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.

Genetic variants in xenobiotic detoxification enzymes, antioxidant defenses and hormonal pathways as biomarkers of susceptibility to prostate cancer.

Cancer is considered a complex disease that in many cases results from the interaction between chemical exposures, either from environmental or dietary sources, and genetic polymorphisms of xenobiotic-metabolizing enzymes (XME) or antioxidant enzymatic defenses. This study explored associations and interactions between genetic and environmental risk factors on the risk of prostate cancer (PCa) in 323 subjects that underwent prostate biopsy due to prostate specific antigen (PSA) levels above 4 ng/ml (161 PCa and 162 non-PCa). Eleven genes involved directly or indirectly in xenobiotic detoxification, oxidative stress and estrogen signaling were studied (GSTM1, GPX1 (rs1050450 and rs17650792), NAT2 (rs1801280), TXNRD1 (rs7310505), PRDX3 (rs3740562), CYP17A1 (rs743572), PON1 (rs662), SOD1 (rs10432782), SOD2 (rs4880), CAT (rs1001179), and ESR1 (rs746432)). A structured questionnaire was administered to all individuals to assess environmental and dietary chemical exposures. Medical data was collected by urologists. GPX1 rs17650792 polymorphism was the only one showing a significant inverse association with PCa risk. PRDX3 and GPX1 (rs17650792) genetic polymorphisms were significantly associated with Gleason score and PSA levels, respectively. The intake of nuts and soya products was associated with a reduced risk of PCa, as well as the performance of physical activity. Moreover, a number of gene-environmental interactions were found to increase the risk of PCa, particularly exposure to pesticides and rs1801280 (NAT2) and tobacco smoking and rs1050450 (GPX1). These findings suggest that the association of genetic and environmental risk factors with PCa risk should be assessed jointly for a better understanding of this complex disease.

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.

[Inpatient candiduria: etiology, susceptibility to antifungal drugs and risk factors]. / Candiduria en pacientes hospitalizados: etiología, sensibilidad a los fármacos antifúngicos y factores de riesgo.

OBJECTIVE: Candida could become the second most frequent cause of nosocomial urinary tract infection. Although Candida albicans is the most important species, others have arisen as emerging pathogens. The aim of this study was to analyze the presence of candiduria in inpatients. METHODS: We performed a retrospective study of Candida isolates from adult inpatient urocultures over five years, gathering and tabulating data on: the species; susceptibility to fluconazole, amphotericin B, and voriconazole (Vitek2, BioMerieux); presence of catheter; hospital department of origin; and patient age and sex. RESULTS: We detected 289 yeast episodes, observing an annual increase: 134 (46.4%) were non-C. albicans yeasts, with 57 (19.7%) being Candida glabrata, 37 (12.8%) Candida tropicalis, 25 (8.6%) Candida parapsilosis, and 10 (3.5%) Candida lusitaniae. Most isolates derived from catheterized (240, 83.0%) and Internal Medicine Department (118, 40.8%) patients, observing an annual increase; 152 (52.6%) isolates were from males, and the mean age was >65 years. Susceptibility to antifungals was >85%. CONCLUSIONS: Inpatient urocultures should include data on the presence of Candida, which is more prevalent in Internal Medicine Department inpatients, in those with urinary catheter, and in over 65-year-olds. Almost half of the isolates were non-C. albicans yeasts, and we recommend complete identification of the species involved.

