Prostate Cancer and the Mevalonate Pathway.

Antineoplastic therapies for prostate cancer (PCa) have traditionally centered around the androgen receptor (AR) pathway, which has demonstrated a significant role in oncogenesis. Nevertheless, it is becoming progressively apparent that therapeutic strategies must diversify their focus due to the emergence of resistance mechanisms that the tumor employs when subjected to monomolecular treatments. This review illustrates how the dysregulation of the lipid metabolic pathway constitutes a survival strategy adopted by tumors to evade eradication efforts. Integrating this aspect into oncological management could prove valuable in combating PCa.

Fístula arterioileal: experiencia en un hospital terciario y revisión de la literatura / Arterial-ileal fistula: experience from a tertiary referral center and literature review

Introducción y objetivo: la fístula entre la arteria ilíaca y el conducto ileal (Bricker) es una patología con un elevado riesgo vital. El objetivo de este artículo es dar a conocer esta entidad, describir su presentación, sus métodos diagnósticos y su tratamiento basados en los casos en un hospital terciario y en la revisión de la literatura. Material y métodos: presentamos los casos de fístulas arterioileales ocurridos en nuestro centro entre 2016 y 2020. Se realizó una exhaustiva revisión de la literatura publicada hasta la fecha mediante la búsqueda en PubMed de artículos publicados entre 1971 y 2020, incluyendo las palabras claves “arterial ileal conduit fistula” y seleccionando únicamente los artículos en español e inglés. Resultados: se identificaron 4 casos en nuestro centro. Se reconocieron en la búsqueda bibliográfica 13 artículos que describían 16 casos de fístulas arterioileales. La mayoría compartía factores comunes de riesgo y el abordaje quirúrgico fue mayoritariamente la cirugía abierta. El abordaje adecuado parece ser la combinación de cirugía abierta y endovascular, efectiva en 3 de nuestros 4 casos. Conclusión: la fístula entre la arteria ilíaca y el conducto ileal es una complicación infrecuente y grave, con una mortalidad en torno al 44 %. Resulta difícil de diagnosticar, salvo que exista alta sospecha clínica, con pocos casos descritos en la literatura. Es fundamental tener en cuenta la historia clínica previa del paciente. (AU)

Introduction and objective: the presence of a fistula between the iliac artery and the ileal conduit is a live-threatening condition that must be known and, therefore, suspected after a massive bleeding through the ileal conduit. The objective of this article is to present the arterial-ileal fistula, describe its presentation, diagnostic methods, and treatments, based on the cases presented in a tertiary referral center and literature review. Material and methods: all cases of arterial-ileal fistulas collected at our center from 2016 through 2020 are presented here. A comprehensive literature review published to date was also conducted based on a search for articles published from 1971 through 2020 on the PubMed database with the keywords “arterial ileal conduit fistula”, including studies only published in English and Spanish languages. Results: a total of 4 cases were identified in our center. A total of 13 articles describing 16 cases of arterial-ileal fistula were identified from the medical literature, most of them with some risk factors in common. The approach followed was mainly open surgery. The proper treatment seems to be a combination between open surgery and endovascular approaches, which turned out to be effective in 3 of our 4 cases. Conclusion: a fistula between the artery and the ileal conduit is a rare but serious complication, with a 44% mortality rate. It is difficult to diagnose unless there is clinical suspicion involved, with only a few cases reported in the medical literature. We should consider the patient’s pathological history to identify this entity. (AU)

Testosterone Recovery after Androgen Deprivation Therapy in Prostate Cancer: Building a Predictive Model.

