Prognostic Value of Liquid-Biopsy-Based Biomarkers in Upper Tract Urothelial Carcinoma.

Currently, there are no reliable prognostic factors to determine which upper tract urothelial carcinoma (UTUC) patients will progress after radical nephroureterectomy (RNU). We aim to evaluate whether liquid-biopsy-based biomarkers (circulating tumor cells (CTCs), cell-free DNA (cfDNA), and circulating tumor DNA (ctDNA)) were able to predict clinical outcomes in localized UTUC patients undergoing RNU. Twenty patients were prospectively enrolled between 2021 and 2023. Two blood samples were collected before RNU and three months later. CTCs and cfDNA were isolated and evaluated using the IsoFlux system and Quant-iT PicoGreen dsDNA kit, respectively. Droplet digital PCR was performed to determine ctDNA status. Cox regression analysis was performed on CTCs, cfDNA, and ctDNA at two different follow-up time points to examine their influence on tumor progression and cancer-specific survival (CSS). During a median follow-up of 18 months, seven (35%) patients progressed and three (15%) died. Multivariate analysis demonstrated that cfDNA levels three months after RNU are a significant predictor of tumor progression (HR = 1.085; p = 0.006) and CSS (HR = 1.168; p = 0.029). No associations were found between CTC enumeration and ctDNA status with any of the clinical outcomes evaluated. The evaluation of cfDNA levels in clinical practice could improve the disease management of UTUC patients.

European Association of Urology Guidelines on Muscle-invasive and Metastatic Bladder Cancer: Summary of the 2023 Guidelines.

CONTEXT: We present an overview of the updated 2023 European Association of Urology (EAU) guidelines for muscle-invasive and metastatic bladder cancer (MMIBC). OBJECTIVE: To provide practical evidence-based recommendations and consensus statements on the clinical management of MMIBC with a focus on diagnosis and treatment. EVIDENCE ACQUISITION: A broad and comprehensive scoping exercise covering all areas of the MMIBC guidelines has been performed annually since 2017. Searches cover the Medline, EMBASE, and Cochrane Libraries databases for yearly guideline updates. A level of evidence and strength of recommendation are assigned. The evidence cutoff date for the 2023 MIBC guidelines was May 4, 2022. EVIDENCE SYNTHESIS: Patients should be counselled regarding risk factors for bladder cancer. Pathologists should describe tumour and lymph nodes in detail, including the presence of histological subtypes. The importance of the presence or absence of urothelial carcinoma (UC) in the prostatic urethra is emphasised. Magnetic resonance imaging (MRI) of the bladder is superior to computed tomography (CT) for disease staging, specifically in differentiating T1 from T2 disease, and may lead to a change in treatment approach in patients at high risk of an invasive tumour. Imaging of the upper urinary tract, lymph nodes, and distant metastasis is performed with CT or MRI; the additional value of flurodeoxyglucose positron emission tomography/CT still needs to be determined. Frail and comorbid patients should be evaluated by a multidisciplinary team. Postoperative histology remains the most important prognostic variable, while circulating tumour DNA appears to be an interesting predictive marker. Neoadjuvant systemic therapy remains cisplatin-based. In motivated and selected women and men, sexual organ-preserving cystectomy results in better functional outcomes without compromising oncological outcomes. Robotic and open cystectomy have comparable outcomes and should be combined with (extended) lymph node dissection. The diversion type is an individual choice after taking patient and tumour characteristics into account. Radical cystectomy remains a highly complex procedure with considerable morbidity and risk of mortality, although lower rates are observed for higher hospital volumes (>20 cases/yr). With proper patient selection, trimodal therapy (chemoradiation) has comparable outcomes to radical cystectomy. Adjuvant chemotherapy after surgery improves disease-specific survival and overall survival (OS) in patients with high-risk disease who did not receive neoadjuvant treatment, and is strongly recommended. There is a weak recommendation for adjuvant nivolumab, as OS data are not yet available. Health-related quality of life should be assessed using validated questionnaires at baseline and after treatment. Surveillance is needed to monitor for recurrent cancer and functional outcomes. Recurrences detected on follow-up seem to have better prognosis than symptomatic recurrences. CONCLUSIONS: This summary of the 2023 EAU guidelines provides updated information on the diagnosis and treatment of MMIBC for incorporation into clinical practice. PATIENT SUMMARY: The European Association of Urology guidelines panel on muscle-invasive and metastatic bladder cancer has released an updated version of the guideline containing information on diagnosis and treatment of this disease. Recommendations are based on studies published up to May 4, 2022. Surgical removal of the bladder and bladder preservation are discussed, as well as updates on the use of chemotherapy and immunotherapy in localised and metastatic disease.

