[Prognostic factors and response predictors in castration resistant prostate cancer.] / Factores pronósticos y predictores de respuesta en cáncer de próstata resistente a la castración.

Prostate cancer is a health problem in many Countries worldwide. Understanding the essential function of androgens in the prostate physiology led to the development of hormonal blockade as a therapeutic option in advanced disease, with limited response with time and development of resistance. In this stage, where castration resistant prostate cancer (CRPC) is defined, it is associated with poor prognosis because survival varies between 18 and 24 months. Even with castration levels, tumors are dependent on the functional androgen receptor (AR). In this paper, we analyze pretreatment clinical parameters such as prognostic or progression-predictive biomarkers, castration resistance mechanisms, the development of new technologies for the use of the so called liquid biopsies from biological ayufluids and the identification of circulating tumor cells as CRPC response and progression biomarkers. Currently ongoing clinical trials are partially oriented to the search of new prognostic and predictive biomarkers, that will enable to open up precision medicine and so to improve oncological patient's quality of life with it.

[Immunotherapy in castration resistant prostate cancer.] / Inmunoterapia en cáncer de próstata resistente a la castración.

We review the role of immunotherapy in castration resistant prostate cancer. Two immunotherapeutic strategies have been applied, isolated or in combination, either with each other or with other agents with demonstrated efficacy in this scenario that would play a role as immunomodulators: vaccines or monoclonal antibodies aimed to block immune response checkpoint inhibitors. Although CRPC presents, a priori, characteristics suggesting that immunotherapy may play a relevant role as a therapeutic strategy, its clinical application has demonstrated a limited and heterogeneous activity, in terms of proportion of responders and response intensity. Generally, the objective response rate is very low, although, in patients who have response it is possible to detect a clear, long-lasting benefit. Only the autologous vaccine Sipuleucel T has demonstrated an overall survival increase in patients with good prognosis criteria. In these treatments, it is characteristic that no progression free survival increase is visible due to its action mechanism. PSA evolution may not be considered a surrogate variable of radiological response or clinical benefit in this environment either. It is necessary to identify what patient's or tumor's characteristics are able to maximize the response. An important limitation is the absence of response predictive biomarkers that serve for patient preselection. As a general rule, the best responses with isolated immunotherapeutic treatments have been observed in patients with low tumor load, which may suggest that their optimal application could be in earlier phases of the disease (high risk localized, biochemical failure, etc) Combination strategy, without doubt the one with best future, is based on additional treatments increasing cell lysis with the subsequent antigen exposure and/ or producing an immunomodulatory effect that can surmount tumor induced immunologic tolerance. The results obtained suggest that immunotherapy may be more effective in combined therapy with other active therapies (abiraterone, enzalutamide, Radium 223, docetaxel) in a fight to achieve disease chronification.

Factores pronósticos y predictores de respuesta en cáncer de próstata resistente a la castración / Prognostic factors and response predictors in castration resistant prostate cancer

El cáncer de próstata es un problema de salud en muchos países a nivel mundial. La comprensión de la función esencial que los andrógenos tienen en la fisiología de la próstata condujo al desarrollo del bloqueo hormonal como opción de tratamiento en la enfermedad avanzada, con respuesta limitada en el tiempo y desarrollo de resistencia. Es en esta etapa donde se define el cáncer de próstata resistente a la castración (CPRC) y se asocia con mal pronóstico ya que la supervivencia oscila entre 18 y 24 meses a partir de ese momento. Aún con niveles de castración, los tumores son dependientes del receptor androgénico (RA) funcional. En el presente trabajo analizamos los parámetros clínicos pre-tratamiento como biomarcadores pronósticos o predictivos de progresión, los mecanismos de resistencia a la castración, el desarrollo de nuevas tecnologías para el uso de las denominadas biopsias líquidas a partir de fluidos biológicos y la identificación de células tumorales circulantes como biomarcadores de respuesta y progresión en CPRC. Los ensayos clínicos actualmente en marcha están en parte orientados hacia la búsqueda de nuevos biomarcadores pronósticos y predictivos, lo que permitirá abrir las puertas a la medicina de precisión y con ello mejorar la calidad de vida del paciente oncológico

Prostate cancer is a health problem in many Countries worldwide. Understanding the essential function of androgens in the prostate physiology led to the development of hormonal blockade as a therapeutic option in advanced disease, with limited response with time and development of resistance. In this stage, where castration resistant prostate cancer (CRPC) is defined, it is associated with poor prognosis because survival varies between 18 and 24 months. Even with castration levels, tumors are dependent on the functional androgen receptor (AR). In this paper, we analyze pretreatment clinical parameters such as prognostic or progression-predictive biomarkers, castration resistance mechanisms, the development of new technologies for the use of the so called liquid biopsies from biological ayufluids and the identification of circulating tumor cells as CRPC response and progression biomarkers. Currently ongoing clinical trials are partially oriented to the search of new prognostic and predictive biomarkers, that will enable to open up precision medicine and so to improve oncological patient's quality of life with it

[Robot-assisted and laparoscopic pyeloplasty.] / Pieloplastia robótica y laparoscópica.

