Manejo del carcinoma in situ de tramo urinario superior diagnosticado por biopsia ureteroscópica: ¿es el bacilo de Calmette-Guérin una alternativa a la nefroureterectomía? / Management of primary upper urinary tract carcinoma in situ diagnosed by ureteroscopic biopsy: Is bacillus Calmette-Guerin an alternative to nephroureterectomy?

Introducción La nefroureterectomía radical (NFU) es el tratamiento estándar del carcinoma de tramo urinario superior (TUS). No obstante, desde 1985 se ha introducido el tratamiento conservador en el manejo del carcinoma in situ en TUS (cis-TUS). El objetivo de este estudio fue comparar la evolución oncológica de los pacientes con cis-TUS tratados en nuestro centro con NFU vs. instilaciones de bacilo de Calmette-Guérin (BCG). Métodos Se trata de un estudio retrospectivo de pacientes con diagnóstico de cis-TUS primario entre 1990-2018. Todos los pacientes presentaban diagnóstico histológico de cis-TUS con ausencia de otro carcinoma de TUS concomitante. La confirmación histológica se obtuvo mediante ureteroscopia con múltiples biopsias. Los pacientes fueron tratados mediante NFU, ureterectomía distal o instilaciones de BCG. Los datos clinicopatológicos y la evolución oncológica fue comparada entre los grupos NFU y BCG. Resultados Se incluyeron un total de 28 pacientes, 29 unidades renales (UR). Dieciséis (57,1%) pacientes (17 UR) recibieron BCG. Las instilaciones fueron administradas por nefrostomía en 4 pacientes, catéter en J simple en 5 y doble J en 7. La respuesta completa y la persistencia o recurrencia fueron detectadas en 10 (58,8%) y 7 (41,2) UR tratadas con BCG. Ocho UR (27,6%) fueron tratadas con NFU, con una recurrencia contralateral detectada en 4 casos (50%). Finalmente, 4 UR con cis-TUS (13,8%) fueron tratadas con ureterectomía distal. No se detectaron diferencias en la supervivencia libre de recurrencia (p=0,841) ni en la supervivencia cáncer específica (p=0,77) entre los grupos de NFU y BCG. Conclusiones Aunque la nefroureterectomía radical representa el tratamiento estándar para el CIS de tramo urinario superior, nuestros resultados confirman que las instilaciones con BCG también son efectivas. La confirmación histológica de cis-TUS debería realizarse previamente a la decisión terapéutica (AU)

Introduction Radical nephroureterectomy (RNU) still represents the gold standard treatment for upper tract urothelial carcinoma (UTUC); however, since the 1980s attempts have been made to treat upper urinary tract CIS (UT-CIS) conservatively. The aim of this study was to compare the outcome of patients with primary UT-CIS treated in our center by means of RNU vs. bacillus Calmette-Guérin (BCG) instillations. Methods This retrospective study included patients with diagnosis of primary UT-CIS between 1990 and 2018. All patients had histological confirmation of UT-CIS in the absence of other concomitant UTUC. Histological confirmation was obtained by ureteroscopy with multiple biopsies. Patients were treated with RNU, distal ureterectomy, or BCG instillations. Clinicopathological features and outcomes were compared between the RNU and BCG groups. Results A total of 28 patients and 29 renal units (RUs) were included. Sixteen (57.1%) patients (17 RUs) received BCG. BCG was administered via a nephrostomy tube in 4 patients, a single-J ureteral stent in 5, and a Double-J stent in 7. Complete response and persistence or recurrence were detected in ten (58.8%) and seven (41.2%) RUs treated with BCG, respectively. Eight (27.6%) RUs underwent RNU, with contralateral recurrence detected in four (50%), and 4 (13.8%) RUs underwent distal ureterectomy. No differences were found in recurrence-free survival (p=0.841) and cancer-specific survival (p=0.77) between the RNU and BCG groups. Conclusions Although RNU remains the gold standard treatment for UT-CIS, our results confirm that BCG instillations are also effective. Histological confirmation of UT-CIS is mandatory before any treatment (AU)

Management of primary upper urinary tract carcinoma in situ diagnosed by ureteroscopic biopsy: Is bacillus Calmette-Guerin an alternative to nephroureterectomy?

BACKGROUND: Radical nephroureterectomy (RNU) represents the gold standard treatment for upper tract urothelial carcinoma (UTUC); however, attempts have been made to treat upper urinary tract CIS (UT-CIS) conservatively. The aim of this study was to compare the outcome of patients with primary UT-CIS treated in our center by means of RNU vs. bacillus Calmette-Guérin (BCG) instillations. METHODS: This retrospective study included patients with diagnosis of primary UT-CIS between 1990 and 2018. All patients had histological confirmation of UT-CIS in the absence of other concomitant UTUC. Histological confirmation was obtained by ureteroscopy with multiple biopsies. Patients were treated with BCG instillations, RNU or distal ureterectomy. Clinicopathological features and outcomes were compared between RNU and BCG groups. RESULTS: A total of 28 patients and 29 renal units (RUs) were included. Sixteen (57.1%) patients (17 RUs) received BCG. BCG was administered via nephrostomy tube in 4 patients, with a single-J ureteral stent in 5, and using a Double-J stent in 7. Complete response and persistence or recurrence were detected in ten (58.8%) and seven (41.2%) RUs treated with BCG, respectively. Eight (27.6%) RUs underwent RNU, and 4 (13.8%) Rus distal ureterectomy. No differences were found in recurrence-free survival (p=0.841) and cancer-specific survival (p=0.77) between the RNU and BCG groups. CONCLUSIONS: Although RNU remains the gold standard treatment for UT-CIS, our results confirm that BCG instillations are also effective. Histological confirmation of UT-CIS is mandatory before any treatment.