Xpert Bladder Cancer Monitor for the Early Detection of Non-Muscle Invasive Bladder Cancer Recurrences: Could Cystoscopy Be Substituted?

XBM was prospectively assessed in spontaneous urine collected just before flexible cystoscopy and washing cytology carried out within the first 2 years follow-up of 337 patients with NMIBC. Recurrences were pathologically confirmed in 49 patients (14.5%), 22 of them being high-risk (6.5%). The XBM sensitivity for detecting any type of recurrence was 69.4% and 63.6% in the cases of high-risk NMIBC. Negative predictive value (NPV) for XBM was 93% for all recurrences and 96.2% for high-risk recurrences. XBM could have avoided 213 invasive controls but missed the detection of 15 recurrences (30.6%)-8 of them of high-risk (36.4%). XBM false positive elevations were detected in 90 patients (26.7%), whereas 10 patients with the invasive method had a false positive result (3%), p <0.001. However, early detection of recurrences during the first year's follow-up after an XBM false positive result was observed in 18 patients (20%). On the other hand, 19 recurrences were detected during this period among the rest of the patients (7.7%)-p = 0.003, and odds ratio (OR) 3.0 (95% CI 1.5-6.0). Regarding one-year follow-up recurrences, 10% were high-risk recurrences in the XBM false positive group and 3.2% in the rest of the patients-p = 0.021, and OR 3.3 (95% CI 1.2-8.9). Additionally, 11.3% of the patients without false positive results developed a recurrence, p = 0.897, for any recurrence, being 10% and 5.2%, respectively, and high-risk and low-risk recurrences, p = 0.506. After searching for the best XBM cutoff for detecting the 38 high-risk initial recurrences and the early high-risk recurrences after a one-year follow-up, a linear discriminant analysis (LDA) of 0.13 could have avoided 11.3% of cystoscopies and bladder wash cytologies, as this cutoff missed only 1 high-risk recurrence (2.6%). More extensive and well-designed studies will confirm if XBM can improve the surveillance of NMIBC.

[Optimization biomarkers in the surveillance of non muscle invasive bladder cancer.] / Optimización del seguimiento de tumores vesicales no músculo invasivo con biomarcadores.

INTRODUCTION: Bladder cancer is thefifth most common tumor in the world. Moreover, it isone of the most expensive due to its high recurrencerate. Urinary biomarkers for surveillance of non muscleinvasive bladder cancer is a promising and growingfield due to the invasiveness of the actual methods, basedon cystoscopy and cytology. Although current EuropeanGuidelines only consider the use of biomarkersin the low risk scenario as an alternative to cystoscopywhen the patient declines invasive methods for the follow-up after surgery, there is increasing evidence oftheir safety in high risk tumors. MATERIAL AND METHODS: We have performeda review of the main urinary biomarkers, includingFDA-approved ones, protein-based and genetic biomarkers.We have also described the different options to incorporatethe biomarkers in the clinical practice. RESULTS: There are not randomized control trialscomparing any biomarker with the gold standard follow-up. Most of the papers published so far are cohortstudies, limitating the evidence of the results. Biomarkerscan be used as an alternative of cystoscopy, in a noninvasive follow-up, or alternating both tests. There arefew economical studies comparing both options, but theevidence supports the efficiency of the main biomarkers. CONCLUSIONS: Cystoscopy and cytology are the goldstandard for non muscle invasive bladder cancer surveillance.2021 European Guidelines suggest, for the firsttime, an alternative use of biomarkers in a concrete lowgrade scenario to avoid invasive explorations to patientswith low risk of progression. Paradoxically, biomarkers(mainly genetic ones) have a very good profile of sensitivityand negative predictive value in the high risk scenario.Although there is increasing evidence to supporttheir implementation, the lack of fase IV trials hinderstheir daily use.

