Mid-Perineal Scrotal Flap for the Repair of Urorectal Fistulas: A New Technique.

Rectourethral fistula (RUF) is an infrequent but severe complication of the treatment of prostate cancer. Herein, we describe a new surgical approach used successfully in 3 patients that incorporates a partially de-epithelialized mid-perineal scrotal flap (MPSF), used as interposition flap, that can be used in almost every patient with RUF after radiotherapy, regardless of having or not a concomitant posterior urethra or bladder neck stricture or contracture that might require a simultaneous urethroplasty. The interposition flap includes well vascularized subcutaneous fat tissue by distal vascular branches of the internal pudendal vessels that reaches without tension the deep perineum up to the posterior bladder neck. The MPSF is a time efficient procedure that allows excellent access to the bulbar urethra and to the surgical plane between rectum and prostate and it does not require a separate incision for the flap harvesting procedure when required.

Quality of Life in Patients with High-grade Non-muscle-invasive Bladder Cancer Undergoing Standard Versus Reduced Frequency of Bacillus Calmette-Guérin Instillations: The EAU-RF NIMBUS Trial.

Background: Adverse events induced by intravesical bacillus Calmette-Guérin (BCG) to treat high-grade non-muscle-invasive bladder cancer (NMIBC) often lead to treatment discontinuation. The EAU-RF NIMBUS trial found a reduced number of standard-dose BCG instillations to be inferior with the standard regimen. Nonetheless, it remains important to evaluate whether patients in the reduced BCG treatment arm had better quality of life (QoL) due to a possible reduction in toxicity or burden. Objective: To evaluate whether patients in the EAU-RF NIMBUS trial experienced better QoL after a reduced BCG instillation frequency. Design setting and participants: A total of 359 patients from 51 European sites were randomized to one of two treatment arms between December 2013 and July 2019. The standard frequency arm (n = 182) was 6 weeks of BCG induction followed by 3 weeks of maintenance at months 3, 6, and 12. The reduced frequency arm (n = 177) was BCG induction at weeks 1, 2, and 6, followed by maintenance instillations at weeks 1 and 3 of months 3, 6, and 12. Outcome measurements and statistical analysis: Analyses were performed using an intention-to-treat analysis and a per-protocol analysis. QoL was measured using the European Organization for Research and Treatment of Cancer (EORTC) Quality of Life Questionnaire Core 30 version 3.0 (QLQ-C30 v.03) prior to the first and last instillations of each BCG cycle. Group differences were determined using linear regression corrected for QoL at baseline. Differences in QoL over time were tested for significance using a linear mixed model. Side effects were recorded by the treating physician using a standardized form. Chi-square tests were used to compare the side-effect frequency between the arms. Results and limitations: There were no significant differences in the means of each QoL scale between the two arms. There were also no significant changes over time in all QoL domains for both arms. However, differences in the incidence of general malaise at T1 (before the last induction instillation), frequency, urgency, and dysuria at T7 (before the last maintenance instillation) were detected in favor of the reduced frequency arm. Conclusions: Reducing the BCG instillation frequency does not improve the QoL in NMIBC patients despite lower storage symptoms. Patient summary: In this study, we evaluated whether a reduction in the number of received bacillus Calmette-Guérin instillations led to better quality of life in patients with high-grade non-muscle-invasive bladder cancer. We found no difference in the quality of life between the standard and the reduced bacillus Calmette-Guérin instillation frequency. We conclude that reducing the number of instillations does not lead to better quality of life in patients with high-grade non-muscle-invasive bladder cancer.

Placental expanded mesenchymal-like cells (PLX-R18) for poor graft function after hematopoietic cell transplantation: A phase I study.

Persistent cytopenia in the post-hematopoietic cell transplantation (HCT) setting can occur despite adequate engraftment of donor cells. PLX-R18, a placental-derived mesenchymal-like cell product, is expanded ex vivo in a 3-dimensional environment. PLX-R18 cells secrete a large array of hematopoietic factors, which promote regeneration, maturation, and differentiation of hematopoietic cells and stimulate their migration to peripheral blood. This phase 1, first-in-human study (NCT03002519), included 21 patients with incomplete hematopoietic recovery post-HCT. Patients were treated with escalating doses of PLX-R18: 3 patients received 1 million cells/kg, 6 received 2 million cells/kg, and 12 received 4 million cells/kg via multiple intramuscular injections. While patients received only two administrations of cells during the first week, peripheral blood counts continued to increase for months, peaking at 6 months for hemoglobin (Hb, p = 0.002), lymphocytes (p = 0.008), and neutrophils (ANC, p = 0.063), and at 9 months for platelets (p < 0.001) and was maintained until 12 months for all but ANC. The need for platelet transfusions was reduced from 5.09 units/month at baseline to 0.55 at month 12 (p = 0.05). Likewise, red blood cell transfusions decreased from 2.91 units/month at baseline to 0 at month 12 (p = 0.0005). PLX-R18 was safe and well tolerated and shows promise in improving incomplete hematopoietic recovery post-HCT.

