Parp Inhibitors and Radiotherapy: A New Combination for Prostate Cancer (Systematic Review).

PARPi, in combination with ionizing radiation, has demonstrated the ability to enhance cellular radiosensitivity in different tumors. The rationale is that the exposure to radiation leads to both physical and biochemical damage to DNA, prompting cells to initiate three primary mechanisms for DNA repair. Two double-stranded DNA breaks (DSB) repair pathways: (1) non-homologous end-joining (NHEJ) and (2) homologous recombination (HR); and (3) a single-stranded DNA break (SSB) repair pathway (base excision repair, BER). In this scenario, PARPi can serve as radiosensitizers by leveraging the BER pathway. This mechanism heightens the likelihood of replication forks collapsing, consequently leading to the formation of persistent DSBs. Together, the combination of PARPi and radiotherapy is a potent oncological strategy. This combination has proven its efficacy in different tumors. However, in prostate cancer, there are only preclinical studies to support it and, recently, an ongoing clinical trial. The objective of this paper is to perform a review of the current evidence regarding the use of PARPi and radiotherapy (RT) in PCa and to give future insight on this topic.

Percutaneous radiofrequency ablation is an effective treatment option for small renal masses, comparable to partial nephrectomy.

OBJECTIVES: The standard therapy for small renal masses (SRMs) remains partial nephrectomy (PN), which is associated with relatively high morbidity and complication rate. Therefore, percutaneous radiofrequency ablation (PRFA) emerges as an alternative therapy. This study aimed to compare the efficacy, safety, and oncological outcomes of PRFA versus PN. METHODS: A multicenter non-inferiority study with retrospective analysis of 291 patients with SRMs (N0M0), who underwent PN or PRFA (2:1), recruited prospectively from two hospitals in the Andalusian Public Health System, Spain, between 2014 and 2021. Comparisons of treatment features were evaluated using the t test, Wilcoxon-Mann-Whitney U test, chi-square test, Fisher test, and Cochran-Armitage trend test. Kaplan-Meier curves depicted overall survival (OS), local recurrence-free survival (LRFS), and metastasis-free survival (MFS) rates in the overall study population. RESULTS: A total of 291 consecutive patients were identified; 111 and 180 patients underwent PRFA and PN, respectively. Median follow-up time was 38 and 48 months, and mean hospitalization days were 1.04 and 3.57 days, respectively. The variables underpinned with high surgical risk were significantly increased in PRFA compared to those in PN (mean age was 64.56 and 57.47 years, the solitary kidney presence was 12.6% and 5.6%, ASA score ≥ 3 was 36% and 14.5%, respectively). The rest of oncological outcomes were comparable amongst PRFA and PN. Patients undergoing PRFA did not improve OS, LRFS, and MFS compared to those undergoing PN. Limitations comprise retrospective design and limited statistical power. CONCLUSION: PRFA for SMRs in high-risk patients is non-inferior in terms of oncological outcomes and safety compared to PN. CLINICAL RELEVANCE STATEMENT: Our study has a direct clinical application as it proves that radiofrequency ablation is an effective and uncomplicated therapeutic option for patients with small renal masses. KEY POINTS: •There are non-inferiority results in overall survival, local recurrence-free survival, and metastasis-free survival between PRFA and PN. •Our two-center study showed that PRFA is non-inferior to PN in oncological outcomes. •Contrast-enhanced power ultrasound-guided PRFA provides an effective therapy for T1 renal tumors.

Strategies to Re-Sensitize Castration-Resistant Prostate Cancer to Antiandrogen Therapy.