INTRODUCCIÓN: El carcinoma vesicales el quinto tumor más frecuente en el mundo. Dehecho, es uno de los que más recursos económicosconsume debido a su alta tasa de recurrencia. Los biomarcadoresurinarios para el seguimiento del tumorvesical no músculo invasivo es un campo prometedory en pleno crecimiento debido a la invasividad de losactuales métodos de seguimiento, basados en la cistoscopiay la citología de orina. A pesar de que las actualesGuías Europeas sólo consideran el uso de biomarcadoresen el escenario del tumor vesical de bajoriesgo como alternativa a la cistoscopia cuando el pacienteno desee procedimientos invasivos para el seguimientotras la cirugía, existe creciente evidencia desu seguridad en los tumores de alto riesgo.MATERIAL Y MÉTODOS: Se ha realizado una revisiónnarrativa de los principales biomarcadores urinarios,incluyendo los aprobados por la FDA, los basados enproteínas y los marcadores genéticos. Se han descritoigualmente las diferentes opciones para la incorporaciónde los biomarcadores en la práctica clínica diaria.RESULTADOS: No existen ensayos clínicos randomizadosque comparen los biomarcadores urinariosfrente al gold estándar en el seguimiento. La mayoría delos artículos hasta la fecha son estudios de cohortes, limitandola evidencia de los resultados. Los biomarcadores pueden ser utilizados como alternativa a la cistoscopia,en un seguimiento no invasivo, o alternandoambas pruebas. Existen pocos estudios económicosque comparen ambas opciones, pero la evidencia parecesoportar la eficiencia de los principales biomarcadores.CONCLUSIONES: La cistoscopia y la citología son elgold estándar para el seguimiento del tumor vesicalno músculo infiltrante. Las Guías Europeas de 2021sugieren, por primera vez, el uso alternativo de losbiomarcadores urinarios en el escenario concreto delbajo grado con el fin de evitar exploraciones invasivasa pacientes con muy bajo riesgo de progresión. Paradójicamente,los biomarcadores (principalmente losgenéticos) presentan un mejor perfil de sensibilidad yvalor predictivo negativo en el escenario del alto riesgo.A pesar de que existe creciente evidencia para recomendarsu implementación, la ausencia de ensayosclínicos fase IV dificulta su aplicación en la práctica diaria.

Optimización del seguimiento de tumores vesicales no músculo-invasivos con biomarcadores / Optimization biomarkers in the surveillance of non muscle invasive bladder cáncer

INTRODUCCIÓN: El carcinoma vesical es el quinto tumor más frecuente en el mundo. Dehecho, es uno de los que más recursos económicosconsume debido a su alta tasa de recurrencia. Los biomarcadores urinarios para el seguimiento del tumorvesical no músculo invasivo es un campo prometedory en pleno crecimiento debido a la invasividad de losactuales métodos de seguimiento, basados en la cistoscopia y la citología de orina. A pesar de que las actuales Guías Europeas sólo consideran el uso de biomarcadores en el escenario del tumor vesical de bajoriesgo como alternativa a la cistoscopia cuando el paciente no desee procedimientos invasivos para el seguimiento tras la cirugía, existe creciente evidencia desu seguridad en los tumores de alto riesgo.MATERIAL Y MÉTODOS: Se ha realizado una revisiónnarrativa de los principales biomarcadores urinarios,incluyendo los aprobados por la FDA, los basados enproteínas y los marcadores genéticos. Se han descritoigualmente las diferentes opciones para la incorporación de los biomarcadores en la práctica clínica diaria.RESULTADOS: No existen ensayos clínicos randomizados que comparen los biomarcadores urinariosfrente al gold estándar en el seguimiento. La mayoría delos artículos hasta la fecha son estudios de cohortes, limitando la evidencia de los resultados. Los biomarcadores pueden ser utilizados como alternativa a la cistoscopia, en un seguimiento no invasivo, o alternandoambas pruebas. Existen pocos estudios económicosque comparen ambas opciones, pero la evidencia parece soportar la eficiencia de los principales biomarcadores.CONCLUSIONES: La cistoscopia y la citología son elgold estándar para el seguimiento del tumor vesicalno músculo infiltrante. Las Guías Europeas de 2021sugieren, por primera vez, el uso alternativo de losbiomarcadores urinarios en el escenario concreto de

INTRODUCTION: Bladder cancer is thefifth most common tumor in the world. Moreover, it isone of the most expensive due to its high recurrencerate. Urinary biomarkers for surveillance of non muscle invasive bladder cancer is a promising and growingfield due to the invasiveness of the actual methods, based on cystoscopy and cytology. Although current European Guidelines only consider the use of biomarkersin the low risk scenario as an alternative to cystoscopywhen the patient declines invasive methods for the follow-up after surgery, there is increasing evidence oftheir safety in high risk tumors. MATERIAL AND METHODS: We have performeda review of the main urinary biomarkers, includingFDA-approved ones, protein-based and genetic biomarkers. We have also described the different options to incorporate the biomarkers in the clinical practice.RESULTS: There are not randomized control trialscomparing any biomarker with the gold standard follow-up. Most of the papers published so far are cohortstudies, limitating the evidence of the results. Biomarkers can be used as an alternative of cystoscopy, in a noninvasive follow-up, or alternating both tests. There arefew economical studies comparing both options, but theevidence supports the efficiency of the main biomarkers.CONCLUSIONS: Cystoscopy and cytology are the goldstandard for non muscle invasive bladder cancer surveillance. 2021 European Guidelines suggest, for the firsttime, an alternative use of biomarkers in a concrete lowgrade scenario to avoid invasive explorations to patientswith low risk of progression. Paradoxically, biomarkers(mainly genetic ones) have a very good profile of sensitivity and negative predictive value in the high risk scenario. Although there is increasing evidence to supporttheir implementation, the lack of fase IV trials hinderstheir daily use.

