Long-term results with custom-linked iodine-125 seeds and real-time brachytherapy in low- and intermediate-risk prostate cancer.

Purpose: Brachytherapy (BT) with iodine-125 (125I) seeds is effective in low- and intermediate-risk prostate carcinoma, with fewer side effects compared to other techniques, but relapses increase in long-term. In the present paper, 10-year biochemical relapse-free survival (BRFS) results are presented. Material and methods: Between 2007 and 2016, 706 patients were treated with real-time technique using Bard-ProLink™ system. 145 Gy was administered to the prostate with exclusive BT and 108 Gy after 46 Gy of external radiotherapy (EBRT). Androgen deprivation therapy was applied in 19.3% of patients. Results: Median follow-up was 96 months (range, 24-163 months). BRFS at 5 and 10 years was 95% and 91.1%, respectively. For 480 low-risk cases, BRFS at 5 and 10 years was 95.7% and 92.7%, and for 226 intermediate-risk cases, it was 92.7% and 88%, respectively (p < 0.05). With combined treatment of EBRT + BT, 133 cases (59%) of intermediate-risk were treated without differences with exclusive BT. Gleason score 4 + 3 cases dropped to 72.8% at 10 years (p < 0.001), with androgen deprivation therapy (ADT) to 90.9% and without ADT to 66.8%; it was worse if patients had exclusive BT. 10-year BRFS for T1c was 95% compared to 84% for T2 (p < 0.001). Initial prostate specific antigen (PSA) > or < 10 showed no differences. With > 50% biopsy cores positive, it fell to 80% at 10 years (p < 0.001). In 154 patients up to 60 years of age, 10-year BRFS was 97.6%. Urinary complications appeared in 16.9% of cases in exclusive BT vs. 26.1% in EBRT + BT. Grade 2+ urinary late complications were observed in 19.1% and grade 3+ in 5.8% of patients. Rectal toxicity was 4% (2.5% in BT alone and 10.1% in RT + BT), while G3+ was seen in 0.1%. Conclusions: Real-time BT with custom-linked 125I seeds is a very effective long-term treatment in low- and intermediate-risk prostate carcinoma. With Gleason score 4 + 3 or > 50% biopsy cores positive, we recommend combined treatment with additional ADT for 6 months.

Outcomes of salvage radical prostatectomy after initial irreversible electroporation treatment for recurrent prostate cancer.

OBJECTIVE: To evaluate: (i) safety, (ii) feasibility, and medium-term (iii) oncological and (iv) functional outcomes of salvage radical prostatectomy (sRP) for recurrent localised prostate cancer (PCa) following initial focal therapy using irreversible electroporation (IRE). PATIENTS AND METHODS: An international, multicentre and retrospective analysis of prospectively collected data of patients that underwent sRP for recurrent localised PCa after initial primary IRE treatment. Data were reported on (i) surgical complications, (ii) feasibility of sRP reported by surgeons, (iii) time interval between IRE and sRP and pathology results, and (iv) urinary continence, erectile function, and quality of life. RESULTS: In four participating centres, a total of 39 patients with a median (interquartile range [IQR]) age 64 (60-67) years were identified. No serious adverse events occurred during or following sRP and surgery was deemed feasible without difficulties. The median (IQR) time to recurrence following IRE was 14.3 (9.1-38.8) months. Pathology results showed localised disease in 21 patients (53.8%) and locally-advanced disease in 18 (46.2%). Positive surgical margins (PSMs) were observed in 10 patients (25.6%), of which six (15.4%) had significant PSMs. A persistent detectable prostate-specific antigen level was found in one case after sRP, caused by metastatic disease. One patient had a biochemical recurrence 6 months after sRP. These two cases, together with a PSM case, required additional therapy after sRP. After a median (IQR) follow-up of 17.7 (11.8-26.4) months, urinary continence and erectile function were preserved in 34 (94.4%) and 18 patients (52.9%), respectively, while quality of life remained stable. CONCLUSIONS: Salvage RP is safe and feasible for patients with recurrent localised PCa following initial IRE treatment. The medium-term oncological and functional outcomes are similar to primary RP. Strict patient selection for focal therapy and standardised follow-up is needed as some patients developed high-grade disease.

Evaluation of Fluorescent Confocal Microscopy for Intraoperative Analysis of Prostate Biopsy Cores.

