS: A prospective pilot study of sildenafil interactions was carried out in 9 stable male renal transplant recipients with severe erectile dysfunction (mean age 50 +/- 8 years, range 38-64). All patients were receiving therapy with calcineurin inhibitors (5 with cyclosporine and 4 with tacrolimus). Erectile dysfunction was evaluated by clinical history, physical examination, International Index of Erectile Function (IIEF) questionnaire and the nocturnal penile tumescence test (RigiScan). Each patient received a first dose of 50 mg of sildenafil, one hour before sexual activity and a second dose at 72 hours of 50 or 100 mg according to the clinical response to the first dose. We evaluated the efficacy and safety of sildenafil and the evolution of cyclosporine-tacrolimus levels. Cyclosporine and tacrolimus trough whole blood concentrations were determined in basal conditions (before starting sildenafil) and on days 1, 4 and 7 after sildenafil therapy. RESULTS: Eighty-nine percent of patients (n = 8) required a complete 100 mg dose of sildenafil. There was a positive clinical response in two-thirds of cases (6 patients). In 5 patients (55%) sildenafil administration produced a complete response, in one patient the response was incomplete, and in the remaining 3 cases (33%) no clinical response was observed. Associated side effects included self-limited tachycardia in one patient and mild visual disturbances in another. Cyclosporine and tacrolimus levels remained stable in all patients. There were no significant differences in circulating levels of cyclosporine (basal 120 +/- 47; day 1: 116 +/- 55; day 4: 123 +/- 56 and day 7: 121 +/- 56 ng/ml p = NS) or tacrolimus (basal 11.6 +/- 1.3; day 1: 11.9 +/- 1.3; day 4: 11.1 +/- 1.0 and day 7: 11.8 +/- 0.9 ng/ml p = NS) over the study period. CONCLUSIONS: Sildenafil therapy is safe and effective for the treatment of erectile dysfunction in renal transplant recipients. Recommended therapeutic doses of sildenafil did not modify cyclosporine and tacrolimus trough blood levels.

Interacción entre sildenafilo y los inhibidores de la calcineurina en trasplantados renales con disfunción eréctil / Interaction study between sildenafil and calcineurin inhibitors in renal transplant recipients with erectile dysfunction

Objetivo: El objetivo de este estudio piloto consistió en evaluar la interacción potencial del sildenafilo con ciclosporina y tacrólimus en un grupo de pacientes trasplantados renales estables con disfunción eréctil (DE). Material y métodos: Se realizó un estudio piloto, prospectivo de interacción de sildenafilo en 9 pacientes varones trasplantados renales estables con DE severa (edad media 50 ñ 8 años, rango 38-64) en tratamiento con inhibidores de la calcineurina (5 pacientes con ciclosporina y 4 pacientes con tacrólimus). La DE se evaluó mediante: historia, exploración física, cuestionario del llEF y test de tumescencia nocturna del pene (RigiScan). Cada paciente recibió dos dosis de sildenafilo. Se evaluó la eficacia, seguridad y evolución de los niveles sanguíneos de Ciclosporina/tacrólimus. Se determinó la Cmin de ciclosporina y tacrólimus en el período basal y día 1, 4 y 7 después del sildenafilo. Resultados: El 89 por ciento de los pacientes (n = 8) requirieron una dosis completa de 100 mg de sildenafilo. Se observó una respuesta clínica positiva en las dos terceras partes de los casos (6 pacientes). En 5 pacientes (55 por ciento) sildenafilo produjo una respuesta completa, en un paciente la respuesta fue incompleta y en los 3 casos restantes (33 por ciento) no se observó respuesta clínica. La terapia con sildenafilo fue segura presentando una taquicardia autolimitada en un paciente y leves alteraciones visuales en otro paciente. Los niveles de ciclosporina y tacrólimus se mantuvieron estables a lo largo del estudio en todos los pacientes. No se observaron diferencias significativas en los niveles sanguíneos de ciclosporina (basal: 120 + 47; día 1: 116 + 55; día 4: 123 ñ 56 y día 7: 121 ñ 56 p = NS) ni en los niveles de tacrólimus (basal: 11,6 ñ 1,3; día 1: 11,9 ñ 1,3; día 4: 11,1 ñ 1,0 y día 7: 11,8 ñ 0,9 p = NS). Conclusiones: Sildenafilo es un tratamiento eficaz y seguro de la DE del paciente trasplantado renal. El régimen de dosificación recomendado de sildenafilo no modifica los niveles valle de ciclosporina y tacrólimus (AU)

Rare secondary carcinoma from bladder to testis.

Metastatic carcinoma to the testis is very unusual in daily urologic practice. We report a case of metastatic cancer to the testis detected as incidental findings in a squamous bladder tumor.

Free to complexed PSA ratio in differentiating benign prostate hyperplasia from prostate cancer.

BACKGROUND: The description of the different forms of circulating PSA has opened a new strategy in the diagnosis of prostate cancer. The aim of our study was to assess the diagnostic potential of PSA and the PSA fractions in the diagnosis of benign prostate hyperplasia (BPH) and prostate cancer. PATIENTS AND METHODS: We measured the serum levels of PSA (Elecsys 2010, Roche Diagnostics, Mannheim, Germany), complexed PSA (Immuno 1 system, Bayer, Tarrytown, NY USA) and free PSA (Elecsys 2010, Roche Diagnostics, Mannheim, Germany) in 178 patients with BPH and 44 patients with prostate cancer. RESULTS: ROC curves were used for comparison of the diagnostic utility of the tests assessed. The biggest areas under the curve were obtained for the ratios between free/complexed PSA and free/total PSA (0.887 and 0.872, respectively). When choosing the cut-off values to obtain a 90% sensibility, we found that the specificity for the free/total PSA ratio was 59% and for the free/complexed PSA ratio 72%. CONCLUSION: Our results suggest that replacement of the measurement of total PSA by complexed PSA in prostate cancer diagnosis may be interesting. Nevertheless, as this is a retrospective study limited to a small number of patients, it is obvious that we need more data to make a final decision with regard to this subject.

Analysis of type T1 and T2 cytokines in patients with prostate cancer.

BACKGROUND: It has been proposed that a dysregulation in the balance between type T1 (IL-2, IFN-gamma) and type T2 (IL-4, IL-10) cytokines may be implicated in the development of cancer. METHODS: We determined the expression of IL-2, IL-4, IL-10, and IFN-gamma in CD4 and CD8 lymphocytes by flow cytometry in 12 patients with prostate cancer and in 7 healthy subjects. In addition to the basal expression of these cytokines, their expression was also determined, following stimulation of lymphocytes with PMA (phorbol 12-mystirate 13 acetate) and ionomycin. RESULTS: The basal expression of cytokines was scarce, while following stimulation this increased markedly. On the other hand, there was a dysregulation in the balance between T1 and T2 lymphocytes in patients with prostate cancer. To this effect, in relation to healthy subjects, we observed an increase in IL-10 expression and a decrease in IL-2 expression. CONCLUSIONS: The disequilibrium observed in the balance between type T1 and type T2 cytokines may be implicated in the evolution of neoplastic disease.