Postoperative Events in Incompatible Living Donor Kidney Transplant Recipients Undergoing Prior Desensitization.

BACKGROUND: Living donor kidney transplantation (LDKT) is one of the best options for patients with chronic renal failure, but approximately one-third of cases are limited by incompatibility ABO and/or HLA between recipient and donor. This study aims to analyze the surgical complications and bleeding events presented in ABO-incompatible (ABOi) and HLA-incompatible (HLAi) patients within a pre-transplant desensitization program compared with ABO-compatible (ABOc) recipients. MATERIAL AND METHODS: We performed a retrospective analysis of ABOi and HLAi recipients undergoing LKDT between 2009 and 2019, resulting in a total of 62 patients that we compared with the same number of ABOc performed consecutively before 2019. The following variables were analyzed: surgical complications, presence, size and rate of reintervention of peri-graft hematomas, and number of transfusions received in the postoperative period. RESULTS: No statistical differences were shown in donor and recipient age, BMI, or sex; in the case of pre-surgical hematocrit, the ABOi group presented slightly lower figures. In the incompatible group (ABOi + HLAi), we found a greater number of postoperative surgical complications when analyzing the number of hematomas, size, need for surgical reintervention, and the number of blood units transfused; incompatible patients showed higher rates of hematomas, need for surgical reinterventions, and transfused units (P < .05). CONCLUSION: Desensitized patients need more transfusions, have a greater number and size of hematomas, and have higher reintervention rates. Although these are present in greater numbers, we did not observe statistically significant differences in the number of surgical complications.

[Kidney transplant future developments.] / Futuro del trasplante renal.

OBJECTIVE: Kidney transplantation process involves a series of challenges such as the shortage of organs worldwide for a population waiting for a first and subsequent kidney transplants and the search forthe most appropriate graft for each recipient, optimizing the ischemia time as much as possible, minimizing the impact of surgery and subsequent immunosuppressive therapy. METHODS: We carry out a review of the different advances and lines of research in the different areas involved in the kidney transplantation process from strategies focused on increasing the donor pool, enabling the expansion of living donor programs as well as orga preservation strategies previous to transplantation surgery.The arrival of robotic surgery in the field of kidney transplantation has been an important milestone in the last decade, showing improvements compared to traditional open surgery, maintaining satisfactory functional results, although its implementation is currently reduced with technical limitations in the extension to any type of recipient. New immunosuppressive agents that minimize potential side effects or reduce anticalcineurinic drugsdoses are also important lines of research. CONCLUSIONS: The future of kidney transplantation involves the search for increasingly global strategies to improve the supply of organs, improvements in the conditioning and preservation of grafts or the global development of minimally invasive surgery in the different areas of kidney transplantation. The weight of biotechnology and gene therapies represent promising tools in the field of tissue generation or targeted immunosuppressive therapies.

OBJETIVO: El proceso del trasplante renal conlleva una serie de retos como son la escasez de órganos para una población a la espera de un primery sucesivos trasplantes renales y la búsqueda del injertomás apropiado para cada receptor optimizando al máximo el tiempo de isquemia, minimizando el impactode la cirugía y posterior terapia inmunosupresora.MÉTODOS: Realizamos una revisión de los diferentes avances y líneas de investigación en las diferentes etapas que conlleva el proceso del trasplante renal desdelas estrategias centradas a incrementar el pool de donantes,posibilitar la expansión de programas de donante vivo así como las estrategias de preservación del órgano previamente a la cirugía del implante.El desembarco de la cirugía robótica en el campo del trasplante renal ha sido un hito importante en la últimadécada, arrojando mejoras frente a la tradicional cirugía abierta manteniendo unos resultados funcionalessatisfactorios aunque su implantación es reducida en la actualidad con limitaciones técnicas en la extensión a cualquier tipo de receptor. Nuevos agentes inmunosupresores que minimicen los potenciales efectos secundarios o consigan reducir las dosis de anticalcineurínicos son también líneas importantes de investigación. CONCLUSIONES: El futuro del trasplante renal pasa por la búsqueda de estrategias cada vez más globales para mejorar la oferta de órganos, mejoras en el acondicionamiento y preservación de los injertos o el desarrollo a escala global de la cirugía mínimamente invasiva en los diferentes ámbitos del trasplante renal. El peso de las biotecnologías y terapias génicas suponen herramientas prometedoras en el campo de la generación de tejidos o terapias inmunosupresoras dirigidas.

