Treatment patterns and outcomes in metastatic castration-resistant prostate cancer patients with and without somatic or germline alterations in homologous recombination repair genes.

BACKGROUND: Although germline BRCA mutations have been associated with adverse outcomes in prostate cancer (PC), understanding of the association between somatic/germline alterations in homologous recombination repair (HRR) genes and treatment outcomes in metastatic castration-resistant PC (mCRPC) is limited. The aim of this study was to investigate the prevalence and outcomes associated with somatic/germline HRR alterations, particularly BRCA1/2, in patients initiating first-line (1L) mCRPC treatment with androgen receptor signalling inhibitors (ARSi) or taxanes. PATIENTS AND METHODS: Data from 729 mCRPC patients were pooled for CAPTURE from four multicentre observational studies. Eligibility required 1L treatment with ARSi or taxanes, adequate tumour samples and biomarker panel results. Patients underwent paired normal and tumour DNA analyses by next-generation sequencing using a custom gene panel including ATM, BRCA1, BRCA2, BRIP1, CDK12, CHEK2, FANCA, HDAC2, PALB2, RAD51B and RAD54L. Patients were divided into subgroups based on somatic/germline alteration(s): with BRCA1/2 mutations (BRCA); with HRR mutations except BRCA1/2 (HRR non-BRCA); and without HRR alterations (non-HRR). Patients without BRCA1/2 mutations were classified as non-BRCA. Radiographic progression-free survival (rPFS), progression-free survival 2 (PFS2) and overall survival (OS) were assessed. RESULTS: Of 729 patients, 96 (13.2%), 127 (17.4%) and 506 (69.4%) were in the BRCA, HRR non-BRCA and non-HRR subgroups, respectively. BRCA patients performed significantly worse for all outcomes than non-HRR or non-BRCA patients (P < 0.05), while PFS2 and OS were significantly shorter for BRCA than HRR non-BRCA patients (P < 0.05). HRR non-BRCA patients also had significantly worse rPFS, PFS2 and OS than non-HRR patients. Exploratory analyses suggested that for BRCA patients, there were no significant differences in outcomes associated with 1L treatment choice (ARSi or taxanes) or with the somatic/germline origin of the alterations. CONCLUSIONS: Worse outcomes were observed for mCRPC patients in the BRCA subgroup compared with non-BRCA subgroups, either HRR non-BRCA or non-HRR. Despite its heterogeneity, the HRR non-BRCA subgroup presented worse outcomes than the non-HRR subgroup. Screening early for HRR mutations, especially BRCA1/2, is crucial in improving mCRPC patient prognosis.

Carcinoma primario de próstata con diferenciación en célula en anillo de sello con respuesta a abiraterona / Primary signet ring cell carcinoma of the prostate with response to abiraterone

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An immunohistochemical study of cytokeratins distribution of the human adult male and female urethra.

Surgical treatment of diseases affecting long urethral areas represents a challenge in urology. Recent developments of tissue-engineered urethral substitutes represent a hope for patients. However finding an ideal tissue source for urethral reconstruction first requires proper understanding of the native human urethra physiology and a deep knowledge of the histological and molecular features of the native human urethra. Here we present a comprehensive characterization of male and female urethra by histological, histochemical and immunohistochemical methods with a panel of 15 antibodies. The results demonstrated that the histology of the male and female urethra depend on the area where the sample is taken along its length. Proximal areas of male and female urethra have differential expression of the epithelial basal and suprabasal layer markers CK14 and CK10 which distinguished the prostatic/membranous and proximal female urethra from the bulbar/penile and distal female areas of the urethra. The distal male (penile) and female may be further divided by the distinct expression pattern of CK19. On the other hand, the expression of CK5/6 and CK19 also make a distinction of the proximal and distal female urethra. These results should facilitate a more informed selection of donor graft tissues for urethral replacement. Besides, novel bioengineered urethral tissue approaches should take into account the characterization of the different areas of the urethra presented in this work.