Phenotypic and Genotypic Antimicrobial Susceptibility Testing of Chlamydia trachomatis Isolates from Patients with Persistent or Clinical Treatment Failure in Spain.

The aim of this multicentre project (seven hospitals across the Spanish National Health Service) was to study the phenotypic and genotypic susceptibility of C. trachomatis to the main antimicrobials used (macrolides, doxycycline, and quinolones) in isolates from patients with clinical treatment failure in whom reinfection had been ruled out. During 2018-2019, 73 clinical isolates were selected. Sixty-nine clinical specimens were inoculated onto confluent McCoy cell monolayers for phenotypic susceptibility testing. The minimum inhibitory concentration for azithromycin and doxycycline was defined as the lowest concentration associated with an at least 95% reduction in inclusion-forming units after one passage in the presence of the antibiotic compared to the initial inoculum for each strain (control). Sequencing analysis was performed for the genotypic detection of resistance to macrolides, analysing mutations in the 23S rRNA gene (at positions 2057, 2058, 2059, and 2611), and quinolones, analysing a fragment of the gyrA gene, and searching for the G248T mutation (Ser83->Ile). For tetracyclines, in-house RT-PCR was used to test for the tet(C) gene. The phenotypic susceptibility testing was successful for 10 isolates. All the isolates had minimum inhibitory concentrations for azithromycin ≤ 0.125 mg/L and for doxycycline ≤ 0.064 mg/L and were considered sensitive. Of the 73 strains studied, no mutations were found at positions T2611C or G248T of the gyrA gene. We successfully sequenced 66 isolates. No macrolide resistance-associated mutations were found at positions 2057, 2058, 2059, or T2611C. None of the isolates carried the tet(C) gene. We found no evidence for genomic resistance in this large, clinically relevant dataset.

Genetic Characterization of Non-Lymphogranuloma venereum Chlamydia trachomatis Indicates Distinct Infection Transmission Networks in Spain.

Chlamydia trachomatis infection is an important public health problem. Our objective was to assess the dynamics of the transmission of this infection, analysing the distribution of circulating ompA genotypes and multilocus sequence types of C. trachomatis in Spain as a function of clinical and epidemiological variables. During 2018 and 2019, we genetically characterized C. trachomatis in tertiary hospitals in six areas in Spain (Asturias, Barcelona, Gipuzkoa, Mallorca, Seville and Zaragoza), with a catchment population of 3.050 million people. Genotypes and sequence types were obtained using polymerase chain reaction techniques that amplify a fragment of the ompA gene, and five highly variable genes (hctB, CT058, CT144, CT172 and pbpB), respectively. Amplicons were sequenced and phylogenetic analysis was conducted. We obtained genotypes in 636/698 cases (91.1%). Overall and by area, genotype E was the most common (35%). Stratifying by sex, genotypes D and G were more common among men, and genotypes F and I among women (p < 0.05). Genotypes D, G and J were more common in men who have sex with men (MSM) than in men who have sex with women (MSW), in whom the most common genotypes were E and F. The diversity index was higher in sequence typing (0.981) than in genotyping (0.791), and the most common sequence types were ST52 and ST108 in MSM, and ST30, ST148, ST276 and ST327 in MSW. Differences in genotype distribution between geographical areas were attributable to differences in population characteristics. The transmission dynamics varied with sexual behaviour: the predominant genotypes and most frequent sequence types found in MSM were different to those detected in MSW and women.

Genital Mutilation in Males.

PURPOSE OF THE REVIEW: Genital mutilation in males can range from minor injuries (cuts from a blade) to severe urological emergencies (testicular or penile amputation). Due to the rarity of these events, there is a lack of extensive reports, as most of the available literature is regarding single cases. Genital mutilation has been associated with psychotic and non-psychotic causes, psychiatric conditions, drug consumption, sexual practices, or even cultural or religious beliefs. It is crucial to perform a psychiatric evaluation of these patients to obtain the best therapeutic approach. This manuscript serves as a review of the currently available knowledge regarding male genital mutilation. RECENT FINDINGS: A great variety of reasons have been associated with genital mutilation. Previous authors have distinguished between those that present with a clear mental health precursor from cases with no psychotic background. Nevertheless, sometimes, it is difficult to make this distinction. Recently, reconstructive techniques for amputation cases have moved towards a microsurgical approach in order to improve outcomes. A holistic therapeutic approach must be performed to increase the chances of effective treatment. Close collaboration between urologists, psychiatrists, and emergency doctors is essential to ensure the best care for patients performing genital mutilation. Future publications must evaluate differences in treatment options and the impact that these have on the long-term well-being of patients undergoing genital self-mutilation.

