Darolutamide in Spanish patients with nonmetastatic castration-resistant prostate cancer: ARAMIS subgroup analysis.

Aim: Darolutamide significantly prolonged metastasis-free survival (MFS) versus placebo in the Phase III ARAMIS study. We analyzed outcomes in Spanish participants in ARAMIS. Patients & methods: Patients with high-risk nonmetastatic castration-resistant prostate cancer were randomized 2:1 to darolutamide 600 mg twice daily or placebo, plus androgen-deprivation therapy. The primary end point was MFS. Descriptive statistics are reported for this post hoc analysis. Results: In Spanish participants, darolutamide (n = 75) prolonged MFS versus placebo (n = 42): hazard ratio 0.345, 95% confidence interval 0.175-0.681. The incidence and type of treatment-emergent adverse events were comparable between treatment arms. Conclusion: For Spanish participants in ARAMIS, efficacy outcomes favored darolutamide versus placebo, with a similar safety profile, consistent with the overall ARAMIS population. Clinical Trials Registration: NCT02200614 (ClinicalTrials.gov).

Darolutamide is an oral treatment for a type of prostate cancer that has stopped responding to other treatments and is at risk of spreading to other parts of the body (termed "nonmetastatic castration-resistant prostate cancer" or "nmCRPC"). In the international ARAMIS study, patients treated with darolutamide lived longer without their cancer spreading than patients who were given placebo (sugar) pills. We wanted to know whether Spanish patients in ARAMIS had similar characteristics and treatment outcomes to other patients in the study. We found that the 75 Spanish patients who were treated with darolutamide had a significantly lower risk of their cancer spreading than the 42 Spanish patients who received placebo. The two groups of Spanish patients had similar side effects.

Nighttime Kidney Transplant From Donor With Controlled Cardiac Death: Greater Functionality at the Cost of More Complications?

BACKGROUND: Kidney transplantation surgery from controlled cardiac death donor (Maastricht III) is frequently performed at night, without taking into account the accumulated fatigue that the surgical team may experience. The objective of the study is to assess whether surgical complications and the functionality of the graft in the short and long term are affected by the time of day in which kidney transplantation from controlled cardiac death donors is performed. METHODS: A retrospective observational study was carried out. Patient were classified according to the start of surgery, daytime hours (8:00 AM to 7:59 PM), and nighttime hours (8:00 PM to 7:59 AM). Baseline and intraoperative parameters, postoperative complications, and parameters related to graft functionality were analyzed. RESULTS: A total of 77 patients were included: 37 patients had kidney transplantations performed during the daytime (48.05%), and 40 patients had kidney transplantations performed at nighttime (51.95%). No statistically significant differences were found between the baseline characteristics of both groups except for sex (55.0% men in daytime vs 78.4% men in nighttime, P = .03) and time on pretransplant dialysis (33.1 months in daytime vs 13.8 months in nighttime, P = .008). The incidence of surgical complications and the functionality of the graft was similar in both groups; however, the surgical time was shorter in night transplants (163.2 minutes in daytime vs 136.5 minutes at nighttime, P = .0006) CONCLUSION: The performance of kidney transplants at night is not associated, either in the short or long term, with an increase in surgical complications or conditions leading to the deterioration in the functionality of the graft.

Prospective study of diagnostic accuracy in the detection of high-grade prostate cancer in biopsy-naïve patients with clinical suspicion of prostate cancer who underwent the Select MDx test.