Since prostate cancer (PCa) was described as androgen-dependent, the androgen receptor (AR) has become the mainstay of its systemic treatment: androgen deprivation therapy (ADT). Although, through recent years, more potent drugs have been incorporated, this chronic AR signaling inhibition inevitably led the tumor to an incurable phase of castration resistance. However, in the castration-resistant status, PCa cells remain highly dependent on the AR signaling axis, and proof of it is that many men with castration-resistant prostate cancer (CRPC) still respond to newer-generation AR signaling inhibitors (ARSis). Nevertheless, this response is limited in time, and soon, the tumor develops adaptive mechanisms that make it again nonresponsive to these treatments. For this reason, researchers are focused on searching for new alternatives to control these nonresponsive tumors, such as: (1) drugs with a different mechanism of action, (2) combination therapies to boost synergies, and (3) agents or strategies to resensitize tumors to previously addressed targets. Taking advantage of the wide variety of mechanisms that promote persistent or reactivated AR signaling in CRPC, many drugs explore this last interesting behavior. In this article, we will review those strategies and drugs that are able to resensitize cancer cells to previously used treatments through the use of "hinge" treatments with the objective of obtaining an oncological benefit. Some examples are: bipolar androgen therapy (BAT) and drugs such as indomethacin, niclosamide, lapatinib, panobinostat, clomipramine, metformin, and antisense oligonucleotides. All of them have shown, in addition to an inhibitory effect on PCa, the rewarding ability to overcome acquired resistance to antiandrogenic agents in CRPC, resensitizing the tumor cells to previously used ARSis.

Inter-observer variability in male pelvic-floor MRI measurements that might predict post-prostatectomy incontinence.

INTRODUCTION: Current studies are focusing on the relationship between anatomical variables in preoperative prostate MRI and the development of post-prostatectomy incontinence (PPI). Nevertheless, there is little evidence regarding the reliability of these measurements. The objective of this study was to analyze the concordance between urologists and radiologists for anatomical measurements that might be PPI predictors. MATERIAL AND METHODS: Pelvic floor measurements with 3T-MRI were performed by two radiologists and two urologists independently and blindly. Interobserver agreement was determined using the intraclass correlation coefficient (ICC) and the Bland-Altman plot. RESULTS: The concordance was good-acceptable for most measurements, except for the levator ani and puborectalis muscle thickness (some ICC values < 0.20/p value > 0.05). The anatomical parameters with the highest degree of agreement were intravesical prostatic protrusion (IPP) and prostate volume (most of the ICC values > 0.60). The membranous urethral length (MUL) and the angle of the membranous urethra-prostate axis (aLUMP) presented ICC > 0.40. The obturator internus muscle thickness (OIT), urethral width and intraprostatic urethral length presented a fair-moderate degree of agreement (ICC > 0.20). Regarding the agreement between different specialists, the highest degree was obtained for the two radiologists and for urologist 1-radiologist 2 (moderate median agreement), while urologist 2 with each of the radiologists had a regular median agreement. CONCLUSIONS: MUL, IPP, prostate volume, aLUMP, OIT, urethral width and prostatic length show acceptable inter-observer concordance and they would be reliable as possible predictors of PPI. Levator ani and puborectalis muscle thickness show bad agreement. Interobserver agreement might not be greatly influenced by previous professional experience.

Randomized and Open Trial to Assess the Effectiveness of the Guided Pelvic Floor Exercises Pre-Radical Robotic Prostatectomy on the Improvement of Urinary Incontinence. Initial Results.

INTRODUCTION AND OBJECTIVES: Radical prostatectomy has an impact on urinary continence. Many factors are involved in continence. The objective of this study is evaluate the effect of guided Pelvic Floor Exercises prior to robotic radical prostatectomy (RRP) on the rate of urinary incontinence compared with written information. MATERIAL AND METHOD: randomized study of 62 patients who are waiting for PRR. They were rondomized in two groups: experimental group (exercises guided by a physiotherapist) or a control group (written information). Primary objective was the continence rate measured by pad test and ICIQ-SF one month after the intervention, Secondary objectives were incontinence severity, quality of life with SF-36 and KHQ questionnaires and the correlation between incontinence and quality of life. RESULTS: We found no differences in continence rate between groups after the intervention. We found differences in "emotional problems" and "personal relationships", in favor of the control group. There is a correlation between the amount of urine leakage and age, urgency and all the domains of the KHQ questionnaire except general quality of life, as well as in the areas "energy/fatigue" and "social function" of the SF-36. CONCLUSIONS: Physiotherapist-guided exercises before RRP do not seem to offer advantages compared to written information, in terms of the incontinence rate and its severity one month after the surgery. Urinary incontinence is correlated with age, urgency, and deterioration in quality of life.