Actividad y concentraciones de antibióticos en muestras clínicas de pacientes con prostatitis crónica bacteriana / Antibiotic activity and concentrations in clinical samples from patients with chronic bacterial prostatitis

Objetivos: La prostatitis crónica bacteriana (PCB) es la enfermedad urológica más frecuente en menores de 50 años, cuya clínica de larga evolución puede estar relacionada con una inadecuada pauta terapéutica. El objetivo fue analizar la sensibilidad de los microorganismos aislados de pacientes con PCB y medir las concentraciones de antibiótico semanalmente en suero, semen y orina. Material y métodos: Para el estudio de la sensibilidad antibiótica, entre enero de 2013 y diciembre de 2014 se incluyeron 60 aislados clínicos procedentes de muestras de semen de pacientes confirmados microbiológicamente con PCB, y se llevó a cabo por microdilución en caldo. Para el estudio de las concentraciones de antibióticos, entre los meses de enero y mayo de 2014 se recogieron muestras de orina, sangre y semen, semanalmente, durante 4 semanas de tratamiento de 8 pacientes con cultivo positivo para PCB, y se midieron las concentraciones mediante cromatografía de líquidos de ultra alta eficacia acoplada a espectrometría de masas en tándem (UHPLC-MS/MS). Resultados: Fosfomicina y nitrofurantoína fueron los antibióticos con mayor actividad (95,2% en ambos casos). Las concentraciones medias de antibiótico en semen durante las 4 semanas estudiadas fueron las siguientes: 1,68 mg/l; 8,30 mg/l; 2,61 mg/l; 0,33 mg/l y 2,90 mg/l, respectivamente para los pacientes 1 a 5, que recibieron levofloxacino; 1,625 mg/l para el paciente 6, que recibió ciprofloxacino 2,67 mg/l para el paciente 7, que fue tratado con ampicilina, y 1,05 mg/l para el paciente 8, que recibió doxiciclina. Se obtuvieron mayores concentraciones en las muestras de orina que en suero y semen, siendo coparables estas 2 últimas. Conclusiones: Fosfomicina se postula como principal alternativa al tratamiento empírico de la PCB por su elevada actividad in vitro. La concentración de antibiótico en semen fue superior a la concentración mínima inhibitoria frente al agente etiológico, aunque no siempre se correlacionó la negativización microbiológica con la evolución clínica favorable

Objectives: Chronic bacterial prostatitis (CBP) is the most common urological disease in patients younger than 50 years, whose long-standing symptoms could be related to an inappropriate therapeutic regimen. The objective was to analyse the sensitivity of microorganisms isolated from patients with CBP and measure the weekly antibiotic concentrations in serum, semen and urine. Material and methods: For the antibiotic sensitivity study, 60 clinical isolates were included between January 2013 and December 2014 from semen samples from patients with microbiologically confirmed CBP. Broth microdilution was performed on the samples. For the antibiotic concentration study from January to May 2014, urine, blood and semen samples were collected weekly, over 4 weeks of treatment from 8 patients with positive cultures for CBP. The concentrations were measured using ultra-high performance liquid chromatography coupled to tandem mass spectrometry (UHPLC-MS/MS). Results: The antibiotics fosfomycin and nitrofurantoin had the highest activity (95.2% in both cases). The mean antibiotic concentrations in semen during the 4 weeks studied were as follows: 1.68 mg/L, 8.30 mg/L, 2.61 mg/L, 0.33 mg/L and 2.90 mg/L, respectively, for patients 1 to 5, who were treated with levofloxacin; 1.625 mg/L for patient 6, who was treated with ciprofloxacin; 2.67 mg/L for patient 7, who was treated with ampicillin; and 1.05 mg/L for patient 8, who was treated with doxycycline. Higher concentrations were obtained in the urine samples than in serum and semen, the latter 2 of which were comparable. Conclusions: Fosfomycin is proposed as the primary alternative to the empiric treatment of CBP due to its high in vitro activity. The antibiotic concentration in semen was higher than the minimal inhibitory concentration against the aetiological agent, although microbiological negativisation was not always correlated with a favourable clinical outcome

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

Antibiotic activity and concentrations in clinical samples from patients with chronic bacterial prostatitis. / Actividad y concentraciones de antibióticos en muestras clínicas de pacientes con prostatitis crónica bacteriana.