Reimplante ureteral directo con catéter ureteral. Imagen endoscópica / Ureteral reimplantation with ureteral stent. Endoscopic image

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¿Es efectiva la realización previa de resonancia magnética multiparamétrica en pacientes candidatos a biopsia prostática? Estudio CAT / Is effective a prior multiparametric magnetic resonance scan in patients candidates to prostate biopsy? CAT Study

Hemos realizado un estudio tipo CAT (Critically Appraised Topic) en el que nos planteábamos si existe evidencia científica relevante para aconsejar la realización previa de una exploración de resonancia magnética multiparamétrica de próstata a todos los pacientes candidatos a biopsia prostática con el fin de mejorar la detección del cáncer de próstata clínicamente significativo y la estratificación de pacientes candidatos a vigilancia activa o tratamiento. Tras una búsqueda bibliográfica reglada y el análisis de los dos artículos más relevantes encontrados sobre el tema, llegamos a la conclusión de que, a pesar de que hay resultados prometedores que apuntan a una potencial utilidad de este planteamiento, no existe todavía evidencia científica clara que lo avale categóricamente. Son necesarios estudios prospectivos aleatorizados multicéntricos amplios y bien diseñados, con criterios ampliamente consensuados, para llegar a una evidencia firme que sustente dicha recomendación (AU)

We carried out a critically appraised topic (CAT)-type study to determine whether the relevant scientific evidence supports the recommendation of doing a multiparametric magnetic resonance imaging study of the prostate in all patients who are candidates for prostate biopsy with the aim of improving the detection of clinically significant prostate cancer and stratifying patients to receive active surveillance or treatment. After a formal literature search and an analysis of the two most relevant articles it found, we reached the conclusion that, despite promising results that point to the potential usefulness of this approach, there is still not enough clear scientific evidence to endorse it categorically. Before this approach can be endorsed, we need evidence from well-designed prospective randomized trials using widely agreed upon criteria and including large numbers of patients at multiple center (AU)

Anastomic urethroplasty in bulbar urethral stricture. 13 years experience in a department of urology. / Uretroplastia anastomótica en el manejo de estenosis de uretra bulbar. Experiencia de 13 años en un Servicio de Urología.

UNLABELLED: Urethral stenosis is a common disease in the clinical practice of urology, with a major impact on the quality of life of patients. The anastomotic urethroplasty is a technique with very precise indications usually membranous or bulbar urethra stenosis with a length of 3 cm or up to 7 cm when it is secondary to urethral disruptions (no stenosis) after pelvic trauma. OBJECTIVE: We review anastomotic urethroplasty performed in our department between 2002 and 2015. METHODS: A retrospective, descriptive and inferential analysis on 107 patients out of 482 treated with Anastomotic urethroplasty by urethral strictures at the Urology Department of the Hospital "Virgen de la Victoria" (Malaga) from January 2002 to September 2015, establishing effectiveness and safety of the technique, as well as factors that might influence the results. The main diagnostic method was retrograde urethrography and voiding cystourethrography in 100% of patients undergoing surgery, using voiding uroflowmetry for subsequent monitoring. The definition of success was a postoperative flowmetry with Qmax>15 ml/s, and in case of lower flow, we perform a cystoscopy to verify recurrence of stenosis or exclude other pathology. RESULTS: The median age was 42 years, with a mean follow up of 59 months. The length of stenosis valued by retrograde urethrography and voiding cystourethrography was in 91.6% of cases of >1 cm and <2 cm. The most common etiology was idiopathic in 72.9%, followed by iatrogenic with 15.9%. Regarding the location, it was observed that the area most often affected was the bulbar urethra with 82.2%, with the membranous urethra in second place. In 77.6% of patients anastomotic urethroplasty was the initial treatment, followed in frequency by direct vision internal urethrotomy 9.3%. In the case of comorbidities associated with treatment with anastomotic urethroplasty it was observed that only Diabetes Mellitus had a tendency to statistical significance, with p=0.092, not demonstrating such significance in the case of hypertension or when the subject presented Diabetes Mellitus together with hypertension. Finally, the intervention was successful in 102 cases (95.3%), with only 5 cases (4.7%) where it failed, 4 of them treated with a new Anastomotic urethroplasty, with resolution of the stricture. CONCLUSIONS: Anastomotic urethroplasty is the treatment of choice for short bulbar urethral stricture, with high success rate and low complication rate, as well as low recurrence of these.

Is effective a prior multiparametric magnetic resonance scan in patients candidates to prostate biopsy? CAT Study. / ¿Es efectiva la realización previa de resonancia magnética multiparamétrica en pacientes candidatos a biopsia prostática? Estudio CAT.

We carried out a critically appraised topic (CAT)-type study to determine whether the relevant scientific evidence supports the recommendation of doing a multiparametric magnetic resonance imaging study of the prostate in all patients who are candidates for prostate biopsy with the aim of improving the detection of clinically significant prostate cancer and stratifying patients to receive active surveillance or treatment. After a formal literature search and an analysis of the two most relevant articles it found, we reached the conclusion that, despite promising results that point to the potential usefulness of this approach, there is still not enough clear scientific evidence to endorse it categorically. Before this approach can be endorsed, we need evidence from well-designed prospective randomized trials using widely agreed upon criteria and including large numbers of patients at multiple centers.