Update on the treatment of metastatic renal cell carcinoma.

Metastatic renal cell cancer (mRCC) management has undergone a paradigm shift in recent decades. The first revolution came with the emergence of vascular endothelial growth factor inhibitors; there was a second wave with the unprecedented success of checkpoint inhibitors, and then the latest approach, which is becoming the new care standard in mRCC, of combining these two strategies in different ways. Updated results of Checkmate-214 after 42 mo of follow-up were consistent with previously published results showing the superiority of nivolumab/ipilimumab over sunitinib in progression free survival (PFS), overall survival (OS), and objective response rate (ORR) in intermediate and high-risk patients. However, several studies presented at the American Society of Clinical Oncology 2020 suggested that the best place, and so far, the only one for nivolumab/ipilimumab is the frontline setting. The update on Keynote-426 after 23 mo of follow-up showed no superiority of pembroli-zumab/axitinib over sunitinib in favorable-risk mRCC, suggesting that it should no longer be the first line of choice in low-risk patients. Finally, the phase III Checkmate 9ER trial results revealed the superiority of nivolumab/cabozantinib vs sunitinib in PFS, OS, and ORR, providing a new first-line option among all International Metastatic RCC Database Consortium risk patients. Some phase II clinical trials also presented this year showed promising results with new combination therapies such as nivolumab/sitravatinib, cabozantinib/atezolizumab, and lenvatinib/pembrolizumab, providing promising grounds upon which to start phase III studies. In addition, other works are using novel therapeutic agents with different mechanisms of action, including telaglenastat (a glutaminase inhibitor), entinostat [an inhibitor of histone deacetylases (HDACs)], and olaparib and talazoparib, poly(ADP-ribose) polymerase inhibitors widely used in other tumors. However, some questions regarding mRCC management still need to be addressed, such as head-to-head comparisons between the current options, treatment sequencing, non-clear cell mRCC, and the role of biomarkers to ascertain the best treatment choice.

[Renal transplant recipient evaluation.] / Estudio urológico del candidato a trasplante renal.

Urological evaluation is essential to guarantee the success of the kidney transplant. Urologists working within a multidisciplinary team have a crucial role to detect and manage certain recipient urological conditions that could jeopardize the function and survival of the graft.The critical aspects that Urologists should consider in thepre-transplant evaluation would be:- Is renal transplantation surgical technique feasible with assumable risks based on the recipient's baseline characteristics? age, life expectancy, performance status,physical examination...- Is bladder function adequate to properly ensure the urine storage and voiding?- Is there a potentially treatable urinary flow obstruction?- Are there urological pathologies in the recipient that could lead to post-transplant complications that compromise graft survival: functional, infectious, oncological comorbidities…?- Based on the patient's cardiovascular risk factors, arteriosclerosis in the aorto-iliac territory colud put at risk thearterial anastomosis? In this chapter, we will try to explain how the pre-transplant urological evaluation should be guided according to the specific recipient characteristics. We will also explain which pre-transplant surgeries are required to avoid some risky that may compromise the recipient and graft survival after renal transplantation, as well as those should be postponed after transplantation.