CDK12 promotes tumorigenesis but induces vulnerability to therapies inhibiting folate one-carbon metabolism in breast cancer.

Cyclin-dependent kinase 12 (CDK12) overexpression is implicated in breast cancer, but whether it has a primary or only a cooperative tumorigenic role is unclear. Here, we show that transgenic CDK12 overexpression in the mouse mammary gland per se is sufficient to drive the emergence of multiple and multifocal tumors, while, in cooperation with known oncogenes, it promotes earlier tumor onset and metastasis. Integrative transcriptomic, metabolomic and functional data reveal that hyperactivation of the serine-glycine-one-carbon network is a metabolic hallmark inherent to CDK12-induced tumorigenesis. Consistently, in retrospective patient cohort studies and in patient-derived xenografts, CDK12-overexpressing breast tumors show positive response to methotrexate-based chemotherapy targeting CDK12-induced metabolic alterations, while being intrinsically refractory to other types of chemotherapy. In a retrospective analysis of hormone receptor-negative and lymph node-positive breast cancer patients randomized in an adjuvant phase III trial to 1-year low-dose metronomic methotrexate-based chemotherapy or no maintenance chemotherapy, a high CDK12 status predicts a dramatic reduction in distant metastasis rate in the chemotherapy-treated vs. not-treated arm. Thus, by coupling tumor progression with metabolic reprogramming, CDK12 creates an actionable vulnerability for breast cancer therapy and might represent a suitable companion biomarker for targeted antimetabolite therapies in human breast cancers.

Carcinoma uretral primario: resultados de la experiencia de un único centro / Primary urethral carcinoma: Results from a single center experience

Introducción y objetivo El carcinoma primario de uretra (CPU) es una enfermedad neoplásica poco frecuente que surge en la uretra, sin evidencia de carcinoma previo o sincrónico en todo el tracto urinario. Dado que las enfermedades raras suelen diagnosticarse y tratarse de forma incorrecta, el objetivo de este estudio fue analizar la experiencia de un único centro urológico en el tratamiento del CPU, centrándose en las neoplasias que surgen de la uretra anterior masculina.Materiales y métodos Se revisaron retrospectivamente las historias clínicas de los pacientes con neoplasias a nivel de la uretra peneana y bulbar que se presentaron en nuestro centro terciario de referencia entre enero de 1988 y diciembre de 2018. Se excluyeron los pacientes con carcinoma de la uretra prostática. El diagnóstico se obtuvo con la ayuda de una uretroscopia y biopsia de la lesión. El estadio patológico local se evaluó mediante resonancia magnética nuclear (RMN) con contraste en pacientes seleccionados. El estadiaje se evaluó mediante examen clínico, ecografía y tomografía computarizada (TC). La cirugía radical (cistectomía radical + penectomía total + linfadenectomía inguinal bilateral) se propuso a los pacientes con tumores ≥ T2 o cN + con un buen estado funcional, tumor proximal y sin comorbilidades graves. En caso de afectación ganglionar, se ofreció adicionalmente quimioterapia neoadyuvante. Los pacientes con enfermedad localizada (< T2) y/o tumor más distal fueron sometidos a uretrectomía o penectomía parcial. Se evaluaron las curvas de Kaplan-Meier para el análisis de la supervivencia global (SG), la supervivencia cáncer específica (SCE) y la supervivencia libre de recidiva (SLR).Resultados Se estudiaron retrospectivamente un total de 13 pacientes varones con CPU anterior. Se realizó penectomía total en siete casos, mientras que cinco casos recibieron uretrectomía parcial y un caso, penectomía parcial. De los siete pacientes que se sometieron a una

Introduction and aim of the study Primary urethral carcinoma (PUC) is a rare neoplastic disease arising in the urethra, without any evidence of a previous or synchronous carcinoma of the entire urinary tract. Since rare diseases are often incorrectly diagnosed and managed, the aim of this study was to analyze the experience of a single urology center in the treatment of PUC, focusing on neoplasms arising from the male anterior urethra.Materials and methods Medical records of patients with neoplasms at the level of the penile and bulbar urethra who presented at our tertiary referral center between January 1988 and December 2018 were retrospectively reviewed. Patients with carcinoma of the prostatic urethra were excluded. The diagnosis was obtained with the aid of urethroscopy and lesion biopsy. Local staging was performed by means of contrast-enhanced MRI in selected patients. Staging was achieved by clinical examination, ultrasonography, and CT scan. Radical surgery (radical cystectomy + total penectomy + bilateral inguinal lymphadenectomy) was proposed to patients with ≥T2 tumors or cN + with a good performance status, proximal tumor and without severe comorbidities. In case of nodal involvement, neoadjuvant chemotherapy was additionally offered. Patients with localized disease (ResultsA total of 13 male patients with anterior PUC were studied retrospectively. Total penectomy was performed in 7 cases, while partial urethrectomy was performed in 5 cases, and partial penectomy in 1 case. Of the 7 patients who underwent total penectomy, 5 underwent radical cystectomy with bilateral inguinal lymphadenectomy. Three patients were treated with neoadjuvant systemic chemotherapy, of which 2 were cT3N + and

Primary urethral carcinoma: Results from a single center experience.

