Genetic variants of antioxidant enzymes and environmental exposures as molecular biomarkers associated with the risk and aggressiveness of bladder cancer.

Bladder cancer (BC) is one of the top 10 most common tumours worldwide; however, no molecular markers are currently available for tumour management and follow-up. BC could benefit from molecular biomarkers in environmental disease, which provide mechanistic understanding of individual susceptibility to exposure-related cancers and allow characterizing genetic alterations in the molecular pathway for malignancy. This case-control study performed a molecular analysis in 99 BC and 125 controls. Buccal swabs were collected to assess SNPs in eleven genes coding for xenobiotic detoxification enzymes, cellular antioxidant defences, and hormone synthesis and signalling (NAT2 (rs1801280), GPX1 (rs1050450 and rs17650792), TXNRD1 (rs7310505), PRDX3 (rs3740562), PON1 (rs662), SOD1 (rs10432782), SOD2 (rs4880), CAT (rs1001179), CYP17A1 (rs743572) and ESR1 (rs746432)). A structured questionnaire was administered to study participants to assess environmental and dietary chemical exposures. Several miRNAs associated with BC and detoxification/antioxidant pathways were analysed in a subsample of the study population, including miR-93-5p, miR-221-3p, miR-126, miR-27a-3p, miR-193b, and miR-193a-5p. Levels of selected environmental pollutants (polycyclic aromatic hydrocarbons and endocrine disrupting chemicals) were determined in urine from a subsample of BC cases and controls. We found that CYP17A1, CAT, SOD1, ESR1, PON1, and GPX1 (rs17650792) were associated with BC risk. Furthermore, exposure to smoke and/or dust, and alcohol intake were identified as risk factors for BC. Increased urinary levels of benzo[a]pyrene and bisphenol A were observed in BC patients relative to controls, along with an increased expression of miR-193b, miR-27a and miR-93-5p in BC. Nevertheless, further studies with a larger sample size are warranted to confirm these exploratory results. This study also shows that the combination of genetic markers (PON1 and CYP17A1) and miRNA (miR-221-3p and miR-93-5p) open a new scenario in the use of non-invasive biomarkers in the stratification of BC to guide personalized medicine, which is extremely urged in the current clinical setting.

Role of IGF2 in the Study of Development and Evolution of Prostate Cancer.

Prostate Cancer (PC) is commonly known as one of the most frequent tumors among males. A significant problem of this tumor is that in early stages most of the cases course as indolent forms, so an active surveillance will anticipate the appearance of aggressive stages. One of the main strategies in medical and biomedical research is to find non-invasive biomarkers for improving monitoring and performing a more precise follow-up of diseases like PC. Here we report the relevant role of IGF2 and miR-93-5p as non-invasive biomarker for PC. This event could improve current medical strategies in PC.

Biopsia líquida y cáncer de próstata. Evidencia actual aplicada a la clínica / Liquid biopsy and prostate cancer. Current evidence applied to clinical practice

CONTEXTO: A pesar de ser una demostrada fuente de biomarcadores, la biopsia líquida aún no ha conseguido dar el paso a la práctica clínica habitual en pacientes con cáncer de próstata. Pocos biomarcadores se someten a una adecuada validación, prospectiva e independiente, de su valor predictivo o pronóstico y ello resulta en una falta de resultados con capacidad de traslación real a la clínica de los diferentes test disponibles. OBJETIVO: Realizar una síntesis, clínicamente pragmática, de la evidencia científica actual sobre la biopsia líquida sanguínea en cáncer de próstata. Adquisición de la evidencia: Revisión no sistemática de la literatura, acotando la búsqueda a trabajos sobre biopsia líquida de origen sanguíneo en cáncer de próstata. Se seleccionaron preferentemente aquellos trabajos en los cuales se estudian end-points clínicos aplicados al cáncer de próstata. Síntesis de la evidencia: Las formas de biopsia líquida más avanzadas en términos clínicos son las células tumorales circulantes (CTC) y el ADN tumoral circulante (ADNtc). Tanto CTC como ADNtc han demostrado su valor pronóstico en enfermedad metastásica. La determinación de ARV7 constituye el primer biomarcador predictivo de la enfermedad. Su traslación a la práctica clínica habitual pasa por la estandarización metodológica y la adecuada validación clínica de las distintas formas de detección disponibles. La detección de CTC en estadios iniciales de la enfermedad depende aún de la optimización de los métodos de detección y del desarrollo de la caracterización biológica de estas células. La información biológica aportada por CTC y ADNtc es distinta; por ello, el estudio de su adecuada conjunción es objeto de la investigación más actual. CONCLUSIONES: La ausencia de protocolos y estándares metodológicos es el factor limitante para llegar a conclusiones de impacto clínico. Por ello, el consenso y la unificación de criterios constituyen el verdadero desafío a corto plazo para la biopsia líquida