La evaluación urológica en el estudio pre-trasplante es una pieza clave para garantizar eléxito del mismo. El papel del urólogo dentro de un equipo multidisciplinar que lleva a cabo esta evaluación es fundamental para detectar y manejar ciertas patologías urológicas del receptor que podrían poner en riesgo la función y supervivencia del injerto. Los puntos clave que el urólogo debe tratar en la consulta pretrasplante serían:- ¿La técnica quirúrgica del trasplante renal es viable con riesgos asumibles en base a las características basales del receptor? Edad biológica, esperanza de vida ,estado basal, exploración física…- ¿La función vesical es adecuada para asegurar un correcto almacenaje de la orina y una adecuada excreción de la misma?- ¿Existe una obstrucción al flujo urinario potencialmente tratable?- ¿Existen en el receptor patologías urológicas que puedan conllevar complicaciones en el post-trasplante que comprometan la función y supervivencia del injerto?:funcionales, infecciosas, oncológicas…- ¿En base a los factores de riesgo cardiovascular del paciente, podría existir una arteriosclerosis en el territorioaorto-iliaco que impida una anastomosis arterial congarantías? En este capítulo, trataremos de exponer cómo debemos orientar la consulta pre-trasplante desde el punto de vista urológico, comenzando por el estudio básico hasta el estudio más específico en base a características concretas del receptor. Además, expondremos cuáles son las cirugías pre-trasplante requeridas para eliminar condiciones de riesgo presentes en el potencial receptor que puedan comprometer la supervivencia del mismo y del injerto tras el trasplante renal así como, aquellos procedimientos programados indicados tras el trasplante.

Prospective study of diagnostic accuracy in the detection of high-grade prostate cancer in biopsy-naïve patients with clinical suspicion of prostate cancer who underwent the Select MDx test.

OBJECTIVES: This study aimed to externally validate the diagnostic accuracy of the Select MDx test for Significant prostate cancer (Sig PCa) (ISUP > 1), in a contemporaneous, prospective, multicenter cohort with a prostate-specific antigen (PSA) between 3 and 10 ng/ml and a non-suspicious digital rectal examination. METHODS AND PARTICIPANTS: For all enrolled patients, the Select Mdx test, the risk calculator ERSPC3 + DRE, and a prostatic magnetic resonance imaging (MRI) were carried out. Subsequently, a systematic 12-core trans-rectal biopsy and a targeted biopsy, in the case of a prostate imaging-reporting and data system (PIRADS) > 2 lesion (max three lesions), were performed. To assess the accuracy of the Select MDx test in the detection of clinically Sig PCa, the test sensitivity was evaluated. Secondary objectives were specificity, negative predictive value (NPV), positive predictive value (PPV), and area under the curve (AUC). A direct comparison with the ERSPC + DRE risk calculator and MRI were also performed. We also studied the predictive ability to diagnose Sig PCa from the combination of the Select MDx test with MRI using clinical decision-curve analysis. RESULTS: There were 163 patients enrolled after meeting the inclusion criteria and study protocol. The Select MDx test showed a sensitivity of 76.9% (95% CI, 63.2-87.5), 49.6% specificity (95% CI, 39.9-59.2), 82.09% (95% CI, 70.8-90.4) NPV, and 41.67% (95% CI, 31.7-52.2) PPV for the diagnosis of Sig PCa. COR analysis was also performed, which showed an AUC of 0.63 (95% CI, 0.56-0.71). There were no differences in the accuracy of Select MDx, ERSPC + DRE, or MRI. The combination of Select MDX + MRI showed the highest impact in the decision-curve analysis, with an NPV of 93%. CONCLUSION: Our study showed a worse performance for the SelectMdx test than previously reported, within a cohort of patients with a PSA 3-10 ng/ml and a normal DRE, with results similar to those from ERSPC + DRE RC and MRI, but with an improvement in the usual PSA pathway. A combination of the Select Mdx test and MRI could improve accuracy, but studies specifically evaluating this scenario with a cost-effective analysis are needed.

Anatomical predictors of long-term urinary incontinence after robot-assisted laparoscopic prostatectomy: A systematic review.