OBJECTIVES: This study aimed to externally validate the diagnostic accuracy of the Select MDx test for Significant prostate cancer (Sig PCa) (ISUP > 1), in a contemporaneous, prospective, multicenter cohort with a prostate-specific antigen (PSA) between 3 and 10 ng/ml and a non-suspicious digital rectal examination. METHODS AND PARTICIPANTS: For all enrolled patients, the Select Mdx test, the risk calculator ERSPC3 + DRE, and a prostatic magnetic resonance imaging (MRI) were carried out. Subsequently, a systematic 12-core trans-rectal biopsy and a targeted biopsy, in the case of a prostate imaging-reporting and data system (PIRADS) > 2 lesion (max three lesions), were performed. To assess the accuracy of the Select MDx test in the detection of clinically Sig PCa, the test sensitivity was evaluated. Secondary objectives were specificity, negative predictive value (NPV), positive predictive value (PPV), and area under the curve (AUC). A direct comparison with the ERSPC + DRE risk calculator and MRI were also performed. We also studied the predictive ability to diagnose Sig PCa from the combination of the Select MDx test with MRI using clinical decision-curve analysis. RESULTS: There were 163 patients enrolled after meeting the inclusion criteria and study protocol. The Select MDx test showed a sensitivity of 76.9% (95% CI, 63.2-87.5), 49.6% specificity (95% CI, 39.9-59.2), 82.09% (95% CI, 70.8-90.4) NPV, and 41.67% (95% CI, 31.7-52.2) PPV for the diagnosis of Sig PCa. COR analysis was also performed, which showed an AUC of 0.63 (95% CI, 0.56-0.71). There were no differences in the accuracy of Select MDx, ERSPC + DRE, or MRI. The combination of Select MDX + MRI showed the highest impact in the decision-curve analysis, with an NPV of 93%. CONCLUSION: Our study showed a worse performance for the SelectMdx test than previously reported, within a cohort of patients with a PSA 3-10 ng/ml and a normal DRE, with results similar to those from ERSPC + DRE RC and MRI, but with an improvement in the usual PSA pathway. A combination of the Select Mdx test and MRI could improve accuracy, but studies specifically evaluating this scenario with a cost-effective analysis are needed.

Impact of COVID-19 in spanish urology residents: Recommendations and perspective. / El impacto del COVID-19 en la residencia en urología en España: perspectivas y recomendaciones.

The COVID-19 pandemic has seriously disrupted the day-to-day running of hospitals, affecting the activity of all medical and surgical departments. It has also affected urology residents, depriving them of training at their usual workplaces and forcing them to support COVID units. This has implied not only the loss of daily activities, but also the uncertainty of job opportunities for the final year residents. In addition, the cancellation of numerous events such as congresses, exams,or courses has affected the annual planning of the specialty. A review of the current literature on the impact of the COVID-19 pandemic, as well as the de-escalation process, on resident training has been carried out using web search and PubMed. The situation of the residents has been analyzed, both through the information generated by recent literature and by the personal experience of the authors, from different areas: evaluation systems, educational and surgical aspects, as well as healthcare work. As a result of this review, the negative impact of the crisison urology resident training can be observed, especially in the surgical field, but new learning opportunities or new forms of communication with the patient can also be observed. These educational and healthcare resources invite the urology resident in particular, and the medical society in general, to reinvent themselves. The aim of this article is to analyse the training of the urology resident in the de-escalation phase. Similarly, the emerging educational resources during the pandemic are synthesized, inviting the reader, and especially the urology resident, to continue their training and learningin these times of uncertainty.

La pandemia por COVID-19 ha irrumpido gravemente en el día a día de los hospitales, afectando a la actividad de todos los servicios médicos y quirúrgicos. Del mismo modo ha afectado a los residentes de urología, privándoles a los mismos de seguir la formación en sus puestos de trabajo habituales y viéndose obligados a dar apoyo a las unidades COVID. Esto ha implicado, no solamente la pérdida de las actividades diarias, si no también la incertidumbre en oportunidades laborales de los residentes de último año. Además, la cancelación de numerosos eventos como congresos, exámenes o cursos, ha afectado a la planificación anual de la especialidad. Se ha realizado una revisión de la literatura actual sobre el impacto de la pandemia por COVID-19, así como el proceso de desescalada, en la formación de los residentes mediante búsqueda web y en PubMed. Se ha analizado la situación de los residentes, tanto através de la información generada por la reciente literatura, como por la experiencia personal de los autores, desde distintos ámbitos: sistemas de evaluación, aspectos docentes y quirúrgicos, así como labor asistencial. Como resultado de esta revisión, se observa el impacto negativo de la crisis en la formación del residente en urología, especialmente, en el ámbito quirúrgico, pero también se observan nuevas oportunidades de aprendizaje o formas de comunicación con el paciente. Estos recursos educativos y asistenciales invitan al residente de urología en concreto, y a la sociedad médica en general, a reinventarse. El objetivo del presente artículo es analizar la formación del residente en urología en la fase de desescalada. Del mismo modo, se sintetizan los recursos educativos emergentes durante la pandemia, invitando al lector y, de manera especial al residente de urología, a continuar su formación y aprendizaje ante estos tiempos de incertidumbre.