BACKGROUND: Diagnosis of prostate cancer is based on histopathological evaluation, which is time-consuming. Fluorescent confocal microscopy (FCM) is a novel technique that allows rapid tissue analysis. OBJECTIVE: To determine if FCM could be used for real-time diagnosis of prostate cancer and evaluate concordance with traditional analysis. DESIGN, SETTING, AND PARTICIPANTS: From January 2019 to March 2020, 182 magnetic resonance imaging-targeted prostate biopsy cores from 57 consecutive biopsy-naïve men with suspected prostate cancer were taken. These were intraoperatively stained with acridine orange for analysis using FCM (VivaScope; MAVIG, Munich, Germany) and subsequently sent for traditional haematoxylin-eosin histopathological (HEH) examination. Two expert uropathologists analysed the FCM and HEH cores blinded to the counterpart results in a single institution. OUTCOME MEASUREMENTS AND STATISTICAL ANALYSIS: Agreement between FCM and HEH analysis in terms of the presence of cancer was analysed at biopsy core and region of interest (ROI) levels, considering HEH as the reference test. RESULTS AND LIMITATIONS: FCM allowed intraoperative assessment of prostate biopsy cores with strong histopathological evaluation agreement: Cohen's κ for agreement was 0.81 at the biopsy core level and 0.69 for the ROI level. Positive predictive values (85% and 83.78%) and negative predictive values (95.1% and 85.71%) were high at the biopsy core and ROI levels. These initial results are encouraging, but given the single-centre and preliminary nature of the study, further confirmation is required. CONCLUSIONS: FCM allowed rapid evaluation of prostate biopsy cores. This technique is feasible and achieves rapid closure with a reliable diagnosis, parallel to the gold standard analysis. Initial results are promising but further studies are needed to validate and define the role of this technique. PATIENT SUMMARY: A novel microscopic technique reduces the time needed to obtain a prostate cancer diagnosis by speeding up biopsy processing. Although the initial results are promising; this development needs to be confirmed in further studies.

Comparison of one-catheter strategy versus conventional two-catheter strategy on the volume of radiological contrast and diagnostic coronary catheterization performance by transradial access: A systematic review and meta-analysis of randomized clinical trials / Comparación de la estrategia de catéter único versus la estrategia convencional de dos catéteres sobre el volumen de contraste radiológico y el rendimiento del cateterismo coronario diagnóstico por acceso transradial: una revisión sistemática y meta-análisis de ensayos clínicos aleatorizados

Abstract Background: One-catheter strategy, based in multipurpose catheters, allows exploring both coronary arteries with a single catheter. This strategy could simplify coronary catheterization and reduce the volume of contrast administration, by reducing radial spasm. To date, observational studies showed greater benefits regarding contrast consumption and catheterization performance than controlled trials. The aim of this work is to perform the first systematic review and meta-analysis of randomized clinical trials (RCT) to adequately quantify the benefits of one-catheter strategy, with multipurpose catheters, over conventional two-catheter strategy on contrast consumption, and catheterization performance. Methods: A search in PubMed, CINALH, and CENTRAL databases was conducted to identify randomized trials comparing one-catheter and two-catheter strategies. The primary outcome was volume of iodinated contrast administrated. Secondary endpoints, evaluating coronary catheterization performance included: arterial spasm, fluoroscopy time, and procedural time. Results: Five RCT were included for the final analysis, with a total of 1599 patients (802 patients with one-catheter strategy and 797 patients with two-catheter strategy). One-catheter strategy required less administration of radiological contrast (difference in means [DiM] [95% confidence interval (CI)]; −3.831 mL [−6.165 mL to −1.496 mL], p = 0.001) as compared to two-catheter strategy. Furthermore, less radial spasm (odds ratio [95% CI], 0.484 [0.363 to 0.644], p < 0.001) and less procedural time (DiM [95% CI], −72.471 s [−99.694 s to −45.249 s], p < 0.001) were observed in one-catheter strategy. No differences on fluoroscopy time were observed. Conclusions: One-catheter strategy induces a minimal reduction on radiological contrast administration but improves coronary catheterization performance by reducing arterial spasm and procedural time as compared to conventional two-catheter strategy.

Resumen Antecedentes: La estrategia de catéter único permite explorar ambas coronarias con un solo catéter. Nuestro objetivo es realizar la primera revisión sistemática y meta-análisis de ensayos clínicos aleatorizados para cuantificar adecuadamente los beneficios de la estrategia de catéter único, con catéteres multipropósito, sobre la estrategia convencional de dos catéteres. Métodos: Se realizó una búsqueda en PubMed, CINALH y CENTRAL, identificando ensayos aleatorizados que compararan estrategias de un catéter y dos catéteres. El resultado primario fue volumen de contraste administrado. Los secundarios, que evaluaron el rendimiento del cateterismo, incluyeron: espasmo radial, tiempo de fluoroscopia y de procedimiento. Resultados: Se incluyeron cinco ensayos, totalizando 1,599 pacientes (802 con estrategia de un catéter y 797 con estrategia de dos catéteres). La estrategia de catéter único requirió menos contraste (diferencia-de-medias; −3.831 mL [−6.165 mL a −1.496 mL], p = 0.001), presentando menos espasmo radial (odds ratio, 0.484 [0.363 a 0.644], p < 0.001) y menos tiempo de procedimiento (diferencia-de-medias; −72.471 s [−99.694 s a −45.249 s], p < 0.001). No hubo diferencias en el tiempo de fluoroscopia. Conclusiones: La estrategia de catéter único induce una reducción mínima en la administración de contraste, pero mejora el rendimiento del cateterismo al reducir el espasmo radial y el tiempo de procedimiento en comparación con la estrategia convencional.

Validation of a 2-gene mRNA urine test for the detection of ≥GG2 prostate cancer in an opportunistic screening population.