Increases in the Macrolide Resistance of Mycoplasma genitalium and the Emergence of the A2058T Mutation in the 23S rRNA Gene: Clonal Spread?

The management of Mycoplasma genitalium sexually transmitted infection (STI) is hindered by increasing resistance to the recommended antibiotics, macrolides and quinolones, worldwide. In Gipuzkoa (Basque Country, Spain), macrolide and quinolone resistance rates in 2014−2018 were reported as <20% and <10%, respectively. The aims of this study were to compare these rates with those in 2019−2021 and analyse the genetic and epidemiological features of the strains and cases associated with striking changes in the resistance trends. Resistance to macrolides (n = 1019) and quinolones (n = 958) was studied, analysing mutations in 23S rRNA and parC/gyrA genes, respectively. The rate of macrolide resistance increased from 17.3% in 2014−2018 to 32.1% in 2019−2021, as much in the more prevalent A2058/2059G mutations (16.6−27.8%) as in the emergent A2058T mutations (0.5−4.1%) but with differences in the odds ratios and the relative risk increase between A2058T and A2058/2059G mutations. MG191 adhesin and MG309 lipoprotein of the 27 emergent strains detected with A2058T mutations were amplified, sequenced, and typed using phylogenetic and variable number tandem repeat analysis, respectively. Genetic clonal spread was ruled out, but most of the A2058T cases were men who had sex with men (24/27) with a history of STI and antibiotic treatments (19/27). No changes were observed in quinolone resistance trends, but the rate of resistance to both antibiotics rose from 2.9% to 8.3%, especially in cases with A2058T mutations. The genetic characterisation of strains and epidemiological surveillance of cases are needed to detect populations at increased risk of treatment failure in this infection.

CyTOF analysis identifies unusual immune cells in urine of BCG-treated bladder cancer patients.

High grade non-muscle-invasive bladder tumours are treated with transurethral resection followed by recurrent intravesical instillations of Bacillus Calmette Guérin (BCG). Although most bladder cancer patients respond well to BCG, there is no clinical parameter predictive of treatment response, and when treatment fails, the prognosis is very poor. Further, a high percentage of NMIBC patients treated with BCG suffer unwanted effects that force them to stop treatment. Thus, early identification of patients in which BCG treatment will fail is really important. Here, to identify early stage non-invasive biomarkers of non-responder patients and patients at risk of abandoning the treatment, we longitudinally analysed the phenotype of cells released into the urine of bladder cancer patients 3-7 days after BCG instillations. Mass cytometry (CyTOF) analyses revealed a large proportion of granulocytes and monocytes, mostly expressing activation markers. A novel population of CD15+CD66b+CD14+CD16+ cells was highly abundant in several samples; expression of these markers was confirmed using flow cytometry and qPCR. A stronger inflammatory response was associated with increased cell numbers in the urine; this was not due to hematuria because the cell proportions were distinct from those in the blood. This pilot study represents the first CyTOF analysis of cells recruited to urine during BCG treatment, allowing identification of informative markers associated with treatment response for sub-selection of markers to confirm using conventional techniques. Further studies should jointly evaluate cells and soluble factors in urine in larger cohorts of patients to characterise the arms of the immune response activated in responders and to identify patients at risk of complications from BCG treatment.

[Usefulness of the g8 questionnaire in predicting frailty in elderly patients with metastatic or castration-resistant prostate cancer.] / Utilidad de cuestionario G8 en la predicción de fragilidad en pacientes ancianos con cáncer de próstata metastásico o resistente a castración.

OBJECTIVE: to assess the capacityof the G8 questionnaire for the detection of frailty inpatients over 75 years of age with metastatic or castrationresistant prostate cancer and the relationshipof the results of this questionnaire with clinical variables,laboratory data, quality of life, functional statusand comorbidity. MATERIAL AND METHODS: Patients over the ageof 75 with metastatic or castration-resistant prostatecancer were evaluated using the G8 questionnaire.Those with a G8 15 were subjected to comprehensivegeriatric assessment in order to evaluate the abilityof this questionnaire to predict frailty. We studiedthe relationship between G8 score and functionalstatus (ECOG), comorbidity (Charlson index), qualityof life (FACT-P and EQ5D 3L questionnaires), diseasecharacteristics and common analytical variables. RESULTS: 64 patients were included in the study,of whom 26 scored 15 in the G8 questionnaireand were referred to geriatrics. 89% (23/26) of thepatients with a G8 score pre-fragile and 7 fragile) and only 11% (3/26) wereconsidered robust. The multivariate model showsthat the Charlson index and the EQ5D 3L score areindependent predictors of frailty. The Charlson index(OR=1.68, p=0.022) increases the probability thatthe patient has a G8 score the EQ5D-3L score (OR-0.64, p-0.021) decreases thatprobability. Both quantitative variables were recodedinto binary variables from the most predictivepoint obtained from the ROC curves and included ina model: patients with Charlson index ≥4 (OR=3.17,p=0.047) and those with EQ5D- 3L score (OR=3.35, p=0.037) increased the likelihood of obtaininga G8 scoreconditions (neither Charlson ≥4 nor EQ5D-3L score 15. However, the presence of the two conditions increasesthe probability to 71.5%. CONCLUSIONS: The score obtained in the G8questionnaire is a good predictor of frailty in elderlypatients with advanced prostate cancer. Comorbidity,as measured by Charlson's index, and quality of life,as measured by the EQ5D-3L questionnaire, are independentpredictors of frailty (score on the G8 questionnairebelow 15).