CONTEXT: Despite being a validated source of biomarkers, liquid biopsy has not yet succeeded in becoming part of the standard clinical practice in prostate cancer PATIENTS: Few biomarkers undergo adequate validation, prospective and independent, of their predictive and/or prognostic value, which results in a lack of the different available tests in the clinical practice. OBJECTIVE: To carry out a pragmatic synthesis of current scientific evidence on liquid biopsy for prostate cancer PATIENTS: Evidence acquisition: Non-systematic literature review, narrowing the search to papers on liquid biopsy from blood samples in prostate cancer PATIENTS: We mainly selected works evaluating clinical endpoints in prostate cancer. Evidence synthesis: The most clinically advanced forms of liquid biopsy are circulating tumor cells (CTCs) and circulating tumor DNA (ctDNA). Both CTCs and ctDNA have demonstrated their prognostic value in metastatic disease. ARV7 determination is the first predictive biomarker of the disease. Its implementation into routine clinical practice requires methodological standardization and adequate clinical validation of the different available ways to detect it. The detection of CTCs in the early stages of the disease still depends on the optimization of the diagnostic methods and on the development of the biological characterization of these cells. The biological information provided by CTCs and ctDNA is different; therefore, the study of its adequate combination is the object of cutting-edge research. CONCLUSIONS: The absence of protocols and methodological standards is the limiting factor when aiming to reach conclusions that could have a potential impact on clinical practice. Therefore, the real short-term challenge for liquid biopsy is the establishment of consensus and common criterio

Liquid biopsy and prostate cancer. Current evidence applied to clinical practice. / Biopsia líquida y cáncer de próstata. Evidencia actual aplicada a la clínica.

CONTEXT: Despite being a validated source of biomarkers, liquid biopsy has not yet succeeded in becoming part of the standard clinical practice in prostate cancer patients. Few biomarkers undergo adequate validation, prospective and independent, of their predictive and/or prognostic value, which results in a lack of the different available tests in the clinical practice. OBJECTIVE: To carry out a pragmatic synthesis of current scientific evidence on liquid biopsy for prostate cancer patients. EVIDENCE ACQUISITION: Non-systematic literature review, narrowing the search to papers on liquid biopsy from blood samples in prostate cancer patients. We mainly selected works evaluating clinical endpoints in prostate cancer. EVIDENCE SYNTHESIS: The most clinically advanced forms of liquid biopsy are circulating tumor cells (CTCs) and circulating tumor DNA (ctDNA). Both CTCs and ctDNA have demonstrated their prognostic value in metastatic disease. ARV7 determination is the first predictive biomarker of the disease. Its implementation into routine clinical practice requires methodological standardization and adequate clinical validation of the different available ways to detect it. The detection of CTCs in the early stages of the disease still depends on the optimization of the diagnostic methods and on the development of the biological characterization of these cells. The biological information provided by CTCs and ctDNA is different; therefore, the study of its adequate combination is the object of cutting-edge research. CONCLUSIONS: The absence of protocols and methodological standards is the limiting factor when aiming to reach conclusions that could have a potential impact on clinical practice. Therefore, the real short-term challenge for liquid biopsy is the establishment of consensus and common criteria.

The role of miRNAs as biomarkers in prostate cancer.