BACKGROUND: A 2-gene urine-based molecular test that targets messenger RNAs known to be overexpressed in aggressive prostate cancer (PCa) has been described as a helpful method for detecting clinically significant prostate cancer (grade group [GG] ≥2). We performed an external validation of this test in men undergoing initial prostate biopsy (Bx) within a Spanish opportunistic screening scenario. METHODS: We analyzed archived samples from 492 men who underwent prostate Bx in an opportunistic screening scenario, with prostate-specific antigen (PSA) 3 to 10 ng/mL and/or suspicious digital rectal exploration (DRE) and without previous multi-parametric magnetic resonance imaging (mpMRI). Urinary biomarker measurements were combined with clinical risk factors to determine a risk score, and accuracy for GG ≥ 2 PCa detection was compared with PCA3, European randomized screening in prostate cancer (ERSPC), and prostate biopsy collaborative group (PBCG) risk calculators in a validation workup that included calibration, discrimination, and clinical utility analysis. RESULTS: In our cohort, the detection rates for GG1 and GG ≥ 2 PCa were 20.3% and 14.0%, respectively. The median PSA level was 3.9 ng/mL and 13.4% of subjects had suspicious DRE findings. The median risk score for men with GG ≥ 2 PCa was 21 (interquartile range: 14-28), significantly higher than benign+GG1 PCa (10, 6-18), P < .001, achieving the highest area under the curve among the models tested, 0.749 (95% confidence interval: 0.690-0.807). The urine test was well-calibrated, while ERSPC showed a slight underestimation and PBCG a slight overestimation of risk. Assuming a GG2 non-detection rate of 11% without using mpMRI, use of the urinary biomarker-based clinical model could have helped avoid 37.2% of excess biopsies while delaying the diagnosis of eight patients (1.6% of the entire cohort) with GG ≥ 2 PCa. CONCLUSIONS: In this first evaluation in an opportunistic screening population, the urinary biomarker-based test improved the detection of clinically significant PCa. Facing men with elevated PSA and/or suspicious DRE, it could be a useful tool to help avoid excess initial Bx and to identify patients most likely to benefit from Bx.

Ex-vivo confocal fluorescence microscopy for rapid evaluation of renal core biopsy.

Small renal mass incidentally diagnosed are common findings nowadays due to the widespread of imaging. Renal mass biopsy is still underutilized by urologists due to its non-diagnostic rates. Confocal microscopy allows for rapid imaging of fresh tissue samples. We report the feasibility of using confocal technology for determining the quality of the renal core at renal mass biopsy on 4 consecutive cases at our institution.

Impact of One-Catheter Strategy with TIG I Catheter on Coronary Catheterization Performance and Economic Costs / Impacto da Estratégia de um Cateter com Cateter TIG I no Desempenho da Coronariografia por Cateterismo e Custos Econômicos

Abstract Background: Coronary angiography with two catheters is the traditional strategy for diagnostic coronary procedures. TIG I catheter permits to cannulate both coronary arteries, avoiding exchanging catheters during coronary angiography by transradial access. Objective: The aim of this study is to evaluate the impact of one-catheter strategy, by avoiding catheter exchange, on coronary catheterization performance and economic costs. Methods: Transradial coronary diagnostic procedures conducted from January 2013 to June 2017 were collected. One-catheter strategy (TIG I catheter) and two-catheter strategy (left and right Judkins catheters) were compared. The volume of iodinated contrast administered was the primary endpoint. Secondary endpoints included radial spasm, procedural duration (fluoroscopy time) and exposure to ionizing radiation (dose-area product and air kerma). Direct economic costs were also evaluated. For statistical analyses, two-tailed p-values < 0.05 were considered statistically significant. Results: From a total of 1,953 procedures in 1,829 patients, 252 procedures were assigned to one-catheter strategy and 1,701 procedures to two-catheter strategy. There were no differences in baseline characteristics between the groups. One-catheter strategy required less iodinated contrast [primary endpoint; (60-105)-mL vs. 92 (64-120)-mL; p < 0.001] than the two-catheter strategy. Also, the one-catheter group presented less radial spasm (5.2% vs. 9.3%, p = 0.022) and shorter fluoroscopy time [3.9 (2.2-8.0)-min vs. 4.8 (2.9-8.3)-min, p = 0.001] and saved costs [149 (140-160)-€/procedure vs. 171 (160-183)-€/procedure; p < 0.001]. No differences in dose-area product and air kerma were detected between the groups. Conclusions: One-catheter strategy, with TIG I catheter, improves coronary catheterization performance and reduces economic costs compared to traditional two-catheter strategy in patients referred for coronary angiography.

