The impact of chemotherapy-naïve open radical cystectomy delay and perioperative transfusion on the recurrence-free survival: A perioperative parameters-based nomogram.

Objective: To develop and internally validate a nomogram to predict recurrence-free survival (RFS) including the time to radical cystectomy (RC) and perioperative blood transfusion (PBT) as potential predictors. Methods: Patients who underwent open RC and ileal conduit between January 1996 to December 2016 were split into developing (n=948) and validating (n=237) cohorts. The time to radical cystectomy (TTC) was defined as the interval between the onset of symptoms and RC. The regression coefficients of the independent predictors obtained by Cox regression were used to construct the nomogram. Discrimination, validation, and clinical usefulness in the validation cohort were assessed by the area under the curve, the calibration plot, and decision curve analysis. Results: In the developing dataset, the 1-, 5-, and 10-year RFS were 83.0%, 47.2%, and 44.4%, respectively. On multivariate analysis, independent predictors were TTC (hazards ratio [HR] 1.07, 95% confidence interval [CI] 1.05-1.08, p<0.001), PBT (one unit: HR 1.40, 95% CI 1.03-1.90, p=0.03; two or more units: HR 1.72, 95% CI 1.29-2.29, p<0.001), bilateral hydronephrosis (HR 1.54, 95% CI 1.21-1.97, p<0.001), squamous cell carcinoma (HR 0.60, 95% CI 0.45-0.81, p=0.001), pT3-T4 (HR 1.77, 95% CI 1.41-2.22, p<0.001), lymph node status (HR 1.53, 95% CI 1.21-1.95, p<0.001), and lymphovascular invasion (HR 1.28, 95% CI 1.01-1.62, p=0.044). The areas under the curve in the validation dataset were 79.3%, 69.6%, and 76.2%, for 1-, 5-, and 10-year RFS, respectively. Calibration plots showed considerable correspondence between predicted and actual survival probabilities. The decision curve analysis revealed a better net benefit of the nomogram. Conclusion: A nomogram with good discrimination, validation, and clinical utility was constructed utilizing TTC and PBT in addition to standard pathological criteria.

Artificial Intelligence in Andrology: From Semen Analysis to Image Diagnostics.

Artificial intelligence (AI) in medicine has gained a lot of momentum in the last decades and has been applied to various fields of medicine. Advances in computer science, medical informatics, robotics, and the need for personalized medicine have facilitated the role of AI in modern healthcare. Similarly, as in other fields, AI applications, such as machine learning, artificial neural networks, and deep learning, have shown great potential in andrology and reproductive medicine. AI-based tools are poised to become valuable assets with abilities to support and aid in diagnosing and treating male infertility, and in improving the accuracy of patient care. These automated, AI-based predictions may offer consistency and efficiency in terms of time and cost in infertility research and clinical management. In andrology and reproductive medicine, AI has been used for objective sperm, oocyte, and embryo selection, prediction of surgical outcomes, cost-effective assessment, development of robotic surgery, and clinical decision-making systems. In the future, better integration and implementation of AI into medicine will undoubtedly lead to pioneering evidence-based breakthroughs and the reshaping of andrology and reproductive medicine.

The Ideal Interval Between Repeated Shockwaves Lithotripsy Sessions for Renal Stones: A Randomized Controlled Trial.

Objectives: To assess the ideal interval between repeated extracorporeal shockwave lithotripsy (SWL) for renal stones. Patient and Methods: Eligible patients with a single renal stone ≤20 mm who required SWL were randomly assigned to one of three groups based on intervals between first and second sessions. Patients underwent the second session after 3, 7, and 14 days in Groups 1, 2, and 3, respectively. Tubular functions were assessed through comparisons of urinary execration of kidney injury molecule-1 (KIM-1), neutrophil gelatinase associated lipocalin (NGAL), and interleukin-18 (IL-18) with pre-SWL values, whereas glomerular function was assessed by comparisons of protein/creatinine ratio with pre-SWL and changes in ipsilateral renal function on isotope scans. Treatment success was assessed by noncontrast CT after 3 months. Results: All demographics of the 166 patients included in the study were comparable between the three groups. There were significant elevations of tubular biomarkers and protein/creatinine ratio after first and second SWL sessions compared with pre-SWL values (p < 0.0001). All tubular biomarkers returned to pre-SWL values at 7 and 14 days after second session, whereas they remained significantly elevated 3 days after second session (p = 0.027, < 0.001 and <0.001 for KIM-1, NGAL, and IL-18, respectively). SWL success was 73.6% in Group 1, 83.7% in Group 2, and 81% in Group 3. A significant decrease in ipsilateral renal split function was observed in Group 1 at the 3-month follow-up. Conclusions: An interval of 7 days is required between SWL sessions when treating renal stones to allow for complete recovery of kidney functions. Clinical Trial Registration: ID: NCT04575480.

Microscopic hematuria and pelvic ultrasonography could rule out flexible cystoscopy during surveillance for T1-low grade non-muscle invasive bladder cancer.