INTRODUCTION AND AIM OF THE STUDY: Primary urethral carcinoma (PUC) is a rare neoplastic disease arising in the urethra, without any evidence of a previous or synchronous carcinoma of the entire urinary tract. Since rare diseases are often incorrectly diagnosed and managed, the aim of this study was to analyze the experience of a single urology center in the treatment of PUC, focusing on neoplasms arising from the male anterior urethra. MATERIALS AND METHODS: Medical records of patients with neoplasms at the level of the penile and bulbar urethra who presented at our tertiary referral center between January 1988 and December 2018 were retrospectively reviewed. Patients with carcinoma of the prostatic urethra were excluded. The diagnosis was obtained with the aid of urethroscopy and lesion biopsy. Local staging was performed by means of contrast-enhanced MRI in selected patients. Staging was achieved by clinical examination, ultrasonography, and CT scan. Radical surgery (radical cystectomy + total penectomy + bilateral inguinal lymphadenectomy) was proposed to patients with ≥T2 tumors or cN+ with a good performance status, proximal tumor and without severe comorbidities. In case of nodal involvement, neoadjuvant chemotherapy was additionally offered. Patients with localized disease (

Primary urethral carcinoma: Results from a single center experience. / Carcinoma uretral primario: resultados de la experiencia de un único centro.

INTRODUCTION AND AIM OF THE STUDY: Primary urethral carcinoma (PUC) is a rare neoplastic disease arising in the urethra, without any evidence of a previous or synchronous carcinoma of the entire urinary tract. Since rare diseases are often incorrectly diagnosed and managed, the aim of this study was to analyze the experience of a single urology center in the treatment of PUC, focusing on neoplasms arising from the male anterior urethra. MATERIALS AND METHODS: Medical records of patients with neoplasms at the level of the penile and bulbar urethra who presented at our tertiary referral center between January 1988 and December 2018 were retrospectively reviewed. Patients with carcinoma of the prostatic urethra were excluded. The diagnosis was obtained with the aid of urethroscopy and lesion biopsy. Local staging was performed by means of contrast-enhanced MRI in selected patients. Staging was achieved by clinical examination, ultrasonography, and CT scan. Radical surgery (radical cystectomy + total penectomy + bilateral inguinal lymphadenectomy) was proposed to patients with ≥T2 tumors or cN + with a good performance status, proximal tumor and without severe comorbidities. In case of nodal involvement, neoadjuvant chemotherapy was additionally offered. Patients with localized disease (

Crioablación total o hemiglandular para el cáncer de próstata primario localizado: resultados oncológicos y funcionales a corto y medio plazo / Whole and hemi-gland cryoablation for primary localized prostate cancer: Short and medium-term oncological and functional outcomes

INTRODUCCIÓN: Comparar los resultados oncológicos, funcionales y postoperatorios de la crioablación hemiglandular (CH) vs. crioablación de toda la glándula (CT) como terapia primaria del cáncer de próstata localizado. MATERIAL Y MÉTODO: Se incluyeron 66 pacientes consecutivos tratados entre 2010 y 2018 con crioablación total (CT = 40) o crioablación hemiglandular (CH = 26) en un centro de referencia terciario. Todos los pacientes tenían cáncer de próstata de riesgo bajo-intermedio según criterios D'Amico. Se propuso crioablación hemiglandular en caso de cáncer de próstata unilateral comprobado por biopsia y RM. La variable principal de evaluación fue el fracaso de la crioterapia, para el que se consideraron y compararon tres definiciones: 1) fallo bioquímico (> PSA nadir + ≥ 2 ng/mL), 2) rebiopsia positiva de próstata Gleason ≥ 7, y 3) inicio de un tratamiento adicional para el cáncer de próstata. RESULTADOS: La edad media de los pacientes durante el tratamiento fue 74 [42-81] vs.76 [71-80] años en el grupo de CT vs. CH, respectivamente (p = 0,08). Los grupos de riesgo bajo e intermedio (D'Amico) fueron 15% y 85% frente a 23% y 77% (p = 0,75), respectivamente. El tiempo medio de seguimiento fue de 41 [1,5-99,0] vs.27 [0,9-93] meses (p = 0,03). La supervivencia libre de fracaso de la crioterapia a cuatro años en CT vs. CH fue de 69% vs.53% con la definición 1 (p = 0,24), 82% vs.80% con la definición 2 (p = 0,95), y 83% vs.77% con la definición 3 (p = 0,73). La continencia urinaria postoperatoria y al año fue de 60% y 83% en CT frente a 72% y 83% en CH (p = 0,26). La impotencia de novo tras la crioterapia fue del 75% frente al 46% (p = 0,33) en CT y CH, respectivamente. CONCLUSIONES: En nuestra cohorte de pacientes altamente seleccionados con CP unilateral de riesgo bajo-intermedio, la crioterapia hemiglandular puede proporcionar resultados oncológicos similares y menos complicaciones tempranas en comparación con la crioablación de toda la glándula

