International consensus panel for transurethral resection of bladder tumours metrics: assessment of face and content validity.

OBJECTIVE: To develop performance metrics that objectively define a reference approach to a transurethral resection of bladder tumours (TURBT) procedure, seek consensus on the performance metrics from a group of international experts. METHODS: The characterisation of a reference approach to a TURBT procedure was performed by identifying phases and explicitly defined procedure events (i.e., steps, errors, and critical errors). An international panel of experienced urologists (i.e., Delphi panel) was then assembled to scrutinise the metrics using a modified Delphi process. Based on the panel's feedback, the proposed metrics could be edited, supplemented, or deleted. A voting process was conducted to establish the consensus level on the metrics. Consensus was defined as the panel majority (i.e., >80%) agreeing that the metric definitions were accurate and acceptable. The number of metric units before and after the Delphi meeting were presented. RESULTS: A core metrics group (i.e., characterisation group) deconstructed the TURBT procedure. The reference case was identified as an elective TURBT on a male patient, diagnosed after full diagnostic evaluation with three or fewer bladder tumours of ≤3 cm. The characterisation group identified six procedure phases, 60 procedure steps, 43 errors, and 40 critical errors. The metrics were presented to the Delphi panel which included 15 experts from six countries. After the Delphi, six procedure phases, 63 procedure steps, 47 errors, and 41 critical errors were identified. The Delphi panel achieved a 100% consensus. CONCLUSION: Performance metrics to characterise a reference approach to TURBT were developed and an international panel of experts reached 100% consensus on them. This consensus supports their face and content validity. The metrics can now be used for a proficiency-based progression training curriculum for TURBT.

BCG priming followed by a novel interleukin combination activates Natural Killer cells to selectively proliferate and become anti-tumour long-lived effectors.

The short-lived nature and heterogeneity of Natural Killer (NK) cells limit the development of NK cell-based therapies, despite their proven safety and efficacy against cancer. Here, we describe the biological basis, detailed phenotype and function of long-lived anti-tumour human NK cells (CD56highCD16+), obtained without cell sorting or feeder cells, after priming of peripheral blood cells with Bacillus Calmette-Guérin (BCG). Further, we demonstrate that survival doses of a cytokine combination, excluding IL18, administered just weekly to BCG-primed NK cells avoids innate lymphocyte exhaustion and leads to specific long-term proliferation of innate cells that exert potent cytotoxic function against a broad range of solid tumours, mainly through NKG2D. Strikingly, a NKG2C+CD57-FcεRIγ+ NK cell population expands after BCG and cytokine stimulation, independently of HCMV serology. This strategy was exploited to rescue anti-tumour NK cells even from the suppressor environment of cancer patients' bone marrow, demonstrating that BCG confers durable anti-tumour features to NK cells.

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.

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.

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.

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.

[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.

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.

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.

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.

[Kidney transplant urinary complications. Diagnosis and treatment.] / Complicaciones urinarias del trasplante renal. Diagnóstico y tratamiento.

There are different surgical techniques for reconstruction of the urinary tract in kidney transplant. However, urinary complications are frequent in the postoperative period, being the ureter the frequent location of these complications. This results in high health care costs, increasing patient morbimortality and sometimes graft loss. For this reason, prevention, correct diagnosis and treatment are important. The aim of this review is to describe the surgical techniques most commonly used in kidney transplant for ureteroneocystostomy. To analyze the advantages and disadvantages of each of them and to compare their complications. On the other hand, we summarize the recent literature on the four most frequent urinary complications in the postoperative period after transplantation. The possible causes and treatment of urine leak, ureteri cobstruction, hematuria and vesicoureteral reflux are presented.