Perioperative and Functional Outcomes of Robot-assisted Ureteroenteric Reimplantation: A Multicenter Study of Seven Referral Institutions.

BACKGROUND: Open revision of ureteroenteric strictures (UESs) is associated with considerable morbidity. There is a lack of data evaluating the feasibility of robotic revisions. OBJECTIVE: To analyze the perioperative and functional outcomes of robot-assisted ureteroenteric reimplantation (RUER) for the management of UESs after radical cystectomy (RC). DESIGN SETTING AND PARTICIPANTS: A retrospective multicenter study of 61 patients, who underwent 63 RUERs at seven high-volume institutions between 2009 and 2020 for benign UESs after RC, was conducted. OUTCOME MEASUREMENTS AND STATISTICAL ANALYSIS: Data were reviewed for demographics, stricture characteristics, and perioperative outcomes. Variables associated with being stricture free after an RUER were evaluated using a multivariate Cox regression analysis. RESULTS AND LIMITATIONS: Among 63 RUERs, 22 were right sided (35%), 34 left sided (54%), and seven bilateral (11%). Twenty-seven (44%) had prior abdominal/pelvic surgery and five (8%) radiotherapy (RT). Thirty-two patients had American Society of Anesthesiologists (ASA) scores I-II (52%) and 29 ASA III (48%). Forty-two (68%) RUERs were in ileal conduits, 18 (29%) in neobladders, and two (3%) in Indiana pouch. The median time to diagnosis of a UES from cystectomy was 5 (3-11) mo. Of the UESs, 28 (44%) failed an endourological attempt (balloon dilatation/endoureterotomy). The median RUER operative time was 195 (175-269) min. No intraoperative complications or conversions to open approach were reported. Twenty-three (37%) patients had postoperative complications (20 [32%] were minor and three [5%] major). The median length of hospital stay was 3 (1-6) d and readmissions were 5%. After a median follow-up of 19 (8-43) mo, 84% of cases were stricture free. Lack of prior RT was the only variable associated with better stricture-free survival after RUER (hazard ratio 6.8, 95% confidence interval 1.10-42.00, p = 0.037). The study limitations include its retrospective nature and the small number of patients. CONCLUSIONS: RUER is a feasible procedure for the management of UESs. Prospective and larger studies are warranted to prove the safety and efficacy of this technique. PATIENT SUMMARY: In this study, we investigate the feasibility of a novel minimally invasive technique for the management of ureteroenteric strictures. We conclude that robotic reimplantation is a feasible and effective procedure.

Prognostic classifier for predicting biochemical recurrence in localized prostate cancer patients after radical prostatectomy.

OBJECTIVE: The purpose of the study was to develop an improved classifier for predicting biochemical recurrence (BCR) in clinically localized PCa patients after radical prostatectomy. METHODS AND MATERIALS: Retrospective study including 122 PCa patients who attended our department between 2000 and 2007. Gene expression patterns were analyzed in 21 samples from 7 localized, 6 locally advanced, and 8 metastatic PCa patients using Illumina microarrays. Expression levels of 41 genes were validated by quantitative PCR in 101 independent PCa patients who underwent radical prostatectomy. Logistic regression analysis was used to identify individual predictors of BCR. A risk score for predicting BCR including clinicopathological and gene expression variables was developed. Interaction networks were built by GeneMANIA Cytoscape plugin. RESULTS: A total of 37 patients developed BCR (36.6%) in a median follow-up of 120 months. Expression levels of 7,930 transcripts differed between clinically localized and locally advanced-metastatic PCa groups (FDR < 0.1). We found that expression of ASF1B and MCL1 as well as Gleason score, extracapsular extension, seminal vesicle invasion, and positive margins were independent prognostic factors of BCR. A risk score generated using these variables was able to discriminate between 2 groups of patients with a significantly different probability of BCR (HR 6.24; CI 3.23-12.4, P< 0.01), improving the individual discriminative performance of each of these variables on their own. Direct interactions between the 2 genes of the model were not found. CONCLUSION: Combination of gene expression patterns and clinicopathological variables in a robust, easy-to-use, and reliable classifier may contribute to improve PCa risk stratification.