INTRODUCTION: To compare oncological, functional and post-operative outcomes of hemi (HC) vs. whole gland (WGC) cryoablation as first line treatment of localized prostate cancer. MATERIAL AND METHOD: Sixty-six consecutive patients undertaking whole-gland cryoablation (WGC = 40) or hemi-cryoablation (HC = 26) in a tertiary referral centre between 2010 and 2018 were included. All patients had a low-intermediate risk prostate cancer according to D'Amico risk classification. Hemi-ablation was proposed in case of biopsy and prostate MRI proven unilateral prostate cancer. Primary endpoint was Cryotherapy Failure for which 3 definitions were considered and compared: 1) biochemical failure (> PSA nadir+ ≥ 2 ng/mL), 2) positive prostate re-biopsy with Gleason score ≥ 7, 3) initiation of further prostate cancer treatment. RESULTS: Median patients age at treatment was 74 [42-81] vs.76 [71-80] years in WGC vs. HC group, respectively (p=.08). Low and intermediate D'Amico risk group were 15% and 85% vs.23% and 77% (p=.75), respectively. Median follow- up time was 41 [1.5-99.0] vs.27 [0.9-93] months (p=.03). Four-years cryotherapy failure free survival in WGC vs. HC were 69% vs.53% with definition 1 (p=.24), 82% vs.80% with definition 2 (p=.95), 83% vs.77% with definition 3 (p=.73). Early and 1-year urinary continence were 60% and 83% in WGC vs.72% and 83% in HC (p=.26). De novo impotency after cryotherapy was 75% vs.46% (p=.33) in WGC vs. HC. CONCLUSIONS: In our cohort of highly selected patients with unilateral low/intermediate risk PCa, hemi-cryoablation may provide similar oncological outcomes and less early complications compared to whole-gland cryoablation

Whole and hemi-gland cryoablation for primary localized prostate cancer: Short and medium-term oncological and functional outcomes. / Crioablación total o hemiglandular para el cáncer de próstata primario localizado: resultados oncológicos y funcionales a corto y medio plazo.

INTRODUCTION: To compare oncological, functional and post-operative outcomes of hemi (HC) vs. whole gland (WGC) cryoablation as first line treatment of localized prostate cancer. MATERIAL AND METHOD: Sixty-six consecutive patients undertaking whole-gland cryoablation (WGC=40) or hemi-cryoablation (HC=26) in a tertiary referral centre between 2010 and 2018 were included. All patients had a low-intermediate risk prostate cancer according to D'Amico risk classification. Hemi-ablation was proposed in case of biopsy and prostate MRI proven unilateral prostate cancer. Primary endpoint was Cryotherapy Failure for which 3 definitions were considered and compared: 1) biochemical failure (> PSA nadir+≥ 2 ng/mL), 2) positive prostate re-biopsy with Gleason score ≥ 7, 3) initiation of further prostate cancer treatment. RESULTS: Median patients age at treatment was 74 [42-81] vs. 76 [71-80] years in WGC vs. HC group, respectively (p=.08). Low and intermediate D'Amico risk group were 15% and 85% vs. 23% and 77% (p=.75), respectively. Median follow- up time was 41 [1.5-99.0] vs. 27 [0.9-93] months (p=.03). Four-years cryotherapy failure free survival in WGC vs. HC were 69% vs. 53% with definition 1 (p=.24), 82% vs. 80% with definition 2 (p=.95), 83% vs. 77% with definition 3 (p=.73). Early and 1-year urinary continence were 60% and 83% in WGC vs. 72% and 83% in HC (p=.26). De novo impotency after cryotherapy was 75% vs. 46% (p=.33) in WGC vs. HC. CONCLUSIONS: In our cohort of highly selected patients with unilateral low/intermediate risk PCa, hemi-cryoablation may provide similar oncological outcomes and less early complications compared to whole-gland cryoablation.

The impact of age on intravesical instillation of Bacille Calmette-Guerin treatment in patients with high-grade T1 bladder cancer.