Resumo Fundamento: A cineangiocoronariografia com dois cateteres é a estratégia tradicional para procedimentos coronarianos de diagnóstico. O cateter TIG I permite canular ambas as artérias coronárias, evitando a troca de cateteres durante a cineangiocoronariografia por acesso transradial. Objetivo: O objetivo deste estudo é avaliar o impacto da estratégia de um cateter, evitando a troca de cateter, no desempenho da coronariografia por cateterismo e nos seus custos econômicos. Métodos: Foram coletados os procedimentos diagnósticos coronarianos transradiais realizados entre janeiro de 2013 e junho de 2017. A estratégia de um cateter (cateter TIG I) e a estratégia de dois cateteres (cateteres coronários direito e esquerdo de Judkins) foram comparadas. O volume de contraste iodado administrado foi o endpoint primário. Os endpoints secundários eram espasmo radial, duração do procedimento (tempo de fluoroscopia) e exposição a radiações ionizantes (produto dose-área e kerma no ar). Os custos econômicos diretos também foram avaliados. Para as análises estatísticas, valores de p < 0,05 bicaudais foram considerados estatisticamente significativos. Resultados: De um total de 1.953 procedimentos em 1.829 pacientes, 252 procedimentos foram atribuídos à estratégia de um cateter e 1.701 procedimentos à estratégia de dois cateteres. Não houve diferenças nas características basais entre os grupos. A estratégia de um cateter exigiu menos contraste iodado [endpoint primário; (60-105) -mL vs. 92 (64-120) -mL; p < 0,001] em comparação com a estratégia de dois cateteres. Além disso, o grupo da estratégia de um cateter apresentou menos espasmo radial (5,2% vs. 9,3%, p = 0,022) e menor tempo de fluoroscopia [3,9 (2,2-8,0) -min vs. 4,8 (2,9-8,3) -min, p = 0,001] e economia de custos [149 (140-160)-€/procedimento vs. 171 (160-183) -€/procedimento; p < 0,001]. Não foram detectadas diferenças no produto dose-área e kerma no ar entre os grupos. Conclusões: A estratégia de um cateter, com cateter TIG I, melhora o desempenho da coronariografia por cateterismo e reduz os custos econômicos em comparação com a estratégia tradicional de dois cateteres em pacientes encaminhados para cineangiocoronariografia.

Long-term functional outcome and complications of male suburethral slings in the management of post-prostatectomy incontinence: A prospective five-year follow-up study.

OBJECTIVES: Suburethral male slings are an alternative option for mild stress urinary incontinence. Our purpose is to evaluate the long-term functional outcomes, efficacy and worsening continence of male suburethral slings. MATERIAL AND METHODS: The functional outcomes of realignment/anatomical slings were evaluated with AdVance ®, and the outcomes of compressive slings were evaluated with InVance®. We considered 55 patients fulfilling 5 years of complete follow-up. We included patients with a 24-hour pad weight test <400 grams. Night-continent patients who also had positive "repositioning tests" were considered for AdVance®, whereas patients without sphincter contraction or previous pelvic radiotherapy were considered for InVance®. RESULTS: Between February 2006 and September 2010, 24 AdVance® and 31 InVance® slings were implanted. The median follow-up times from sling insertion were 75 months in the AdVance® group (range: 64-97) and 86 months in the InVance® group (range: 61-108). At three months of follow-up, 43 of 55 patients were considered to be cured (pad-free) (78.1%), 79.1% in the AdVance® group and 77.4% in the InVance® group. Postoperatively, 16.6% of patients with AdVance® and 22.5% of patients with InVance® presented "de novo" urgency. At 5 years of follow-up, we observed 10 cases of some deterioration of continence, 3 patients in the AdVance® group and 7 in the InVance® group (15.8% and 29.1% of the initially cured, respectively). To date, there have been no reports of urethral sling erosion. CONCLUSIONS: Male slings are safe and effective. Although we observed an increase in "de novo" urgency, in our experience, slings seemed to maintain their efficacy during long-term follow-up, and the risks of urethral erosion are low.

OBJETIVOS: Los cabestrillos suburetrales masculinos son una opción alternativa para la incontinencia urinaria de esfuerzo leve. El objetivo del trabajo es evaluar los resultados funcionales a largo plazo, la eficacia y el empeoramiento de la continencia en los cabestrillos suburetrales masculinos. METODOS: Se evaluaron los resultados funcionales de los cabestrillos de realineamiento/anatómicos con Ad- Vance® y compresivos con InVance®. Se incluyeron 55 pacientes que cumplían con los 5 años de seguimiento completo. Incluimos pacientes con un peso en el test de la compresa de 24 h menor de 400 gramos. Los pacientes con continencia nocturna que tenían también positivas las pruebas de reposicionamiento se consideraron para AdVance®, mientras que los pacientes sin contracción esfinteriana o con radioterapia pélvica previa fueron considerados para InVance®. RESULTADOS: Entre febrero 2006 y septiembre 2010 se implantaron 24 cabestrillos AdVance® y 31 InVance ®. La mediana de seguimiento fue de 75 meses desde la inserción del cabestrillo en el grupo de AdVance® (rango 64-97) y 86 meses en el grupo de InVance® (rango: 61-108). A los tres meses de seguimiento, 43 de los 55 pacientes fueron considerados curados (sin compresa) (78,1%), 79,1% en el grupo de AdVance® y 77,4% en el de InVance®. En el postoperatorio, el 16,6% de los pacientes con AdVance® y el 22,5% de los InVance® presentaron urgencia "de novo". A los 5 años de seguimiento, observamos 10 casos con algún deterioro de la continencia, 3 pacientes en el grupo de AdVance® y 7 en el de InVance® (15,8% y 29,1% de los pacientes inicialmente curados, respectivamente). Hasta la fecha, no se han presentado casos de erosión del cabestrillo. CONCLUSIONES: Los cabestrillos masculinos son seguros y eficaces. Aunque observamos un incremento de la urgencia "de novo", en nuestra experiencia, los cabestrillos parecen mantener su eficacia durante el seguimiento a largo plazo, y los riesgos de erosión uretral son bajos.