AIMS: There is scarce evidence of anatomical risk factors that might affect long-term post-prostatectomy incontinence (PPI) in patients undergoing robot-assisted laparoscopic prostatectomy (RALP). This systematic review aims to identify anatomical measurements in preoperative magnetic resonance imaging (MRI) that might be associated with increased risk of urinary incontinence (UI) 1 year after RALP. METHODS: A comprehensive search on Pubmed and Scopus databases up to November 2020 was performed. Eight articles met the inclusion criteria and were finally selected. RESULTS: The selected studies included 1146 patients. Seven articles focused on membranous urethral length (MUL); all of them related MUL to long-term PPI in univariate analysis and five of them in multivariate analysis. Four studies presented MUL difference to measure the magnitude of the effect. Average MUL (mm) was 15.9 (SD, 2.6), 16.1 (95% confidence interval [CI]: 13.9-18.9), 12.1 (95% CI 9.7-14.9) and 14.5 in continent patients and 13.9 (SD, 2.9), 10 (95% CI: 8.7-12.1), 10.3 (95% CI: 8.7-12.4) and 9.3 in incontinent patients, with statistically significant differences in all cases. Five studies presented the odds ratio as a result; although there was substantial heterogeneity in the methods used to obtain it, there was consistency in finding an inverse association between MUL and PPI. Other measurements including prostatic-urethral angle, membranous urethral thickness, intraprostatic urethral length and intravesical prostatic protrusion have been reported in few studies, and no association with long-term PPI was found. Levator ani muscle thickness was related to long-term PPI in one article. CONCLUSION: Greater MUL on preoperative MRI is associated with lower risk of UI 1 year after RALP.

Climacturia after robot-assisted laparoscopic radical prostatectomy.

INTRODUCTION: Adverse effects in the sexual sphere are common in patients who have undergone radical prostatectomy (RP). Climacturia, involuntary loss of urine during orgasm, occurs in 20-40% of cases after PR. We analyse its prevalence and associated risk factors after Robotic-assisted laparoscopic radical prostatectomy (RALRP). OBJECTIVES: We analyse the climacturia prevalence after robotic-assisted laparoscopic radical prostatectomy (RALRP) and the association with other related factors. MATERIALS AND METHODS: Retrospective study of 100 patients underwent PRLAR from May 2011 to July 2014. After excluding patients who received radiotherapy after surgery (17), those who did not have sexual activity (7) and those with whom it could not be possible contacted (14), a structured telephone interview was conducted in 62 patients, investigating: presence and intensity of climacturia, orgasmic quality, incontinence and erectile dysfunction (ED). Other factors analysed included neurovascular preservation and rehabilitative treatment for ED. The statistical analysis consisted of Chi2test and logistic regression to evaluate associated factors. RESULTS: The mean age was 56 vs 59 years and the mean follow-up time was 26.6 vs 20.3 months, in the group with climacturia and without climacturia, respectively. The prevalence of climacturia was 17.9% (slight leaks-82% and severe leaks-18%). In 37% of these patients occurred in all orgasms. The quality of orgasm after surgery was worse in 47%, better in 13% and equal in 40%. The quality of the orgasm worsened more frequently in the climacturia group (63% vs 37%). The urinary incontinence rate was 41%, always effort incontinence. It was more frequent in patients with climacturia (62% vs 38%). In all patients with climacturia, bilateral neurovascular bundles preservation was performed. 32% of the patients had undergone post-surgical erectile rehabilitation with oral drugs. No statistically significant differences were found between patients with or without climacturia respect to the parameters analysed. CONCLUSIONS: Climacturia rate after PRLAR in our series was 17.9%. Patients with climacturia presented worse quality orgasms and a higher incontinence rate (p> 0.05). None of the analysed parameters could be defined as predictors of climacturia.

[Recurrence and progression after BCG.] / Concepto de recidiva, recurrencia y progresión tras BCG.

BCG is currently the standard of care in intermediate and high risk non-invasive bladder tumors. In high-risk patients treated with BCG up to 30% will recurand 10% will progress within 2 years. Oncological outcomes with bladder preserving strategies are limited so radical cystectomy is recommended after BCG failure. Some promising treatments, such as check point inhibitors (PD1, PDL-1), are being studied for non-responders to BCG. Knowing the management of critical situations during BCG treatment its crucial in daily practice and clinical trials design. The aim of this study is to present these definitions and to remember some important aspect sof BCG management.

