MetSCORE: a molecular metric to evaluate the risk of metabolic syndrome based on serum NMR metabolomics.

BACKGROUND: Metabolic syndrome (MetS) is a cluster of medical conditions and risk factors correlating with insulin resistance that increase the risk of developing cardiometabolic health problems. The specific criteria for diagnosing MetS vary among different medical organizations but are typically based on the evaluation of abdominal obesity, high blood pressure, hyperglycemia, and dyslipidemia. A unique, quantitative and independent estimation of the risk of MetS based only on quantitative biomarkers is highly desirable for the comparison between patients and to study the individual progression of the disease in a quantitative manner. METHODS: We used NMR-based metabolomics on a large cohort of donors (n = 21,323; 37.5% female) to investigate the diagnostic value of serum or serum combined with urine to estimate the MetS risk. Specifically, we have determined 41 circulating metabolites and 112 lipoprotein classes and subclasses in serum samples and this information has been integrated with metabolic profiles extracted from urine samples. RESULTS: We have developed MetSCORE, a metabolic model of MetS that combines serum lipoprotein and metabolite information. MetSCORE discriminate patients with MetS (independently identified using the WHO criterium) from general population, with an AUROC of 0.94 (95% CI 0.920-0.952, p < 0.001). MetSCORE is also able to discriminate the intermediate phenotypes, identifying the early risk of MetS in a quantitative way and ranking individuals according to their risk of undergoing MetS (for general population) or according to the severity of the syndrome (for MetS patients). CONCLUSIONS: We believe that MetSCORE may be an insightful tool for early intervention and lifestyle modifications, potentially preventing the aggravation of metabolic syndrome.

[Background historical views of systemic treatment for muscle invasive bladder cancer.] / Perspectiva histórica del tratamiento sistémico del cáncer de vejiga músculo invasivo.

OBJECTIVES: Bladder cancer is a frequent, chemosensitive disease and has shown good outcomes on several chemotherapy regimens over last 60 years. However, very little improvement has been shown in terms of overall survival and side-effects decrease. EVIDENCE ACQUISITION: A review on manuscripts published in English and Spanish from 1949 including the terms chemotherapy and bladder cancer has been performed. EVIDENCE SYNTHESIS: Locally advanced or metastatic bladder cancer chemotherapy was initially introduced for metastasis management. The utilization of cisplatin base regimens has shown superiority over single therapy. The most commonly used regimens are cisplatine-metotrexate-vinblastine, metotrexate-vinblatine-adriamicine-cisplatin y gemcitabine-cisplatin. Neoadjuvant chemotherapy has shown to provide a minimal overall survival advantage, based on level 1 evidence. Neoadjuvant chemotherapy utilizes the same cisplatin-based regimens. Neoadjuvant chemotherapy is underutilized due to the inability to identify non-responders. Adjuvant chemotherapy is more controversial due to the lack of strong evidence. It is used when neoadjuvant chemotherapy has been utilized and the cystectomy pathology report is locally advanced. The best outcomes are for low-volume node positive patients.In bladder preservation protocols (aiming to decreased morbidity associated with cystectomy and chemotherapy), several regimens have been utilized in combination with radiation therapy. No standardized treatmentis available as no comparisons with cystectomy have been done. CONCLUSION: Chemotherapy has been utilized for several decades in muscle invasive bladder cancer without any major survival improvements or decreaseon side-effects. That is the rational why the treatment regimen are widely different amongst groups without a standard treatment.