OBJECTIVES: Chronic bacterial prostatitis (CBP) is the most common urological disease in patients younger than 50 years, whose long-standing symptoms could be related to an inappropriate therapeutic regimen. The objective was to analyse the sensitivity of microorganisms isolated from patients with CBP and measure the weekly antibiotic concentrations in serum, semen and urine. MATERIAL AND METHODS: For the antibiotic sensitivity study, 60 clinical isolates were included between January 2013 and December 2014 from semen samples from patients with microbiologically confirmed CBP. Broth microdilution was performed on the samples. For the antibiotic concentration study from January to May 2014, urine, blood and semen samples were collected weekly, over 4 weeks of treatment from 8 patients with positive cultures for CBP. The concentrations were measured using ultra-high performance liquid chromatography coupled to tandem mass spectrometry (UHPLC-MS/MS). RESULTS: The antibiotics fosfomycin and nitrofurantoin had the highest activity (95.2% in both cases). The mean antibiotic concentrations in semen during the 4 weeks studied were as follows: 1.68mg/L, 8.30mg/L, 2.61mg/L, 0.33mg/L and 2.90mg/L, respectively, for patients 1 to 5, who were treated with levofloxacin; 1.625mg/L for patient 6, who was treated with ciprofloxacin; 2.67mg/L for patient 7, who was treated with ampicillin; and 1.05mg/L for patient 8, who was treated with doxycycline. Higher concentrations were obtained in the urine samples than in serum and semen, the latter 2 of which were comparable. CONCLUSIONS: Fosfomycin is proposed as the primary alternative to the empiric treatment of CBP due to its high in vitro activity. The antibiotic concentration in semen was higher than the minimal inhibitory concentration against the aetiological agent, although microbiological negativisation was not always correlated with a favourable clinical outcome.

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.

Papel de la tomografía por emisión de positrones/tomografía computarizada con análogos radiomarcados de colina en el cáncer de próstata / The role of positron emission tomography/computed tomography imaging with radiolabeled choline analogues in prostate cancer

Introducción: El cáncer de próstata es el tumor maligno sólido más frecuente en los países occidentales. La tomografía por emisión de positrones/tomografía computarizada con análogos radiomarcados de colina es una herramienta útil en la re-estadificación de pacientes con aumento del antígeno prostático específico después de tratamiento radical -donde las técnicas de imagen convencional tienen limitaciones importantes- así como en un seleccionado grupo de pacientes en la valoración inicial de esta neoplasia. Esta situación nos lleva a plantear una revisión de la literatura donde se evalúe la utilidad de esta exploración en la toma de decisiones diagnóstico-terapéuticas en el cáncer de próstata. Evidencia de adquisición: Realizamos una búsqueda bibliográfica a través de la base de datos Medline (vía Pubmed) utilizando los términos Prostate cancer y Choline-PET/CT a los que añadimos los términos Biochemical failurey/o Staging y/o PSA kinetics. Así mismo, seleccionamos los trabajos en lengua inglesa y española e incluimos artículos originales, revisiones, revisiones sistemáticas, metaanálisis y guías de práctica clínica. Conclusiones: De acuerdo con los datos disponibles los análogos radiomarcados de colina desempeñan un papel importante en el manejo del cáncer de próstata, especialmente en la recurrencia bioquímica, donde la exactitud de la técnica se correlaciona bien con el valor del antígeno prostático específico y su cinética. Aunque esta técnica se perfila como una modalidad diagnóstica de aplicación en la planificación del tratamiento del cáncer de próstata, aún no se han realizado recomendaciones finales sobre su uso