Intravesical instillation of Bacille Calmette-Guèrin (BCG) is the standard adjuvant treatment for high-risk non muscle invasive bladder cancer (NMIBC). Since its mechanism of action is supposed to be linked to the immune system efficiency and senescence could negatively affect this efficiency, BCG efficacy in the elderly has been questioned. This study aimed to assess the impact of age on BCG efficacy and safety in patients with high-grade T1 bladder cancer (BC).Among 123 patients with high-grade T1 BCG scheduled for BCG treatment, 82 were <75 year-old (group A) and 41 were ≥75 year-old (group B). Follow-up: urine cytology and cystoscopy every 3 months for the first 2 years, every 6 months for the third year, and then yearly. Tumor recurrence was defined as pathological evidence of disease at the bladder biopsy; tumor progression was defined as pathological shift to muscle invasive disease at the bladder biopsy or the imaging techniques showing recurrent BC and distant metastasis likely related to it.The median follow-up was 65 months (range 11-152). Recurrence occurred in 35 patients, 19 (23.2%) in the group A and 16 (39%) in the group B. Progression occurred in 18 patients, 12 (14.6%) in the group A and 6 (14.6%) in the group B. Recurrence free rate was similar in both groups up to 2 years. The 5 years progression rate was almost the same in both groups A and B (85.9% vs 84.7%), whereas the 5 years cancer-specific survival (CSS) was 92.6% in the group A and 85.4% in the group B. Of the 18 patients with progression, 11 underwent cystectomy; 12 patients died because of their BC. Kaplan-Meier plots pointed out no difference in recurrence-free, progression-free, and CSS between the 2 groups. Adverse events were similar in the 2 groups. Only 4 (3.3%) patients, 2 (2.4%) in the group A and 2 (4.8%) in the group B, experienced mild adverse reactions compatible with treatment.Elderly patients with high-grade T1 BC are not poorer candidates to BCG treatment, as they had similar benefit and adverse reactions than those aging ≥75 years.

Fragmentación dirigida a discontinuidades preferentes: un nuevo concepto en endolitotricia con láser Holmium:YAG / Fragmentation targeted at preferred discontinuities: A new concept in endolithotripsy with Holmium laser:YAG

Introducción: En la actualidad existen 3 modalidades técnicas de endolitotricia con láser Holmium:YAG (Ho:YAG) consideradas básicas (fragmentación, pulverización, "pop-corn"). Presentamos la técnica de fragmentación dirigida por discontinuidades preferentes (FDDP), un nuevo concepto de endolitotricia con láser Ho:YAG. Material y métodos: La técnica de FDDP se basa en la aplicación selectiva (dirigida a un punto concreto preseleccionado) de la energía sobre una zona visualmente proclive a la formación de una línea de fractura o discontinuidad preferente (condicionada por la anisotropía de la urolitiasis). El régimen energético (setting) idóneo consiste en un elevado rango de energía de trabajo (2-3J) con un muy bajo rango de frecuencia (5-8 Hz) y pulso de amplitud corta. Entre enero del 2015 y febrero del 2017 se ha realizado la técnica de FDDP en 37 procedimientos (7 NLP, 16 RIRS, 12 URS, 2 cistolitotomía), con un láser Ho:YAG (Lumenis Pulse 120H(R), Tel-Aviv, Israel). Potencia máxima empleada: 24 W (3 J/8Hz) con fibras de 365 y 273 mi. (URS, RIRS), y 32 W (4 J/8Hz) con fibras de 550 mi. (NLP, cistolitotomía). Resultados: Con técnica de FDDP se obtuvo en todos los casos una mejora estratégica para continuar la endolitotricia o extraer fragmentos. No se registraron complicaciones derivadas de la aplicación de esta modalidad. Conclusiones: La FDDP puede ser considerada como una opción complementaria en combinación con las modalidades básicas de fragmentación y pulverización. En nuestra experiencia, significa un avance para optimizar el rendimiento de la endolitotricia con láser Ho:YAG

Introduction: There are currently 3holmium laser, YAG (Ho:YAG) endolithotripsy procedures that are considered basic (fragmentation, pulverisation, "pop-corn" technique). We present the technique of fragmentation targeted at preferred discontinuities (FTPD), a new concept of endolithotripsy by Ho:YAG laser. Material and methods: The FTPD technique is based on the selective application of energy (targeting a specific preselected point) to an area that is visually prone to the formation of a fracture line or preferred discontinuity (conditioned by the anisotropy of the urolithiasis). The ideal energy regimen (setting) is a high range of working energy (2-3J) with a very low frequency range (5-8Hz) and short pulse width. Between January 2015 to February 2017, the FTPD technique was used in 37 procedures (7 NLP, 16 RIRS, 12 URS, 2 cystolithotomies), with a Ho:YAG laser (Lumenis Pulse 120H (R), Tel-Aviv, Israel). Maximum power used: 24W (3J/8Hz) with fibres of 365 mi. and 273 mi. (URS, RIRS), and 32W (4J/8Hz) with fibres of 550 mi. (NLP, cystolithotomy). Results: Strategic improvement was achieved in all cases using the TFPD technique to continue the endolithotripsy or remove fragments. No complications were recorded after the use of this method. Conclusions: FTPD can be considered a complementary option in combination with the basic methods of fragmentation and pulverisation. In our experience, it constitutes significant progress in optimising the performance of Ho:YAG laser endolithotripsy

Fragmentation targeted at preferred discontinuities: A new concept in endolithotripsy with Holmium laser:YAG. / Fragmentación dirigida a discontinuidades preferentes: un nuevo concepto en endolitotricia con láser Holmium:YAG.