Radical Prostatectomy after Vascular Targeted Photodynamic Therapy with Padeliporfin: Feasibility, and Early and Intermediate Results.

PURPOSE: Vascular targeted photodynamic therapy with TOOKAD® is a new therapeutic option for localized prostate cancer management. The objectives of this study were to assess the feasibility of radical prostatectomy after vascular targeted photodynamic therapy and describe functional and oncologic outcomes. MATERIALS AND METHODS: We retrospectively included in study 45 patients who underwent salvage radical prostatectomy after vascular targeted photodynamic therapy for recurrent prostate cancer at a total of 14 surgical centers in Europe between October 2008 and March 2017. Of the 42 radical prostatectomies performed 16 were robot-assisted, 6 were laparoscopic and 20 were open surgery. Primary end points were morbidity and technical difficulties. Secondary end points were early and intermediate postoperative functional and oncologic outcomes. RESULTS: Median operative time was 180 minutes (IQR 150-223). Median blood loss was 200 ml (IQR 155-363). According to the surgeons the surgery was easy in 29 patients (69%) and difficult in 13 (31%). Nerve sparing was feasible in 14 patients (33%). Five postoperative complications (12%) were found, including 2 Clavien I, 2 Clavien II and 1 Clavien IIIB complications. Of the cases 13 (31%) were pT3 and 21 (50%) were pT2c. Surgical margins were positive in 13 patients (31%). Prostate specific antigen was undetectable at 6 to 12 months in 37 patients (88%). Nine patients underwent complementary radiotherapy. Four patients had final prostate specific antigen greater than 0.2 ng/ml at a median followup of 23 months (IQR 12-36). At 1 year 27 patients (64%) were completely continent (no pads) and 10 (24%) had low incontinence (1 pad). Four patients (11%) recovered potency without treatment and 23 (64%) recovered potency with appropriate treatment. CONCLUSIONS: Salvage radical prostatectomy after vascular targeted photodynamic therapy treatment was feasible and safe without difficulty for most of the surgeons.

Indocyanine Green Guided Pelvic Lymph Node Dissection: An Efficient Technique to Classify the Lymph Node Status of Patients with Prostate Cancer Who Underwent Radical Prostatectomy.

PURPOSE: We evaluated the effectiveness of indocyanine green guided pelvic lymph node dissection for the optimal staging of prostate cancer and analyzed whether the technique could replace extended pelvic lymph node dissection. MATERIALS AND METHODS: A solution of 25 mg indocyanine green in 5 ml sterile water was transperineally injected. Pelvic lymph node dissection was started with the indocyanine green stained nodes followed by extended pelvic lymph node dissection. Primary outcome measures were sensitivity, specificity, predictive value and likelihood ratio of a negative test of indocyanine green guided pelvic lymph node dissection. RESULTS: A total of 84 patients with a median age of 63.55 years and a median prostate specific antigen of 8.48 ng/ml were included in the study. Of these patients 60.7% had intermediate risk disease and 25% had high or very high risk disease. A median of 7 indocyanine green stained nodes per patient was detected (range 2 to 18) with a median of 22 nodes excised during extended pelvic lymph node dissection. Lymph node metastasis was identified in 25 patients, 23 of whom had disease properly classified by indocyanine green guided pelvic lymph node dissection. The most frequent location of indocyanine green stained nodes was the proximal internal iliac artery followed by the fossa of Marcille. The negative predictive value was 96.7% and the likelihood ratio of a negative test was 8%. Overall 1,856 nodes were removed and 603 were stained indocyanine green. Pathological examination revealed 82 metastatic nodes, of which 60% were indocyanine green stained. The negative predictive value was 97.4% but the likelihood ratio of a negative test was 58.5%. CONCLUSIONS: Indocyanine green guided pelvic lymph node dissection correctly staged 97% of cases. However, according to our data it cannot replace extended pelvic lymph node dissection. Nevertheless, its high negative predictive value could allow us to avoid extended pelvic lymph node dissection if we had an accurate intraoperative lymph fluorescent analysis.

Comparison of permanent (125)I seeds implants with two different techniques in 500 cases of prostate cancer.

PURPOSE: To perform a comparative study of 500 consecutive (125)I seeds implants for intracapsular prostate carcinoma with two techniques differing in terms of both strand implantation and planning. MATERIAL AND METHODS: From 2002 to 2007 we performed 250 implants with fixed stranded seeds (RapidStrand™) and a preplanning system and from 2007 to 2010, 250 with real-time and ProLink™ system. Mean age was 68 and 66, respectively, median PSA (prostate-specific antigen) 7.3 and 7.2, stage T1-T2a in 98% and 94%, and Gleason ≤ 6 in 96% and 86%. Low risk cases were 81% and 71%. The prescribed dose was 145 Gy to the prostate volume, or 108 Gy plus EBRT 46 Gy in some intermediate risk cases. Hormonal treatment was given to 42% and 28%. RESULTS: Median follow-up was 48 and 47 months, respectively, 14 patients in the first group and 7 patients in the second developed biochemical failure (BF). Actuarial biochemical relapse-free survival (bRFS) at 5 years increased from 90.2% to 97.2% (low risk from 91.3% to 97.2%, intermediate risk from 84.2% to 97.1%). Biochemical failure was independent of hormone treatment. Rectal complications were G1-2 in 1.2% and 5.2%, respectively. A urinary catheter was necessary in 6.9% and 9.6%, and urethral resection in 1.9% and 4.4%. Genitourinary toxicity was G1-2 in 4.6% and 12%, G3-4 in 1.9% and 4.8%. An assessment of mean D90 in a sample of patients showed that the dosimetry in postoperative planning based on CT improved from a mean D90 of 143 Gy to 157 Gy. CONCLUSIONS: The outcome of patients with low risk prostate carcinoma treated with (125)I seed is very good with low complications rate. The real-time approach in our hands achieved a more precise seed implantation, better dosimetry, and a statistically non-significant better biochemical control. We have made this our standard technique.