There is an urged need of non-invasive biomarkers for the implementation of precision medicine. These biomarkers are required to these days for improving prostate cancer (PCa) screening, treatment or stratification in current clinical strategies. There are several commercial kits (Oncotype DX genomic prostate score®, Prolaris®, among others) that use genomic changes, rearrangement or even non-coding RNA events. However, none of them are currently used in the routine clinical practice. Many recent studies indicate that miRNAs are relevant molecules (small single-stranded non-coding RNAs that regulate gene expression of more than 30% of human genes) to be implement non-invasive biomarkers. However, contrasting to others tumors, such as breast cancer where miR-21 seems to be consistently upregulated; PCa data are controversial. Here we reported an extended revision about the role of miRNAs in PCa including data of AR signaling, cell cycle, EMT process, CSCs regulation and even the role of miRNAs as PCa diagnostic, prognostic and predictive tool. It is known that current biomedical research uses big-data analysis like Next Generation Sequencing (NGS) analysis. We also conducted an extensive online search, including the main platforms and kits for miRNAs massive analysis (like MiSeq, Nextseq 550, or Ion S5™ systems) indicating their pros, cons and including pre-analytical and analytical issues of miRNA studies.

Papel de la tomografía por emisión de positrones-tomografía computerizada con 18F-fluorocolina en la recidiva bioquímica tras tratamiento con intención curativa del cáncer de próstata / Role of PET-CT with 18F-fluorocholine in biochemical recurrence after treatment of prostate cancer with curative intent

Objetivos: Analizar la capacidad de la PET-TC con 18F-fluorocolina (18F-FCH) para detectar enfermedad en el momento de la recidiva bioquímica tras tratamiento con intención curativa. Determinar qué variables clínicas serían capaces de optimizar la rentabilidad diagnóstica de la prueba. Material y métodos: Estudio retrospectivo de las PET-TC con 18F-FCH realizadas a 61 pacientes con cáncer de próstata sometidos a tratamiento con intención curativa y que cumplían criterios de recidiva bioquímica. Los resultados del estudio PET-TC se categorizaron en positivos o negativos y fueron validados según criterios preestablecidos. Se estudió la relación entre el resultado de la PET-TC y el PSA inicial, PSA nadir, PSA trigger, velocidad de ascenso del PSA (PSAva) y PSA doubling time (PSAdt). Se analizó la relación entre las localizaciones metastásicas en la PET-TC y el resto de variables. Resultados: La tasa de detección de enfermedad fue del 34,4%. El PSA inicial, el PSA nadir, el PSA trigger y el PSAva demostraron diferencias estadísticamente significativas según el resultado de la PET-TC. El mejor punto de corte discriminatorio entre una PET-TC positiva o negativa para el PSA trigger y la PSAva fue 3,5ng/ml y 0,25ng/ml/mes respectivamente. El PSAdt fue significativamente menor en los pacientes con enfermedad a distancia frente a los pacientes con enfermedad localizada (5.1 vs 16.8 meses, p=0.01). La probabilidad de que la PET-TC detectara enfermedad a distancia vs localizada fue 3,2 veces mayor si el PSAdt era menor de 6 meses (80% vs 20%, OR: 3,2, p=0,02). En el análisis multivariante solo el PSA inicial y el hecho de no haberse sometido a prostatectomía radical demostraron ser factores predictores independientes del resultado positivo de la PET-TC. Conclusiones: La PET-TC con 18F-FCH es capaz de detectar enfermedad en un alto porcentaje de pacientes con recidiva bioquímica, y proporciona información sobre la localización anatómica de la misma. La cinética del PSA y el tratamiento previo del paciente son variables clave para aumentar el rendimiento diagnóstico de la exploración