A Robot-Assisted Complete Urinary Tract Extirpation in a Patient with Simultaneous Panurothelial Carcinoma: A Case Report.

Background: Despite concomitant bladder and upper urinary tract cancers are present in 17% of cases, the simultaneous affection of the urethra, bladder, and both upper urinary tracts is extremely rare. Treatment decisions in this setting could be challenging because of the lack of evidence in the literature. Case Presentation: A 65-year-old Caucasian man with a history of nine low-grade (LG) and multifocal bladder tumor recurrences during the past 4 years is referred to our department with a newly diagnosed panurothelial carcinoma involving the bladder, urethra, and both upper urinary tracts. Because of the large and recurrent LG bladder tumor, the urethral involvement and the presence of bilateral pyelocaliceal tumors >4 cm the patient underwent a robot-assisted complete urinary tract extirpation (CUTE). Operating time was 360 minutes and blood loss 460 mL. No intraoperative complications were reported and blood transfusion was not required. The patient developed a surgical site infection in the glans that was solved with antibiotics without any other postoperative complication. He started renal replacement therapy and was discharged 6 days after the surgery. Pathologic analysis showed multifocal urothelial carcinomas; pTa LG involving the bladder and the prostatic-bulbar-membranous-penile urethra, pT3 high grade (HG) in right renal pelvis, pT1 HG in left renal pelvis, and pN0 in pelvic lymph node dissection. After a reasonable free-recurrence period of time the patient could be evaluated for a robot-assisted intracorporeal urinary diversion in preparation for a later renal transplantation. Conclusion: Robot-assisted CUTE could be a feasible and safe technique for selected patients with simultaneous panurothelial carcinoma. Further multicentric studies are warranted to determine the safety of this minimally invasive approach in patients with different comorbidities.

Comparison of standard vs. palliative management for bladder cancer in patients older than 85 years: multicenter study of 317 de novo tumors.

BACKGROUND: The peak incidence of bladder cancer (BCa) occurs at 85 years but data on treatment and outcome are sparse in this age group. We aimed to compare the outcomes of high-grade nonmuscle invasive BCa (HG NMIBC) and muscle invasive BCa (MIBC) treated with standard therapies vs. palliative management in patients >85 years. METHODS: Retrospective multicenter study of 317 patients >85 years who underwent transurethral resection (TURB) for de novo BCa between 2014 and 2016. Standard management consisted in following EAU-guidelines and palliative in monitoring patients without applying oncological treatments after TURB. Low-grade tumors were not compared because all of them were considered to have followed a standard management. RESULTS: Median age was 87 years (85-97). ASA-score was as follows: II, 34.7%; III, 52.1%; IV, 13.2%. Pathological examination showed: 86 Low-grade NMIBC (27.1%), 156 HG NMIBC (49.2%), and 75 MIBC (23.7%). Median follow-up of the series was 21 months (3-61) and median overall survival (OS) 29 (24-33). Among HG NMIBC, 77 patients (49.4%) received standard treatments (BCG, restaging TURB) and 79 (50.6%) palliative management. Among MIBC, 24 (32%) received standard management (cystectomy, radiotherapy, chemotherapy) and 51 (68%) palliative. Applying standard management in HG NMIBC was an independent prognostic factor of OS (44 months vs. 24, HR 1.95; P = 0.013) and decreased the emergency visit rate (33% vs. 43%). In MIBC, the type of management was not a related to OS (P = 0.439) and did not decrease the emergency visit rate (33% vs. 33%). ASA and Charlson-score were not predictors of OS in HG NMIBC (P = 0.368, P = 0.386) and MIBC (P = 0.511, P = 0.665). CONCLUSIONS: Chronological age should not be a contraindication for applying standard therapies in NMIBC. In MIBC the survival is low regardless of the type of management. The lack of correlation between OS and ASA or Charlson-score raises the necessity of a geriatric assessment for selecting the best treatment strategy.

Comparison of Outcomes between Standard and Palliative Management for High Grade Non-Muscle Invasive Bladder Cancer in Patients Older than 85 Years.

