[Aggressive variants of castration resistant prostate cancer (CRPC): neuroendocrine prostate cancer.] / Variantes agresivas de cáncer de próstata resistente a la castracion (CPRC): cáncer de próstata neuroendocrino.

Castration resistant prostate cancer (CRPC) is characterized by an important molecular, pathological and clinical heterogeneity. Although most of them present androgen receptor (AR) signal dependence, there are independent phenotypes. Neuroendocrine prostate cancer (NEPC) is a rare histologic subtype with adverse prognosis due to late diagnosis, heterogeneous clinical features and lack of effective systemic treatments. Platinum based chemotherapy is the standard treatment, presenting short limited responses. There are pure forms or mixed with adenocarcinoma component. De novo diagnosis is unusual, being more frequent in advanced stages of prostate cancer, as a consequence of the inhibition of androgen receptor performed by various treatments. Thus, it could represent an aggressive evolution from carcinoma through a NEEpithelial transdifferentiation. Development of preclinical studies has permitted characterization of molecular and genomic alterations associated with this evolution and they may help to develop new therapeutic targets. Over the last years, there have been important advances in identification and characterization of clinical and pathological CRPC variants. NEPC is one of the most aggressive subtypes. A better knowledge of the disease biology is necessary to develop new treatments and biomarkers that help to manage this aggressive variant of PC.

Variantes agresivas de cáncer de próstata resistente a la castración (cprc): cáncer de próstata neuroendocrino / Recommendations for follow up in castration resistant prostate cancer

El cáncer de próstata resistente a la castración (CPRC) se caracteriza por una importante heterogeneidad molecular, patológica y clínica. Aunque la mayoría presentan dependencia a la señal del receptor androgénico (RA), existen fenotipos independientes a ésta. El cáncer de próstata neuroendocrino (CPNE) es un subtipo histológico poco frecuente y de pronóstico adverso debido al diagnóstico tardío, características clínicas heterogéneas y a la falta de tratamientos sistémicos efectivos. El tratamiento estándar es la quimioterapia (QT) basada en platino, presentando respuestas de escasa duración. Existen formas puras o mixtas con un componente de adenocarcinoma. Es raro su diagnóstico de novo, siendo más frecuente su aparición en estados avanzados del cáncer de próstata (CP), como consecuencia de la inhibición del receptor androgénico (RA) realizada por diversos tratamientos. Así, podría representar una evolución agresiva desde un adenocarcinoma (CPAD) a través de un mecanismo de transdiferenciación epitelio-NE. El desarrollo de estudios preclínicos han permitido la determinación de alteraciones moleculares y genómicas asociadas a esta evolución y que pueden ayudar al desarrollo de nuevas dianas terapéuticas. En los últimos años se han producido importantes avances en la identificación y caracterización de variantes clínicas y patológicas del CPRC. El CPNE es uno de los subtipos más agresivos. Un mayor conocimiento de la biología de la enfermedad es necesario para desarrollar nuevos tratamientos y biomarcadores que ayuden al manejo de esta variante agresiva del CP

Castration resistant prostate cancer (CRPC) is characterized by an important molecular, pathological and clinical heterogeneity. Although most of them present androgen receptor (AR) signal dependence, there are independent phenotypes. Neuroendocrine prostate cancer (NEPC) is a rare histologic subtype with adverse prognosis due to late diagnosis, heterogeneous clinical features and lack of effective systemic treatments. Platinum based chemotherapy is the standard treatment, presenting short limited responses. There are pure forms or mixed with adenocarcinoma component. De novo diagnosis is unusual, being more frequent in advanced stages of prostate cancer, as a consequence of the inhibition of androgen receptor performed by various treatments. Thus, it could represent an aggressive evolution from carcinoma through a NEEpithelial transdifferentiation. Development of preclinical studies has permitted characterization of molecular and genomic alterations associated with this evolution and they may help to develop new therapeutic targets. Over the last years, there have been important advances in identification and characterization of clinical and pathological CRPC variants. NEPC is one of the most aggressive subtypes. A better knowledge of the disease biology is necessary to develop new treatments and biomarkers that help to manage this aggressive variant of PC

The management of active surveillance in prostate cancer: validation of the Canary Prostate Active Surveillance Study risk calculator with the Spanish Urological Association Registry.