CONTEXTO: A pesar de que el tumor vesical es un proceso oncológico frecuente, ser quimiosensible y haber comunicado resultados con distintos quimioterápicos desde hace más de 60 años, pocos han sido los avances logrados en supervivencia global y disminución de efectos secundarios.ADQUISICIÓN DE LA EVIDENCIA: Se realiza una revisión de los artículos publicados en lengua españolae inglesa desde enero de 1949 con las palabras quimioterapia, cáncer y vejiga en cualquier campo de la publicación. SINTESIS DE LA EVIDENCIA: La quimioterapia en el cáncer localmente avanzado o metastásico fue la primera empleada para intentar hacer regresar las metásta-sis. El empleo de combinaciones basadas en cisplatino ha demostrado superioridad sobre la monoterapia. Los regímenes más utilizados son cisplatino-metotrexate-vinblastina, metotrexate-vinblastina-adriamicina-cisplatino y gemcitabina-cisplatino. Como quimioterapia neoadyuvante, su utilización, aunque la mejoría en supervivencia es modesta, está basada en niveles de altos evidencia. Los regímenes son los mismos que para el avanzado y la imposibilidad de diferenciar los respondedores de los resistentes a la quimioterapia ha hecho que esté infrautilizada. La aplicación de quimioterapia adyuvante tiene más controversia porque los niveles de evidencia no son tan robustos. Se emplea cuando no se ha tratado con quimioterapianeoadyuvante y en la pieza de cistectomía el estadío es avanzado y tiene mejores resultados cuando es N+ con poca carga tumoral. En la preservación de órgano, para intentar disminuir la morbimortalidad del tratamiento de neoadyuvancia más cistectomía considerado el tratamiento con mayor evidencia, se han empleado diversas drogas combinadas en general con radioterapia sin conseguir un estándar de tratamiento al no haber comparaciones con la cistectomía.CONCLUSIÓN: La quimioterapia utilizada desde hace varias décadas en los tumores músculo-infiltrantes de vejiga no ha conseguido grandes mejoras en supervivencia ni disminución de los efectos secundarios. Por este motivo los esquemas de tratamiento varían de unos grupos a otros sin que haya un estándar de tratamiento.

Integrative analysis of transcriptomics and clinical data uncovers the tumor-suppressive activity of MITF in prostate cancer.

The dysregulation of gene expression is an enabling hallmark of cancer. Computational analysis of transcriptomics data from human cancer specimens, complemented with exhaustive clinical annotation, provides an opportunity to identify core regulators of the tumorigenic process. Here we exploit well-annotated clinical datasets of prostate cancer for the discovery of transcriptional regulators relevant to prostate cancer. Following this rationale, we identify Microphthalmia-associated transcription factor (MITF) as a prostate tumor suppressor among a subset of transcription factors. Importantly, we further interrogate transcriptomics and clinical data to refine MITF perturbation-based empirical assays and unveil Crystallin Alpha B (CRYAB) as an unprecedented direct target of the transcription factor that is, at least in part, responsible for its tumor-suppressive activity in prostate cancer. This evidence was supported by the enhanced prognostic potential of a signature based on the concomitant alteration of MITF and CRYAB in prostate cancer patients. In sum, our study provides proof-of-concept evidence of the potential of the bioinformatics screen of publicly available cancer patient databases as discovery platforms, and demonstrates that the MITF-CRYAB axis controls prostate cancer biology.

[Radium 223 in castration resistant prostate cancer.] / Radio 223 en cáncer de próstata resistente a la castración.

OBJECTIVE: To analyze the available evidence on Radium 223 therapy, an alfa particle emitter with specific action on bone metastases, studied on patients with castration resistant prostate cancer. EVIDENCE ACQUISITION: We review the pivotal study ALSYMPCA, that served to get the drug approval for this phase of the disease, and the new data obtained from its use. We also performed a search of ongoing studies with Radium 223 alone or in combination with other molecules. EVIDENCE SINTHESIS: According to the ALSYMPCA study, Radium 223 significantly prolongs the overall survival of patients with castration resistant prostate cancer and bone metastases; approximately 3.6 months in comparison with patients who received placebo, which turns into a median life expectancy of 14.9 months, and a 36-month survival of 46%, associated with a 30% reduction in death risk. Overall survival results were consistent both in patients who receive Docetaxel previously and those who did not. RESULTS: for secondary variables support the positive effect of Radium 223 therapy on symptomatic skeletal events (for example, the use of external beam radiotherapy to alleviate pain) and bone markers, confirming its efficacy in bone metastases. CONCLUSIONS: Radium 223 is the first treatment directed to bone that has demonstrated significant improvement on overall survival. It also prolonged the time to the first skeletal event and the median time to PSA increase significantly. All this in addition to its manageable adverse effects, lower than those appeared in the placebo arm of the pivotal study ALSYMPCA.