OBJECTIVES: Uretero-pelvic junction (UPJ) obstruction has been classically treated by open dismembered pyeloplasty. Recently, laparoscopic (LP) and robotic pyeloplasty (RP) have become the techniques of choice for the treatment of UPJ stenosis in adult and pediatric population. Our objective in this paper is to review the results of minimally invasive surgery as the treatment of UPJ obstruction, the trend to use these approaches and the current limits of LP and RP. METHODS: A review of most relevant papers and meta-analysis about LP and RP in pediatric and adult population was performed using PubMed. RESULTS: In pediatric population, comparative studies and meta-analysis of relevant series show an overlap of results between LP, RP and open surgery in terms of success rate, rate of complications and hospital stay, being operating time shorter in open pyeloplasty compared to minimally invasive techniques. In infants and pre-school age open surgery remains as technique of choice for pediatric surgeons. In adults, comparative studies and meta-analysis of the most relevant series show also an overlap of results in terms of success rate and complication rate between LP and RP. Nonetheless, minimally invasive techniques seem to offer a significant shortening of hospital stay and need for analgesics compared to open surgery, reason why laparoscopic techniques are recommended over open pyeloplasty in adult population. CONCLUSIONS: In view of published literature, minimally invasive surgery has been postulated as the standard treatment in UPJ stenosis, with superimposable results to open surgery. The high cost of robotic approach limits its use in this type of pathology.

Staghorn stones in renal graft. Presentation on two cases report and review the bibliography.

OBJECTIVE: To describe two clinical cases of staghorn stones in renal allografts and to perform a review of this condition. METHODS/RESULTS: Case 1. 71-year-old woman with a renal transplant and recurrent UTI presented lithiasis in the graft on renal ultrasound. We started medical treatment and later one ESWL session was performed. The subsequent evolution of the patient was bad, requiring transplant nephrectomy. Case 2. 68-year old woman with renal transplant presented acute deterioration of renal function due to staghorn stones. Emergency ureteral catheter insertion was carried out, medical treatment was started and after one ESWL session she had a good subsequent evolution and normal function of the graft. CONCLUSIONS: Staghorn stones occupy most of the collecting system. They are usually made of struvite. They form in the context of urinary tract infections caused by urea splitting germs. Long-term persistence of staghorn calculi in the kidney causes functional and anatomical deterioration that can lead to kidney loss.

Litiasis coraliforme en injerto renal. presentación de dos casos clínicos y revisión de la bibliografía / Staghorn stones in renal graft. presentation on two cases report and review the bibliography

OBJETIVO: Describir los casos clínicos de dos pacientes trasplantadas renales con litiasis coraliforme del injerto. MÉTODOS/RESULTADOS: Caso 1. Mujer de 71 años trasplantada renal con episodios de ITU de repetición, presenta en ecografía doppler renal litiasis en el injerto. Se instaura inicialmente tratamiento médico y después se realiza LEOC. El desarrollo posterior es tórpido llevando la realización de trasplantectomía. Caso 2. Mujer de 68 años trasplantada renal que presenta deterioro agudo de la función renal por litiasis coraliforme. Se realiza cateterismo de urgencia, se inicia tratamiento médico y LEOC con buena evolución posterior y normofunción del injerto. CONCLUSIONES: Los cálculos coraliformes ocupan gran parte del sistema colector. Suelen estar constituidos por estruvita. Se forman en el contexto de infecciones urinarias producidas por gérmenes urolíticos. A largo plazo la persistencia de litiasis coraliforme en el riñón ocasiona un deterioro funcional y anatómico que puede llevar a la pérdida del riñón

OBJECTIVE: To describe two clinical cases of staghorn stones in renal allografts and to perform a review of this condition. METHODS/RESULTS: Case 1. 71-year-old woman with a renal transplant and recurrent UTI presented lithiasis in the graft on renal ultrasound. We started medical treatment and later one ESWL session was performed. The subsequent evolution of the patient was bad, requiring transplant nephrectomy. Case 2. 68-year-old woman with renal transplant presented acute deterioration of renal function due to staghorn stones. Emergency ureteral catheter insertion was carried out, medical treatment was started and after one ESWL session she had a good subsequent evolution and normal function of the graft. CONCLUSIONS: Staghorn stones occupy most of the collecting system. They are usually made of struvite. They form in the context of urinary tract infections caused by urea splitting germs. Long-term persistence of staghorn calculi in the kidney causes functional and anatomical deterioration that can lead to kidney loss

[Renal cell carcinoma molecular biology. Prognostic and therapeutic usefulness]. / Biología molecular en adenocarcinoma renal (RCC). Su utilidad pronóstica y terapéutica.