OBJETIVO: Valorar la capacidad delcuestionario G8 para la detección de fragilidad enpacientes mayores de 75 años con cáncer de próstatametastásico o resistente a castración y la relación de losresultados de este cuestionario con variables clínicas,datos de laboratorio, calidad de vida, estado funcionaly comorbilidad.MATERIAL Y MÉTODOS: Se evaluó a pacientes ≥ 75años con cáncer de próstata metastásico o resistente acastración mediante el cuestionario G8. Aquellos conuna puntuación menor de 15 fueron sometidos a valoracióngeriátrica integral. Se evaluó la capacidad dedicho cuestionario para predecir fragilidad y se relacionaronlos hallazgos con el estado funcional (ECOG),comorbilidad (índice de Charlson), calidad de vida(cuestionarios FACT-P y EQ5D 3L), características de laenfermedad y variables analíticas habituales. RESULTADOS: Se incluyeron en el estudio 64 pacientes,de los cuales 26 obtuvieron una puntuación inferior a 15 en el cuestionario G8 y fueron remitidosal servicio de geriatría. El 89% (23/26) de los pacientescon una puntuación en el G8 por debajo de 15 presentabandatos de fragilidad (11 prefrágiles y 7 frágiles) ysolo el 11% (3/26) fueron considerados robustos. Elmodelo multivariado muestra, que de manera independiente,el índice de Charlson (OR=1,68, p=0,022)aumenta la probabilidad de que el paciente tenga unapuntuación en el cuestionario G8 por debajo de 15 y lapuntuación en el EQ5D-3L (OR=0,64, p=0,021) disminuyadicha probabilidad. Ambas variables cuantitativasse recodificaron en variables de tipo binario a partir delpunto más predictivo obtenido de las curvas ROC y seincluyeron en un modelo en el cual se objetivó, que pacientescon índice de Charlson ≥4 (OR= 3,17, p=0,047)y aquellos con puntuación en el cuestionario EQ5D-3Lde presentar una puntuación en el cuestionario G8Los pacientes que no presentan ninguna de estas condiciones(ni Charlson ≥4 ni EQ5D-3L score un 19% de probabilidad de presentar una puntuaciónen el cuestionario G8 condiciones aumenta la probabilidad hasta el 71,5%. CONCLUSIONES: La puntuación obtenida en elcuestionario G8 es un buen predictor de fragilidad enpacientes con cáncer de próstata avanzado con edad≥ 75 años. La comorbilidad, medida por el índice deCharlson, y la calidad de vida, medida por el cuestionarioEQ5D-3L, son predictores independientes de fragilidad,entendida como la obtención de una puntuaciónen el cuestionario G8 por debajo de 15.

[Analysis of renal tumor size as a predictive factor of oncological aggressiveness.] / Análisis del tamaño del tumor renal como factor predictivo de agresividad oncológica.

INTRODUCTION: The increased incidenceof diagnosis of kidney tumours has driveninvestigation in the area. It is known that the risk ofmalignancy is correlated with tumour size, but thereare still no specific and objective parameters to characterizethe degree of aggressiveness and to be ableto guide a treatment reliably. OBJECTIVE: To identify the relationship betweenrenal tumour size and the incidence of tumour aggressivecharacteristics. PATIENTS AND METHODS: A retrospective analysisof our series of renal cancers operated between 1998and 2018 was performed. The specific and cumulativeincidence of aggressive characteristics was studied.The following where considered as aggressive characteristics:Presence of sarcomatoid or epidermoiddifferentiation, tumour necrosis, stage pT3-4, histologicalhigh grade (3-4) and the presence of histologicalaggressive variants. RESULTS: A total of 651 patients that had undergonerenal mass surgery were analysed. In tumours below2 cm the appearance of aggressive characteristicsoccurred in less than 5%. For renal masses greaterthan 2 cm, each centimetre increase correlated with arise in cumulative incidence of 2-3% for each characteristicstudied. CONCLUSIONS: In tumours below 2cm and patientswith significant comorbidities active surveillance maybe a reliable alternative to surgery.