Review of evidence on handling hazardous drugs and Products in Urology Services; consensus document between the Spanish Urology Association and the Spanish Society of Health-System Pharmacists.

OBJECTIVE: The intravesical administration of hazardous drug products is a  standard practice in the urology setting, which potentially exposing medical  personnel to these drug products. It was deemed necessary to have a consensus document among the scientific societies involved (the Spanish Urological  Association and the Spanish Society of Hospital Pharmacy) that collects the best  available evidence on the safest handling possible of dangerous drug products in the setting of urology departments. METHOD: We reviewed the legislation and recommendations on the handling of  dangerous drug products, both at the national and international level. RESULTS: There is national legislation and regulations for protecting workers who  handle dangerous drugs and products, as well as  recommendations for handling to protect both the product and workers. DISCUSSION: Following the strategic lines of the European Parliament for 2014- 2020 in the chapter on occupational safety and health, the Spanish Urological  Association and the Spanish Society of Hospital Pharmacy proposed a series of  actions that decrease the risks of exposure for practitioners and caregivers  involved in the handling of these products. CONCLUSIONS: After this review, 19 recommendations were established for  handling dangerous drug products, which can be summarised as the need to  train all individuals involved (from management teams to patients and  caregivers), adopt systems that prevent contaminating leaks, implement  exposure surveillance programmes and optimise available resources.

Objetivo: La administración intravesical de medicamentos peligrosos es una  práctica habitual en el ámbito de la urología, con posible exposición del personal  sanitario a dichos medicamentos. Se considera necesario disponer de un  documento de consenso entre las sociedades científicas implicadas ­Asociación  Española de Urología y Sociedad Española de Farmacia Hospitalaria­ que recoja la mejor evidencia disponible para el manejo, de la forma más segura posible,  de medicamentos peligrosos en el ámbito de los servicios de Urología.Método: Se ha realizado una revisión de la legislación y de las recomendaciones sobre el manejo de medicamentos peligrosos tanto a nivel estatal como internacional.Resultados: Se dispone de legislación nacional y de normativas para la  protección de los trabajadores que manipulen medicamentos y productos peligrosos, así como recomendaciones de manipulación para la protección tanto del producto, como de los trabajadores.Discusión: Siguiendo las líneas estratégicas del Parlamento Europeo para el  período 2014-2020 en el capítulo de seguridad y salud laboral, la Asociación Española de Urología y la Sociedad Española de Farmacia Hospitalaria proponen una serie de actuaciones que hagan disminuir los riesgos de exposición de los profesionales y cuidadores implicados en su manejo. Conclusiones: Tras esta revisión se establecen 19 recomendaciones para el  manejo de medicamentos peligrosos que pueden resumirse en la necesidad de  formación de todas las personas implicadas (desde los equipos directivos hasta  los pacientes y cuidadores), la adopción de sistemas que no permitan fugas  contaminantes, programas de vigilancia de las exposiciones y optimización de  los recursos disponibles.

Erratum: The metabolic co-regulator PGC1α suppresses prostate cancer metastasis.

This corrects the article DOI: 10.1038/ncb3357.

The metabolic co-regulator PGC1α suppresses prostate cancer metastasis.