Renal cell adenocarcinoma requires different therapeutic pathways because it is one of the most therapy-resistant tumors, on the other hand it is biologically one of the most attractive tumors. Its pathological classification has a genetic base. There is an anomaly of the Von Hippel Lindau gene in 80% of adenocarcinomas, being this fact determinant to know the biological characteristics of tumor initiation and development, as well as the identification of factors susceptible to be used as therapeutic targets. Since 2005 a group of molecules have been used in the treatment of metastatic adenocarcinomas and, even though therapeutic results are significant but not clinically relevant yet, we are sure they are a key way for more efficient future developments. The present study tries to make a tour on the research of the biological anomalies in renal adenocarcinoma with special emphasis in the Von HippelLindau gene.

Biologia molecular en adenocarcinoma renal (RCC). Su utilidad pronóstica y terapéutica / Renal cell carcinoma molecular biology. Prognostic and therapeutic usefulness

El adenocarcinoma renal requiere caminos terapéuticos diferentes porque es uno de los tumores más resistentes a tratamiento, por contra es uno de los tumores biológicamente más atractivos. Su clasificación anatomopatológica tiene un fundamento genético. En el 80% de los adenocarcinomas existe una alteración del gen Von Hippel Lindau y este hecho ha sido determinante para conocer las características biológicas de la aparición y desarrollo tumoral así como la identificación de factores que pueden ser susceptibles de ser utilizados como dianas terapéuticas. Desde 2005 un grupo de moléculas se ha utilizado en el tratamiento de los adenocarcinomas metastásicos y aunque los resultados terapéuticos son significativos pero no todavía clínicamente relevantes, estamos seguros que son un camino clave para desarrollos posteriores más eficientes. El presente estudio pretende hacer un recorrido por la investigación de las alteraciones biológicas en adenocarcinoma renal haciendo especial énfasis en las alteraciones del gen Von Hippel Lindau(AU)

Renal cell adenocarcinoma requires different therapeutic pathways because it is one of the most therapy-resistant tumors, on the other hand it is biologically one of the most attractive tumors. Its pathological classification has a genetic base. There is an anomaly of the Von Hippel Lindau gene in 80% of adenocarcinomas, being this fact determinant to know the biological characteristics of tumor initiation and development, as well as the identification of factors susceptible to be used as therapeutic targets. Since 2005 a group of molecules have been used in the treatment of metastatic adenocarcinomas and, even though therapeutic results are significant but not clinically relevant yet, we are sure they are a key way for more efficient future developments. The present study tries to make a tour on the research of the biological anomaliesin renal adenocarcinoma with special emphasis in the Von HippelLindau gene(AU)

Impact of renal retransplantation on graft and recipient survival.

OBJECTIVES: The aim of this study was to evaluate the influence of retransplantation in graft and recipient survival. METHODS: We carried out a retrospective study in 419 renal transplants and studied the influence of retransplantation in graft and patient survival. A homogeneity study was performed between the two groups with a Student`s T and a chi-square tests. Graft survival analysis was performed with Kaplan-Meyer and log rank tests. RESULTS: Of 419 transplants, 370 (88.3%) were first transplantations, 45 (10.7%) second transplantations and 4(1%) third ones. Mean follow-up of the whole group was 72.5 months (±54.1 SD). There were no differences in follow-up between groups (Mean Follow-up 73.1 months ±54.4 SD in first transplantations vs. 61.6 months ±51.2 SD in repeat transplantation. p >0.05). The actuarial graft survival showed no differences between patients with first transplantation and those with a repeat one. [3 and 5 year SV of 89% (95% CI: 87-91%) and 84%(95% CI: 82-86%) Vs 88% (95% CI; 83-93%) and 85% (95% CI:i; 80-90%) respectively]. After adjusting for all the heterogeneity variables we still did not find differences on graft survival. The actuarial recipient survival showed no differences between patients with first transplantation and those with a repeat one. [3 and 5 year SV of 98% and 96% Vs.97%]. CONCLUSIONS: There are no differences of graft and recipient survival between patients with a first transplantation and those with a repeat one.