Introduction: prostate cancer is the most frequent solid malignant tumor in Western Countries. Positron emission tomography/x-ray computed tomography imaging with radiolabeled choline analogues is a useful tool for restaging prostate cancer in patients with rising prostate-specific antigen after radical treatment (in whom conventional imaging techniques have important limitations) as well as in the initial assessment of a selected group of prostate cancer patients. For this reason a literature review is necessary in order to evaluate the usefulness of this imaging test for the diagnosis and treatment of prostate cancer. Evidence acquisition: a MEDLINE (PubMed way) literature search was performed using the search parameters: «Prostate cancer» and «Choline-PET/CT». Other search terms were «Biochemical failure» and/or «Staging» and/or «PSA kinetics». English and Spanish papers were selected; original articles, reviews, systematic reviews and clinical guidelines were included. Conclusions: according to available data, radiolabeled choline analogues plays an important role in the management of prostate cancer, especially in biochemical relapse because technique accuracy is properly correlated with prostate-specific antigen values and kinetics. Although is an emerging diagnostic technique useful in treatment planning of prostate cancer, final recommendations have not been submitted

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.

Implicación de las moléculas HLA de clase I en el escape inmunitario de tumores urológicos / Involvement of HLA Class I Molecules in the Immune Escape of Urologic Tumors

Contexto y objetivo: Analizar la influencia de las distintas alteraciones de las moléculas del antígeno leucocitario humano de clase i (HLA I ) en la promoción del cáncer renal, vesical y prostático. También estudiaremos la correlación entre la expresión de estas moléculas y la progresión de la enfermedad neoplásica, además de la respuesta al tratamiento. Adquisición de evidencias: Se ha podido constatar, experimentalmente, que el sistema inmunitario puede reconocer y destruir células tumorales. Mediante el análisis de la expresión de las moléculas HLA I, en la superficie de células tumorales, hemos podido estudiar este mecanismo de escape tumoral frente al sistema inmunitario. Síntesis de evidencias: Una alteración o daño irreversible en las moléculas HLA de clase i es utilizado por las células cancerígenas como mecanismo de escape frente al sistema inmunitario. La función de estas moléculas es reconocer péptidos endógenos y presentarlos a los linfocitos T del sistema inmunitario. Existe una clara relación entre alteraciones reversibles de HLA I y el éxito de la terapia, mientras que las lesiones irreversibles implican una falta de respuesta al tratamiento. La activación del sistema inmunitario puede revertir la expresión de moléculas HLA I en aquellos tumores con lesiones reversibles, mientras que los tumores con lesiones irreversibles no responden a dicha activación. Determinar el tipo de alteración HLA I en los tumores es de vital importancia a la hora de elegir el tipo de tratamiento a seguir buscando el éxito terapéutico. Aquellos tumores con lesiones reversibles pueden ser tratados con inmunoterapias clásicas, sin embargo, los tumores con alteraciones irreversibles deberían seguir protocolos alternativos, como el uso de vectores virales que trasporten los genes HLA dañados para conseguir la reexpresión de la proteína. Conclusión: A partir de los estudios realizados, en tumores urológicos, podemos concluir que las moléculas HLA de clase i tienen un papel fundamental en el escape de estos tumores frente al sistema inmunitario

Context and objective: To analyze the influence of different alterations in human leukocyte antigen class I molecules (HLA I) in renal cell carcinoma, as well as in bladder and prostate cancer. We also study the correlation between HLA I expression and the progression of the disease and the response after immunotherapy protocols. Evidences acquisition: It has been shown, experimentally, that the immune system can recognize and kill neoplastic cells. By analyzing the expression of HLA I molecules on the surface of cancer cells, we were able to study the tumor escape mechanisms against the immune system. Evidences synthesis: Alteration or irreversible damage in HLA I molecules is used by the neoplastic cells to escape the immune system. The function of these molecules is to recognize endogenous peptides and present them to T cells of the immune system. There is a clear relationship between HLA I reversible alterations and success of therapy. Irreversible lesions also imply a lack of response to treatment. The immune system activation can reverse HLA I molecules expression in tumors with reversible lesions, whereas tumors with irreversible ones do not respond to such activation. Determine the type of altered HLA I molecules in tumors is of paramount importance when choosing the type of treatment to keep looking for therapeutic success. Those tumors with reversible lesions can be treated with traditional immunotherapy; however, tumour with irreversible alterations should follow alternative protocols, such as the use of viral vectors carrying the HLA genes to achieve damaged re-expression of the protein. Conclusion: From studies in urologic tumors, we can conclude that the HLA I molecules play a key role in these tumors escape to the immune system

The role of positron emission tomography/computed tomography imaging with radiolabeled choline analogues in prostate cancer.