La BCG es en la actualidad el tratamiento de elección en tumores vesicales no músculo invasivo de riesgo intermedio y alto. De los pacientes de alto riesgo tratados con BCG, hasta un 30% recidivarán y un 10% progresarán en 2 años. Los resultados oncológicos de estos pacientes con estrategias de conservación vesical son modestos, por lo que la cistectomía radicales el tratamiento de elección tras fallo de BCG. Están siendo estudiadas diferentes opciones de tratamiento para pacientes no respondedores a BCG, como son los inhibidores de los puntos de control (PD1, PDL-1). Para el diseño de los ensayos clínicos (EC) y para homogeneizar nuestra práctica clínica diaria, es necesario tener clara la definición de una serie de situaciones, en las que nos podemos encontrar durante un tratamiento con BCG. El objetivo de este trabajo es revisar estas definiciones y recordar algunos aspectos del manejo de la BCG implicados en las mismas.

[Analysis of the quality of the information on the erectile dysfunction in YouTube.] / Análisis de la calidad de la información sobre disfunción eréctil en YouTube.

OBJECTIVE: The objective of our study is to stablish the scientific quality of the available information in YouTube about erectile dysfunction (ED). MATERIAL AND METHODS: We searched on YouTube thrree terms ("Problemas de Erección" (PE), "Impotencia"(I) y "Disfunción Eréctil" (DE)). The sixteen first videos from each term were selected for the analysis. Two independent urologists reviewed all videos and classified all of them in scientific evidence-based (SEB) or not scientific evidence-based (NSEB) according to the current literature. In the subgroup analysis we compare: number of visits, duration, time of publication, source and type of information. RESULTS: After excluding the repeated links and non-concordant videos between both urologists, we analysed 147 videos. The Kappa statistic was 0.89 (95% CI0.85-0.96). 37% were considered SEB and 63% were considered NSEB. The median of reproductions in the SEB group was 24.356 (96-126.410) and 44.416 for NSEB (190-10.318.642); this difference was statistically significant. The median duration was 254 seconds(46-984) for the SEB group and 228 seconds for the NSEB (23-2.880); the median time of publication was 42 (16-103) months for the SEB group and 29 (11-134) months for the other one. 83% of SEB videos were published in health networks and television programs,while 58% of NSEB were published in user blogs. The SEB videos show more information about pathophysiology,aetiology, endothelial dysfunction, diagnosis and treatment than NSEB (p<0.001). CONCLUSIONS: 37% of the videos were consideredSEB. The NSEB videos were significantly more playedthan SEB group.

OBJETIVO: Nuestro objetivo es analizar la calidad de la información disponible en YouTube acerca de la disfunción eréctil.MATERIAL Y MÉTODOS: Realizamos una búsqueda en YouTube usando los términos "Problemas de Erección" (PE), "Impotencia" (I) y "Disfunción Eréctil" (DE); incluimos los 60 primeros vídeos para cada uno de ellos. Dos urólogos revisaron de forma independiente los videos clasificándolos en "Basados en evidenciacientífica" (BEC) y "No basados en evidencia científica" (NBEC) según la bibliografía actual. Se describen y comparan el número de visitas, la duración, el tiempo publicado, la información médica y el origen de cada vídeo por grupos. RESULTADOS: Analizamos 147 videos tras eliminar los repetidos y no concordantes. El índice Kappa fue 0,89 (IC95% 0,82-0,96). El 37% se consideraron BEC y el 63% NBEC. La mediana de reproducciones en el grupo BEC fue 24.356 (rango 96-126.410) y 44.416 entre los NBEC (190-10.318.642), siendo esta diferencia estadísticamente significativa. La mediana de duración fue 254 segundos (46-984) y 228 segundos(23-2.880) respectivamente; la mediana de tiempo publicado fue de 42 meses en los BEC (16-103) y de 29 en los NBEC (11-134). El 83% de los vídeos BEC provenían de webs de salud y programas de televisión,mientras que el 58% de los NBEC procedían de blogs.Los vídeos BEC trataban más de fisiopatología, etiología,disfunción endotelial, diagnóstico y tratamiento frente a los NBEC (p<0,001).CONCLUSIÓN: Del total de videos revisados, el 37% se consideraron BEC. Los videos NBEC se reprodujeron más veces que los BEC.