INTRODUCTION: There are currently 3holmium laser, YAG (Ho:YAG) endolithotripsy procedures that are considered basic (fragmentation, pulverisation, "pop-corn" technique). We present the technique of fragmentation targeted at preferred discontinuities (FTPD), a new concept of endolithotripsy by Ho:YAG laser. MATERIAL AND METHODS: The FTPD technique is based on the selective application of energy (targeting a specific preselected point) to an area that is visually prone to the formation of a fracture line or preferred discontinuity (conditioned by the anisotropy of the urolithiasis). The ideal energy regimen (setting) is a high range of working energy (2-3J) with a very low frequency range (5-8Hz) and short pulse width. Between January 2015 to February 2017, the FTPD technique was used in 37 procedures (7 NLP, 16 RIRS, 12 URS, 2 cystolithotomies), with a Ho:YAG laser (Lumenis Pulse 120H®, Tel-Aviv, Israel). Maximum power used: 24W (3J/8Hz) with fibres of 365µ and 273µ (URS, RIRS), and 32W (4J/8Hz) with fibres of 550µ (NLP, cystolithotomy). RESULTS: Strategic improvement was achieved in all cases using the TFPD technique to continue the endolithotripsy or remove fragments. No complications were recorded after the use of this method. CONCLUSIONS: FTPD can be considered a complementary option in combination with the basic methods of fragmentation and pulverisation. In our experience, it constitutes significant progress in optimising the performance of Ho:YAG laser endolithotripsy.

A prospective randomized comparison among SWL, PCNL and RIRS for lower calyceal stones less than 2 cm: a multicenter experience : A better understanding on the treatment options for lower pole stones.

PURPOSE: To prospectively evaluate the efficacy and safety of RIRS, SWL and PCNL for lower calyceal stones sized 1-2 cm. MATERIALS AND METHODS: Patients with a single lower calyceal stone with an evidence of a CT diameter between 1 and 2 cm were enrolled in this multicenter, randomized, unblinded, clinical trial study. Patients were randomized into three groups: group A: SWL (194 pts); group B: RIRS (207 pts); group C: PCNL (181 pts). Patients were evaluated with KUB radiography (US for uric acid stones) at day 10 and a CT scan after 3 months. The CONSORT 2010 statement was adhered to where possible. The collected data were analyzed. RESULTS: The mean stone size was 13.78 mm in group A, 14.82 mm in group B and 15.23 mm in group C (p = 0.34). Group C compared to group B showed longer operative time [72.3 vs. 55.8 min (p = 0.082)], fluoroscopic time [175.6 vs. 31.8 min (p = 0.004)] and hospital stay [3.7 vs. 1.3 days (p = 0.039)]. The overall stone-free rate (SFR) was 61.8% for group A, 82.1% for group B and 87.3% for group C. The re-treatment rate was significantly higher in group A compared to the other two groups, 61.3% (p < 0.05). The auxiliary procedure rate was comparable for groups A and B and lower for group C (p < 0.05). The complication rate was 6.7, 14.5 and 19.3% for groups A, B and C, respectively. CONCLUSIONS: RIRS and PCNL were more effective than SWL to obtain a better SFR and less auxiliary and re-treatment rate in single lower calyceal stone with a CT diameter between 1 and 2 cm. RIRS compared to PCNL offers the best outcome in terms of procedure length, radiation exposure and hospital stay. ISRCTN 55546280.

Kidney cancer focal cryoablation trend: does location or approach matter?

PURPOSE: We evaluated the current indications and surgical and survival outcomes for cryoablation (CA) using either a percutaneous (PCA) or a laparoscopic approach (LCA). We also investigated the ability of the PADUA score to predict the risk of complications and local recurrence. METHODS: A retrospective analysis was performed at two European tertiary referral centers. Parameters analyzed included size, location, approach, operative time, hospital stay, complications, and functional and oncologic outcomes. Univariate and multivariate analyses were performed. An ROC analysis was conducted to evaluate the accuracy of the PADUA score. RESULTS: Eighty patients were included. Mean tumor size was 2.6 cm. PCA was more often performed in posterior (95 vs. 60 %), inferior (72 vs. 32 %), and lateral (87 vs. 55 %) tumors. The global complication rate was 8.75 %, although proximity to the renal sinus resulted in a higher rate (30 vs. 4 %). Mean follow-up was 34 and 23 months for LCA and PCA, respectively. The 5-year recurrence-free survival was 76 and 90 % for LCA and PCA, respectively. Multivariate analysis showed that tumor involvement of the collecting system was predictive of recurrence. Under ROC analysis, PADUA score was a mild predictor for complications (AUC = 0.601) and a good predictor for recurrence (AUC = 0.723); PADUA ≥8 was identified as a cutoff for patients to a higher risk of recurrence. CONCLUSIONS: The percutaneous approach is confirmed to be the preferred CA technique for posterior and lateral tumors. CA in deeper renal lesions and tumors with PADUA score ≥8 might entail a higher risk of recurrence, and closer follow-up should be considered in these patients.

Role of Runx2 phosphorylation in prostate cancer and association with metastatic disease.