Uretroplastia anastomótica en el manejo de estenosis de uretra bulbar. Experiencia de 13 años en un Servicio de Urología / Anastomic urethroplasty in bulbar urethral stricture. 13 years experience in a department of urology

La estenosis de uretra es una patología frecuente en la práctica clínica diaria de las consultas de Urología, con un impacto importante en la calidad de vida de los pacientes. La Uretroplastia anastomótica es una técnica con indicaciones muy precisas en estenosis generalmente de uretra bulbar o membranosa con una longitud de hasta 3 cm o de hasta 7 cm cuando se trata de disrupciones uretrales (no estenosis) tras traumatismos pelvianos. OBJETIVO: Realizamos una revisión de las Uretroplastias anastomóticas llevadas a cabo en nuestro servicio entre 2002 y 2015. MÉTODO: Análisis retrospectivo, descriptivo e inferencial sobre 107 pacientes de un total de 482 estenosis uretrales tratadas mediante Uretroplastia anastomótica en el Servicio de Urología del Hospital 'Virgen de la Victoria' de Málaga desde enero de 2002 a septiembre de 2015, estableciendo eficacia y seguridad de dicha técnica, así como factores que pudiesen influir en los resultados. El método diagnóstico principal fue la uretrografía retrograda y miccional en el 100% de los pacientes sometidos a tratamiento quirúrgico, recurriendo a la flujometría miccional para el seguimiento posterior. La definición de éxito fue una flujometría postoperatoria con un Qmax >15 ml/s, y en caso de flujos inferiores se realizaron uretrografías o uretroscopias para verificar la recidiva de la estenosis o descartar otra patología. RESULTADOS: La mediana de edad fue de 42 años, con un seguimiento medio de 59 meses. La longitud de la estenosis valorada mediante uretrografía miccional y retrógrada fue en un 91.6% de los casos de >1 cm y <2cm. La etiología más frecuente fue la Idiopática con un 72.9%, seguida por la Iatrógena con un 15.9%. Respecto a la localización se objetivó como la zona más frecuentemente afecta fue la uretra bulbar con un 82.2%, continuándole la uretra membranosa. En un 77.6% de los pacientes la Uretroplastia anastomótica fue el tratamiento inicial, continuando en frecuencia la Uretrotomía Interna con un 9.3%. En el caso de las comorbilidades asociadas al tratamiento con la Uretroplastia anastomótica se objetivó como únicamente la Diabetes Mellitus presenta una tendencia a la significación estadística, con una p = 0.092, no demostrándose dicha significación ni en el caso de la Hipertensión arterial ni cuando el sujeto presentaba Diabetes Mellitus conjuntamente con Hipertensión. Por último, la intervención resultó un éxito en 102 casos (95.3%), con sólo 5 casos (4.7%) en los que fracasó, siendo tratados 4 de ellos con una nueva Uretroplastia anastomótica con resolución de la estenosis. CONCLUSIONS: La Uretroplastia anastomótica es el tratamiento de elección en las estenosis cortas de uretra bulbar por su alto porcentaje de éxitos y baja tasa de complicaciones, así como en las recidivas de éstas

Urethral stenosis is a common disease in the clinical practice of urology, with a major impact on the quality of life of patients. The anastomotic urethroplasty is a technique with very precise indications usually membranous or bulbar urethra stenosis with a length of 3 cm or up to 7 cm when it is secondary to urethral disruptions (no stenosis) after pelvic trauma. OBJECTIVE: We review anastomotic urethroplasty performed in our department between 2002 and 2015. METHODS: A retrospective, descriptive and inferential analysis on 107 patients out of 482 treated with Anastomotic urethroplasty by urethral strictures at the Urology Department of the Hospital 'Virgen de la Victoria' (Malaga) from January 2002 to September 2015, establishing effectiveness and safety of the technique, as well as factors that might influence the results. The main diagnostic method was retrograde urethrography and voiding cystourethrography in 100% of patients undergoing surgery, using voiding uroflowmetry for subsequent monitoring. The definition of success was a postoperative flowmetry with Qmax>15 ml/s, and in case of lower flow, we perform a cystoscopy to verify recurrence of stenosis or exclude other pathology. RESULTS: The median age was 42 years, with a mean follow up of 59 months. The length of stenosis valued by retrograde urethrography and voiding cystourethrography was in 91.6% of cases of >1 cm and <2cm. The most common etiology was idiopathic in 72.9%, followed by iatrogenic with 15.9%. Regarding the location, it was observed that the area most often affected was the bulbar urethra with 82.2%, with the membranous urethra in second place. In 77.6% of patients anastomotic urethroplasty was the initial treatment, followed in frequency by direct vision internal urethrotomy 9.3%. In the case of comorbidities associated with treatment with anastomotic urethroplasty it was observed that only Diabetes Mellitus had a tendency to statistical significance, with p = 0.092, not demonstrating such significance in the case of hypertension or when the subject presented Diabetes Mellitus together with hypertension. Finally, the intervention was successful in 102 cases (95.3%), with only 5 cases (4.7%) where it failed, 4 of them treated with a new Anastomotic urethroplasty, with resolution of the stricture. CONCLUSIONS: Anastomotic urethroplasty is the treatment of choice for short bulbar urethral stricture, with high success rate and low complication rate, as well as low recurrence of these