PURPOSE: To analyze the variability, associated actors, and the design of nomograms for individualized testosterone recovery after cessation of androgen deprivation therapy (ADT). MATERIALS AND METHODS: A longitudinal study was carried out with 208 patients in the period 2003 to 2019. Castrated and normogonadic testosterone levels were defined as 0.5 and 3.5 ng/mL, respectively. The cumulative incidence curve described the recovery of testosterone. Univariate and multivariate analyzes were performed to predict testosterone recovery with candidate prognostic factors prostate-specific antigen at diagnosis, clinical stage, Gleason score from biopsy, age at cessation of ADT, duration of ADT, primary therapy and use of LHRH (luteinizing hormone-releasing hormone) agonists. RESULTS: The median follow-up duration in the study was 80 months (interquartile range, 49-99 mo). Twenty-five percent and 81% of patients did not recover the castrate and normogonadic levels, respectively. Duration of ADT and age at ADT cessation were significant predictors of testosterone recovery. We built two nomograms for testosterone recovery at 12, 24, 36, and 60 months. The castration recovery model had good calibration. The C-index was 0.677, with area under the receiver operating characteristic curve (AUC-ROC) of 0.736, 0.783, 0.782, and 0.780 at 12, 24, 36, and 60 months, respectively. The normogonadic recovery model overestimated the higher values of probability of recovery. The Cindex was 0.683, with AUC values of 0.812, 0.711, 0.708 and 0.693 at 12, 24, 36, and 60 months, respectively. CONCLUSIONS: Depending on the age of the patient and the length of treatment, clinicians may stop ADT and the castrated testosterone level will be maintained or, if the course of treatment has been short, we can estimate if it will return to normogonadic levels.

Teaching Urology to Undergraduates: A Prospective Survey of What General Practitioners Need to Know.

BACKGROUND: Higher education training in Medicine has considerably evolved in recent years. One of its main goals has been to ensure the training of students as future adequately qualified general practitioners (GPs). Tools need to be developed to evaluate and improve the teaching of Urology at the undergraduate level. Our objective is to identify the knowledge and skills needed in Urology for the real clinical practice of GPs. METHODS: An anonymous self-administered survey was carried out among GPs of Primary Care and Emergencies which sought to evaluate urological knowledge and necessary urological skills. The results of the survey were exported and descriptive statistics were performed using IBM SPSS Statistics version 19.0. RESULTS AND LIMITATIONS: A total of 127 answers were obtained, in which 'Urological infections', 'Renal colic', 'PSA levels and screening for prostate cancer', 'Benign prostatic hyperplasia', 'Hematuria', 'Scrotal pain', 'Prostate cancer diagnosis', 'Bladder cancer diagnosis', 'Urinary incontinence', and 'Erectile dysfunction' were rated as Very high or High formative requirements (>75%). Regarding urological skills, 'Abdominal examination', 'Interpretation of urinalysis', 'Digital rectal examination', 'Genital examination', and 'Transurethral catheterization' were assessed as needing Very high or High training in more than 80% of the surveys. The relevance of urological pathology in clinical practice was viewed as Very high or High in more than 80% of the responses. CONCLUSIONS: This study has shown helpful results to establish a differentiated prioritization of urological knowledge and skills in Primary Care and Emergencies. Efforts should be aimed at optimizing the teaching in Urology within the Degree of Medicine which consistently ensures patients' proper care by future GPs.

[Usefulness of clinical nomograms and predictive models for pca. Predictive clinical factors of tumor agressiveness]. / Utilidad de los nomogramas clínicos y modelos predictivos del cáncer de próstata. Factores clínicos de predicción de agresividad tumoral.

In this narrative review we present the natural evolution of predictive models to their presentation in the nomogram format. We show their clinical usefulness and the objective parameters that contribute to their clinical use: calibration, discrimination, decision curves and probability density functions. We continue detailing the various existing predictive models/nomograms in relation to prostate cancer aggressiveness before and after biopsy, before and after primary treatment, recurrence and castration resistance. Finally we include future markers in advanced stage of implementation in the context of nomograms and related to the aggressiveness of prostate cancer: PCA3, PHI coefficient, 4Kscore, cell cycle progression (Prolaris®) and single nucleotid polymorphisms.