Objectives: To analyse the ability of the PET-CT with 18F-fluorocholine (18F-FCH) to detect disease on biochemical recurrence after treatment with curative intent. To determine the clinical variables that would be able to optimise the test’s diagnostic yield. Material and methods: A retrospective study of PET-CTs with 18F-fluorocholine performed on 61 patients with prostate cancer who had undergone treatment with curative intent and met the criteria for biochemical recurrence. The results of the PET-CT were categorised into positive or negative and were validated using pre-established criteria. The relationship between the result of the PET-CT and the initial PSA nadir, PSA trigger, rising PSA velocity (PSAva) and PSA doubling time (PSAdt). The relationship between the metastatic sites on the PET-CT and the remaining variables was analysed. Results: There was a 34.4% detection rate of the disease. The initial PSA, PSA nadir, PSA trigger and PSAva showed statistically significant differences according to the result of the PET-CT. The best discriminatory cut-off point between a positive or negative PET-CT for PSA trigger and PSAva was 3.5ng/ml and 0.25ng/ml/month respectively. The PSAdt was significantly lower in patients with remote disease compared to patients with localised disease (5.1 vs 16.8 months, P=.01). The probability that the PET-CT would detect remote disease vs localised disease was 3.2 times higher if the PSAdt was under 6 months (80% vs 20%, OR: 3.2, P=.02). In the multivariate analysis, only the initial PSA and not having undergone radical prostatectomy were demonstrated as independent predictive factors of a positive PET-CT result. Conclusions: The PET-CT with 18F-FCH can detect disease in a high percentage of patients with biochemical recurrence and provides information on its anatomical location. PSA kinetics and the patient's previous treatment are key variables in increasing the test's diagnostic

Role of PET-CT with 18F-fluorocholine in biochemical recurrence after treatment of prostate cancer with curative intent. / Papel de la tomografía por emisión de positrones-tomografía computerizada con 18F-fluorocolina en la recidiva bioquímica tras tratamiento con intención curativa del cáncer de próstata.

OBJECTIVES: To analyse the ability of the PET-CT with 18F-fluorocholine (18F-FCH) to detect disease on biochemical recurrence after treatment with curative intent. To determine the clinical variables that would be able to optimise the test's diagnostic yield. MATERIAL AND METHODS: A retrospective study of PET-CTs with 18F-fluorocholine performed on 61 patients with prostate cancer who had undergone treatment with curative intent and met the criteria for biochemical recurrence. The results of the PET-CT were categorised into positive or negative and were validated using pre-established criteria. The relationship between the result of the PET-CT and the initial PSA nadir, PSA trigger, rising PSA velocity (PSAva) and PSA doubling time (PSAdt). The relationship between the metastatic sites on the PET-CT and the remaining variables was analysed. RESULTS: There was a 34.4% detection rate of the disease. The initial PSA, PSA nadir, PSA trigger and PSAva showed statistically significant differences according to the result of the PET-CT. The best discriminatory cut-off point between a positive or negative PET-CT for PSA trigger and PSAva was 3.5ng/ml and 0.25ng/ml/month respectively. The PSAdt was significantly lower in patients with remote disease compared to patients with localised disease (5.1 vs 16.8 months, P=.01). The probability that the PET-CT would detect remote disease vs localised disease was 3.2 times higher if the PSAdt was under 6 months (80% vs 20%, OR: 3.2, P=.02). In the multivariate analysis, only the initial PSA and not having undergone radical prostatectomy were demonstrated as independent predictive factors of a positive PET-CT result. CONCLUSIONS: The PET-CT with 18F-FCH can detect disease in a high percentage of patients with biochemical recurrence and provides information on its anatomical location. PSA kinetics and the patient's previous treatment are key variables in increasing the test's diagnostic.

Validación psicométrica de la versión en castellano del cuestionario USS-PROM para pacientes sometidos a cirugía de uretra anterior / Psychometric validation of the Spanish version of the USS-PROM questionnaire for patients who undergo anterior urethral surgery