The follow up of patients on active surveillance requires to repeat prostate biopsies. Predictive models that identify patients at low risk of progression or reclassification are essential to reduce the number of unnecessary biopsies. The aim of this study is to validate the Prostate Active Surveillance Study risk calculator (PASS-RC) in the multicentric Spanish Urological Association Registry of patients on active surveillance (AS), from common clinical practice. RESULTS: We find significant differences in age, PSA and clinical stage between our validation cohort and the PASS-RC generation cohort (p < .0001), with a reclassification rate of 10-22% on the follow-up Bx, no cancer was found in 43% of the first follow-up Bx. The calibration curve shows underestimation of real appearance of reclassification. The AUC is 0.65 (C.I.95%: 0.60-0.71). PDF and CUC do not suggest a specific cut-off point of clinical use. METHODS: We select 498 patients on AS with a minimum of one follow-up biopsy (Bx) from the 1,024 males registered by 36 Spanish centers recruiting patients on the Spanish Urological Association Registry on AS. PASS-RC external validation is carried by means of calibration curve and area under de ROC-curve (AUC), identifying cut-offs of clinical utility by probability density functions (PDF) and clinical utility curves (CUC). CONCLUSIONS: In our first external validation of the PASS-RC we have obtained a moderate discrimination ability, although we cannot recommend cut-off points of clinical use. We suggest the exploration of new biomarkers and/or morpho-functional parameters from multiparametric magnetic resonance image, to improve those necessary tools on AS.

[Renal angiomyolipoma causing inferior vena cava thrombus and secondary Budd-Chiari's syndrome]. / Angiomiolipoma renal causante de trombo en cava y síndrome de Budd-Chiari secundario.

OBJECTIVE: We report one case of renal angiomyolipoma with three characteristics: renal sinus origin, inferior vena cava tumor thrombus reaching the right atrium and Budd-Chiari syndrome. METHODS: The characteristics of the case are presented and discussed. RESULTS/CONCLUSIONS: Renal angiomyolipoma is a benign mesenchymal tumor. It is an uncommon tumor (2-6.4% of all kidney tumors), with a female predominance. Angiomyolipoma most often originate from the renal parenchyma but they can rarely originate from the renal sinus. They can involve the renal vein, the inferior vena cava and even the right atrium as a tumor thrombus. Angiomyolipoma commonly present as an incidental finding on radiographic studies, but the clinical presentation varies from flank pain to fatal pulmonary tumor embolism. The Budd-Chiari syndrome is an extremely rare presentation. Because of the risk of potentially fatal cardiopulmonary embolism and death, surgical treatment (radical nephrectomy plus tumor thrombectomy) of these lesions is indicated even when they are asymptomatic.

[Immunosuppression and surgical complications after renal transplantation]. / Inmunosupresión y complicaciones quirúrgicas post-trasplante renal.

OBJECTIVES: The new immunosuppressive regimens in kidney transplantation have diminished the rate of acute rejection and improved graft survival. However, the use of new agents results in the development of surgical complications. The authors analyze the incidence of such complications accordingly to the type of drug. METHODS: This study included 350 kidney transplantations performed between January 1997 and December 2004. The average age was 54 years. The incidence of diabetes mellitus was 8.5% and the rate of obese recipients (BMI >30 kg/m2) was 15.4%. The average follow-up rate was 44 +/- 5.6 months (5-96). A surgical complication was defined as any complication directly related to the surgical transplant that occurs along the first year after transplantation. RESULTS: The incidence of surgical complications was 34.8% (122/350). The rates of perigraft collections and bleeding posttransplant were significantly higher in the CsA group than in the Tacro one: 12% vs. 3.8% (p = 0.005) and 11.5% vs. 3% (p = 0.002). The Sirolimus and Everolimus-based immunosuppresive regimens led to a higher incidence of lymphocele (16% vs. 3.7%) (p = 0.012). There were no significant difference in the incidence of surgical complications in recipients immunosuppressed with and without MMF, and in diabetic vs. no diabetic patients. Surgical complications were higher in obese patients (66.5% vs. 33.5%) (p = 0.002). CONCLUSIONS: Recipients receiving Sirolimus/Everolimus demonstrated a significantly higher lymphocele rate. The CsA regimens were associated with bleeding and post transplant pararenal fluid collections. The introduction of MMF did not result in a significant increase in posttransplant surgical complications. The obesity was a risk factor associated with those complications.