El impacto del COVID-19 en la residencia en urología en España: perspectivas y recomendaciones / No disponible

La pandemia por COVID-19 ha irrumpido gravemente en el día a día de los hospitales, afectando a la actividad de todos los servicios médicos y quirúrgicos. Del mismo modo ha afectado a los residentes de urología, privándoles a los mismos de seguir la formación en sus puestos de trabajo habituales y viéndose obligados a dar apoyo a las unidades COVID. Esto ha implicado, no solamente la pérdida de las actividades diarias, si no también la incertidumbre en oportunidades laborales de los residentes de último año. Además, la cancelación de numerosos eventos como congresos, exámenes o cursos, ha afectado a la planificación anual de la especialidad. Se ha realizado una revisión de la literatura actual sobre el impacto de la pandemia por COVID-19, así como el proceso de desescalada, en la formación de los residentes mediante búsqueda web y en PubMed. Se ha analizado la situación de los residentes, tanto a través de la información generada por la reciente literatura, como por la experiencia personal de los autores, desde distintos ámbitos: sistemas de evaluación, aspectos docentes y quirúrgicos, así como labor asistencial. Como resultado de esta revisión, se observa el impacto negativo de la crisis en la formación del residente en urología, especialmente, en el ámbito quirúrgico, pero también se observan nuevas oportunidades de aprendizaje o formas de comunicación con el paciente. Estos recursos educativos y asistenciales invitan al residente de urología en concreto, y a la sociedad médica en general, a reinventarse. El objetivo del presente artículo es analizar la formación del residente en urología en la fase de desescalada. Del mismo modo, se sintetizan los recursos educativos emergentes durante la pandemia, invitando al lector y, de manera especial al residente de urología, a continuar su formación y aprendizaje ante estos tiempos de incertidumbre

The COVID-19 pandemic has seriously disrupted the day-to-day running of hospitals, affecting the activity of all medical and surgical departments. It has also affected urology residents, depriving them of training at their usual workplaces and forcing them to support COVID units. This has implied not only the loss of daily activities, but also the uncertainty of job opportunities for the final year residents. In addition, the cancellation of numerous events such as congresses, exams, or courses has affected the annual planning of the specialty. A review of the current literature on the impact of the COVID-19 pandemic, as well as the de-escalation process, on resident training has been carried out using web search and PubMed. The situation of the residents has been analyzed, both through the information generated by recent literature and by the personal experience of the authors, from different areas: evaluation systems, educational and surgical aspects, as well as healthcare work. As a result of this review, the negative impact of the crisis on urology resident training can be observed, especially in the surgical field, but new learning opportunities or new forms of communication with the patient can also be observed. These educational and healthcare resources invite the urology resident in particular, and the medical society in general, to reinvent themselves. The aim of this article is to analyse the training of the urology resident in the de-escalation phase. Similarly, the emerging educational resources during the pandemic are synthesized, inviting the reader, and especially the urology resident, to continue their training and learning in these times of uncertainty

Functional results in the treatment of localized prostate cancer. An updated literature review / Resultados funcionales del tratamiento del cáncer de próstata localizado. Revisión actualizada de la bibliografía

Prostate cancer is the second most frequently diagnosed cancer in men. The initial diagnosis is made in increasingly younger patients, so it seems to be essential to guarantee optimal functional results. We carried out a systematic search to define the functional results of each of the therapeutic options for localized prostate cancer. Radical prostatectomy generates a greater negative effect on urinary continence and erectile function compared to active surveillance and radiotherapy. Robotic surgery seems to offer better functional results, especially at the level of erectile function. Urinary and bowel symptoms are more pronounced after radiotherapy compared to other options. Patients must be warned of the possible functional results prior to choice of treatment

El cáncer de próstata es el segundo cáncer que se diagnostica con mayor frecuencia en varones. El diagnóstico inicial se establece en pacientes cada vez más jóvenes, por lo que parece que es fundamental para garantizar resultados funcionales óptimos. Se realizó una búsqueda sistemática para definir los resultados funcionales de cada una de las opciones terapéuticas para el cáncer de próstata localizado. La prostatectomía radical genera mayor efecto negativo sobre la continencia urinaria y la función eréctil en comparación con la vigilancia activa y la radioterapia. Parece que la cirugía robótica ofrece mejores resultados funcionales, sobre todo respecto a la función eréctil. Los síntomas urinarios e intestinales son más pronunciados después de la radioterapia en comparación con otras opciones. Se debe advertir a los pacientes de los posibles resultados funcionales antes de elegir el tratamiento

Functional results in the treatment of localized prostate cancer. An updated literature review.