Cellular transformation and cancer progression is accompanied by changes in the metabolic landscape. Master co-regulators of metabolism orchestrate the modulation of multiple metabolic pathways through transcriptional programs, and hence constitute a probabilistically parsimonious mechanism for general metabolic rewiring. Here we show that the transcriptional co-activator peroxisome proliferator-activated receptor gamma co-activator 1α (PGC1α) suppresses prostate cancer progression and metastasis. A metabolic co-regulator data mining analysis unveiled that PGC1α is downregulated in prostate cancer and associated with disease progression. Using genetically engineered mouse models and xenografts, we demonstrated that PGC1α opposes prostate cancer progression and metastasis. Mechanistically, the use of integrative metabolomics and transcriptomics revealed that PGC1α activates an oestrogen-related receptor alpha (ERRα)-dependent transcriptional program to elicit a catabolic state and metastasis suppression. Importantly, a signature based on the PGC1α-ERRα pathway exhibited prognostic potential in prostate cancer, thus uncovering the relevance of monitoring and manipulating this pathway for prostate cancer stratification and treatment.

Quality of life in patients with lower urinary tract symptoms associated with BPH: change over time in real-life practice according to treatment--the QUALIPROST study.

PURPOSE: To evaluate change in quality of life (QoL) and symptoms in patients with lower urinary tract symptoms/benign prostatic hyperplasia (LUTS/BPH) in conditions of current clinical practice. METHODS: Prospective, longitudinal, multicenter open-label study was carried out in urology outpatient clinics. Patients were ≥40 years of age with an International Prostate Symptom Score (IPSS) score ≥ 8. QoL and symptoms were measured at baseline and 6 months using the Benign Prostatic Hyperplasia Impact Index (BII) and the IPSS. RESULTS: 1713 patients were included for analysis. Mean (SD) IPSS and BII scores at baseline were 16.8 (5.4) and 6.8 (2.6), respectively. 8.9 % (n = 153) of study participants did not receive treatment (watchful waiting, WW), 70.3 % (n = 1204) were prescribed monotherapy (alpha-adrenergic blockers [AB]; phytotherapy [PT, of which 95.2 % was the hexanic extract of Serenoa repens, HESr]; or 5-alpha-reductase inhibitors [5ARI]), and 20.8 % (n = 356) received combined treatment (AB + 5ARI; AB + HESr; others). At 6 months, improvements in QoL were similar across the different medical treatment (MT) groups, both for monotherapy (AB: mean improvement [SD] of 2.4 points [2.4]; PT: 1.9 [2.4]; 5ARI: 2.5 [2.3]) and combined therapy (AB + 5ARI: 3.1 [2.9]; AB + PT: 3.1 [2.5]). There were no clinically significant differences between MT groups and all showed significant improvement over WW (p < 0.05). HESr showed similar efficacy to AB and 5ARI both as monotherapy and in combination with AB. Results on the IPSS were similar. CONCLUSIONS: Improvements in QoL and symptoms were equivalent across the medical treatments most widely used in real-life practice to manage patients with moderate or severe LUTS. HESr showed an equivalent efficacy to AB and 5ARI with fewer side effects.

A Pilot Study on the Potential of RNA-Associated to Urinary Vesicles as a Suitable Non-Invasive Source for Diagnostic Purposes in Bladder Cancer.

Bladder cancer is one of the most common cancers and, together with prostate carcinoma, accounts for the majority of the malignancies of the genitourinary tract. Since prognosis ameliorates with early detection, it will be beneficial to have a repertoire of diagnostic markers that could complement the current diagnosis protocols. Recently, cell-secreted extracellular vesicles have received great interest as a source of low invasive disease biomarkers because they are found in many body fluids, including urine. The current work describes a pilot study to generate an array-based catalogue of mRNA associated to urinary vesicles, and also a comparison with samples obtained from bladder cancer patients. After an analysis of presence/absence of transcripts in bladder cancer EVs, a list of genes was selected for further validation using PCR technique. We found four genes differentially expressed in cancer samples. LASS2 and GALNT1 were present in cancer patients, while ARHGEF39 and FOXO3 were found only in non-cancer urinary vesicles. Previous studies have pointed to the involvement of those genes in tumour progression and metastasis.

Key areas in the learning curve for robotic urological surgery: a Spanish multicentre survey.