Quiste epidermoide testicular: una rara entidad clínica / Testicular epidermoid cyst: a rare entity

OBJETIVO: El quiste epidermoide testicular es una rara entidad clínica, representando un 1% de las neoplasias testiculares. Método y resultados: Presentamos dos pacientes de 18 y 19 años de edad respectivamente con una lesion indolora a nivel de testículo. Se realiza una ecografía testicular donde se evidencia un nódulo hipoecogénico en ambos casos. Con la sospecha de tumor testicular se realiza una orquiectomía inguinal con colocación de una prótesis testicular en mismo acto. El resultado anatomopatológico fue de quiste epidermoide testicular en los dos casos. CONCLUSIÓN: Los quistes epidermoides testiculares son una rara entidad clínica benigna, que en caso de ser sospechada en función a los marcadores testiculares y la ecografía o la RMN, debe intentarse una cirugía conservadora

OBJECTIVE: Testicular epidermoid cyst is a rare clinical entity that accounts for 1% of testicular neoplasias. METHODS AND RESULTS: We report two cases of testicular epidermoid cysts in a 18 and 19 year old males with a painless testicular lesion. Testicular US was carried out showing a hypoechoic nodule in both cases. With the suspicion of testicular neoplasm inguinal orchiectomy was carried out with placement of testicular prostheses in the same act. The pathology report was testicular epidermoid cyst in both cases. CONCLUSIONS: Testicular epidermoid cysts are an uncommon benign entity. When there is a suspicion of this diagnosis, based on tumor markers and ultrasound or MRI images, testicular parenchyma-sparing surgery must be attempted

Carcinoma de células transicionales localizado en fosa navicular / Urothelial transitional cell carcinoma located in fossa navicularis

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Syringocele in adult patient. Case report.

OBJECTIVE: To describe one case of syringocele in an adult patient. METHODS/RESULTS: We report the case of a 26 year old man who presented frequency, hematuria and fever during one year, mictional cystourethrography showed a syringocele. Treatment consisted in endoscopic surgery, with good results in the follow-up. CONCLUSIONS: The syringocele is a relatively infrequent entity, that is necessary to study in a young patient with voiding symptoms, accompanied or not of haematuria and fever. The diagnosis is based on the cystourethrography, and treatment consisted, usually, in endoscopic surgery.

Siringocele uretral en adulto. A propósito de un caso / Syringocele in adult patient. Case report

OBJETIVO: Presentación de un caso de siringocele en la edad adulta. MÉTODO/RESULTADO: Describimos el caso de un paciente que consultó en nuestro centro por un síndrome irritativo vesical, hematuria y fiebre de un año de evolución, que en el seguimiento se objetiva mediante cistouretrografía miccional un siringocele simple. El tratamiento consistió en una marsupialización endoscópica, presentando buenos resultados en el seguimiento. CONCLUSIONES: El siringocele es una entidad relativamente infrecuente, pero que es necesaria tenerla en cuenta ante un paciente joven con clínica miccional, acompañada o no de hematuria y fiebre. El diagnóstico se basa en la uretrografía, y como modalidad terapéutica más habitual destaca la marsupialización endoscópica(AU)

OBJECTIVE: To describe one case of syringocele in an adult patient. METHODS/RESULTS: We report the case of a 26 year old man who presented frequency, hematuria and fever during one year, mictional cystourethrography showed a syringocele. Treatment consisted in endoscopic surgery, with good results in the follow-up. CONCLUSIONS: The syringocele is a relatively infrequent entity, that is necessary to study in a young patient with voiding symptoms, accompanied or not of haematuria and fever. The diagnosis is based on the cystourethrography, and treatment consisted, usually, in endoscopic surgery(AU)

Ultrasound diagnosis of three cases of Mondor's disease.