Prostate cancer is the second most frequently diagnosed cancer in men. The initial diagnosis is made in increasingly younger patients, so it seems to be essential to guarantee optimal functional results. We carried out a systematic search to define the functional results of each of the therapeutic options for localized prostate cancer. Radical prostatectomy generates a greater negative effect on urinary continence and erectile function compared to active surveillance and radiotherapy. Robotic surgery seems to offer better functional results, especially at the level of erectile function. Urinary and bowel symptoms are more pronounced after radiotherapy compared to other options. Patients must be warned of the possible functional results prior to choice of treatment.

[Sequencing and combination of agents in castration resistant prostate cancer.] / Secuenciación y combinación de agentes en cáncer de próstata resistente a la castración.

Prostate Cancer is the second most frequent malignant neoplasm in males in the world. At the end of the disease, when the tumor becomes resistant to castration, we have a wide range of treatment possibilities aimed at the Androgenic Receptor, androgens synthesis, the skeleton, chemotherapy, and even new molecular targets that are still under investigation. Today, the best sequence of treatment for each patient has not been established yet. OBJECTIVE: The objective of this work is to review the current scene of treatment in castrate resistant prostate cancer, as well as the latest developments and strategies to choose the best sequence in each patient. MATERIAL AND METHODS: A literature review was performed through Medline Database (Pubmed) using as key words: "Castrate Resistant Prostate Cancer", "Sequencing", "Biomarkers", "Systemic Therapy". We also reviewed ASCO GU 2017 abstracts. RESULTS: Since Docetaxel was approved in 2004, which increased overall survival by about 2 months in patients with Metastatic Castration Resistant Prostate Cancer, in recent years a large number of therapies have been approved, demonstrating an increase in overall survival after several phase III clinical trials: Cabacitaxel, Abiraterone, Enzalutamide, Sipuleucel-T, Denosumab, Radium 223. And more recently, some investigations about new targeted therapies directed to the androgen receptor, with greater affinity than enzalutamide, or more accurate inhibitors of CYP 17 enzyme than abiraterone, as well as, agents as monoclonal antibodies (anti PD1), vaccines, poly adenosine diphosphate- ribose polymerase inhibitors, are coming to the light. In the future, these outcomes could tune up the treatment sequencing, through the study of predictive biomarkers that will indicate the right target of each therapy. CONCLUSIONS: In the near future, outcomes of different clinical trials that are studying new molecules, will allow us to apply the sequencing of different therapies based on biomarkers present in blood (circulating tumor cells) or in specimen biopsies, achieving an increase in overall survival and improving quality of life of patients in the advanced stage of the disease, however the best choice of sequence is unknown at this moment.

Secuenciación y combinación de agentes en cáncer de próstata resistente a la castración / Sequencing and combination of agents in castration resistant prostate cancer

El cáncer de próstata (CP) es la segunda neoplasia maligna más frecuente en el mundo dentro del sexo masculino. Para la fase final de la enfermedad, cuando el tumor se hace resistente a castración tenemos un amplio abanico de posibilidades de tratamiento dirigidos al Receptor Androgénico, a la síntesis de andrógenos, al esqueleto, quimioterapia, incluso nuevas dianas moleculares que están aún en estudio. Aún así hoy en día no se ha establecido la secuencia idónea de tratamiento para cada paciente. Objetivos: El objetivo de este trabajo es plantear el panorama actual de tratamiento en la fase de resistencia a la castración y las últimas novedades y estrategias para elegir la mejor secuencia en el paciente adecuado. Métodos: Se ha realizado una búsqueda a través de Medline Database (Pubmed) usando como palabras Clave: "Castrate Resistant Prostate Cancer", "Sequencing", "Biomarkers", "Systemic Therapy". Revisión de abstract de ASCO GU 2017. Resultados: Desde que se aprobara Docetaxel en 2004 que aumentaba la supervivencia global unos 2 meses en pacientes afectos Cáncer de Próstata Resistente a la Castración Metastásicos, en los últimos años se han aprobado un buen número de terapias demostrando aumento de la supervivencia global tras ensayos clínicos en fase III: Cabacitaxel, abiraterona, enzalutamida, sipuleucel T, denosumab, Radium 223. Y más recientemente están saliendo a la luz investigaciones de nuevas terapias dirigidas al receptor androgénico, con una mayor afinidad que enzalutamida, o inhibidores de la enzima CYP 17 más precisos que abiraterona, así como anticuerpos monoclonales (anti PD1), vacunas, inhibidores de la poli adenosina difosfato-ribosa polimerasa, que en un futuro podrían afinar la secuencia de tratamiento de cada paciente, siendo necesario el estudio de biomarcadores predictores que indiquen la diana de cada terapia. Conclusiones: En un futuro próximo con los resultados de los distintos ensayos clínicos que estudian las nuevas moléculas podremos aplicar la secuenciación de las distintas terapias en función de biomarcadores presentes en la sangre (células tumorales circulantes) o en las biopsias, consiguiendo aumentar la supervivencia y la calidad de vida de los pacientes en la fase avanzada de la enfermedad, pero por el momento la mejor elección de secuencia es desconocida