BACKGROUND: The number of robotic-assisted procedures offered in Spain is rapidly increasing despite a lack of consensus criteria for training and credentialling. OBJECTIVE: This national multicentre study was designed to analyze the different areas of the robotic urological surgery learning curve. MATERIAL AND METHODS: A questionnaire was sent to all 13 urology units in Spain with an active robotics programme requesting information on training and problems encountered. RESULTS: In most centres (n = 11, 84.6%), training programmes were animal-based; cadavers were used at only 2 (15.4%). Proctoring in initial procedures was practiced by 12 groups (92.3%). When initiating the robotics programme, the console was shared at 8 units (61.5%). Prior experience in open and/or laparoscopic surgery was reported by 10 of the groups (76.9%), and experience in open surgery only by 2 (15.4%) or robotic surgery alone by 1 (7.7%). The procedure with which the robotics programme was started in all 13 participating units was radical prostatectomy. The number of cases needed to complete the learning curve for this procedure was 20-25 cases according to 8 (61.5%) surgery teams. CONCLUSIONS: Up until March 26, 2010, 1,692 operations, mostly radical prostatectomies, were conducted using the da Vinci robot in our country.

[Inflammatory aortic aneurysm and its relationship to urological disease: a case report and a literature review]. / Aneurismas de aorta inflamatorios y su relación con la patología urológica: caso clínico y revisión de la literatura científica.

OBJECTIVE: To report a successfully treated case of inflammatory aortic aneurysm. MATERIALS AND METHODS: A 57-year-old patient reported low back pain and urinary infections. An abdominal CT scan revealed a large inflammatory aneurysm in the abdominal aorta. An aortic bypass was performed with no complications. RESULTS: Patient course since surgery has been uneventful, and currently has no symptoms. CONCLUSIONS: Contribution of the radiographic team, mainly with the CT scan, is of great value both for differential diagnosis and adequate management and follow-up. Surgery is indicated to prevent aneurysm rupture, but an increased postoperative morbidity and mortality should be assumed.

[Does a pT0 cystectomy specimen imply being tumour-free in the long term?]. / ¿Implica el T0 en la pieza de cistectomía encontrarse libre de tumor a largo plazo?

INTRODUCTION AND OBJECTIVES: The aim of this study was to evaluate the progress of patients with a pT0 radical cystectomy specimen in order to know what factors are helpful in deciding when the bladder can be preserved. MATERIAL AND METHODS: We reviewed 153 cases of radical cystectomies performed due to bladder tumours without neoadjuvant therapy between 1995 and 2005 and with a minimum of three years of follow-up. Stage pT0 patients were selected. We considered age at time of diagnosis, sex, pathological stage and grade of the tumour at the time of transurethral resection (TUR), number of resections, surgical factors, tumour characteristics (multifocal, papillary or solid), progression-free survival, cancer-specific survival and cause of death. We ran a univariate analysis of the different factors studied along with disease progression. RESULTS: 12.8% of cystectomy specimens were pT0N0. Progression occurred in 35% between 6 months and 4 years after the cystectomy. Cancer-specific survival was 75%. Five patients died within an average of 18 months. The cause of death for all of them was tumour progression with distant metastasis. Statistical studies in the univariate analysis were only related to progression and the number of prior TURs, which is probably due to the number of cases, but the tumour multifocality, grade and stage were noteworthy. 15% of the pT0 patients had a papillary phenotype and 33% of them died. Of those with a non-papillary phenotype, 23.5% died. CONCLUSIONS: A stage pT0N0 cystectomy specimen does not define this surgery as curative, and these cases require the same follow-up as for the rest of the patients. It is of particular interest that out of all of our cases, there was no local recurrence, but there was distant metastasis. This leads us to believe that these patients could have benefitted from systemic chemotherapy with no need for radical surgery. In our study, the number of previous relapses was the only prognostic factor with statistical significance.

[Current treatment of small renal masses]. / Tratamiento actual de las masas renales pequeñas.