How to obtain a 3D printed model of renal cell carcinoma (RCC) with venous tumor thrombus extension (VTE) for surgical simulation (phase I NCT03738488).

This is the phase 1 of a multicenter clinical trial (NCT03738488), which aims to assess the efficacy and efficiency of surgery planning with 3D models of renal cell carcinoma (RCC) with venous tumor thrombus extension (VTE) compared to the standard images (CT). The objective of this phase is to obtain a 3D printed model of RCC with VTE that is feasible, accurate, reproducible, suitable for surgical simulation, and affordable. A specific protocol was developed to obtain the computed tomography (CT) image: early arterial and nephrogenic phase. ITK-snap® and VirSSPA Software® were used to segment the areas of interest. The resulting 3D mesh was processed with MeshMixer® and Cura®. Ten models from seven different cases were segmented and printed using different 3D printers and materials. We evaluated the material, scale, wall thickness, anatomy printed, 3D conformation, accuracy compared to the CT, suitability to perform the surgery, material, cost, and time (segmentation + design + fabrication + finishing). The four selected models were printed with a BQ Witbox FDM printer in polyurethane filament with a 0.8 mm wall thickness and 100% scale. All the relevant anatomical structures could be correctly identified, the 3D conformation was maintained with good accuracy compared to the CT and the surgery could be performed on them. Mean design time, model cost and printing time were 8.3 h, 33.4 €, and 38.5 h respectively. Various feasible 3D models of RCC with VTE were obtained after a few attempts. The final models were proved to be reproducible, accurate compared to the CT, and suitable for surgery simulation. The printing process was standardized making it possible to manufacture affordable 3D printed models.

Outcomes and Safety of Biweekly and Monthly Nivolumab in Patients with Metastatic Renal Cell Carcinoma and Dialysis: Three Case Reports and Literature Review.

Nivolumab is a fully human immunoglobulin G4 programmed death-1 (PD-1) immune checkpoint inhibitor antibody that selectively blocks the interaction between PD-1, which is expressed on activated T cells, and its ligands PD-L1 and PD-L2, which are expressed on immune cells and tumour cells. Patients with severe renal dysfunction and haemodialysis are not enrolled in clinical trials. However, in daily clinical practice, we have patients with metastatic renal cell carcinoma (mRCC) and end-stage renal disease (ESRD). The scientific evidence about the efficacy and safety of nivolumab in these patients is scarce. We report three cases of mRCC patients with ESRD treated with second-line nivolumab therapy. They received both biweekly and monthly schemes. None of our patients showed grade 2-4 toxicities. Two patients achieved partial response and one progressive disease as best response. Our patients did not show increased toxicity by ESRD; also, two of the three patients had objectifiable clinical benefit. Nivolumab seems to be similarly safe for ESRD or dialysis patients as for patients without impaired kidney function (IKF). Dose adjustments might not be necessary. We suggest that patients on dialysis could be treated with nivolumab in the same way as populations without IKF.

[Therapeutic compliance in patients with renal lithiasis and biochemical risk factors.] / Cumplimiento terapéutico en pacientes con litiasis renal con factores de riesgo bioquímico.

OBJECTIVE: To evaluate patient compliance with treatment for urinary lithiasis and to detect differences in adherence, causes of this behavior and associated factors. METHODS: We performed a retrospective study of 93 patients with positive urinary metabolic study (UMS) for lithogenic pathology, diagnosed between 2013 and 2015, gathering data from the digital medical records and a structured telephonic questionnaire in 75 of them. Results were analyzed using the X2 test. RESULTS: 68% of the patients were males. Median age 42.92 (12.17) years. Mean follow up was 2.65 years. Most frequent metabolic alterations were: Hyperoxaluria (42.7%), Hypercalciuria (33.3%) and hipocitraturia (30.7%). Most frequently prescribed drugs: Potassium citrate (70.7%), Thiazide diuretics (26.7%) and calcium supplements (15.1). 84.2% of the patients did not know their UMS and 29.8% did not know the treatment prescribed. 41.9% followed the doses prescribed less than 50% of the times. Dietetic treatment was abandoned by 65% of the patients and pharmacological treatment by 43.5%, mainly due to laziness (62.9% vs 46.2%). 72.6% of the compliant patients experienced improvement. We find a significant relationship between academic level and diagnosis knowledge (p=0.022) and treatment (p=0.036). There were no differences in compliance depending on the number of drugs taken. CONCLUSIONS: Despite urine metabolic study being well valued and treatment well tolerated therapeutic compliance is very low. Most patients would repeat or restart the treatment prescribed in case of recurrence. Diagnostic and therapeutic information provided was not understood.