INTRODUCCIÓN: El aumento de incidenciade diagnóstico de tumores renales ha conllevadoun mayor estudio y conocimiento de los mismos.Se conoce que el riesgo de malignidad se correlacionacon el tamaño tumoral, pero seguimos sin tener parámetrosespecíficos y objetivos para caracterizar elgrado de agresividad de los mismos y poder orientarun tratamiento de forma fiable. OBJETIVO: Identificar la relación que existe entre eltamaño tumoral y la incidencia de características deagresividad.MATERIAL Y MÉTODOS: Análisis retrospectivo denuestra serie de cáncer renal intervenido quirúrgicamenteen el periodo entre 1998 y 2018. Se estudia laincidencia específica y acumulada de las característicasde agresividad en dichas lesiones y su relación conel tamaño tumoral. Se consideraron característicasde agresividad: la presencia diferenciación sarcomatoiode epidermoide, necrosis tumoral, estadio pT3-4,grado histológico alto (3-4) y la presencia de variantesde histología agresiva. RESULTADOS: Se analizan un total de 651 pacientesintervenidos por cáncer renal. En tumores por debajode 2 cm la aparición de características de agresividadse observó en menos del 5%. A partir de ese tamaño, laincidencia acumulada se incrementa en un 2-3% paracada característica con cada centímetro que aumentael tamaño tumoral. CONCLUSIONES: Este análisis demuestra que conformeaumenta el tamaño de los tumores renales, aumentala incidencia de características de agresividadde los mismos. En tumores por debajo de 2 cm y pacientescon comorbilidades importantes la vigilanciaactiva puede ser una alternativa con cierta seguridad.

Utilidad del cuestionario g8 en la predicción de fragilidad en pacientes ancianos con cáncer de próstata metastásico o resistente a castración / Usefulness of the g8 questionnaire in predicting frailty in elderly patients with metastatic or castration-resistant prostate cancer

OBJECTIVE: to assess the capacityof the G8 questionnaire for the detection of frailty inpatients over 75 years of age with metastatic or castration resistant prostate cancer and the relationshipof the results of this questionnaire with clinical variables, laboratory data, quality of life, functional statusand comorbidity.MATERIAL AND METHODS: Patients over the ageof 75 with metastatic or castration-resistant prostatecancer were evaluated using the G8 questionnaire.Those with a G8 < 15 were subjected to comprehensive geriatric assessment in order to evaluate the ability of this questionnaire to predict frailty. We studiedthe relationship between G8 score and functionalstatus (ECOG), comorbidity (Charlson index), qualityof life (FACT-P and EQ5D 3L questionnaires), diseasecharacteristics and common analytical variables.RESULTS: 64 patients were included in the study,of whom 26 scored < 15 in the G8 questionnaireand were referred to geriatrics. 89% (23/26) of thepatients with a G8 score <15 had fragility data (11pre-fragile and 7 fragile) and only 11% (3/26) wereconsidered robust. The multivariate model showsthat the Charlson index and the EQ5D 3L score areindependent predictors of frailty. The Charlson index(OR=1.68, p=0.022) increases the probability thatthe patient has a G8 score <15 and on the contrarythe EQ5D-3L score (OR-0.64, p-0.021) decreases thatprobability. Both quantitative variables were recoded into binary variables from the most predictivepoint obtained from the ROC curves and included ina model: patients with Charlson index ≥4 (OR=3.17,p=0.047) and those with EQ5D- 3L score <0.87(OR=3.35, p=0.037) increased the likelihood of obtaining a G8 score<15. Patients without any of theseconditions (neither Charlson ≥4 nor EQ5D-3L score<0.87) have a 19% chance of presenting a G8 score< 15. However, the presence of the two conditions increases the probability to 71.5%.