Existen diferentes técnicas quirúrgicas para la reconstrucción del tracto urinario en el trasplante renal. Sin embargo es frecuente la aparición de complicaciones urinarias en el postoperatorio, siendo el uréterla localización frecuente de las mismas. Esto implica un alto gasto sanitario, aumentando la morbimortalidad del paciente y pudiendo llegar a desencadenar la pérdida del injerto. Por ello es importante la prevención, el correcto diagnóstico y su tratamiento. El objetivo de esta revisión es describir las técnicas quirúrgicas más usadas en el trasplante renal para la ureteroneocistostomía. Analizar las ventajas y desventajas de cada una de ellas y comparar sus complicaciones. Por otro lado se resume la literatura reciente sobre las cuatro complicaciones urinarias más frecuentes en el postoperatorio del trasplante. Se exponen las posibles causas y tratamiento de la fuga urinaria, la obstrucción ureteral, la hematuria y el reflujo ureterovesical.

Long-Term Experience with Hyperthermic Chemotherapy (HIVEC) Using Mitomycin-C in Patients with Non-Muscle Invasive Bladder Cancer in Spain.

(1) Background: Intravesical mitomycin-C (MMC) combined with hyperthermia is increasingly used in non-muscle invasive bladder cancer (NMIBC), especially in the context of a relative BCG shortage. We aim to determine real-world data on the long-term treatment outcomes of adjunct hyperthermic intravesical chemotherapy (HIVEC) with MMC and a COMBAT® bladder recirculation system (BRS); (2) Methods: A prospective observational trial was performed on patients with NMIBC treated with HIVEC using BRS in nine academic institutions in Spain between 2012-2020 (HIVEC-E). Treatment effectiveness (recurrence, progression and overall mortality) was evaluated in patients treated with HIVEC MMC 40mg in the adjuvant setting, with baseline data and a clinical follow-up, that comprise the Full Analysis Set (FAS). Safety, according to the number and severity of adverse effects (AEs), was evaluated in the safety (SAF) population, composed by patients with at least one adjunct HIVEC MMC instillation; (3) Results: The FAS population (n = 502) received a median number of 8.78 ± 3.28 (range 1-20) HIVEC MMC instillations. The median follow-up duration was 24.5 ± 16.5 (range 1-81) months. Its distribution, based on EAU risk stratification, was 297 (59.2%) for intermediate and 205 (40.8%) for high-risk. The figures for five-year recurrence-free and progression-free survival were 50.37% (53.3% for intermediate and 47.14% for high-risk) and 89.83% (94.02% for intermediate and 84.23% for high-risk), respectively. A multivariate analysis identified recurrent tumors (HR 1.83), the duration of adjuvant HIVEC therapy <4 months (HR 1.72) and that high-risk group (HR 1.47) were at an increased risk of recurrence. Independent factors of progression were high-risk (HR 3.89), recurrent tumors (HR 3.32) and the induction of HIVEC therapy without maintenance (HR 2.37). The overall survival was determined by patient age at diagnosis (HR 3.36) and the treatment duration (HR 1.82). The SAF population (n = 592) revealed 406 (68.58%) patients without AEs and 186 (31.42%) with at least one AE: 170 (28.72%) of grade 1-2 and 16 (2.7%) of grade 3-4. The most frequent AEs were dysuria (10%), pain (7.1%), urgency (5.7%), skin rash (4.9%), spasms (3.7%) and hematuria (3.6%); (4) Conclusions: HIVEC using BRS is efficacious and well tolerated. A longer treatment duration, its use in naïve patients and the intermediate-risk disease are independent determinants of success. Furthermore, a monthly maintenance of adjunct MMC HIVEC diminishes the progression rate of NMIBC.

The benefit of a neoadjuvant instillation of chemotherapy in non-muscle invasive bladder cancer: Interim analysis of the PRECAVE randomized clinical trial. / El beneficio de una instilación neoadyuvante de quimioterapia en el carcinoma vesical no músculo invasivo: análisis intermedio del ensayo clínico aleatorizado PRECAVE.