Inmunosupresión y complicaciones quirúrgicas post-trasplante renal / Immunosuppression and surgical complications after renal transplantation

OBJETIVO: Los nuevos inmunosupresores disminuyen las tasas de rechazo agudo en el transplante renal y mejoran la supervivencia del injerto, aunque modifican la incidencia y tipo de complicaciones quirúrgicas. En este estudio se analiza la incidencia de complicaciones quirúrgicas postransplante renal según el tipo de inmunosupresión recibida. MÉTODOS: Desde enero de 1997 a diciembre de 2004 se han realizado 350 transplantes renales, con edad media de los pacientes de 54.6+/- 6.2 años y tiempo medio de seguimiento de 44+/-5.6 meses. Son diabéticos 30 pacientes (8.5%) y obesos 54 (15.4%) con Índice de Masa Corporal (IMC) media de 32.2+/- 6.5 kg/m2. Definimos complicación quirúrgica a cualquier complicación directamente relacionada con el acto quirúrgico durante el primer año tras la intervención. RESULTADOS: Se objetivan un 34.8% de complicaciones generales (122/350). Las complicaciones más frecuentes son las fístulas (7%), estenosis (6.5%), colección (6%), hemorragia (5.7%), complicaciones vasculares (5.1%) y de herida quirúrgica (4.6%). La incidencia de complicaciones quirúrgicas fue semejante para las pautas con y sin MMF. Los tratados con CsA presentan 45.4% de complicaciones frente a los tratados con Tacro que tienen un 30%, con significación estadística para hematoma (3.6% vs. 0.4%, p<0.05), linfocele (8.2% vs. 2.1%, p<0.05), y hemorragia (11.8% vs. 2.9%, p<0.05). La tasa de complicaciones en los tratados con inhibidores mTOR en comparación con los no tratados es del 44% vs. 34.1%, con significación estadística para linfocele (16% vs. 5.2%, p<0.05). El 66.5% de los pacientes obesos presentan complicaciones (p<0.05). CONCLUSIONES: El uso de CsA se asocia a mayor tasa de colecciones (hematoma/linfocele) y hemorragia; los inhibidores de mTOR aumentan el riesgo de linfoceles postransplante; el MMF no aumenta de forma significativa el porcentaje de complicaciones quirúrgicas. La obesidad es un factor de riesgo para las complicaciones quirúrgicas en los pacientes transplantados

OBJECTIVES: The new immunosuppressive regimens in kidney transplantation have diminished the rate of acute rejection and improved graft survival. However, the use of new agents results in the development of surgical complications. The authors analyze the incidence of such complications accordingly to the type of drug. METHODS: This study included 350 kidney transplantations performed between January 1997 and December 2004. The average age was 54 years. The incidence of diabetes mellitus was 8.5% and the rate of obese recipients (BMI> 30 kg/m2) was 15.4%. The average follow-up rate was 44+/- 5.6 months (5-96). A surgical complication was defined as any complication directly related to the surgical transplant that occurs along the first year after transplantation. RESULTS: The incidence of surgical complications was 34.8% (122/350). The rates of perigraft collections and bleeding posttransplant were significantly higher in the CsA group than in the Tacro one: 12% vs. 3.8% (p=0.005) and 11.5% vs. 3% (p=0.002). The Sirolimus and Everolimus-based immunosuppresive regimens led to a higher incidence of lymphocele (16% vs. 3.7%) (p= 0.012). There were no significant difference in the incidence of surgical complications in recipients immunosuppressed with and without MMF, and in diabetic vs. no diabetic patients. Surgical complications were higher in obese patients (66.5% vs. 33.5%) (p= 0.002). CONCLUSIONS: Recipients receiving Sirolimus/Everolimus demonstrated a significantly higher lymphocele rate. The CsA regimens were associated with bleeding and post transplant pararenal fluid collections. The introduction of MMF did not result in a significant increase in posttransplant surgical complications. The obesity was a risk factor associated with those complications

[Ultrasound for the diagnosis of female urinary incontinence]. / Ecografía en el diagnóstico de la incontinencia urinaria femenina.