OBJETIVO: Valorar la capacidad delcuestionario G8 para la detección de fragilidad enpacientes mayores de 75 años con cáncer de próstatametastásico o resistente a castración y la relación de losresultados de este cuestionario con variables clínicas,datos de laboratorio, calidad de vida, estado funcionaly comorbilidad.MATERIAL Y MÉTODOS: Se evaluó a pacientes ≥ 75años con cáncer de próstata metastásico o resistente acastración mediante el cuestionario G8. Aquellos conuna puntuación menor de 15 fueron sometidos a valoración geriátrica integral. Se evaluó la capacidad dedicho cuestionario para predecir fragilidad y se relacionaron los hallazgos con el estado funcional (ECOG),comorbilidad (índice de Charlson), calidad de vida(cuestionarios FACT-P y EQ5D 3L), características de laenfermedad y variables analíticas habituales.RESULTADOS: Se incluyeron en el estudio 64 pacientes, de los cuales 26 obtuvieron una puntuación inferior a 15 en el cuestionario G8 y fueron remitidosal servicio de geriatría. El 89% (23/26) de los pacientescon una puntuación en el G8 por debajo de 15 presentaban datos de fragilidad (11 prefrágiles y 7 frágiles) ysolo el 11% (3/26) fueron considerados robustos. Elmodelo multivariado muestra, que de manera independiente, el índice de Charlson (OR=1,68, p=0,022)aumenta la probabilidad de que el paciente tenga unapuntuación en el cuestionario G8 por debajo de 15 y lapuntuación en el EQ5D-3L (OR=0,64, p=0,021) disminuya dicha probabilidad. Ambas variables cuantitativasse recodificaron en variables de tipo binario a partir delpunto más predictivo obtenido de las curvas ROC y seincluyeron en un modelo en el cual se objetivó, que pacientes con índice de Charlson ≥4 (OR= 3,17, p=0,047)y aquellos con puntuación en el cuestionario EQ5D-3L<0,87. (OR=3,35, p=0,037) aumentaban la probabilidadde presentar una puntuación en el cuestionario G8<15.Los pacientes que no presentan ninguna de estas condiciones (ni Charlson ≥4 ni

Análisis del tamaño del tumor renal como factor predictivo de agresividad Oncológica / Analysis of renal tumor size as a predictive factor of oncological aggressiveness

INTRODUCCIÓN: El aumento de incidencia de diagnóstico de tumores renales ha conllevado un mayor estudio y conocimiento de los mismos.Se conoce que el riesgo de malignidad se correlacionacon el tamaño tumoral, pero seguimos sin tener parámetros específicos y objetivos para caracterizar elgrado de agresividad de los mismos y poder orientarun tratamiento de forma fiable.OBJETIVO: Identificar la relación que existe entre eltamaño tumoral y la incidencia de características deagresividad.MATERIAL Y MÉTODOS: Análisis retrospectivo denuestra serie de cáncer renal intervenido quirúrgicamente en el periodo entre 1998 y 2018. Se estudia laincidencia específica y acumulada de las características de agresividad en dichas lesiones y su relación conel tamaño tumoral. Se consideraron característicasde agresividad: la presencia diferenciación sarcomatoiode, epidermoide, necrosis tumoral, estadio pT3-4,grado histológico alto (3-4) y la presencia de variantesde histología agresiva.RESULTADOS: Se analizan un total de 651 pacientesintervenidos por cáncer renal. En tumores por debajode 2 cm la aparición de características de agresividadse observó en menos del 5%. A partir de ese tamaño, laincidencia acumulada se incrementa en un 2-3% paracada característica con cada centímetro que aumentael tamaño tumoral.CONCLUSIONES: Este análisis demuestra que conforme aumenta el tamaño de los tumores renales, aumenta la incidencia de características de agresividadde los mismos. En tumores por debajo de 2 cm y pacientes con comorbilidades importantes la vigilanciaactiva puede ser una alternativa con cierta seguridad. (AU)

INTRODUCTION: The increased incidence of diagnosis of kidney tumours has driveninvestigation in the area. It is known that the risk ofmalignancy is correlated with tumour size, but thereare still no specific and objective parameters to characterize the degree of aggressiveness and to be ableto guide a treatment reliably. OBJECTIVE: To identify the relationship betweenrenal tumour size and the incidence of tumour aggressive characteristics.PATIENTS AND METHODS: A retrospective analysisof our series of renal cancers operated between 1998and 2018 was performed. The specific and cumulativeincidence of aggressive characteristics was studied.The following where considered as aggressive characteristics: Presence of sarcomatoid or epidermoiddifferentiation, tumour necrosis, stage pT3-4, histological high grade (3-4) and the presence of histologicalaggressive variants.RESULTS: A total of 651 patients that had undergone renal mass surgery were analysed. In tumours below 2 cm the appearance of aggressive characteristicsoccurred in less than 5%. For renal masses greaterthan 2 cm, each centimetre increase correlated with arise in cumulative incidence of 2-3% for each characteristic studied.CONCLUSIONS: In tumours below 2cm and patientswith significant comorbidities active surveillance maybe a reliable alternative to surgery. (AU)

[Urinary biomarkers in the diagnosis of prostate cancer.] / Biomarcadores urinarios en el diagnóstico de cancer de próstata.

