A Single-Center Experience With Third and Fourth Kidney Transplants and Second Kidney Transplant After Pancreas-Kidney Transplant: Surgical Aspects and Outcomes.

OBJECTIVES: Overall, 25% to 33% of patients on kidney transplant wait lists present with prior graft loss. In addition, the number of patients who require a retransplant seems to be increasing. Here, we describe our experience with patients who had a second kidney transplant after a previous pancreas-kidney transplant or a third or fourth kidney transplant. We focused specifically on the technical aspects and outcomes related to this patient group. MATERIALS AND METHODS: A single-center retrospective study was performed. The cohortincluded 15 patients > 18 years old who had received a second kidney graft after pancreas-kidney transplant or a second or greater kidney graft between 2013 and 2019. RESULTS: Median age of recipients was 45 years (range, 20-58 y). In 10 patients, the transperitoneal approach was selected. In 5 patients, the retroperitoneal heterotopic kidney retransplant technique was used. Early surgical complications (≤ 30 days posttransplant) were reported in 4 patients. Three patients had late ureteral stenosis (> 90 days posttransplant). All grafts were functioning at time of patient discharge. Mean creatinine level was 2.69 mg/dL (range, 1.23-6.26 mg/dL). The 1-year and 2-year graft survivalrates were 85% and 75%, respectively. No grafts were lost because of surgical complications. CONCLUSIONS: Retransplant of a second graft after pancreas-kidney transplant or retransplant of a third or fourth renal graft is challenging but feasible, with evidence of reasonably positive outcomes after retransplant.

[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.

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

Revisamos el papel de la inmunoterapia en el cáncer de próstata resistente a castración. Se han aplicado dos estrategias inmunoterápicas, de forma aislada o en combinación, bien entre ellas o bien con otros agentes de eficacia demostrada en este escenario y que ejercerían un papel inmunomodulador: vacunas o anticuerpos monoclonales destinados al bloqueo de puntos de control inhibidores de la respuesta inmune. Aunque a priori el CPRC presenta características que sugieren que la inmunoterapia podría jugar un papel relevante como estrategia terapéutica, su aplicación clínica ha demostrado una actividad limitada y heterogénea, en cuanto a la proporción de respondedores e intensidad de respuesta. En términos generales, la tasa de respuestas objetivas es muy baja, aunque, en los pacientes que responden, es posible detectar un beneficio claro y duradero. Sólo la vacuna autóloga Sipuleucel T ha demostrado un aumento de la supervivencia global en pacientes con criterios de buen pronóstico. Es característico en estos tratamientos que no se observe un incremento en la supervivencia libre de progresión debido a su propio mecanismo de acción. Tampoco la evolución del PSA puede considerarse una variante subrogada de respuesta radiológica o beneficio clínico en este entorno. Se hace necesario identificar qué características de los pacientes o del tumor son capaces de maximizar la respuesta. Una limitación importante es la ausencia de biomarcadores predictores de respuesta que sirvan para la preselección de pacientes. Como norma general, las mejores respuestas con tratamientos inmunoterápicos aislados se han observado en pacientes con baja carga tumoral, lo cual puede sugerir que su aplicación óptima podría ser en fases más precoces de la enfermedad (localizado de alto riesgo, fracaso bioquímico, etc.). La estrategia de combinación, sin lugar a dudas la de más futuro, se fundamenta en que los tratamientos adicionales incrementan la lisis celular con la consiguiente exposición antigénica y/o ejercen un efecto inmunomodulador capaz de vencer la tolerancia inmunológica inducida por el tumor. Los resultados obtenidos sugieren que la inmunoterapia puede ser más efectiva en modo tratamiento combinado con otros tratamientos activos (abiraterona, enzalutamida, Radio 223, docetaxel) en la lucha por lograr cronificar la enfermedad

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

[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)

Association of crossed renal ectopia and aortic aneurism. Case report.

OBJECTIVE: Renal malformations are rare entities and rarely have clinical consequences. Crossed renal ectopia has an incidence of 1/2.000 autopsies. The association with aortic aneurysm is even more exceptional. METHODS: We present our case and perform a bibliographic review. RESULTS: To date and in our knowledge, seven cases of crossed renal ectopia associated with aortic aneurysm were described on the literature. This malformation makes the treatment of the aneurysm more complex. The possibility of renal function decrease caused by injuries to the renal arteries during the surgical procedure is always present. Because of this risk of injury of the kidney during surgery preoperative evaluation of the vascularization must include image technologies as the MRI, CT-angiography or conventional arteriography. During the aortic intervention vascular conservation must be performed and it is necessary to minimize the time of renal ischemia. CONCLUSIONS: The association of crossed renal ectopia and aortic aneurysm is a rare event. The surgical intervention of the aorta does not have to necessarily originate a loss of renal function. Anyway the worsening of the renal clearance must be foreseen.

Asociación entre ectopia renal cruzada con fusión y aneurisma aórtico. A propósito de un caso / Association of crossed renal ectopia and aortic aneurism. Case report

OBJETIVO: La malformación renal es una entidad poco frecuente y rara vez tiene traducción clínica. La ectopia renal cruzada tiene una incidencia de 1 de cada 2.000 autopsias. Su asociación con un aneurisma aórtico es todavía más excepcional.MÉTODOS: Presentamos nuestro caso y revisamos la literatura.RESULTADOS: Hasta la fecha y en nuestro conocimiento hay descritos 7 casos de ectopia renal cruzada con fusión asociados a aneurisma aórtico. Este fenómeno hace que el tratamiento del aneurisma sea más complejo pudiendo ocasionar una disminución de la función renal por lesiones en su vascularización. Para evitarlo, la vascularización renal debe ser estudiada preoperatoriamente mediante pruebas como la RM, el Angio-Tac o la Arteriografía. Durante la intervención sobre la aorta se deben realizar técnicas de conservación vascular y se debe de minimizar el tiempo de isquemia renal.CONCLUSIONES: La asociación de riñón ectópico cruzado y aneurisma de aorta es un evento raro. La cirugía o procedimientos sobre la aorta no tienen por qué acarrear una perdida de función renal importante y ésta debe ser prevista antes de la intervención (AU)

OBJECTIVE: Renal malformations are rare entities and rarely have clinical consequences. Crossed renal ectopia has an incidence of 1/2.000 autopsies. The association with aortic aneurysm is even more exceptional.METHODS: We present our case and perform a bibliographic review.RESULTS: To date and in our knowledge , seven cases of crossed renal ectopia associated with aortic aneurysm were described on the literature. This malformation makes the treatment of the aneurysm more complex. The possibility of renal function decrease caused by injuries to the renal arteries during the surgical procedure is always present. Because of this risk of injury of the kidney during surgery preoperative evaluation of the vascularization must include image technologies as the MRI, CT-angiography or conventional arteriography. During the aortic intervention vascular conservation must be performed and it is necessary to minimize the time of renal ischemia.CONCLUSIONS: The association of crossed renal ectopia and aortic aneurysm is a rare event. The surgical intervention of the aorta does not have to necessarily originate a loss of renal function. Anyway the worsening of the renal clearance must be foreseen (AU)