INTRODUCTION: prostate cancer is the most frequent solid malignant tumor in Western Countries. Positron emission tomography/x-ray computed tomography imaging with radiolabeled choline analogues is a useful tool for restaging prostate cancer in patients with rising prostate-specific antigen after radical treatment (in whom conventional imaging techniques have important limitations) as well as in the initial assessment of a selected group of prostate cancer patients. For this reason a literature review is necessary in order to evaluate the usefulness of this imaging test for the diagnosis and treatment of prostate cancer. EVIDENCE ACQUISITION: a MEDLINE (PubMed way) literature search was performed using the search parameters: «Prostate cancer¼ and «Choline-PET/CT¼. Other search terms were «Biochemical failure¼ and/or «Staging¼ and/or «PSA kinetics¼. English and Spanish papers were selected; original articles, reviews, systematic reviews and clinical guidelines were included. CONCLUSIONS: according to available data, radiolabeled choline analogues plays an important role in the management of prostate cancer, especially in biochemical relapse because technique accuracy is properly correlated with prostate-specific antigen values and kinetics. Although is an emerging diagnostic technique useful in treatment planning of prostate cancer, final recommendations have not been submitted.

Involvement of HLA class I molecules in the immune escape of urologic tumors.

CONTEXT AND OBJECTIVE: To analyze the influence of different alterations in human leukocyte antigen class I molecules (HLA I) in renal cell carcinoma, as well as in bladder and prostate cancer. We also study the correlation between HLA I expression and the progression of the disease and the response after immunotherapy protocols. EVIDENCES ACQUISITION: It has been shown, experimentally, that the immune system can recognize and kill neoplastic cells. By analyzing the expression of HLA I molecules on the surface of cancer cells, we were able to study the tumor escape mechanisms against the immune system. EVIDENCES SYNTHESIS: Alteration or irreversible damage in HLA I molecules is used by the neoplastic cells to escape the immune system. The function of these molecules is to recognize endogenous peptides and present them to T cells of the immune system. There is a clear relationship between HLA I reversible alterations and success of therapy. Irreversible lesions also imply a lack of response to treatment. The immune system activation can reverse HLA I molecules expression in tumors with reversible lesions, whereas tumors with irreversible ones do not respond to such activation. Determine the type of altered HLA I molecules in tumors is of paramount importance when choosing the type of treatment to keep looking for therapeutic success. Those tumors with reversible lesions can be treated with traditional immunotherapy; however, tumour with irreversible alterations should follow alternative protocols, such as the use of viral vectors carrying the HLA genes to achieve damaged re-expression of the protein. CONCLUSION: From studies in urologic tumors, we can conclude that the HLA I molecules play a key role in these tumors escape to the immune system.

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.

Pólipo fibroepitelial ureteral gigante resuelto con resección y sustitución intestinal / Giant fibroepithelial polyp of the ureter: treatment with ureteral resection and intestinal substitution

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[Ureterocutaneous fistula after nephrectomy: two cases]. / Fístula ureterocutánea tras nefrectomía: aportación de dos casos y revisión de la literatura.

The ureteral fistulas are related to the gynecological surgery, digestive surgery and reconstructive urologic surgery of the upper urinary tract. Fistulas are described ureterovaginal, ureteroduodenal, ureterocolonic, ureteropleural, ureterovascular, etc. However, the ureterocutaneous fistulas of the ureteral stump after nephrectomy are a very unusual entity. We report two cases as well as their resolution by means of surgery.