Prostate Cancer is the second most frequent malignant neoplasm in males in the world. At the end of the disease, when the tumor becomes resistant to castration, we have a wide range of treatment possibilities aimed at the Androgenic Receptor, androgens synthesis, the skeleton, chemotherapy, and even new molecular targets that are still under investigation. Today, the best sequence of treatment for each patient has not been established yet. Objective: The objective of this work is to review the current scene of treatment in castrate resistant prostate cancer, as well as the latest developments and strategies to choose the best sequence in each patient. Material and methods: A literature review was performed through Medline Database (Pubmed) using as key words: "Castrate Resistant Prostate Cancer", "Sequencing", "Biomarkers", "Systemic Therapy". We also reviewed ASCO GU 2017 abstracts. RESULTS: Since Docetaxel was approved in 2004, which increased overall survival by about 2 months in patients with Metastatic Castration Resistant Prostate Cancer, in recent years a large number of therapies have been approved, demonstrating an increase in overall survival after several phase III clinical trials: Cabacitaxel, Abiraterone, Enzalutamide, Sipuleucel-T, Denosumab, Radium 223. And more recently, some investigations about new targeted therapies directed to the androgen receptor, with greater affinity than enzalutamide, or more accurate inhibitors of CYP 17 enzyme than abiraterone, as well as, agents as monoclonal antibodies (anti PD1), vaccines, poly adenosine diphosphate-ribose polymerase inhibitors, are coming to the light. In the future, these outcomes could tune up the treatment sequencing, through the study of predictive biomarkers that will indicate the right target of each therapy. Conclusions: In the near future, outcomes of different clinical trials that are studying new molecules, will allow us to apply the sequencing of different therapies based on biomarkers present in blood (circulating tumor cells) or in specimen biopsies, achieving an increase in overall survival and improving quality of life of patients in the advanced stage of the disease, however the best choice of sequence is unknown at this moment

Evaluación de competencias en Urología. Esscolap® basic, como aproximación a la mejora de las capacidades de los urólogos / Evaluation of competencies in urology. Esscolap® basic, as aproximation to urologists skills improvement

Introducción: La Urología necesita de modelos de evaluación de capacidades, a pesar de que existe una variada oferta de herramientas que no están integradas en los programas de formación. Contexto: No existe un criterio universal para medir el nivel de competencia. Los programas de formación deben proporcionar conocimientos y destrezas, y deben considerar las habilidades cognitivas, la formación basada sobre simulación y modelo animal. La validez es un concepto complejo que hace referencia a la capacidad del instrumento de evaluación, por lo que es necesario establecer varios tipos de validación para asegurar la capacidad de un método, reforzarse con distintos test de fiabilidad y cálculo de consistencia interna entre evaluadores. Objetivo: A partir de un dossier estructurado de competencias quirúrgicas, clasificadas por grupos, se planteó el sistema ESSCOLAP® Basic con 5 ejercicios sobre simulador, para la evaluación de las competencias básicas en Laparoscopia. Una vez validado, en el CCMIJU, se planteó ampliar el alcance e implementación del mismo en otras localizaciones. Resultados: Nuestro sistema no ha demostrado aún su validez en el ámbito clínico real, porque no presenta una validez predictiva con datos clínicos de resultados en salud. Existe, además, un cierto rango de subjetividad, por lo que se requiere establecer criterios claros y definidos para cualquier situación. El número de evaluadores y de los ejercicios a evaluar, va a influir en los test de fiabilidad que miden el grado de acuerdo entre evaluadores, de modo que sólo obteniendo un elevado número de casos evaluados, podremos acercarnos a una mayor fiabilidad de nuestro sistema. Por último, asumimos que la incorporación de este tipo de herramientas implica un coste añadido a cargo de las instituciones públicas y privadas responsables, que sólo se considerará rentable cuando se demuestre su trazabilidad real y positiva en resultados sanitarios. Conclusiones: ESSCOLAP® Basic, con capacidad de implementación rápida y sencilla, ha sido validado y contrastado para la evaluación de las habilidades técnicas básicas en laparoscopia (AU)