Futuro del trasplante renal / Future of kidney transplantation

Objetivo: El proceso del trasplante renalconlleva una serie de retos como son la escasez deórganos para una población a la espera de un primery sucesivos trasplantes renales y la búsqueda del injerto más apropiado para cada receptor optimizando almáximo el tiempo de isquemia, minimizando el impactode la cirugía y posterior terapia inmunosupresora. Métodos: Realizamos una revisión de los diferentesavances y líneas de investigación en las diferentes etapas que conlleva el proceso del trasplante renal desdelas estrategias centradas a incrementar el pool de donantes, posibilitar la expansión de programas de donante vivo así como las estrategias de preservación delórgano previamente a la cirugía del implante. El desembarco de la cirugía robótica en el campo deltrasplante renal ha sido un hito importante en la últimadécada, arrojando mejoras frente a la tradicional cirugía abierta manteniendo unos resultados funcionalessatisfactorios aunque su implantación es reducida en laactualidad con limitaciones técnicas en la extensión acualquier tipo de receptor. Nuevos agentes inmunosupresores que minimicen los potenciales efectos secundarios o consigan reducir las dosis de anticalcineurínicosson también líneas importantes de investigación.Conclusiones: El futuro del trasplante renal pasapor la búsqueda de estrategias cada vez más globales para mejorar la oferta de órganos, mejoras en elacondicionamiento y preservación de los injertos o eldesarrollo a escala global de la cirugía mínimamenteinvasiva en los diferentes ámbitos del trasplante renal. Elpeso de las biotecnologías y terapias génicas suponenherramientas prometedoras en el campo de la generación de tejidos o terapias inmunosupresoras dirigidas.(AU)

Objetive: Kidney transplantation process involves a series of challenges such as the shortageof organs worldwide for a population waiting for a firstand subsequent kidney transplants and the search forthe most appropriate graft for each recipient, optimizingthe ischemia time as much as possible, minimizing theimpact of surgery and subsequent immunosuppressivetherapy.Methods: We carry out a review of the differentadvances and lines of research in the different areas involved in the kidney transplantation process from strategies focused on increasing the donor pool, enablingthe expansion of living donor programs as well as organpreservation strategies previous to transplantation surgery. The arrival of robotic surgery in the field of kidneytransplantation has been an important milestone in thelast decade, showing improvements compared to traditional open surgery, maintaining satisfactory functionalresults, although its implementation is currently reducedwith technical limitations in the extension to any type ofrecipient. New immunosuppressive agents that minimizepotential side effects or reduce anticalcineurinic drugsdoses are also important lines of research.Conclusions: The future of kidney transplantationinvolves the search for increasingly global strategies toimprove the supply of organs, improvements in the conditioning and preservation of grafts or the global development of minimally invasive surgery in the differentareas of kidney transplantation. The weight of biotechnology and gene therapies represent promising tools inthe field of tissue generation or targeted immunosuppressive therapies.(AU)

Laparoscopic radical prostatectomy with no anastomosis.

From the first radical prostatectomy (RP), this kind of surgeries have always led to the need of a vesicourethral anastomosis (VUA). We present a case of a 65 year-old patient with diagnosis of prostate cancer and candidate for laparoscopic RP. The approach was a conventional extraperitoneal access with complete urethral sparing that avoids the need of VUA. Bladder catheter was removed on the third postoperative day observing immediate urinary continence. The anatomopathological analysis revealed a pT2 adenocarcinoma with negative margins. We report for the first time, a minimally invasive technique that avoids the need of VUA with favorable functional results.

[Castration resistance mechanisms in prostate cancer.] / Mecanismos de resistencia a la castración.

The androgen-signaling axis plays a pivotal role in the pathogenesis of prostate cancer. Since the landmark discovery by Huggins and Hodges, gonadal depletion of androgens has remained a mainstay of therapy for advanced disease. However, invariably progression to castration-resistant prostate cancer (CRPC) occurs within 2-3 years of initiation of ADT. Multiple mechanisms of resistance help contribute to the progression to castration resistant disease, and the androgen receptor (AR) remains an important driver in this progression. Molecular mechanisms behind AR reactivation in CRPC include AR gene amplification and overexpression, AR mutations, expression of constitutively active AR variants, intratumoral and adrenal androgen synthesis and promiscuous AR activation by other factors. Other AR-independent resistance mechanisms, including activation of glucocorticoid receptor, impairment of DNA repair pathways, immune-mediated resistance, neuroendocrine differentiation and microRNA expression, are also discussed. Castration-resistant prostate cancer is a complicated disease, characterized by multiple resistance mechanisms to androgen deprivation treatment, and it remains an incurable disease. An understanding of the mechanisms underlying this resistance is necessary to identify future therapeutic targets as well as the identification and validation of novel predictive biomarkers of resistance; they may lead to improved therapeutics for mCRPC patients.