OBJECTIVES: To analyze outcomes of patients > 85 years with de novo bladder cancer (BCa). To compare outcomes of high grade (HG) non-muscle invasive BCa (NMIBC) treated with standard therapies versus palliative management. METHODS: Retrospective revision of 65 patients > 85 years who underwent transurethral resection of the bladder (TURB) for de novo BCa. According to functional status each patient was offered a standard or palliative management after TURB. RESULTS: Median age was 87.3 years (85.2-95.4) and 51 were men (78.5%). Twenty-eight (43%) were American Society of Anesthesiologists (ASA) II and 37 ASA III-IV (57%). Pathological examination: 29 pTx-pTa (44.6%), 28 pT1 (43.1%) and 8 pT2 (12.3%). Twenty were low grade (30.8%) and 45 HG (69.2%). Among 37 HG NMIBC patients, 43% followed standard therapies (BCG or re-staging TURB + BCG), and 57% a palliative management (no oncological treatments). With a median follow-up of 20 months (3-108), 2 (12.5%) died in standard group compared to 11 (52.4%) in palliative. In univariate analysis, age (p = 0.024), stage (p = 0.009), and standard management (p = 0.019) were related to overall survival (OS). In multivariate, standard management was an independent prognostic factor of OS (hazard ratio 0.164, 95% CI 0.036-0.744, p = 0.048). CONCLUSIONS: Advanced age should not be a contraindication for standard therapies in BCa. A geriatric assessment could identify patients who may benefit from adjuvant therapies after TURB.

Urinary cell microRNA-based prognostic classifier for non-muscle invasive bladder cancer.

Current prognostic tools for non-muscle invasive bladder cancer (NMIBC) do not have enough discriminative capacity to predict the risk of tumour progression. This study aimed to identify urinary cell microRNAs that may be useful as non-invasive predictive biomarkers of tumour progression in NMIBC patients. To this end, 210 urine samples from NMIBC patients were included in the study. RNA was extracted from urinary cells and expression of 8 microRNAs, previously described by our group, was analysed by quantitative PCR. A tumour progression predicting model was developed by Cox regression analysis and validated by bootstrapping. Regression analysis identified miR-140-5p and miR-92a-3p as independent predictors of tumour progression. The risk score derived from the model containing these two microRNAs was able to discriminate between two groups with a highly significant different probability of tumour progression (HR, 5.204; p<0.001) which was maintained when patients were stratified according to tumour risk. The algorithm was also able to identify two groups with different cancer-specific survival (HR, 3.879; p=0.021). Although the data needs to be externally validated, miRNA analysis in urine appears to be a valuable prognostic tool in NMIBC patients.

Prior Lubrication of the Urethra Does Not Reduce Pain Perception in Men Undergoing Flexible Cystoscopy.

OBJECTIVE: The study aimed to test the hypothesis that the instillation of lidocaine gel does not reduce the pain related to flexible cystoscopy. MATERIAL AND METHODS: A prospective randomized study was designed to compare the pain perception between intraurethral instillation of lidocaine gel and saline solution in flexible cystoscopy. One hundred consecutive male patients attending for flexible cystoscopy were randomized to receive 10 ml of lidocaine gel or 10 ml of saline solution. Saline solution was also used for the irrigation pressure. Patients recorded their pain on a 10 cm Visual Analog Scale before and after the procedure. Patients also assessed whether the cystoscopy was more painful than the previous one. Statistical comparison was made using the t test for parametrical data and the Mann-Whitney U test for non-parametrical data. RESULTS: Mean pain score in the lidocaine group was 0.67 ± 1.11 cm (range 0-5) compared to 0.55 ± 1.10 cm (range 0-5) in the saline solution group. Pain perception did not differ significantly between the 2 groups (mean difference 0.12 cm, 95% CI -0.32 to 0.55, p = 0.40). CONCLUSIONS: Prior lubrication of the urethra does not reduce the pain produced during flexible cystoscopy. The introduction of flexible cystoscopes under direct vision and with an irrigation pressure might guarantee sufficient comfort and the lubricant gel instillation could be avoided.

Intraoperative prognostic factors and atypical patterns of recurrence in patients with upper urinary tract urothelial carcinoma treated with laparoscopic radical nephroureterectomy.