Optimizing the clinical utility of PCA3 to diagnose prostate cancer in initial prostate biopsy.

BACKGROUND: PCA3 has been included in a nomogram outperforming previous clinical models for the prediction of any prostate cancer (PCa) and high grade PCa (HGPCa) at the initial prostate biopsy (IBx). Our objective is to validate such IBx-specific PCA3-based nomogram. We also aim to optimize the use of this nomogram in clinical practice through the definition of risk groups. METHODS: Independent external validation. Clinical and biopsy data from a contemporary cohort of 401 men with the same inclusion criteria to those used to build up the reference's nomogram in IBx. The predictive value of the nomogram was assessed by means of calibration curves and discrimination ability through the area under the curve (AUC). Clinical utility of the nomogram was analyzed by choosing thresholds points that minimize the overlapping between probability density functions (PDF) in PCa and no PCa and HGPCa and no HGPCa groups, and net benefit was assessed by decision curves. RESULTS: We detect 28% of PCa and 11 % of HGPCa in IBx, contrasting to the 46 and 20% at the reference series. Due to this, there is an overestimation of the nomogram probabilities shown in the calibration curve for PCa. The AUC values are 0.736 for PCa (C.I.95%:0.68-0.79) and 0.786 for HGPCa (C.I.95%:0.71-0.87) showing an adequate discrimination ability. PDF show differences in the distributions of nomogram probabilities in PCa and not PCa patient groups. A minimization of the overlapping between these curves confirms the threshold probability of harboring PCa >30 % proposed by Hansen is useful to indicate a IBx, but a cut-off > 40% could be better in series of opportunistic screening like ours. Similar results appear in HGPCa analysis. The decision curve also shows a net benefit of 6.31% for the threshold probability of 40%. CONCLUSIONS: PCA3 is an useful tool to select patients for IBx. Patients with a calculated probability of having PCa over 40% should be counseled to undergo an IBx if opportunistic screening is required.

[Dynamic sentinel node biopsy in penile cancer. Indications, technique and results in a Spanish oncological center]. / BIOPSIA DINÁMICA DE GANGLIO CENTINELA EN CÁNCER DE PENE. INDICACIONES, TÉCNICA Y RESULTADOS EN UN CENTRO ONCOLÓGICO ESPAÑOL.

OBJECTIVE: Penile cancer has a predominantly lymphatic dissemination. Lymph nodes metastatic involvement conditions disease prognosis and inguinal lymph node dissection has both prognostic and therapeutic value. High and intermediate risk patients with non-palpable lymph nodes will benefit of a precise diagnosis by means of selective sentinel node biopsy with minimal surgical aggressiveness. METHODS: Retrospective review of our experience on dynamic sentinel node biopsy in penile cancer from November 1999 to July 2014. RESULTS: We performed this procedure in 33 patients, technically successful in 29 (88%). The patients who did not undergo lymph node dissection due to positive sentinel node biopsy have been followed a mean of 60.4 months (Median 59, range 5-145). 20 patients underwent simultaneous sentinel node biopsy and surgical treatment of the primary lesion and in 13 it was performed posteriorly. In these cases the time lapse was 5.5 months (median 5, range 2-12). In 6 (18.9%) of the 29 patients successfully biopsied, metastasis was founded in any of the lymph nodes identified as sentinel. Two patients were false negative (6,25%). Sensitivity (S), specificity (Sp), positive predictive value (PPV) and negative predictive value (NPV) of successfully performed sentinel node biopsies were 66, 100, 100 and 93%, respectively. CONCLUSION: Sentinel node biopsy enables a correct lymph node staging avoiding the morbidity of inguinal lymph node dissection. The rate of technical failure and false negative results is low and it may be considered the diagnostic technique of choice in high and intermediate risk penile cancer with non-palpable lymph nodes.

Identification of miR-187 and miR-182 as biomarkers of early diagnosis and prognosis in patients with prostate cancer treated with radical prostatectomy.