INTRODUCTION: The use of prostatespecific antigen (PSA) is useful for the diagnosis ofprostate cancer. Its main limitation is its low specificity,which has led to the search for new biomarkersin order to identify clinically significant prostatecancer and to reduce overdiagnosis and overtreatment.The aim of this article is to summarize the currentliterature on urinary biomarkers used in thediagnosis of prostate cancer.A PubMed-based literature search was conductedup to December 2020. We selected the most recentand relevant original articles, clinical trials and reviewsthat have provided relevant information onthe use of biomarkers.In this review, we have discussed four importanturinary biomarkers useful for prostate cancer diagnosis:PCA3, Select MDX, ExoDX, TMPRSS2:ERG. CONCLUSION: The use of urinary biomarkers hasimproved of clinically significant prostate cancerdiagnosis. Their use reduces the number of unnecessarybiopsies and avoids overtreatment of indolentprostate cancer.

INTRODUCCIÓN: El uso del antígenoprostático específico (PSA) es útil para el diagnósticodel cáncer de próstata. Su principal limitación es labaja especificidad, esto ha llevado a la búsqueda denuevos biomarcadores con el fin de identificar el cáncerde próstata clínicamente significativo y poder disminuirel sobrediagnóstico y sobretratamiento.El objetivo de este artículo es resumir la literaturaactual sobre los biomarcadores urinarios utilizados enel diagnóstico de cáncer de próstata.Se llevó a cabo una búsqueda bibliográfica en Pub-Med hasta diciembre del 2020. Hemos seleccionadolos artículos originales, ensayos clínicos y revisionesmás recientes que proporcionan información sobre eluso de biomarcadores.En esta revisión, hemos discutido cuatro importantesbiomarcadores urinarios útiles para el diagnósticodel cáncer de próstata: PCA3, Select MDX, ExoDX, TMPRSS2:ERG.CONCLUSIÓN: El uso de biomarcadores urinariosha mejorado del diagnóstico de cáncer de próstata clínicamentesignificativo. Su uso reduce el número debiopsias innecesarias y evita el sobretratamiento delcáncer de próstata indolente.

Biomarcadores urinarios en el diagnóstico de cáncer de próstata / Urinary biomarkers in the diagnosis of prostate cáncer

INTRODUCCIÓN: El uso del antígenoprostático específico (PSA) es útil para el diagnósticodel cáncer de próstata. Su principal limitación es labaja especificidad, esto ha llevado a la búsqueda denuevos biomarcadores con el fin de identificar el cáncer de próstata clínicamente significativo y poder disminuir el sobrediagnóstico y sobretratamiento.El objetivo de este artículo es resumir la literaturaactual sobre los biomarcadores urinarios utilizados enel diagnóstico de cáncer de próstata.Se llevó a cabo una búsqueda bibliográfica en PubMed hasta diciembre del 2020. Hemos seleccionadolos artículos originales, ensayos clínicos y revisionesmás recientes que proporcionan información sobre eluso de biomarcadores.En esta revisión, hemos discutido cuatro importantes biomarcadores urinarios útiles para el diagnósticodel cáncer de próstata: PCA3, Select MDX, ExoDX, TMPRSS2:ERG.CONCLUSIÓN: El uso de biomarcadores urinariosha mejorado del diagnóstico de cáncer de próstata clínicamente significativo. Su uso reduce el número debiopsias innecesarias y evita el sobretratamiento delcáncer de próstata indolente. (AU)

INTRODUCTION: The use of prostatespecific antigen (PSA) is useful for the diagnosis ofprostate cancer. Its main limitation is its low specificity, which has led to the search for new biomarkersin order to identify clinically significant prostatecancer and to reduce overdiagnosis and overtreatment.The aim of this article is to summarize the current literature on urinary biomarkers used in thediagnosis of prostate cáncer.A PubMed-based literature search was conductedup to December 2020. We selected the most recentand relevant original articles, clinical trials and reviews that have provided relevant information onthe use of biomarkers.In this review, we have discussed four importanturinary biomarkers useful for prostate cancer diagnosis: PCA3, Select MDX, ExoDX, TMPRSS2:ERG.CONCLUSION: The use of urinary biomarkers hasimproved of clinically significant prostate cancerdiagnosis. Their use reduces the number of unnecessary biopsies and avoids overtreatment of indolent prostate cancer. (AU)

The effect of neoadjuvant chemotherapy among patients undergoing radical cystectomy for variant histology bladder cancer: A systematic review.