Objective The aims of this study were to identify clinical, intraoperative and pathological prognostic factors for predicting extraurothelial recurrence and cancer-specific survival (CSS) in patients with upper urinary tract urothelial carcinoma (UTUC) who had undergone laparoscopic radical nephroureterectomy (LRNU), and to investigate the site-specific patterns of recurrence and the associated outcomes. Materials and methods A retrospective revision was undertaken of 117 consecutive patients who had undergone transperitoneal LRNU for UTUC between 2007 and 2012. Univariate and multivariate Cox regression analyses were used to identify prognostic factors and Kaplan-Meier was used to estimate CSS. Results With a median follow-up of 20 months, 36 patients (30%) developed extraurothelial recurrence (local and/or distant). In the multivariate analysis, entering the urinary tract during LRNU was related to local recurrence (p = 0.04), management of the distal ureter to CSS (p = 0.003), pathological stage and positive margins to local (p = 0.001, p = 0.013), distant (p = 0.028, p = 0.009) and global recurrence (p = 0.05, p = 0.012) and CSS (p = 0.011, p = 0.042), and multifocality to distant recurrence (p = 0.024). Median time to recurrence was 11.4 months after LRNU. Of 36 patients with progression, 23 (64%) had simultaneous local and distant recurrence and eight had atypical metastases: two port-site metastases, five peritoneal, two subcutaneous and two abdominal wall implants. The 5 year CSS was 61% for all patients with UTUC and 9% for those with recurrence. Conclusions Intraoperative events could have a negative impact on the oncological outcomes of patients with UTUC treated with LRNU. The use of laparoscopy for advanced UTUC may be related to atypical ways of spreading.

Perioperative outcome and female sexual function after laparoscopic transvaginal NOTES-assisted nephrectomy.

PURPOSE: There is a concern about the impact that this surgery could have on a patient's sexuality, although this has not been well documented. The objective of our study is to describe the surgical results and assess sexual function and patient satisfaction after transvaginal NOTES-assisted laparoscopic radical and living donor nephrectomy. METHODS: Between March 2008 and October 2014, 100 women underwent transvaginal NOTES-assisted nephrectomy (78 living donor and 22 radical nephrectomy) in our centre. The procedure was performed using two different techniques depending on the indication as described previously, but using the same vaginal approach. Variables evaluated were operative time, blood loss, intra-operative complications, hospital stay, satisfaction, first-month creatinine and warm ischaemia time in donors. Sexual function was assessed with the Female Sexual Function Index questionnaire before and after surgery. All variables were accrued in a prospective database. RESULTS: The procedure was completed in all cases. Mean age and body mass index was higher in the radical nephrectomy group. Mean operative time and hospital stay were similar for both techniques. All sexually active women reported unaltered sexual function after surgery and satisfaction with the results. The pre- and post-FSFI scores for living donor (n = 54) and radical nephrectomy (n = 4) were 27.47 ± 1.02/27.27 ± 1.10 (p > 0.05) and 31.17 ± 0.81/31.87 ± 0.97 (p > 0.05). CONCLUSIONS: Transvaginal NOTES-assisted or hybrid NOTES nephrectomy offers a safe technique with excellent cosmetic results and no sexual effect. Despite promising results, randomized controlled studies with longer follow-up are warranted to further elucidate the potential of this novel technique.

Marked testosterone deficiency-related symptoms may be associated to higher metabolic risk in men with low testosterone levels.

INTRODUCTION: Testosterone deficiency syndrome (TDS) is usually suspected on the basis of signs/symptoms. However, some men with low testosterone levels (low T) are asymptomatic or present mild, unnoticed symptoms. Would they have the same cardiovascular risk as symptomatic men? AIMS: This study aims to assess the relationship between presence/severity of low T-related symptoms and the likelihood of metabolic syndrome (MetS). METHODS: Data were taken from a multicenter, cross-sectional study conducted in Spain among men visiting men's healthcare offices aged ≥45 with low T (total T <8 nmol/L or <12 nmol/L and calculated free T <250 nmol/L). Only subjects whose MetS components and symptoms had been assessed were selected. Data available included anthropometrics, toxic habits, comorbidities, and total testosterone (TT) levels. MAIN OUTCOME MEASURES: MetS was defined using the harmonized definition. Erectile dysfunction was classified using the International Index of Erectile Function questionnaire. The Ageing Male Symptoms (AMS) scale assessed symptoms. Symptom severity was classified as "none/mild" and "moderate/severe." Bivariate and multivariate logistic regression analyses were performed to calculate the effect of moderate/severe symptoms on the odds ratio (OR) for MetS. RESULTS: Mean age (SD) was 61.2 (8.1) years. Erectile dysfunction (ED), AMS, and MetS prevalence were 97.4%, 94.9%, and 69.6%. Prevalence of MetS was higher in men with moderate/severe symptoms vs. men with no/mild ones (75.3% vs. 57.9%, P < 0.001). Age and prevalence of TT <8 nmol/L, moderate/severe ED, and obesity were significantly higher in men with moderate/severe symptoms. Multivariate analysis showed that besides obesity and moderate/severe ED, moderate/severe symptoms increased the likelihood of MetS. This effect disappeared in men with severe ED and in the nonobese. Three symptoms showed relationship with MetS after adjusting for all confounding factors. CONCLUSION: Severity of TDS symptoms may indicate higher cardiovascular risk in men with low T.