OBJECTIVE: To describe clinical features and ultrasound findings of three cases of a little-known and relatively infrequent entity in daily clinical activity, which is often unnoticed and under-reported: penile Mondor's disease or superficial penile veins thrombophlebitis. METHODS: We are reporting the cases of three patients aged 33, 25 and 39 years who were referred to our department, the first case with suspicion of inguinal hernia, the second one to rule out testicular pathology because of pubic and perineal discomfort, and the third one for painful induration of the dorsal region of the penis. The three patients underwent Doppler-ultrasound examination (Toshiba®, using a 13-18MHz linear transducer) to establish definitive diagnosis, and had a favorable evolution with conservative management. RESULTS: Ultrasound examination revealed: Case 1. Penile superficial dorsal vein and lateral superficial veins thrombosis. Case 2. Thrombosis of the right branch of the superficial dorsal vein and its perineal distal connections. Case 3. Penile superficial dorsal vein thrombosis. Definitive diagnosis of the three cases was Mondor's disease. CONCLUSIONS: Mondor's disease is an often under-reported entity in daily clinical activity. Doppler-ultrasound findings (echogenic material within veins, lack of any response after compression by the transducer and absence of color flow) confirm de diagnosis. This disease has a favorable evolution and functional prognosis. Knowledge of Mondor's disease by echographists is basic to avoid false-negative results in radiologic examination.

Diagnóstico ecográfico de tres caso de enfermedad de Mondor del pene / Ultrasound diagnosis of three cases of Mondor`s disease

OBJETIVO: Describir las características clínicas y los hallazgos ecográficos de tres casos de una entidad poco conocida y relativamente infrecuente en la actividad clínica diaria, lo que ocasiona que sea infradiagnosticada: la enfermedad de Mondor del pene o tromboflebitis aislada de las venas superficiales del pene. MÉTODOS: Los casos corresponden a pacientes de 33, 25 y 39 años remitidos el primero por sospecha de hernia inguinal, el segundo para descartar patología testicular por molestias púbicas y perineales, y el tercero por induración dolorosa del dorso del pene. Se realizó ecografía-Doppler color de alta resolución (Toshiba®, con transductor lineal de 13-18 MHz) y tras el diagnóstico se instauró tratamiento conservador, evolucionando los tres casos de forma favorable. RESULTADOS: En el estudio ecográfico se apreció: Caso 1. Trombosis de la vena dorsal superficial y venas laterales superficiales. Caso 2. Trombosis de la rama derecha de la vena dorsal superficial y de sus conexiones distales perineales. Caso 3. Trombosis de la vena superficial dorsal del pene. Los tres casos fueron diagnosticados como enfermedad de Mondor. CONCLUSIONES: La enfermedad de Mondor es una entidad frecuentemente infradiagnosticada en la práctica diaria. Los hallazgos ecográficos-Doppler (contenido ecogénico en el interior de la vena, falta de respuesta a la compresión y ausencia de flujo) son diagnósticos. Se trata de una entidad clínica con buena evolución y pronóstico funcional. Es fundamental el conocimiento de esta entidad por parte del ecografista para evitar falsos negativos en el estudio radiológico(AU)

OBJECTIVE: To describe clinical features and ultrasound findings of three cases of a little-known and relatively infrequent entity in daily clinical activity, which is often unnoticed and under-reported: penile Mondor’s disease or superficial penile veins thrombophlebitis. METHODS: We are reporting the cases of three patients aged 33, 25 and 39 years who were referred to our department, the first case with suspicion of inguinal hernia, the second one to rule out testicular pathology because of pubic and perineal discomfort, and the third one for painful induration of the dorsal region of the penis. The three patients underwent Doppler-ultrasound examination (Toshiba®, using a 13-18MHz linear transducer) to establish definitive diagnosis, and had a favorable evolution with conservative management. RESULTS: Ultrasound examination revealed: Case 1. Penile superficial dorsal vein and lateral superficial veins thrombosis. Case 2. Thrombosis of the right branch of the superficial dorsal vein and its perineal distal connections. Case 3. Penile superficial dorsal vein thrombosis. Definitive diagnosis of the three cases was Mondor’s disease. CONCLUSIONS: Mondor’s disease is an often under-reported entity in daily clinical activity. Doppler-ultrasound findings (echogenic material within veins, lack of any response after compression by the transducer and absence of color flow) confirm de diagnosis. This disease has a favorable evolution and functional prognosis. Knowledge of Mondor’s disease by echographists is basic to avoid false-negative results in radiologic examination(AU)