OBJECTIVE: Although an immediate postoperative instillation of chemotherapy (IPOIC) after transurethral resection of bladder tumors (TURBT) is recommended for the prevention of recurrences of non-muscleinvasive bladder cancer (NMIBC), evidence shows there is an important compliance failure worldwide. We believe that an immediate neoadjuvant instillation of chemotherapy (INAIC) can act similarly, reducing the recurrence risk of NMIBC. Here we present the interim analysis of the PRECAVE clinical trial. MATERIAL AND METHODS: Patients with clinically diagnosed NMIBC were randomized to receive an INAIC with mitomycin C before TURBT (Group A) or to a control group with TURBT only (Group B). Primary end point was to compare the efficacy of an INAIC in the early recurrence-free survival (RFS). Secondary end points were: RFS in patients who did not receive adjuvant treatments, toxicity, and feasibility. RESULTS: A total of 124 patients with Ta/T1 G1-G3NMIBC were included in the initial analysis (Group A:64, Group B: 60). Demographics, risk classification, complications, and adjuvant treatments were balanced between groups. Eighty-four patients (Group A: 45, Group B: 39) who completed a one-year follow-up were included in the efficacy analysis and no difference was observed in the RFS between groups (p=0.3). In the subgroup of patients who did not receive adjuvant treatments, we found a significant difference in favor of an INAIC (p=0.009) and an 80% reduction in the risk of early recurrences (Hazard Ratio: 0.20; 95% confidence interval: 0.05-0.81; p=0.0024). No differences were observed in adverse events. Only 4 patients did not receive an INAIC despite being planned. CONCLUSIONS: In this interim analysis, although we could not demonstrate a reduction in the RFS of all patients, we did find a significant decrease of recurrences in patients who did not receive adjuvant treatments. The administration of an INAIC seems to be safe and our protocol appears feasible and reproductive.

OBJETIVO: Aunque el uso de una instilación postoperatoria inmediata de quimioterapia (IPOIQ) tras una resección transuretral vesical (RTUV) esta recomendada para prevenir recurrencias de carcinoma vesical no músculo invasivo (CVNMI), no se llega a realizar en muchos casos debido a fallos en su cumplimiento. Nosotros creemos que una instilación neoadyuvante inmediata de quimioterapia (INAIQ) puede actuar de manera similar reduciendo el riesgo de recurrencias. Presentamos el análisis intermedio del ensayo clínico PRECAVE.MATERIAL Y MÉTODOS: Se aleatorizó a pacientes diagnosticados de CVNMI a recibir una INAIQ con mitomicina C antes de la RTUV (Grupo A) o a un grupo control con RTUV solamente (Grupo B). El objetivo primario fue comparar la eficacia de una INAIQ en la supervivencia libre de recurrencia (SLR) temprana. Los objetivos secundarios fueron la SLR en pacientes que no recibieron tratamientos adyuvantes, toxicidad y viabilidad. RESULTADOS: Analizamos un total de 124 pacientes con CVNMI Ta/T1G1-G3 fueron analizados (Grupo A:64, Grupo B: 60). No se encontraron diferencias entre datos demográficos, grupos de riesgo, complicaciones o tratamientos adyuvantes. Para el análisis de eficacias e incluyeron 84 pacientes (Grupo A: 45, Grupo B:39) con al menos un año de seguimiento, sin observar diferencias en la SLR (p=0,3). Sin embargo, en el subgrupo que no recibió tratamientos adyuvantes, sí encontramos una diferencia significativa a favor de la INAIQ (p=0,009), y una reducción del riesgo de recurrencias tempranas del 80% (Hazard Ratio: 0,20; intervalo de confianza 95%: 0,05-0,81; p=0,0024). No se observaron diferencias en la aparición de eventos adversos. Solo 4 pacientes no recibieron un INAIC a pesar de estar planificado. CONCLUSIONES: En este análisis intermedio, aunque no pudimos demostrar una reducción en la SLR de todos los pacientes, sí encontramos una diferencia en el subgrupo que no recibió tratamientos adyuvantes. La administración de una INAIC parece ser segura, y nuestro protocolo parece factible y reproducible.