Impacto del retrasplante renal en la supervivencia del injerto y receptor / Impact of renal retransplantation on graft and recipient survival

OBJETIVO: Nuestro objetivo es valorar si un segundo o tercer trasplante tienen influencia en la supervivencia del injerto renal y en la del receptor.MÉTODOS: Analizamos retrospectivamente 419 trasplantes renales consecutivos realizados entre 1994 y 2010, analizando la influencia del retrasplante en la supervivencia del injerto renal. Se ha realizado un estudio de homogeneidad de los dos grupos mediante Tablas de contingencia para las variables cualitativas y t de student para las cuantitativas. La supervivencia y comparación de supervivencia con Kaplan-Meyer y log-rank..RESULTADOS: De los 419 trasplantes, 370 (88,3%) fueron primeros trasplantes 45(10,7%) segundos trasplantes y 4(1%) terceros. Media de seguimiento de todo el grupo de 72,5 meses (+/- 54,1 DE) y mediana de 68,8 meses( Rango de 0 a 188 meses ).No existen diferencias en el tiempo de seguimiento (Media del grupo de pacientes con un solo trasplante de 73,1 meses +/-54,4DE Vs. 61,6 meses +/-51,2DE del grupo de pacientes retrasplantados. p >0,05).El análisis de la supervivencia actuarial del injerto revela que no existen diferencias estadísticamente significativas entre los pacientes con un primer trasplante y los retrasplantados [SPV 89% (95% IC; 87- 91%) y 84% (95% IC; 82-86%) a los 3 y 5 años frente a 88% (95% IC; 83-93%) a los 3 años y 85% (95% IC; 80-90%) a los 5 años]. Al ajustar por las variables para las que los grupos no fueron homogeneos las diferencias se siguen manteniendo.El análisis de supervivencia de los receptores revela que tampoco existen diferencias entre los dos grupos [SPV del 98% y 96% a los 3 y 5 años en los primeros trasplantes frente a 97% a los 3 años y 5 años en los retrasplantados].CONCLUSIONES: No existen diferencias en la supervivencia del injerto ni en la de los receptores entre pacientes trasplantados por primera vez y aquellos que reciben un retrasplante(AU)

OBJECTIVES: The aim of this study was to evaluate the influence of retransplantation in graft and recipient survival.METHODS: We carried out a retrospective study in 419 renal transplants and studied the influence of retransplantation in graft and patient survival.A homogeneity study was performed between the two groups with a Student`s T and a chi-square tests. Graft survival analysis was performed with Kaplan-Meyer and log rank tests.RESULTS: Of 419 transplants, 370 (88.3%) were first transplantations, 45(10.7%) second transplantations and 4(1%) third ones. Mean follow-up of the whole group was 72.5 months (+/-54.1 SD).There were no differences in follow-up between groups (Mean Follow-up 73.1 months +/-54.4 SD in first transplantations vs. 61.6 months +/-51.2 SD in repeat transplantation. p >0.05). The actuarial graft survival showed no differences between patients with first transplantation and those with a repeat one. [3 and 5-year SV of 89% (95% CI: 87-91%) and 84% (95% CI: 82-86%) Vs 88% (95% CI; 83-93%) and 85% (95% CI; 80-90%) respectively].After adjusting for all the heterogeneity variables we still did not find differences on graft survival.The actuarial recipient survival showed no differences between patients with first transplantation and those with a repeat one. [3 and 5 year SV of 98% and 96% Vs. 97%].CONCLUSIONS: There are no differences of graft and recipient survival between patients with a first transplantation and those with a repeat one(AU)

[Bilharziasis. Case report]. / Bilharziasis: presentación de un caso clínico.

OBJECTIVE: To report one case of bilharziasis treated at our centre and to briefly comment the literature in the current context of increase of parasitical diseases in Europe, imported from the Third World by immigrants and tourists. METHODS: We report the case of a male patient from a Central African country referred to our department due to penile pain with painful voiding and ejaculation for several months, without other clinical symptoms. We performed a bibliographic search in the PubMed and Up-to-date databases with the following search terms: schistosomiasis, bilharziasis, hematuria, bladder infection, parasitosis, combined by boolean operators. RESULTS: After cystoscopy and pathologic study of the biological material the final diagnosis was chronic bilharziasis. The patient remains asymptomatic 14 months after treatment with praziquantel. CONCLUSIONS: Bilharziasis or schistosomiasis is a rare parasite disease, potentially severe which can severely compromise the urinary tract. In developed countries the cases are mainly imported from sub-saharian countries and other areas of North Africa, South Africa, Asia and Middle East. The cause is a parasite, Schistosoma haematobium, from the family of trematodes, genus helmints. In the active phasee the diagnosis is facilitated by the presence of Schistosomal eggs in urine. In latent or non active phase it is necessary the performance of cystoscopy and analysis of the biological material to reach the diagnosis.