OBJECTIVE: To systematically review the evidence about the effect of neoadjuvant chemotherapy (NAC) for muscle-invasive bladder cancer (MIBC) with pure urothelial carcinoma (pUC) in radical cystectomy (RC) candidates affected by variant histology (VH) bladder cancer. METHODS: A review of the current literature was conducted through the Medline and National Center for Biotechnology Information (NCBI) PubMed, Scopus databases in May 2020. The updated Preferred Reporting Items for Systematic Reviews and Meta-Analyses guidelines were followed for this systematic review. Keywords used were 'bladder cancer', 'bladder carcinoma', 'bladder tumour' and 'bladder cancer variants' and 'neoadjuvant chemotherapy'. Only original articles in English published after 2000 and reporting oncological outcomes a series of more than five patients with VH were included. We excluded series in which the oncological outcomes of patients with pUC and VH were undistinguishable. RESULTS: The literature search identified 2231 articles. A total of 51 full-text articles were assessed for eligibility, with 17 eventually considered for systematic review, for a cohort of 450,367 patients, of which 5010 underwent NAC + RC. The median age at initial diagnosis ranged from 61 to 71 years. Most patients received cisplatin-gemcitabine, methotrexate-vinblastine-adriamycin-cisplatin, or carboplatin-based chemotherapy. Only one study reported results of neoadjuvant immunotherapy. The median follow-up ranged from 1 to 120 months. The results showed that squamous cell carcinoma (SCC) is less sensitive to NAC than pUC and that SCC predicts poorer prognosis. NAC was found to be a valid approach in treating small cell carcinoma and may have potential benefit in micropapillary carcinoma. CONCLUSIONS: NAC showed the best oncological outcomes in small cell variants and micropapillary carcinoma, while NAC survival benefit for SCC and adenocarcinoma variants needs further studies. Drawing definite considerations on the efficacy of NAC in VH is complicated due to the heterogeneity of present literature. Present results need to be confirmed in randomised controlled trials.

Blockade of ß2-Adrenergic Receptor Reduces Inflammation and Oxidative Stress in Clear Cell Renal Cell Carcinoma.

Von Hippel-Lindau (VHL) syndrome is a rare inherited cancer disease where the lack of VHL protein triggers the development of multisystemic tumors such us retinal hemangioblastomas (HBs), CNS-HBs, and clear cell renal cell carcinoma (ccRCC). Since standard therapies in VHL have shown limited response, leaving surgery as the only possible treatment, targeting of the ß2-adrenergic receptor (ADRB2) has shown therapeutic antitumor benefits on VHL-retinal HBs (clinical trial), VHL-CNS HBs, and VHL-ccRCC (in vitro and in vivo). In the present study, we wanted to look deep into the effects of the ADRB2 blockers propranolol and ICI-118,551 on two main aspects of cancer progression: (i) the changes on the inflammatory response of ccRCC cells; and (ii) the modulation on the Warburg effect (glycolytic metabolism), concretely, on the expression of genes involved in the cell reactive oxygen species (ROS) balance and levels. Accordingly, in vitro studies with primary VHL-ccRCC and 786-O cells measuring ROS levels, ROS-expression of detoxifying enzymes, and the expression of p65/NF-κB targets by RT-PCR were carried out. Furthermore, histological analyses of ccRCC samples from heterotopic mouse xenografts were performed. The obtained results show that ADRB2 blockade in ccRCC cells reduces the level of oxidative stress and stabilizes the inflammatory response. Thus, these data further support the idea of targeting ADRB2 as a promising strategy for the treatment of VHL and other non-VHL tumors.

Repair of Traumatic Urethral Strictures: La Paz University Hospital Experience.

INTRODUCTION: The management of traumatic urethral strictures remains a challenge for urologists. Alteration of the pelvic anatomy and the significant fibrosis generated by the trauma make surgical repair complex. In most cases, the existing defect between the urethral ends is small, and the ideal treatment is end-to-end perineal urethroplasty. Cases of extensive strictures that are left with long gap defects may require the use of different sequential maneuvers to achieve a tension-free anastomosis. OBJECTIVE: To describe the experience at our center with urethral strictures induced by closed perineal trauma. MATERIALS AND METHODS: A retrospective analysis of 116 patients who underwent urethroplasty for urethral stricture after blunt perineal trauma at our center between 1965 and 2020 was conducted. Demographic data, date, mechanism of action of the trauma, emergency management, previous urethral interventions, surgical technique carried out in our center, complications, presence of erectile dysfunction, and urinary incontinence were collected. RESULTS: 82 patients (70.7%) presented with pelvic fractures. The most frequent etiology of trauma was traffic accidents (68%), followed by crushing injuries (24%). Suprapubic cystostomy was placed in 50.2% of patients, and urethral realignment was performed in 25.3%. The mean stricture length was 2.2 cm, affecting mostly the membranous urethra (67%). During surgery, it was necessary to perform crural separation in 61.5% and partial pubectomy in 18.8% of the cases. Erectile dysfunction developed after trauma in 40.5% of cases, while new erectile dysfunction was noted in 4.3% of patients after surgery. Surgery was successful in 91.3% of cases, with a median follow-up of 16 (6-47) months. CONCLUSION: Delayed anastomotic urethroplasty offers a high success rate in traumatic urethral strictures.