Utilidad de los nomogramas clínicos y modelos predictivos del CaP. Factores clínicos de predicción de agresividad tumoral / Usefulness of clinical nomograms and predictive models for pca. predictive clinical factors of tumor agressiveness

En la presente revisión narrativa hemos presentado la evolución natural de los modelos predictivos hacia su presentación en formato de nomogramas. A continuación hemos puesto de manifiesto su utilidad clínica y los parámetros objetivos que han de contribuir a su uso clínico: calibración, discriminación, curvas de decisión y funciones de densidad de probabilidad. Seguidamente se han detallado los diferentes modelos predictivos/nomogramas existentes en relación a la agresividad pre y post-biopsia, pre y post-tratamiento primario, a la recidiva y resistencia a la castración en cáncer de próstata. Finalmente se han incluido futuros marcadores en avanzado estado de implementación clínica en el contexto de nomogramas y relacionados con la agresividd del cáncer de próstata: PCA3, coeficiente PHI, 4Kscore, cell cicle progression (Prolaris®), y polimorfismos de un solo nucleótido (SNPs)

In this narrative review we present the natural evolution of predictive models to their presentation in the nomogram format. We show their clinical usefulness and the objective parameters that contribute to their clinical use: calibration, discrimination, decision curves and probability density functions. We continue detailing the various existing predictive models/nomograms in relation to prostate cancer aggressiveness before and after biopsy, before and after primary treatment, recurrence and castration resistance. Finally we include future markers in advanced stage of implementation in the context of nomograms and related to the aggressiveness of prostate cancer: PCA3, PHI coefficient, 4Kscore, cell cycle progression (Prolaris®) and single nucleotid polymorphisms

[Management of chylous fistulas, a rare complication after urologic surgery]. / Manejo de las fístulas de quilo, una rara complicación tras cirugía urológica.

OBJECTIVE: To analyze the different treatments for postoperative chylous fistulae. METHODS: A literature review of the main treatments for postoperative chylous fistula, providing our initial experience of two cases of patients with postsurgical chylorrea, with conservative treatment. RESULTS: There is very limited experience in the treatment of chylous ascites. According to the literature reviewed, Octreotide (somatostatin analogue) can be used, to decrease fistula output. Both our cases cases were treated successfully with subcutaneous octreotide, with drain debit decrease in about 3 days. CONCLUSIONS: The use of octreotide appears to be an effective treatment in the management of chylous fistulae, and it is suggested by some authors as first-line treatment in the management of these, thus decreasing the complications that can appear due to chyle loss.

Manejo de las fístulas de quilo, una rara complicación tras cirugía urológica / Management of chylous fistulas, a rare complication after urologic surgery

OBJETIVO: Analizar los diferentes tratamientos para la fístula de quilo postoperatorias. MÉTODOS: Realizamos una revisión bibliográfica de los principales tratamientos para la fístula de quilo postoperatorias, aportando nuestra experiencia inicial de dos casos de pacientes con quilorrea postquirúrgica, con tratamiento conservador. RESULTADO: Existe muy poca experiencia del tratamiento de la ascitis quilosa, puede utilizarse, según la literatura revisada, el octreótide (análogo de la somatostatina), aportamos fueron tratados exitosamente con octreótide subcutáneo, disminuyendo el débito del drenaje en 3 días aproximadamente. CONCLUSIONES: El uso del octreótide aparece como un tratamiento efectivo en el manejo de las fístulas quilosas, y sugerido por algunos autores como tratamiento de primera línea en el manejo de estas, disminuyendo así las complicaciones que la pérdida de quilo puede conllevar

OBJECTIVE: To analyze the different treatments for postoperative chylous fistulae. METHODS: A literature review of the main treatments for postoperative chylous fistula, providing our initial experience of two cases of patients with postsurgical chylorrea, with conservative treatment. RESULTS: There is very limited experience in the treatment of chylous ascites. According to the literature reviewed, Octreotide (somatostatin analogue) can be used, to decrease fistula output. Both our cases cases were treated successfully with subcutaneous octreotide, with drain debit decrease in about 3 days. CONCLUSIONS: The use of octreotide appears to be an effective treatment in the management of chylous fistulae, and it is suggested by some authors as first-line treatment in the management of these, thus decreasing the complications that can appear due to chyle loss

Extravasación urinaria renal espontánea / Spontaneous renal urinary extravasation