Introduction: Urology needs models of competencies assessment, although there is a wide range of tools not yet integrated into the official training programs. Context: At present, there is no universal framework for measuring surgeons ́ level of competence. Urology training programs should provide and consider knowledge, pyschomotor/cognitive skills, and simulator, cadaver or animal models-based training. Validity is a complex concept that refers to the capacity of the evaluation tool, so it is necessary to demonstrate several types of validation to assure the capacity of a method, reinforced with different reliability tests and calculation of internal consistency between evaluators. Objective: Based on a structured dossier of surgical skills, classified by groups, the ESSCOLAP® Basic system was proposed with 5 simulator tasks to evaluate basic laparoscopic skills. Once validated in the JUMISC (Spain), the tool was proposed to extend its scope and implementation in other locations. Results: Our system has not yet demonstrated a full validity in the real clinical setting because a predictive validity needs to be demonstrated on the basis of clinical data. It also suffers from a certain range of subjectivity, thus implying clear and defined criteria for any situation. Factors like the number of evaluators and tasks to assess will influence the reliability tests that measure the degree of agreement between evaluators, so that a higher number of evaluated cases would imply a greater reliability of our system. Finally, we assume that the incorporation of this type of tools implies an added cost, charged to the public and private responsible institutions, which will only be considered cost-effective when it is demonstrated its real and positive traceability in health outcomes. Conclusions: ESSCOLAP® Basic, of quick and simple implementation capacity, has been validated and calibrated for the evaluation of basic technical skills in laparoscopy (AU)

[Evaluation of competencies in urology. Esscolap® basic, as aproximation to urologists skills improvement.] / Evaluación de competencias en Urología. Esscolap® basic, como aproximación a la mejora de las capacidades de los urólogos.

Urology needs models of competencies assessment, although there is a wide range of tools not yet integrated into the official training programs. CONTEXT: At present, there is no universal framework for measuring surgeons' level of competence. Urology training programs should provide and consider knowledge, pyschomotor/cognitive skills, and simulator, cadaver or animal models-based training. Validity is a complex concept that refers to the capacity of the evaluation tool, so it is necessary to demonstrate several types of validation to assure the capacity of a method, reinforced with different reliability tests and calculation of internal consistency between evaluators. OBJECTIVE: Based on a structured dossier of surgical skills, classified by groups, the ESSCOLAP® Basic system was proposed with 5 simulator tasks to evaluate basic laparoscopic skills. Once validated in the JUMISC (Spain), the tool was proposed to extend its scope and implementation in other locations. RESULTS: Our system has not yet demonstrated a full validity in the real clinical setting because a predictive validity needs to be demonstrated on the basis of clinical data. It also suffers from a certain range of subjectivity, thus implying clear and defined criteria for any situation. Factors like the number of evaluators and tasks to assess will influence the reliability tests that measure the degree of agreement between evaluators, so that a higher number of evaluated cases would imply a greater reliability of our system. Finally, we assume that the incorporation of this type of tools implies an added cost, charged to the public and private responsible institutions, which will only be considered cost-effective when it is demonstrated its real and positive traceability in health outcomes. CONCLUSIONS: ESSCOLAP® Basic, of quick and simple implementation capacity, has been validated and calibrated for the evaluation of basic technical skills in laparoscopy.

Cognitive Function in Patients With Prostate Cancer Receiving Luteinizing Hormone-Releasing Hormone Analogues: A Prospective, Observational, Multicenter Study.