Bilharziasis: presentación de un caso clínico / Bilharziasis. Case report

OBJETIVO: Presentar un caso clínico atendido en nuestro centro y comentar brevemente la literatura en el contexto actual del incremento de las enfermedades parasitarias en Europa, importadas del tercer mundo con la inmigración y el turismo. MÉTODO: Estudio de un paciente varón procedente de un país centroafricano que fue remitido a nuestro servicio debido a dolor en pene acompañado de micciones y eyaculaciones dolorosas de varios meses de evolución sin otra clínica acompañante. Como estrategia de búsqueda bibliográfica se utilizó la bases Pubmed y Uptodate con los siguientes descriptores: Schistosomiasis, Bilharziasis, Haematuria, Vesical Infection, Parasitosis, combinados con operadores boleanos. RESULTADO: Tras cistoscopia y estudio anatomopatológico del material biológico se llegó al diagnóstico de Bilharziasis en estadio crónico. El paciente permanece asintomático 14 meses tras tratamiento con Praziquantel. CONCLUSIONES: La bilharziasis o esquistosomiasis es una enfermedad parasitaria poco frecuente pero potencialmente grave que puede comprometer seriamente el aparato urinario. En los países desarrollados los casos son importados principalmente del África subsahariana y también de otras zonas como África del Norte, Sudáfrica, zonas de Asia y de Oriente Medio. Su causante es el parásito Schistosoma haematobium del género platelminto, familia de los tremátodos. En fase activa el diagnóstico es facilitado por la presencia de los huevos del schistosoma en la orina. En fase latente o inactiva es necesario la realización de uretrocistoscopia y el análisis de materiales biológicos para llegar al diagnóstico

OBJECTIVE: To report one case of bilharziasis treated at our centre and to briefly comment the literature in the current context of increase of parasitical diseases in Europe, imported from the Third World by immigrants and tourists. METHODS: We report the case of a male patient from a Central African country referred to our department due to penile pain with painful voiding and ejaculation for several months, without other clinical symptoms. We performed a bibliographic search in the PubMed and Up-to-date databases with the following search terms: schistosomiasis, bilharziasis, hematuria, bladder infection, parasitosis, combined by boolean operators. RESULTS: After cystoscopy and pathologic study of the biological material the final diagnosis was chronic bilharziasis. The patient remains asymptomatic 14 months after treatment with praziquantel. CONCLUSIONS: Bilharziasis or schistosomiasis is a rare parasite disease, potentially severe which can severely compromise the urinary tract. In developed countries the cases are mainly imported from sub-saharian countries and other areas of North Africa, South Africa, Asia and Middle East. The cause is a parasite, Schistosoma haematobium, from the family of trematodes, genus helmints. In the active phasee the diagnosis is facilitated by the presence of Schistosomal eggs in urine. In latent or non active phase it is necessary the performance of cystoscopy and analysis of the biological material to reach the diagnosis

[Initial experience with radiofrequency percutaneous ablation of renal tumors]. / Experiencia inicial en la ablación percutánea con radiofrecuencia de los tumores renales.

OBJECTIVES: To evaluate the usefulness of percutaneous or laparoscopic application of radiofrequency for ablation of tumoral tissue in patients with the diagnosis of solitary renal tumor. METHODS: 3 male patients (one with bilateral renal tumor) underwent 4 radiofrequency ablation treatments (1 laparoscopic, 3 percutaneous) for renal masses between 1.5 and 5 cm (average 3.15 cm). Percutaneous approach was gained under ultrasound control. Energy was applied progressively, following standardized tables, requiring between 2 (tumor diameter 1.5 cm) and 4 cycles (diameter 5 cm) applied in quadrants. Postoperative control was performed in all cases by IV contrast helical CT scan. RESULTS: Treatment was completed in all cases. In one case, laparoscopic tumorectomy was also performed. Radiofrequency cycles oscillated between 30 and 19 minutes depending on tumor size. There were not procedure-derived complications. IV contrast CT scan controls at 3 and 6 months showed absence of tumor in one case (1.5 cm) and absence of intratumoral contrast uptake in the rest of them. CONCLUSIONS: Radiofrequency ablation of small renal tumors, either percutaneous or laparoscopic, is a well-tolerated and minimally invasive procedure. Adequate parameters to consider complete tumor tissue destruction remain to be determined and validated.