PURPOSE: miRNAs are noncoding RNAs that negatively regulate target mRNA gene expression. Aberrant miRNA expression is associated with prostate cancer pathogenesis. We identified miRNAs as potential biomarkers for prostate cancer diagnosis and prognosis. MATERIALS AND METHODS: Total RNA was obtained from 10 normal prostate and 50 prostate cancer samples, and analyzed using the GeneChip® miRNA 2.0 Array. At a median followup of 92 months (range 2 to 189) an independent cohort of 273 paraffin embedded prostate cancer samples was used for validation by quantitative reverse transcriptase-polymerase chain reaction. Another 92 urine samples from patients undergoing prostate biopsy were evaluated for these miRNAs. RESULTS: miR-182 and 187, the miRNAs most differentially expressed between normal and tumor tissue, were selected for further validation. miR-187 inversely correlated with cT (p = 0.125) and pT (p = 0.0002) stages, Gleason score (p = 0.003) and TMPRSS2-ERG status (p = 0.003). The log rank test showed associations of miR-182 with biochemical (p = 0.026) and clinical (p = 0.043) progression-free survival, as also noted on multivariate analysis. A significant independent improvement in the definition of risk of progression was achieved by combining miR-182 expression with Gleason score (p <0.0001). miR-187 detection in urine provided an independent predictive value for positive biopsy. A prediction model including serum prostate specific antigen, urine PCA3 and miR-187 provided 88.6% sensitivity and 50% specificity (AUC 0.711, p = 0.001). CONCLUSIONS: Results show that miR-182 and 187 are promising biomarkers for prostate cancer prognosis to identify patients at risk for progression and for diagnosis to improve the predictive capability of existing biomarkers.

Importance of previous transurethral resection of the prostate before eerpe.short-term functional outcomes in a single surgeon series.

OBJECTIVES: Laparoscopic Radical Prostatectomy (LRP) is technically a very demanding procedure and potentially even more challenging in patients with previous transurethral resection (TURP). This study evaluates the impact of previous TURP on the short-term functional outcome of patients undergoing extraperitoneal LRP. METHODS: Retrospective analysis of a prospectively collected database, comprising a single-surgeon cohort of 155 consecutive LRP cases, 19 of which had previous history of TURP. Demographics, clinical and functional outcomes were evaluated and compared among patients with and without previous TURP. Multivariate analysis was performed to identify potential variables independently associated with continence outcomes. Incontinence was defined as the need of more than 1 pad/day. Potency was defined as the ability for sexual intercourse with or without the use of phosphodiesterase inhibitors. RESULTS: Demographic and clinical variables were comparable among the two study groups. Neurovascular bundle preservation was possible in 26% and 37% of patients with and without previous TURP, respectively. No major complications were recorded and the incidence of minor complications was comparable. Overall continence rate at 3 months was 82,58%, for the entire cohort. Subset analysis demonstrated a 3-month continence rate of 73.7% vs. 83.8% (p>0.05) in patients with and without TURP, respectively. Multivariate analysis demonstrated age, BMI and ASA were variables independently associated with continence outcomes. In the cohort of patients with previous TURP, 2 out of 7 undergoing preservation recovered erections, with a mean follow up of 15.5 months, comparable to the 30% achieved in patients without TURP and nerve sparing procedure. CONCLUSIONS: Laparoscopic Radical Prostatectomy in patients with previous TURP is feasible, with complication rates and short-term functional outcomes comparable to those in patients without previous resection.

Feasibility of radical transurethral resection as monotherapy for selected patients with muscle invasive bladder cancer.

PURPOSE: We proved the feasibility of radical transurethral bladder tumor resection in selected patients with muscle invasive bladder cancer with a minimum followup of more than 15 years and investigated the impact of patient age on survival. A followup schedule was developed based on progression and recurrence during this period. MATERIALS AND METHODS: A phase II nonrandomized trial was designed including patients with muscle invasive bladder cancer with negative biopsies of tumor bed who were apparently healthy after undergoing complete transurethral bladder tumor resection. Patients with positive biopsies, or with macroscopically residual tumor, hydronephrosis or metastasis were excluded from study. In this trial 133 patients fulfilled the inclusion criteria and had a minimum followup of more than 15 years. RESULTS: Cancer specific survival was 81.9%, 79.5% and 76.7%, and progression-free survival with bladder preservation was 75.5%, 64.9% and 57.8% at 5, 10 and 15 years, respectively. Patient age had a negative impact on overall survival on univariate (HR 0.842, p = 0.049) and multivariate analyses (HR 1.062, p = 0.000), and according to median and quartile age stratifications (p = 0.000 and p = 0.000, respectively). However, age did not have a negative impact on cancer specific survival even when following the same stratifications. Although progression and recurrence were concentrated during the first 3 years (70% and 65%, respectively), both steadily increased afterward. A followup schedule was developed according to this sequence of events. CONCLUSIONS: Radical transurethral bladder tumor resection is a reliable therapeutic approach for patients with muscle invasive bladder cancer after complete tumor resection and with negative biopsies of the tumor bed. These results are consistent in all age ranges.

Bladder preservation in selected patients with muscle-invasive bladder cancer by complete transurethral resection of the bladder plus systemic chemotherapy: long-term follow-up of a phase 2 nonrandomized comparative trial with radical cystectomy.