Higher second fourth digit ratio predicts higher incidence of prostate cancer in prostate biopsy.

OBJECTIVES: To analyze the validity of the ratio between the second and fourth finger (digit ratio; 2D/4D) of the left hand as a predictor for prostate cancer (PCa) in a group of men undergoing prostate biopsy. METHODS: We prospectively recruited 204 consecutive patients referred for transrectal prostate biopsy due to PSA elevation or abnormal digital rectal examination between January 2008 and June 2009. The same physician performed all clinical examinations, digit ratio measurements and transrectal biopsy in all cases. Digit ratio determination was done with a Vernier caliper in the left hand. Patients underwent determination of hormone profile (testosterone and sexual hormone binding globulin (SHBG)) between 7:00AM and 11:00AM. Age, digital rectal examination, PSA, free PSA, PSA density, testosterone and SHBG, pathological report and D2 and D4 measurements were recorded prospectively. RESULTS: Variables age and SHBG were directly related to PCa. Prostate volume was inversely related to neoplasia. 2D/4D ratio >0,95 (OR (CI 95%) 4,4 (1,491-13,107) was related to neoplasia. No differences in PCa were seen regarding PSA, free PSA, PSA density, digital rectal examination and testosterone. CONCLUSION: High digit ratio predicts PCa in men undergoing prostate biopsy. Digit ratio >0,95 has 4-fold risk of PCa compared to men with digit ratio ≤0.95.

Un mayor cociente de la longitud del segundo y el cuarto dedo de la mano está en relación con mayor incidencia de Cáncer de próstata en biopsia de próstata / High digit ratio predicts prostate cancer in prostate biopsy

OBJETIVO: Analizar la validez del cociente entre las longitudes del 2º y 4º dedos (2D/4D) de la mano izquierda como predictor de cáncer de próstata en hombres sometidos a biopsia transrectal ecodirigida de próstata. MÉTODOS: Recogimos prospectivamente los datos de 204 pacientes consecutivos referidos para biopsia de próstata transrectal por elevación de PSA o tacto rectal sospechoso entre enero 2008 y junio 2009. El mismo médico realizó todas las exploraciones físicas, medidas y biopsias transrectales. La determinación 2D/4D se realizó mediante un pie de rey en la mano izquierda. Se determinó en todos los pacientes un perfil hormonal (testosterona y SHBG) entre las 07:00 y las 11:00. Las variables edad, tacto rectal, PSA, PSA libre, densidad del PSA, testosterona y SHBG, diagnóstico anatomopatológico y 2D/4D se analizaron prospectivamente. RESULTADOS: Las variables edad y SHBG estuvieron directamente relacionadas con la presencia de neoplasia. El volumen de próstata correlacionó inversamente con la presencia de neoplasia. La ratio 2D/4D >0,95 (OR (IC 95%) 4,4 (1,491-13,107) se relacionó con la presencia de cáncer de próstata (CP). No se encontraron diferencias en el CP respecto al PSA, PSA libre, densidad del PSA, tacto rectal y testosterona. CONCLUSIONES: Los hombres sometidos a biopsia de próstata con 2D/4D >0,95 tienen cuatro veces más probabilidades de presentar CP que aquellos con una ratio digital ≤0,95(AU)

OBJECTIVES: To analyze the validity of the ratio between the second and fourth finger (digit ratio; 2D/4D) of the left hand as a predictor for prostate cancer (PCa) in a group of men undergoing prostate biopsy. METHODS: We prospectively recruited 204 consecutive patients referred for transrectal prostate biopsy due to PSA elevation or abnormal digital rectal examination between January 2008 and June 2009. The same physician performed all clinical examinations, digit ratio measurements and transrectal biopsy in all cases. Digit ratio determination was done with a Vernier caliper in the left hand. Patients underwent determination of hormone profile (testosterone and sexual hormone binding globulin (SHBG)) between 7:00AM and 11:00AM.Age, digital rectal examination, PSA, free PSA, PSA density, testosterone and SHBG, pathological report and D2 and D4 measurements were recorded prospectively. RESULTS: Variables age and SHBG were directly related to PCa. Prostate volume was inversely related to neoplasia. 2D/4D ratio >0,95 (OR (CI 95%) 4,4 (1,491-13,107) was related to neoplasia. No differences in PCa were seen regarding PSA, free PSA, PSA density, digital rectal examination and testosterone. CONCLUSION: High digit ratio predicts PCa in men undergoing prostate biopsy. Digit ratio >0,95 has 4-fold risk of PCa compared to men with digit ratio <0.95(AU)