Mecanismos de resistencia a la castración / Castration resistance mechanisms in prostate cancer

El eje de señalización de andrógenos desempeña un papel fundamental en la patogénesis del cáncer de próstata. Desde el descubrimiento histórico de Huggins y Hodges, la depleción androgénica permanece como la piedra angular en el tratamiento de la enfermedad avanzada. Sin embargo, de forma invariable, la progresión a cáncer de próstata resistente a la castración se produce dentro de los 2-3 años posteriores al inicio de la terapia de deprivación androgénica (TDA). Múltiples mecanismos de resistencia ayudan a la progresión a la enfermedad resistente a la castración, y el receptor de andrógenos (RA) sigue siendo un impulsor importante en esta progresión. Los mecanismos moleculares que subyacen a la reactivación del RA en el cáncer de próstata resistente a la castración (CPRC) incluyen la amplificación y sobreexpresión del RA, mutaciones del RA, expresión de variantes constitutivamente activas del RA, síntesis de andrógenos intratumorales y suprarrenales y activación promiscua del RA por otros factores. También se discuten otros mecanismos de resistencia independientes del RA, que incluyen la activación del receptor de glucocorticoides, la alteración de las vías de reparación del ADN, la resistencia mediada por mecanismos inmunes, la diferenciación neuroendocrina y la expresión de microARN. El cáncer de próstata resistente a la castración es una enfermedad compleja, se caracteriza por múltiples mecanismos de resistencia al tratamiento de deprivación de andrógenos, y sigue siendo una enfermedad incurable. La comprensión de los mecanismos que subyacen a esta resistencia es necesaria para identificar objetivos terapéuticos futuros, así como la identificación y validación de nuevos biomarcadores predictivos de resistencia, lo que puede conducir a una mejora terapéutica para pacientes con CPRC

The androgen-signaling axis plays a pivotal role in the pathogenesis of prostate cancer. Since the landmark discovery by Huggins and Hodges, gonadal depletion of androgens has remained a mainstay of therapy for advanced disease. However, invariably progression to castration-resistant prostate cancer (CRPC) occurs within 2-3 years of initiation of ADT. Multiple mechanisms of resistance help contribute the progression to castration resistant disease, and the androgen receptor (AR) remains an important driver in this progression. Molecular mechanisms behind AR reactivation in CRPC include AR gene amplification and overexpression, AR mutations, expression of constitutively active AR variants, intratumoral and adrenal androgen synthesis and promiscuous AR activation by other factors. Other AR-independent resistance mechanisms, including activation of glucocorticoid receptor, impairment of DNA repair pathways, immune-mediated resistance, neuroendocrine differentiation and microRNA expression, are also discussed. Castration-resistant prostate cancer is a complicated disease, characterized by multiple resistance mechanisms to androgen deprivation treatment, and it remains an incurable disease. An understanding of the mechanisms underlying this resistance is necessary to identify future therapeutic targets as well as the identification and validation of novel predictive biomarkers of resistance; they may lead to improved therapeutics for mCRPC patients

Renal cell carcinoma with inferior vena cava involvement: Prognostic effect of tumor thrombus consistency on cancer specific survival.

BACKGROUND: Renal cell carcinoma forming a venous tumor thrombus (VTT) in the inferior vena cava (IVC) has a poor prognosis. Recent investigations have been focused on prognostic markers of survival. Thrombus consistency (TC) has been proposed to be of significant value but yet there are conflicting data. The aim of this study is to test the effect of IVC VTT consistency on cancer specific survival (CSS) in a multi-institutional cohort. METHODS: The records of 413 patients collected by the International Renal Cell Carcinoma-Venous Thrombus Consortium were retrospectively analyzed. All patients underwent radical nephrectomy and tumor thrombectomy. Kaplan-Meier estimate and Cox regression analyses investigated the impact of TC on CSS in addition to established clinicopathological predictors. RESULTS: VTT was solid in 225 patients and friable in 188 patients. Median CSS was 50 months in solid and 45 months in friable VTT. TC showed no significant association with metastatic spread, pT stage, perinephric fat invasion, and higher Fuhrman grade. Survival analysis and Cox regression rejected TC as prognostic marker for CSS. CONCLUSIONS: In the largest cohort published so far, TC seems not to be independently associated with survival in RCC patients and should therefore not be included in risk stratification models. J. Surg. Oncol. 2016;114:764-768. © 2016 Wiley Periodicals, Inc.