Objetivo: Traducir y validar en lengua castellana el cuestionario Urethral Stricture Surgery Patient-Reported Outcome Measure (USS-PROM), evaluar sus propiedades psicométricas y determinar su idoneidad para su uso clínico en nuestro medio. Adicionalmente, se valoraron los posibles cambios en la función eyaculatoria mediante el Male Sexual Health Questionnaire-Ejaculatory Dysfunction (MSHQ-EjD). Material y métodos: Se realizó una traducción sistemática de la versión británica. De forma prospectiva, entre septiembre 2014 y septiembre 2015 se incluyeron pacientes programados para cirugía de estenosis de uretra anterior. Todos los pacientes completaron el cuestionario antes y después de la cirugía. Se realizó un estudio psicométrico en profundidad del cuestionario. Resultados: Se evaluaron las respuestas de un total de 40 pacientes. El cuestionario demostró su validez presentando excelente correlación negativa entre las puntuaciones de los síntomas de vaciado y el flujo máximo (r = −0,6, p < 0,001), y mostrando también mejoría significativa en el EQ5D-visual analogue scale (VAS) y el time trade-off (TTO). Para la consistencia interna, el alfa de Cronbach fue de 0,701. Para la fiabilidad test-retest el coeficiente de correlación intraclase (CCI) global fue de 0,974 y los CCI de cada ítem por separado oscilaron entre 0,799 y 0,980. Se observaron mejoras significativas en todos los ítems de síntomas miccionales y calidad de vida relacionada con la salud (CVRS) (p < 0,001), quedando demostrada la capacidad de respuesta al cambio del cuestionario. No observamos cambios significativos en el MSHQ-EjD. Conclusiones: La versión en castellano del cuestionario USS-PROM es un instrumento válido para cuantificar los cambios en los síntomas de vaciado y la CVRS de los pacientes sometidos a cirugía de uretra anterior

Ojective: To translate into Spanish and validate the Urethral Stricture Surgery Patient-Reported Outcome Measure (USS-PROM) questionnaire, assessing its psychometric properties and determining its suitability for clinical use in our community. We also assessed the potential changes in ejaculatory function using the Male Sexual Health Questionnaire-Ejaculatory Dysfunction (MSHQ-EjD). Material and methods: A systematic translation of the British version was performed. Patients scheduled for anterior urethral stricture surgery between September 2014 and September 2015 were prospectively included in the study. All patients completed the questionnaire before and after the surgery. We conducted an in-depth psychometric study of the questionnaire. Results: We assessed the responses of a total of 40 patients. The questionnaire showed its validity, presenting an excellent negative correlation between the voiding symptom scores and the maximum flow (r = −0.6,P < .001), and also showed significant improvement in the EQ5D-VAS (visual analogue scale) and the time trade-off. For internal consistency, the Cronbach's alpha was 0.701. For the test-retest reliability, the overall intraclass correlation coefficient (ICC) was 0.974, and the ICC for each item separately ranged from 0.799 to 0.980. We observed significant improvement in all items regarding urinary symptoms and health-related quality of life (P < .001), thereby demonstrating the response capacity to changing the questionnaire. There were no significant changes in the MSHQ-EjD. Conclusions: The Spanish version of the USS-PROM questionnaire is a valid instrument for quantifying changes in voiding symptoms and the health-related quality of life of patients undergoing anterior urethral surgery

Psychometric validation of the Spanish version of the USS-PROM questionnaire for patients who undergo anterior urethral surgery. / Validación psicométrica de la versión en castellano del cuestionario USS-PROM para pacientes sometidos a cirugía de uretra anterior.

OBJECTIVE: To translate into Spanish and validate the Urethral Stricture Surgery Patient-Reported Outcome Measure (USS-PROM) questionnaire, assessing its psychometric properties and determining its suitability for clinical use in our community. We also assessed the potential changes in ejaculatory function using the Male Sexual Health Questionnaire-Ejaculatory Dysfunction (MSHQ-EjD). MATERIAL AND METHODS: A systematic translation of the British version was performed. Patients scheduled for anterior urethral stricture surgery between September 2014 and September 2015 were prospectively included in the study. All patients completed the questionnaire before and after the surgery. We conducted an in-depth psychometric study of the questionnaire. RESULTS: We assessed the responses of a total of 40 patients. The questionnaire showed its validity, presenting an excellent negative correlation between the voiding symptom scores and the maximum flow (r=-0.6, P<.001), and also showed significant improvement in the EQ5D-VAS (visual analogue scale) and the time trade-off. For internal consistency, the Cronbach's alpha was 0.701. For the test-retest reliability, the overall intraclass correlation coefficient (ICC) was 0.974, and the ICC for each item separately ranged from 0.799 to 0.980. We observed significant improvement in all items regarding urinary symptoms and health-related quality of life (P<.001), thereby demonstrating the response capacity to changing the questionnaire. There were no significant changes in the MSHQ-EjD. CONCLUSIONS: The Spanish version of the USS-PROM questionnaire is a valid instrument for quantifying changes in voiding symptoms and the health-related quality of life of patients undergoing anterior urethral surgery.