PURPOSE: The effect of androgen deprivation therapy (ADT) on cognitive performance (CP) in prostate cancer (PCa) patients is not well understood. We evaluated changes in CP after 6 months of medical castration with luteinizing hormone-releasing hormone (LHRH) analogues. METHODS AND MATERIALS: We performed a prospective, observational, multicenter, open-label study of PCa patients scheduled to receive LHRH analogues for ≥6 months. We assessed 4 domains of CP at baseline and after 6 months of ADT: (1) working memory, assessed with the Wechsler Adult Intelligence Scale III (WAIS III) Digit Span subtest; (2) visual memory, assessed with an ad hoc visual memory test; (3) visuospatial ability, assessed with the Judgment of Line Orientation test and Mental Rotation of Three-Dimensional Objects test; and (4) nonverbal analytical reasoning, assessed with the WAIS III Matrix Reasoning test. Changes outside the baseline 95% confidence intervals were considered significant. RESULTS: A total of 308 patients completed the study. Of these, 245 (79.6%) experienced no statistically significant changes on any test whereas 63 (20.4%) experienced significant changes on ≥1 test. Most of these patients showed a change on only 1 test, distributed evenly between improvement (58 patients, 18.8%) and worsening (56 patients, 18.2%). For individual tests, most patients (87.8%-91.8%) had no change from baseline; however, the significant changes (improvement vs deterioration) were as follows: WAIS III Digit Span subtest (6.3% vs 5.9%), visual memory (5.3% vs 5.7%), Judgment of Line Orientation test (5.3% vs 4.5%), Mental Rotation of Three-Dimensional Objects test (4.1% vs 4.1%), and WAIS III Matrix Reasoning test (4.8% vs 5.8%). CONCLUSIONS: CP in patients with PCa does not appear to be adversely affected by 6 months of LHRH analogue administration.

Everolimus safety and efficacy for renal angiomyolipomas associated with tuberous sclerosis complex: a Spanish expanded access trial.

BACKGROUND: Renal angiomyolipomas (AML) are usual manifestations of tuberous sclerosis complex (TSC) that may cause aneurism-related haemorrhages and renal impairment. Everolimus has emerged as an alternative to surgery/embolization. We provide further insight into everolimus safety and efficacy for TSC-related AML. METHODS: This was a Spanish expanded access trial including patients aged ≥18 years with TSC-related AML. They received 10 mg everolimus once daily until AML progression, unacceptable toxicity, death/withdrawal, commercialisation for TSC-related AML, or 1 year after first patient enrolment. The primary outcome was dose-limiting safety according to grade 3/4 adverse events, serious adverse events, or adverse events leading to treatment modification. Secondary outcomes included overall safety and efficacy. RESULTS: Nineteen patients were enrolled and received everolimus for a median of 6.6 (5.3-10.9) months. Eleven (57.9 %) remained on 10 mg/day throughout the study and eight (42.1 %) required treatment modifications due to adverse events; none permanently discontinued treatment. Adverse events were overall grade 1/2 and most frequently included aphthous stomatitis/mucosal inflammation, hypercholesterolaemia/hypertriglyceridaemia, urinary tract infection, hypertension, dermatitis acneiform, and insomnia. Four (21.1 %) patients experienced grade 3 adverse events, none was grade 4, and only one (5.3 %) was serious (pneumonia). AML volume was reduced ≥30 % in 11 (57.9 %) patients and ≥50 % in 9 (47.4 %); none progressed. Right and left kidney sizes decreased in 16 and 14 patients, respectively. CONCLUSIONS: These findings support the benefit of everolimus for renal AML due to a manageable safety profile accompanied by reduced AML and kidney volumes. TRIAL REGISTRATION: EudraCT number 2012-005397-63 ; date of registration 22 Nov 2012.

Methylation of tumor suppressor genes in a novel panel predicts clinical outcome in paraffin-embedded bladder tumors.

DNA methylation of tumor suppressor genes (TSGs) represents a frequent and early epigenetic event with potential applications for cancer detection and disease evolution. Our aim was to examine the stratification and prognostic biomarker role of the methylation of a novel panel of TSGs in bladder cancer. The methylation status of 18 TSGs was evaluated in bladder cancer cells (n=14) and paraffin-embedded primary bladder tumors (n=61), using a methylation-specific multiplex ligation-dependent probe amplification assay (MS-MLPA). Recurrence, progression, and disease-specific survival were analyzed using univariate and multivariate Cox models. PRDM2, HLTF, ID4, DLC1, BNIP3, H2AFX, CACNA1G, TGIF, and CACNA1A were discovered methylated in bladder cancer. The methylation of RUNX3 (p=0.026), TWIST1 (p=0.009), SFRP4 (p=0.002), and CCND2 (p=0.027) correlated to tumor stage. Univariate analyses indicated prognostic associations for recurrence (DLC1, SFRP5, H2AFX, CACNA1G), progression (DLC1, SFRP5, CACNA1G), disease-specific (PRDM2, DLC1, SFRP5, CACNA1G, and TIMP3), and overall survival (SFRP5 and TIMP3). In multivariate analyses, several TSGs remained as independent prognosticators for recurrence (SFRP5, H2AFX), progression (CACNA1G), and disease-specific survival (SFRP5). Thus, a novel set of TSGs was identified, frequently methylated in bladder cancer cells and tumors. TSG methylation allowed histopathologic and outcome stratification using paraffin-embedded tumors. This is clinically relevant by offering a strategy for the management of patients affected with uroepithelial neoplasias in pathology routine laboratories.