The osteogenic transcription factor, Runx2, is abnormally expressed in prostate cancer (PCa) and associated with metastatic disease. During bone development, Runx2 is activated by signals known to be hyperactive in PCa including the RAS/MAP kinase pathway, which phosphorylates Runx2 on multiple serine residues including S301 and S319 (equivalent to S294 and S312 in human Runx2). This study examines the role of these phosphorylation sites in PCa. Runx2 was preferentially expressed in more invasive PCa cell lines (PC3>C4-2B>LNCaP). Furthermore, analysis using a P-S319-Runx2-specific antibody revealed that the ratio of P-S319-Runx2/total Runx2 as well as P-ERK/total ERK was highest in PC3 followed by C4-2B and LNCaP cells. These results were confirmed by immunofluorescence confocal microscopy, which showed a higher percentage of PC3 cells staining positive for P-S319-Runx2 relative to C4-2B and LNCaP cells. Phosphorylated Runx2 had an exclusively nuclear localization. When expressed in prostate cell lines, wild-type Runx2 increased metastasis-associated gene expression, in vitro migratory and invasive activity as well as in vivo growth of tumor cell xenografts. In contrast, S301A/S319A phosphorylation site mutations greatly attenuated these Runx2 responses. Analysis of tissue microarrays from 129 patients revealed strong nuclear staining with the P-S319-Runx2 antibody in primary PCas and metastases. P-S319-Runx2 staining was positively correlated with Gleason score and occurrence of lymph node metastases while little or no Runx2 phosphorylation was seen in normal prostate, benign prostate hyperplasia or prostatitis indicating that Runx2 S319 phosphorylation is closely associated with PCa induction and progression towards an aggressive phenotype. These studies establish the importance of Runx2 phosphorylation in prostate tumor growth and highlight its value as a potential diagnostic marker and therapeutic target.

Versión española del cuestionario USSQ: evaluación de la tolerancia clínica al catéter ureteral doble jota / Spanish version of the USSQ questionnaire: evaluation of clinical tolerance to double J uretheral catheter

INTRODUCCIÓN: La evaluación de los síntomas debidos a catéter ureteral doble jota (CUJJ) precisa de una herramienta fiable como el cuestionario USSQ. Se presenta una versión traducida al español de este cuestionario (USSQ-E). MATERIAL Y MÉTODOS: La versión en inglés del USSQ ha sido traducida al español siguiendo una sofisticada sistemática lingüística. Una vez obtenido el USSQ-E ha sido probado en un grupo de 70 pacientes portadores de CUJJ. Como grupo control se han tomado 40 personas sin catéter. RESULTADOS: Se ha evaluado el USSQ-E con pruebas de consistencia interna, test-retest, validez convergente, sensibilidad al cambio y validez discriminatoria, siendo todas ellas satisfactorias. CONCLUSIÓN: El USSQ-E es una herramienta válida y fiable para evaluar la sintomatología derivada del CUJJ en población hispanoparlante (AU)

INTRODUCTION: The assessment of symptoms due to double J ureteral catheter (CUJJ) requires a reliable tool like USSQ questionnaire. A translation in Spanish of this questionnaire (USSQ-E) version is presented. MATERIAL AND METHODS: The English version of USSQ has been translated into Spanish language following a systematic sophisticated. After obtaining the USSQ-E has been tested in a group of 70 patients with CUJJ. A control group of 40 people have been taken without catheter. RESULTS: We evaluated the USSQ-E with evidence of internal consistency, test-retest reliability, convergent validity, sensitivity to change and discriminant validity, all of which are satisfactory. CONCLUSION: USSQ-E is a valid and reliable for assessing symptomatology derived CUJJ tool in speaking population (AU)

Use of flexible ureteroscopy in the clinical practice for the treatment of renal stones: results from a large European survey conducted by the EAU Young Academic Urologists-Working Party on Endourology and Urolithiasis.

Treatment of renal stones using flexible ureteroscopy (fURS) is increasingly common despite the poor evidence in literature supporting its use and indications. With this study, we wanted to investigate the current use and indication of fURS for the treatment of renal stones in the clinical practice across the European countries. A survey was conducted using an emailed questionnaire consisting of 21 items; 2,894 recipients were selected via the EAU membership database. The questionnaires were collected through the SurveyMonkey system and the data were processed with the SPSS statistical package. Frequencies, cross tabs and Pearson correlation coefficients were applied as appropriate. 1,168 questionnaires were collected (response rate 40.4%). fURS was performed in 72.9% of the respondents' institutions, and 54.2% of the respondents were performing the procedure. For 95% of the users, fURS was considered first-line treatment, for stone of lower pole stone (45.9%) and <1 cm (44.2%) and 2 cm (43.8%) in size. The ureteral access sheaths were used routinely by more than 70% of the respondents. Lower pole stone repositioning technique was routinely performed by 45.9% of the surgeons. After fragmentation, 47.2% of the responders preferred to retrieve only the bigger fragments. At the end of fURS, lower volume surgeons were more likely to place routinely a double-J stent (p = 0.001). Higher volume surgeons estimated a higher durability of devices, both optical and digital ones (p < 0.001), and were more prone to consider fURS cost-effective when compared to other treatment modalities (p < 0.001). fURS is widely used for the treatment of renal stones and its use and indication can vary according to the age and surgeons' case volume. Higher volume surgeons are more prompt to extend international guidelines indications and to consider the technology cost-effective.

The use of mannitol in partial and live donor nephrectomy: an international survey.