OBJECTIVES: The value of ultrasonography for the study of female urinary incontinence has been redefined over the last years. METHODS: We review the literature about the value of ultrasound in the workup of females with urinary incontinence, mainly transperineal ultrasound for the female stress urinary incontinence (SUI). RESULTS: Many papers have been published over the last few years. Upper urinary tract ultrasound has not a place in the workup of genuine female SUI. Transperineal ultrasound allows to evaluate the mobility of the bladder neck and urethra, the thickness of the bladder wall, the funnel shape of the bladder neck, the presence of SUI or pelvic organ prolapse (POP), to visualize mesh implants, to help with biofeedback, and to evaluate changes after surgical treatment. CONCLUSIONS: Ultrasounds in general, and transperineal or translabial ultrasound in particular, are in the process of becoming the standard diagnostic method in urogynecology. Their wide availability, the standardization of parameters, the possibility of evaluating not only the bladder but also the levator ani muscle or pelvic organ prolapses (POP) contribute to this fact. It allows to obtain data in a non invasive way before and after therapy.

Ecografía en el diagnóstico de la incontiencia urinaria femenina / Ultrasound for the diagnosis of female urinary incontinence

OBJETIVO: El valor de la Ecografía en el estudio de la Incontinencia Urinaria Femenina (IUF) ha sido redefinido en los últimos años MÉTODOS: Se revisa la literatura sobre el valor de la Ecografía en el estudio de las mujeres con Incontinencia urinaria, fundamentalmente en la ecografía transperineal en la Incontinencia Urinaria de esfuerzo femenina RESULTADOS: En los últimos años son numerosos los trabajos publicados. La ecografía del TUS tiene poco lugar en la evaluación de la IUF de esfuerzo pura. La ecografía transperineal permite evaluar movilidad del cuello vesical y uretra, grosor de la pared vesical, embudización del cuello, presencia de IUF de esfuerzo, presencia de prolapso de órganos pelvianos (POP), visualización de mallas, ayudar al biofeedback y valorar cambios tras tratamiento quirúrgico. CONCLUSIONES: Los ultrasonidos y en particular la ECO transperineal o translabial está en proceso de convertirse un método diagnóstico estándar en uroginecología. A ello contribuye su amplia disponibilidad, estandarización de los parámetros y la posibilidad de evaluar no sólo la vejiga, sino también el elevador del ano o los Prolapsos de órganos pelvianos (POP). Permite obtener, de forma no invasiva datos pre y postratamiento

OBJECTIVES: The value of ultrasonography for the study of female urinary incontinence has been redefined over the last years. METHODS: We review the literature about the value of ultrasound in the workup of females with urinary incontinence, mainly transperineal ultrasound for the female stress urinary incontinence (SUI). RESULTS: Many papers have been published over the last few years. Upper urinary tract ultrasound has not a place in the workup of genuine female SUI. Transperineal ultrasound allows to evaluate the mobility of the bladder neck and urethra, the thickness of the bladder wall, the funnel shape of the bladder neck, the presence of SUI or pelvic organ prolapse (POP), to visualize mesh implants, to help with biofeedback, and to evaluate changes after surgical treatment. CONCLUSIONS: Ultrasounds in general, and transperineal or translabial ultrasound in particular, are in the process of becoming the standard diagnostic method in urogynecology. Their wide availability, the standardization of parameters, the possibility of evaluating not only the bladder but also the levator ani muscle or pelvic organ prolapses (POP) contribute to this fact. It allows to obtain data in a non invasive way before and after therapy

[Treatment of upper urinary tract tumors. Report of our experience]. / Tratamiento de los tumores del tracto urinario superior. Aportación de nuestra experiencia.

OBJECTIVES: The objective of this article is to perform a comprehensive exposition of the various non-endourological treatment options for upper urinary tract tumors in order to set the bases to choose the most adequate surgical indication depending on tumors' and patients' characteristics; we consider the various surgical approaches, and the historic evolution from the classic indication established by Albarran (radical nephroureterectomy with bladder cuff) to the current ones more conservative. We also consider the role of radiotherapy and chemotherapy in the treatment of these tumors. METHODS/RESULTS: We refer to the conclusions of various authors and their large series published in the literature, series considered classic already, and provide support adding our experience by reviewing 223 patients treated from 1977 to 2003 with a mean follow-up of 45 months (maximum 238 months). CONCLUSIONS: We can state that it is acceptable to indicate less aggressive ways of treatment (nephroureterectomy without bladder cuff, distal or partial ureterectomy, and conservative operations) if the oncological radicality requirements are met, remembering that site, tumor grade and stage are determinant in the outcome.