Cistocele escrotal incidental. Signo de la mancuerna / Incidental finding of scrotal. Cystocele dumbbell sign

No disponible

Primary treatment of painful varicocoele through percutaneous retrograde embolization with fibred coils.

The literature on the treatment of painful varicocoele is limited, likely because of the short period since it was recognized as a clinical entity and the limitations posed by the subjectivity of pain. Our aim was to systematically analyse the results of percutaneous embolization as the chosen treatment for this condition. We conducted a retrospective study of patients undergoing percutaneous embolization as primary treatment for painful varicocoele from January 2007 to November 2013. Radiologic and ultrasonographic successes were evaluated according to the existence or absence of venous reflux on venography after embolization and on Echo Doppler control at 3-6 months. Clinical success was assessed by Visual Analog Scale pain questionnaires before surgery and at 3-6 months; in addition, at the time of the study, telephone interviews were conducted to update the clinical situation and development. A total of 154 patients received operations. The median pain before surgery, at 3-6 months and at the time of interview was 7, 1 and 0 points respectively (p < 0.001). The ultrasonographic success rate at 3-6 months was 68.6%. With a median follow-up of 39 months, the success and relapse/clinical persistence rates were 86.9 and 13.1% respectively. By studying the degree of agreement between clinical success and ultrasonographic success, a kappa index = 0.443 was obtained. Patients with success recounted greater pre-operative pain scores than those who relapsed or persisted (7.5 vs. 5.0; p = 0.004). In patients with painful varicocoele, the ultrasonographic recurrence of venous reflux does not imply the recurrence of pain; hence, the proper assessment of success in these patients should include a systematic assessment of their pain and grade of reflux. Percutaneous retrograde embolization as a primary treatment for painful varicocoele is a clinically effective option with a high success rate that can be maintained in the long term, especially in patients with high pre-operative pain.

Sphenoid sinus metastasis as the presenting manifestation of a prostatic adenocarcinoma: case report and overview of the literature.

Although a metastatic presentation of an occult prostatic adenocarcinoma is not uncommon, the majority of these patients present with bone metastasis affecting the axial skeleton. Cranial metastases to the paranasal sinuses are extremely rare. A 56-year-old man presented with loss of vision and numbness of the right side of the face. Computed tomography (CT) scan and cranial magnetic resonance imaging (MRI) revealed a mass invading the sphenoid sinus. The patient underwent surgery to remove the lesion, and the histopathological examination suggested metastasis of an adenocarcinoma, with positive staining to prostatic specific antigen (PSA). However, serum PSA was 4 ng/mL, and the patient did not report any lower urinary tract symptoms or bone pain. Transrectal ultrasound-guided biopsy revealed prostatic adenocarcinomas with a Gleason score of 8 [4 + 4]. The subsequent treatment consisted of radiotherapy and androgen deprivation, followed by first- and second-line chemotherapy (docetaxel and cabazitaxel) when the disease progressed. The patient achieved a good response with the last cycle of cabazitaxel and after a 5-year followup is currently alive. Cranial metastases of prostate adenocarcinoma are rare, and there is currently no standard treatment for these patients. Whenever possible, surgery combined with radiotherapy and hormonotherapy is the recommended option.

Primary renal lymphoma: long-term results of two patients treated with a chemotherapy + rituximab protocol.

Primary renal lymphoma (PRL) is a rare disease of which the etiology and pathogenesis remain controversial, and there is currently no standard treatment for it. We present the results of a long-term followup of two patients who were diagnosed with PRL and treated with cyclophosphamide, adriamycin, vincristine, prednisolone and rituximab (CHOP + R) regimen. Both patients reached a complete response, and there is no evidence of recurrence after 4.5- and 5-year followup periods. Based on our experience and other recently published studies, we recommend the combination of CHOP + rituximab as the elective treatment for this disease. To our knowledge, this is the longest followup period with a complete response that has been reported with this modality of treatment.