PURPOSE: Animal studies have shown the potential benefits of mannitol as renoprotective during warm ischemia; it may have antioxidant and anti-inflammatory properties and is sometimes used during partial nephrectomy (PN) and live donor nephrectomy (LDN). Despite this, a prospective study on mannitol has never been performed. The aim of this study is to document patterns of mannitol use during PN and LDN. MATERIALS AND METHODS: A survey on the use of mannitol during PN and LDN was sent to 92 high surgical volume urological centers. Questions included use of mannitol, indications for use, physician responsible for administration, dosage, timing and other renoprotective measures. RESULTS: Mannitol was used in 78 and 64 % of centers performing PN and LDN, respectively. The indication for use was as antioxidant (21 %), as diuretic (5 %) and as a combination of the two (74 %). For PN, the most common dosages were 12.5 g (30 %) and 25 g (49 %). For LDN, the most common doses were 12.5 g (36.3 %) and 25 g (63.7 %). Overall, 83 % of centers utilized mannitol, and two (percent or centers??) utilized furosemide for renoprotection. CONCLUSIONS: A large majority of high-volume centers performing PN and LDN use mannitol for renoprotection. Since there are no data proving its value nor standardized indication and usage, this survey may provide information for a randomized prospective study.

Cirugía endoscópica renal combinada en la posición de Galdakao. Apuntes técnicos / Endoscopic combined renal surgery in Galdakao position. Technical notes

En 1955 Goodwin et al. describieron el primer acceso percutáneo renal con el paciente en prono1; posteriormente en 1976 Fernston y Johansson describieron la primera extracción litiásica a través de un tracto de nefrostomía2; mas adelante en el año 1981 Alken et al. publicarían una serie de litotricias renales percutáneas utilizando un litotriptor ultrasónico que se diseñó originalmente para litotricias endovesicales3. Este fue el nacimiento de una nueva técnica que se ha ido afianzando a lo largo de los años con algunas modificaciones a medida que surgen nuevas herramientas. Aunque inicialmente se practicaba con el paciente en posición oblicua-supina con el paso del tiempo se afianzó la posición en prono en favor de una mayor área de punción y un mayor campo de trabajo. Describimos la posición propuesta inicialmente por Valdivia y modificada posteriormente por Ibarluzea para la utilización de un abordaje combinado anterógrado y retrogrado en casos de alta complejidad en nuestro Centro (AU)

In 1995 Goowin et al. described the first percutaneous access to the kidney with the patient in prone position1; in 1976 Fernston y Johansson described the first kidney stone removal through a nephrostomy tract2; latter in 1981 Alken et al. published a series of percutaneous stone manipulation using an ultrasound lithotrite originally developed for f bladder stones3. A new surgical technique was born and since then it has developed and as new tools arrive. Although initially practiced with the patient in the supine-oblique position, with the passage of time the prone position has been favored, probably due to a greater puncture area and working field. We describe the position initially proposed by Valdivia and later modified by Ibarluzea for a combined anterograde and retrograde approach high complexity cases in our centre (AU)

Catéter ureteral metálico (Resonance®) en litiasis y patología en compresiva benigna: experiencia inicial / Metallic ureteral stent (Resonance®) in lithiasis and benign compressive pathology: initial experience

INTRODUCCIÓN: La uropatía obstructiva del tramo urinario superior en pacientes con altamorbilidad, puede ser solucionada con la colocación de un catéter doble J metálico (Resonance®), de un año de duración y con recambios periódicos. Valoramos a los pacientes a los que se les ha colocado dicho catéter por patología extrínseca/intrínseca, o por litiasis con más de un año de seguimiento. MATERIAL Y MÉTODOS: Se analizan retrospectivamente a 15 pacientes ASA IV (10 varones y 5mujeres), con edad media de 76 años (rango 45-95) a los que se colocó el catéter doble J tipoResonance®, valorando las complicaciones a corto y largo plazo así como las dificultades enel recambio y la evolución.RESULTADOS: La indicación del catéter metálico fue litiasis 7 casos y compresión extrínseca 8 casos. Un paciente presentó hematuria y 3 irritabilidad vesical. En 9 casos (60%) se ha cambiado el catéter al año de la colocación. Dos pacientes fallecieron antes del recambio porotras causas. Ningún paciente presentó incrustaciones.CONCLUSIONES: El catéter ureteral metálico doble J tipo Resonance® es una buena opción para pacientes complejos con elevada comorbilidad y/o edad avanzada, que presentan uropatíaobstructiva, incluida la litiasis. Es de fácil manejo y tiene escasos efectos secundarios (AU)

INTRODUCTION: Upper urinary tract obstructive uropathy in high-morbidity patients can beresolved by placing a double-J metal catheter (Resonance®) over one year, with regular replacements.We evaluated those patients who received the above catheter due to either extrinsic or intrincic disease or lithiasis, by following them up for longer than one year. MATERIAL AND METHODS: Fifteen ASA IV patients (10 males and 5 females) 76 years old (range: 45-95) who received the Resonance®-type double-J catheter were prospectively evaluated;short-term and long-term complications were assessed, as well as replacement troublesand patient progress. RESULTS: Indication was stone in 7 cases and extrinsic pathology in 8. One patient developed haematuria and 3 long-term bladder irritability. Nine patients (60%) needed a change of the catheter one year following placement. Two patients died due to other causes before replacement.Upon catheter removal no patient showed inlays. CONCLUSIONS: Long-time use of double-J metal catheters is a therapeutic alternative to be considered for patients with high morbidity and associated advanced age, both in an extrinsic pathology and in lithiasis (AU)