La extravasación espontánea de orina, descrita por Albarrán y publicada por Sole se consideraba como un hallazgo radiológico poco frecuente y la definió en 198 como la salida de orina fuera del tracto urinario en ausencia de trauma, de intervención quirúrgica previa o reciente y tampoco sin antecedente de instrumentación urológica o de urografía excretora practicada con compresión externa. Se presenta a un paciente de 28 años, sin antecedentes de interés, que acudió con cuadro astenia de 1 mes de evolución, asociado a dolor en fosa lumbar izquierda. Que fue estudiado mediante ecografía y tomografía computarizada (TC). Las exploraciones radiológicas identificaron múltiples litiasis en uréter proximal y distal izquierdo. Voluminosa colección de baja densidad rodeando al riñón izquierdo, limitada por la fascia pararrenal sugestiva de urinoma, identificando solución de continuidad en cáliz superior, que se comunica con el urinoma. El tratamiento inicial del paciente fue la colocación de Nefrostomía percutánea de urgencia, para realizar posteriormente, ureteroscopia con ascensión de las litiasis y extracción de estas mediante pielolitotomía abierta. Conclusión: El conocimiento de la clínica y de los hallazgos radiológicos de la extravasación urinaria espontánea por litiasis ureteral en las distintas pruebas de imágenes son cruciales para el manejo de los pacientes afectados por esta infrecuente complicación...

Spontaneous extravasation of urine, described by Albarran and published by Sole was considered a rare radiological finding in 198 and defined as the flow of urine out of the urinary tract in the absence of trauma, previous surgery or recent nor no history of urological instrumentation or excretory urography performed with external compression. We report a patient of 28 years, with no history of interest came with asthenia of 1 month’s duration, associated with pain in left lumbar fossa. That was studied by ultrasound and computed tomography (CT). The radiological identified multiple stones in proximal and distal left ureter. Collection bulky low density surrounding the left kidney limited by suggesting pararenal urinoma fascia, identifying continuity solution upper calyx, which communicates with the urinoma. The patient’s initial treatment was percutaneous nephrostomy placement of urgency for later ascension of the stones with ureteroscopy and removal of these by open pyelolithotomy. The knowledge of the clinical and radiological findings of spontaneous urinary extravasation with ureteral stones in various imaging tests are crucial for the management of patients affected by this rare complication...

Valor actual de la biopsia de vesículas seminales en pacientes con cáncer de próstata e influencia de la prostatecmía radical en pacientes con infiltración seminal / Current value of seminal vesicle biopsy in patients with prostate cancer and influence of radical prostatectomy in patients with seminal vesicle invasion

OBJETIVO: Comprobar si la prostatectomíaradical puede influir favorablemente en la supervivenciacáncer-específica (SCE), tiempo libre de hormonorresistenciay tiempo libre de metástasis (TLM) y calidad de vida (CV), en pacientes con adenocarcinomade próstata e invasión de vesículas seminales, así como, realizar una actualización de nuestro pensamientosobre la biopsia de vesículas seminales.MÉTODOS: Se incluyeron 114 pacientes En 46 se diagnosticó invasión de vesículas seminales tras la realizaciónde prostatectomía radical (PRVS) de intención curativa y en 68 casos, la invasión fue diagnosticada mediante la biopsia de las mismas (BxVS) no practicándosela prostatectomía radical. Se compararon la SCE, tiempo hasta la hormonorresistencia desde el inicio del tratamiento hormonal (THR), TLM y CV medida en necesidadesde atención hospitalaria en ambos grupos. La mediana del tiempo de seguimiento fue de 52,6 meses.RESULTADOS: No hubo diferencias estadísticamente signi- ficativas entre ambos grupos en SCE, THR, TLM y CV. La SCE a 3 y 5 años fue del 100% y 80.77% para el grupo PRVS y del 92.03% y 77,46% para el grupo BxVS. El THR a 3 y 5 años fue del 90.6% y 58.7% para el grupo PRVS y del 74,4% y 56,2% para el grupo BxVS. En la regresión de Cox se mostraron predictores independientes de SCE el grado primario y suma de Gleason y de THR el estadio clínico.CONCLUSIONES: La prostatectomía radical como monoterapiano influye de forma estadísticamente significativaen el tiempo de seguimiento realizado, en la SCE, THR, TLM y CV de los pacientes con cáncer de próstata e invasión de vesículas seminales asociada a otros factoresde mal pronóstico (Gleason y PSA desfavorables). El valor de la biopsia de vesículas seminales permaneceen el estudio de nuevos tratamientos multimodales, como pueden ser la quimioterapia en combinación con la cirugía, y esta pendiente de definir en la planificaciónde la radioterapia y la criocirugía