BACKGROUND: Many phase 2 bladder-sparing programmes using transurethral resection of the bladder (TURB) plus chemotherapy or radio-chemotherapy have been undertaken, but some controversies remain. OBJECTIVE: To determine the efficacy of complete TURB plus three cycles of cisplatin-based chemotherapy in selected patients with muscle-invasive bladder cancer (MIBC). DESIGN, SETTING, AND PARTICIPANTS: A phase 2 nonrandomized trial was designed that included patients with MIBC who underwent complete TURB with positive biopsies of the tumour bed. Patients with negative biopsies of the tumour bed, with macroscopically residual tumour, with hydronephrosis, or with distant metastasis were excluded from this trial. Patients included in this trial were offered three cycles of systemic chemotherapy or radical cystectomy (RC). Clinical response (cR) was denoted by either no tumour or the presence of Ta1-Tis bladder tumour at 3-mo evaluation; clinical non-response (cNR) was denoted by cases of muscle-invasive tumour or distant metastasis. Of 146 patients who entered this trial, 75 choose the bladder-sparing programme and 71 chose RC. MEASUREMENTS: At 5 yr and 10 yr, the cancer-specific survival (CSS) rate was 64.5% and 59.8%, respectively, with no significant difference compared to the RC arm (p=0.544). The progression-free survival with bladder preserved was 52.6% and 34.5%, respectively. In multivariate analysis, cR was the only predictive factor for survival (p=0.001) and bladder preservation (p=0.000). RESULTS AND LIMITATIONS: This was not a randomized trial, and patients were included over 16 yr. However, no modifications were made to the therapy schedule except from chemotherapy schemes considered standard at the time. CONCLUSIONS: Patients with microscopic residual cancer after complete TURB seem to be good candidates for the bladder-sparing programme using three cycles of systemic chemotherapy, with CSS comparable to RC.

Risk factors for surgical site infection in children.

OBJECTIVES: To assess the appropriateness of using the indices developed by the Study on the Efficacy of Nosocomial Infection Control (SENIC) and the National Nosocomial Infections Surveillance (NNIS) project to determine risk factors for surgical site infection (SSI) in children and, if not appropriate, to explore the factors related to SSI in children so these factors could be used in a risk index for pediatric patients. DESIGN: Cohort study during more than 4 years. SETTING: La Paz University Hospital, a national reference center that serves Health Area 5 of Madrid, Spain, which has approximately 500,000 inhabitants. PATIENTS: Convenience sample consisting of the 3,646 children admitted for surgery who had a postsurgical stay of more than 2 days. RESULTS: A model with 8 predictive factors (degree of surgical contamination; duration of surgery; type of surgery; use of a peripheral venous catheter, central venous catheter, or urinary catheter; number of diagnoses; and SSI exposition time) was created. Its relation to the SSI rate was better than that of the SENIC or NNIS indices. Its sensitivity, specificity, and area under the receiver-operating characteristic curve were higher than that of the SENIC index. CONCLUSIONS: The model that we created seems to be more adequate for predicting SSI and evaluating pediatric patients' intrinsic risk than the SENIC and NNIS indices.

The optimum timing of radical cystectomy for patients with recurrent high-risk superficial bladder tumour.

OBJECTIVE: To establish the optimum time of radical cystectomy (RC) for patients with recurrent high-risk superficial bladder tumours after the failure of intravesical therapy. PATIENTS AND METHODS: Among 318 patients with transitional cell carcinoma treated with RC and with no neoadjuvant therapy, there were 46 with clinical stage Ta, T1 or Tis refractory to transurethral resection associated with intravesical therapy. These patients had at least one of: (i) high-risk superficial bladder tumours after failure of two consecutive induction courses of intravesical therapy; (ii) superficial bladder tumours with prostatic stromal invasion; (iii) superficial bladder tumours with mucosa/ducts involvement after failure of one course of intravesical therapy; (iv) uncontrolled superficial tumours with transurethral resection associated or not with intravesical therapy. Progression and cause-specific survival of these patients were compared to those with muscle-invasive tumours. Univariate and multivariate analyses of predictive factors for cause-specific survival were also used in patients with superficial tumours. The incidence of significant prognostic factors was compared in both superficial and muscle-invasive tumours, as were the progression pattern and survival. RESULTS: The progression-free and cause-specific survival of patients with superficial tumours was 54% and 67%, respectively, with no significant difference from those with muscle-invasive tumours. In multivariate analysis, positive lymph-nodes and prostatic stromal invasion were significant and independent variables for survival. The incidence of positive lymph nodes was 15% vs 30% (P < 0.05) and of stromal invasion was 32% vs 1.5% (P < 0.001) in patients with superficial and muscle-invasive tumours, respectively. Accounting for the progression pattern in patients with superficial tumours, extravesical urothelial recurrence prevailed over local or distant recurrences (30% vs 15%), whereas in patients with muscle-invasive tumours the opposite occurred (5% vs 33%, respectively). The cause-specific survival of patients with superficial tumour and prostatic stromal invasion was one of three, and in those who developed extravesical urothelial recurrence was 28.5%. CONCLUSION: In patients with recurrent high-risk superficial bladder cancer after intravesical therapy, our criteria for RC were inappropriate, and patients had a survival rate similar to those with muscle-invasive tumours. RC might have been used too late, as there was a high incidence of prostatic stromal invasion and extravesical urothelial recurrence after RC. Both events seem to be responsible of the low cause-specific survival. Predictive factors for progression are needed to indicate early RC in patients with recurrent high-risk superficial tumours. From a previous analysis the pathological pattern of the clinical lack of response (T1, G3, bladder carcinoma in situ and prostate involvement) to intravesical therapy evaluated at 3 months might be important for predicting progression, and an early RC at that time might be useful.