Methylation of a novel panel of tumor suppressor genes in urine moves forward noninvasive diagnosis and prognosis of bladder cancer: a 2-center prospective study.

PURPOSE: Changes in DNA methylation of tumor suppressor genes early in carcinogenesis represent potential indicators of cancer detection and disease evolution. We examined the diagnostic, stratification and prognostic biomarker roles in urine of the methylation of a novel panel of tumor suppressor genes in bladder cancer. MATERIAL AND METHODS: We evaluated the methylation of 18 tumor suppressor genes in 2 prospective, independent sets of urine samples (training set of 120 preparations and validation set of 128) from patients with bladder cancer (170) and controls (78) using methylation specific multiplex ligation-dependent probe amplification. Diagnostic performance was evaluated with ROC curves. Recurrence, progression and disease specific survival were analyzed using univariate and multivariate Cox models. RESULTS: PRDM2, HLTF, ID4, DLC1, BNIP3, H2AFX, CACNA1G, TGIF and CACNA1A were methylated in bladder cancer. CCND2, SCGB3A1, BNIP3, ID4 and RUNX3 were the most frequently methylated tumor suppressor genes in each urine set. Methylation of several tumor suppressor genes correlated with clinicopathological variables, such as stage, tumor grade, focality or age. ROC analysis revealed significant diagnostic accuracy for RUNX3 and CACNA1A in the training set, and for RUNX3 and ID4 in the validation set. On univariate and multivariate analysis CACNA1A methylation correlated with recurrence in the training set, while in the validation set PRDM2 and BNIP3 were significantly associated with recurrence and disease specific survival, respectively. CONCLUSIONS: Tumor suppressor gene methylation allowed for histopathological and clinical stratification. Urine methylation has noninvasive usefulness not only for diagnostic assessment but also as independent bladder cancer prognosticators.

Ureteral inverted papilloma: laparoscopic distal ureterectomy and boari flap.

OBJECTIVE: To report a case of ureteral inverted papilloma (IP) with laparoscopic resolution. METHODS: We report the case of a 30-year-old male patient who consulted for asymptomatic hematuria with the radiological finding of a filling defect at the distal right ureter. Ureteroscopy biopsy was not diagnostic, so laparoscopic ureterectomy with a Boari flap technique was performed. The pathology report showed a ureteral inverted papilloma. CONCLUSION: Laparoscopic ureteral replacement by Boari flap is a safe surgical alternative for defects in the distal ureter with the advantages of a minimally invasive procedure.

Papiloma invertido ureteral: ureterectomía distal y flap de Boari laparoscópico / Ureteral inverted papilloma: laparoscopic distal ureterectomy and boari flap

OBJETIVO: Presentar un caso de Papiloma Invertido (PI) ureteral con resolución laparoscópica mediante la confección de Flap Boari. MÉTODOS: Presentamos un paciente varón de 30 años de edad que consultó por hematuria asintomática con único hallazgo de defecto de repleción a nivel del tercio distal del uréter derecho. Debido a biopsia ureteroscopica no concluyente, se realizó una ureterectomía distal con neoimplante vesico-ureteral con técnica de Flap Boari laparoscópico. El informe histopatológico informó un papiloma invertido ureteral .CONCLUSIÓN: El reemplazo ureteral laparoscópico con Flap de Boari es una alternativa quirúrgica segura para defectos del uréter medio y distal con las ventajas de un procedimiento mínimamente invasivo (AU)

OBJECTIVE: To report a case of ureteral inverted papilloma (IP) with laparoscopic resolution. METHODS: We report the case of a 30-year-old male patient who consulted for asymptomatic hematuria with the radiological finding of a filling defect at the distal right ureter. Ureteroscopy biopsy was not diagnostic, so laparoscopic ureterectomy with a Boari flap technique was performed. The pathology report showed a ureteral inverted papilloma. CONCLUSION: Laparoscopic ureteral replacement by Boari flap is a safe surgical alternative for defects in the distal ureter with the advantages of a minimally invasive procedure (AU)