[Molecular biology of castration resistant prostate cancer.] / Biología molecular del cáncer de próstata resistente a la castración.

OBJECTIVES: Castration resistant prostate cancer (CRPC) is an heterogeneous disease the molecular basis of which we are starting to know in depth. Currently, there are various pathways and targets under study, and probably many others to be characterized. In this paper, we review the most recent knowledge concerning the molecular biology of CRPC with a special focus on the therapeutic application of this knowledge. METHODS: We performed a bibliographic review using PUBMED as the search engine, including the following terms: "Castration resistant prostate cancer", "genomics", "molecular biology", "AR", "WNT", "mTOR", "PTEN", "cell-cycle", "DNA damage repair gene"and "chromatin modifier genes". RESULTS: CRPC has a high load of genetic alterations, probably derived from therapeutic pressure. The most frequent alterations involve the androgen receptor (RA) [60-70%] and the PI3K- AKT-mTOR [40-60%], even though other relevant pathways alterations have been identified such as those relative to cellular cycle [25%], DNA lesion repair genes [20%] and other pathway like WNT-ßcatenin [15-22%]. The knowledge of these pathways is helping as a base for development of new therapeutic targets with promising results and multiple ongoing studies. CONCLUSIONS: Over the last decade, the progress in the knowledge of the molecular bases of CRPC has been very relevant. Even though AR alterations are the most frequent and best characterized, anomalies in other pathways have been also identified as important in the biology of CRPC and derived a notable therapeutic development.

[Endosalpingiosis of the bladder. A case report]. / Endosalpingiosis vesical. Presentación de un caso.

OBJECTIVE: To describe a case of endo-salpingiosis of bladder and review of the literature. METHOD: A 38 years old women referred to an outpatient urology clinic with postmenstrual voiding symptoms. RESULTS: We studied her and ultrasound imaging detects tumor that was confirmed by cystoscopy. She is diagnosed of endosalpingiosis of the bladder after transurethral resection, and a CT shows a consistent mass next to left adnexal with high probablility of being an endometrioma. CONCLUSIONS: Endosalpingiosis of the bladder is a rare disease that occurs in young women with cyclic urinary symptoms. The implantation of tubular tissue in the bladder is diagnosed and treated definitively by tumor excision and anatomopathologic examination.

[Selective arterial embolization in the treatment of intractable hematuria]. / Embolización arterial selectiva en el tratamiento de la hematuria incoercible.

OBJECTIVES: Non tractable hematuria has a varied etiology. It may be a complication difficult to treat. We report the case treated in our hospital by selective arterial embolization. METHODS: We report the case of an 86-year-old patient who underwent radiotherapy for transitional cell carcinoma. Later on, she presented with hematuria, not responding to usual therapeutic management. Urinary diversion did not solve the problem either. We decided to proceed with selective arterial embolization of the hypogastric arteries using polyvinylalcohol microspheres and metallic coils. RESULTS: Hematuria disappeared after embolization, without the recurrence after nine months of follow-up. Immediate outcome was characterized by a post-embolization syndrome which was treated with antipyretics, antibiotic and morphine derivatives. It diminished progressively and disappeared in 48 hours. CONCLUSIONS: Arterial selective embolization is a useful therapeutic resource for the management of non tractable hematuria, mainly in cancer patients, which present a deteriorated general status.