UNLABELLED: Incidental diagnosis of renal carcinoma (RC) is increasingly common due to widespread use of radiodiagnostic techniques for other conditions. In developed countries, incidental tumor account for more than 40% of detected tumors, and 80% of solid kidney tumors less than 4 cm in size are malignant. Standard treatment for these tumors is partial nephrectomy, and their relapse rate is 1%-2% The higher increase in diagnosis of this disease has occurred in patients aged 70 to 90 years, a group where associated comorbidities are very common. In the past two decades, in parallel to development of radiographic techniques, two ablation procedures achieving tumor necrosis through cold, cryotherapy, and through heat, radiofrequency, have become established. These procedures achieve 95% short- and long-term remissions in tumors less than 4 cm in size. In addition, since these procedures may be performed percutaneously, both complications and hospital stay have decreased. As early as in 1995, Bosniak, based on observation of the growth and behavior of small RCs for longer than 8 years, advocated a watchful waiting or active surveillance attitude. This article reports cryotherapy, our radiofrequency series, and a literature review. CONCLUSIONS: In the event of elderly patients, concomitant diseases advising against surgery, multiple renal tumors, a solitary kidney, or patients who reject surgery, ablation procedures may be safe and effective when performed by expert hands, achieving mid-term oncological results similar to partial nephrectomy. Active surveillance has also been shown to be safe in the mid-term in adequately informed patients. To improve indications, new diagnostic procedures that help us differentiate the potentially more aggressive tumors will be required. Larger series and longer follow-ups are neede to confirm current results.

Pelvic hydatid disease as an example of pelvic masses of uncertain aetiology.

We describe two new cases of pelvic hydatid cysts, one with a clinical profile of local compression and the other one asymptomatic. The first case is a 75 year-old man who reported difficulty in defecating and urinating. An ultrasound revealed a large pelvic cystic mass displacing the bladder and rectosigmoid region. Computed tomography showed images compatible with hydatid disease and a hydatid liver cyst. The patient underwent a surgical procedure, with the pelvic cyst being partially excised. The other case of pelvic hydatid disease was asymptomatic, and was discovered by chance while examining a 75 year-old man for a prostatic adenoma. Because he was asymptomatic, we opted for observation. The pathology confirmed the diagnosis in the first case and radiological findings confirmed the second. Both patients are now asymptomatic. Hydatid disease must be considered in the differential diagnosis of any cystic masses in the pelvic organs, especially in countries where the disease is endemic. Although there are no serological tests which are 100% specific, there are some radiological procedures which can help to confirm the disease. Surgery is the treatment of choice.

New case of an infrarenal abdominal aortic aneurysm associated with horseshoe kidney.

We review the association between surgically resolvable aortic disease and horseshoe kidney with a discussion of diagnostic problems and therapeutic options. Male patient 81 years of age with horseshoe kidney and an abdominal aortic aneurysm that was discovered by chance in an abdominal ultrasound during a check-up for his prostate condition. A retroperitoneal approach was used in order to resect the aneurysm and perform an aorto-aortic bypass with no complications occurring. Two years after the diagnosis, the patient is still asymptomatic from a vascular point of view. The co-presence of horseshoe kidney and aortic disease needing surgical correction is infrequent, but it significantly increases the technical complexity of aortic reconstruction. A literature review is included.

[Prostatic utricle ductal carcinoma. Case report and bibliographic review]. / Carcinoma ductal del utrículo prostático. Caso clínico y revisión de la literatura.

OBJECTIVE: A case of ductal carcinoma of the prostatic utricle is described, previously known as endometrial carcinoma, and literature is reviewed. METHODS: 75-years-old patient who consults for lower urinary tract obstructive symptoms, with a PSA of 8.1 ng/ml., without more symptoms. Digital rectal examination and ultrasound showed a small and stony prostate. Deobstructive transurethral resection of the prostate was performed and the biopsy revealed ductal carcinoma of the utricle. RESULTS: Nine years after diagnosis signs of dissemination are not present. CONCLUSIONS: As incidental finding in the biopsy, ductal carcinoma of the utricle is a rare tumor, the incidence of which among all prostatic carcinomas has been cited as 0.2-0.8%. We report a review about this topic for improving its knowledge. Symptoms, pathological findings and treatment of this carcinoma have been reviewed.