OBJECTIVES: To evaluate if radicalprostatectomy may positively influence cancer-specific survival (CSS), hormone-resistance-free time, metastasis-free time, and quality of life(QoL) of patients with prostate adenocarcinoma and seminal vesicle invasion, and also to update our thoughts about seminal vesicle biopsy.METHODS: 114 patients were included. Forty-six cases were diagnosed of seminal vesicle invasion after radical prostatectomy; 68 cases were diagnosed of seminal vesicle invasion after biopsy, not undergoing then surgery. Cancer specific survival, time to hormone resistance from the start of hormonal treatment, metastasis free time and QoL, measured as need for hospital care, were compared between groups. Median follow-up time was 52.6 mos.RESULTS: There were not statistically significant differences between groups in CSS, time to hormone resistance, metastasis free time and QoL. Three and five-year cancer specific survival were 100% and 80.77% for the radical prostatectomy group and 74.4% and 56.2% for the biopsy group. Primary grade and Gleason Score were independent predictors for CSS in the Cox regression test; clinical stage was independent predictor for time to hormone resistance.CONCLUSIONS: Radical prostatectomy as monotherapy does not show a statistically significant influence onfollow-up time, CSS, time to hormone resistance, metastasis free time or QoL in patients with prostate cancer and seminal vesicle invasion associated with other bad prognostic factors (unfavourable Gleason and PSA). The value of seminal vesicle biopsy remains for the study of new multimodal treatments, such as chemotherapy + surgery, and it is to be defined in the planning of radio and cryosurgery

Vigencia actual de los nomogramas en la estadificación del cáncer de próstata / Current validity of nomograms for prostate cancer staging

OBJETIVO: En este trabajo se presenta una revisión del concepto de “nomograma” aplicado al cáncer de próstata y específicamente como medio de estadificación.MÉTODOS/RESULTADOS: Para ello se describen los parámetros indispensables para evaluar este tipo de modelos predictivos, a saber: Calibración, Discriminacióny Utilidad Clínica. Estos requisitos son analizados sobre un caso práctico real en nuestro medio asistencial comparando las “Tablas de Partin” y el “Nomograma del Hospital Universitario Miguel Servet”, demostrando su correcta calibración, discriminación y utilidad clínica previa selección de adecuados puntos de corte.CONCLUSIÓN: La aplicación del modelo predictivo a nuestra práctica asistencial ha logrado una infraestadificaciónclínica tras prostatectomía radical del 17,3%

OBJETIVE: This paper presents a review of the concept of “nomogram” applied to prostate cancer, and specifically as a staging tool.METHODS/RESULTS: We describe the essentialparameters for the evaluation of such type of predictive models: Calibration, discrimination and clinical usefulness. Such requisites are analyzed using a real clinical case in our clinical setting, comparing the “Partin`s tables” and the “Miguel Servet University Hospital´s nomogram”. We demonstrate its correct calibration, discrimination and clinical usefulness after previous selection of proper cut points.CONCLUSION: The application of the predictivemodel to our clinical practice has achieved a clinical understaging of 17.3% after radical prostatectomy

Controversies related to epithelioid variant of renal angiomyolipoma: a review of the literature.

We performed a review of the epithelioid-type angiomas to determine their clinical course and propose an appropriate plan for follow-up. We present the case of a patient with possible adrenal carcinoma suggested by computed tomography for whom the histopathologic study revealed an epithelioid angiomyolipoma arising from the kidney. In the absence of consensus, we consider it worthwhile to register the very few cases diagnosed and record a detailed follow-up of the clinical course. We recommend surgical treatment and a follow-up regimen similar to that for renal carcinoma.