Purpose: Cystoscopy (rigid/flexible [FC]) is the standard surveillance tool for non-muscle invasive bladder cancer (NMIBC). Nevertheless, it has its drawbacks. The objective of this study is to evaluate the performance of microscopic hematuria (MH), abdominal ultrasonography (US), and urine cytology (UC) as potential substitutes for FC in patients with T1-low-grade (T1-LG) NMIBC. Methods: Over a 12-month period, patients attending our tertiary referral center for T1-LG NMIBC follow-up underwent urine analysis for MH and UC, and then US and FC were performed as outpatient surveillance procedures. Those with positive findings underwent inpatient rigid cystoscopy under anesthesia and biopsy. The negative predictive values (NPV) and sensitivity of different combinations of MH, UC, US, and FC were compared with the standard histopathology. Results: In 218 evaluated patients, FC had the highest NPV (97.9%). However, this figure showed no statistically significant difference if compared with the combination of negative MH and US (93.8%) (difference = 0.04, p = 0.1) or the combination of MH, US, and UC (94.9%) (difference = 0.03, p = 0.2). The reported sensitivity results were similarly comparable between FC (94.2%) and the aforementioned combinations (90.4% and 92.3%; differences: 0.038 and 0.019; p = 0.4 and 0.7, respectively). Conclusions: During the surveillance of NMIBC for patients diagnosed with T1-LG disease, the combination of MH/US has comparable sensitivity and NPV with FC. This non-invasive combination could be considered the first station that might preclude the need for FC in a considerable percentage of this group of patients.

Could the bulbar urethral end location on the cystourethrogram predict the outcome after posterior urethroplasty for pelvic fracture urethral injury?

Objectives: To identify cystourethrogram (CUG) findings that independently predict the outcome of posterior urethroplasty (PU) following pelvic fracture urethral injury (PFUI). Methods: Findings of CUG included the location of the proximal end of the bulbar urethra in zones A (superficial) or B (deep) according to its relationship with the pubic arch. Others included the presence of pelvic arch fracture, bladder neck, and posterior urethral appearance. The primary outcome was the need for reintervention either endoscopically or by redo urethroplasty. Independent predictors were modeled using a logistic regression model and a nomogram was constructed and internally validated using 100-bootstrap resampling. Time-to-event analysis was performed to validate the results. Results: A total of 196 procedures in 158 patients were analyzed. The success rate was 83.7% with 32 (16.3%) procedures requiring direct vision internal urethrotomy, urethroplasty, or both in 13 (6.6%), 12 (6.1%), and 7 (3.6%) patients, respectively. On multivariate analysis, bulbar urethral end located at zone B (odds ratio [OR]: 3.1; 95% confidence interval [CI]: 1.1-8.5; p = 0.02), pubic arch fracture (OR: 3.9; 95%CI: 1.5-9.7; p = 0.003), and previous urethroplasty (OR: 4.2; 95% CI: 1.8-10.1; p = 0.001) were independent predictors. The same predictors were significant in the time-to-event analysis. The nomogram discrimination was 77.3% and 75% in the current data and after validation. Conclusions: The location of the proximal end of the bulbar urethra and redo urethroplasty could predict the need for reintervention after PU for PFUI. The nomogram could be used preoperatively for patient counseling and procedure planning.

Controversy and Consensus on Indications for Sperm DNA Fragmentation Testing in Male Infertility: A Global Survey, Current Guidelines, and Expert Recommendations.

PURPOSE: Sperm DNA fragmentation (SDF) testing was recently added to the sixth edition of the World Health Organization laboratory manual for the examination and processing of human semen. Many conditions and risk factors have been associated with elevated SDF; therefore, it is important to identify the population of infertile men who might benefit from this test. The purpose of this study was to investigate global practices related to indications for SDF testing, compare the relevant professional society guideline recommendations, and provide expert recommendations. MATERIALS AND METHODS: Clinicians managing male infertility were invited to take part in a global online survey on SDF clinical practices. This was conducted following the CHERRIES checklist criteria. The responses were compared to professional society guideline recommendations related to SDF and the appropriate available evidence. Expert recommendations on indications for SDF testing were then formulated, and the Delphi method was used to reach consensus. RESULTS: The survey was completed by 436 experts from 55 countries. Almost 75% of respondents test for SDF in all or some men with unexplained or idiopathic infertility, 39% order it routinely in the work-up of recurrent pregnancy loss (RPL), and 62.2% investigate SDF in smokers. While 47% of reproductive urologists test SDF to support the decision for varicocele repair surgery when conventional semen parameters are normal, significantly fewer general urologists (23%; p=0.008) do the same. Nearly 70% would assess SDF before assisted reproductive technologies (ART), either always or for certain conditions. Recurrent ART failure is a common indication for SDF testing. Very few society recommendations were found regarding SDF testing. CONCLUSIONS: This article presents the largest global survey on the indications for SDF testing in infertile men, and demonstrates diverse practices. Furthermore, it highlights the paucity of professional society guideline recommendations. Expert recommendations are proposed to help guide clinicians.

Voiding and renal function 10 years after radical cystectomy and orthotopic neobladder in women.

OBJECTIVES: To assess long-term voiding and renal function (RF) changes after radical cystectomy (RC) and orthotopic neobladder (ONB) surgery in women without disease recurrence. MATERIAL AND METHODS: Women who underwent RC and ONB reconstruction between 1995 and 2011 were included in this study. Patients who developed disease failure or were lost to follow-up were excluded. The study outcomes were long-term voiding function and the incidence and predictors of RF deterioration (defined as >20% decline of baseline). Analysis was performed using the log-rank test and Cox regression analysis. RESULTS: The study included 195 patients with a median (interquartile range) follow-up of 98 (53-151) months, of whom 95 had >10 years of follow-up. Daytime continence, night-time continence and chronic urine retention (CUR) were identified in 170 (87%), 134 (69%) and 52 patients (27%), respectively. Among patients with >10 years of follow-up, 82 (86%), 66 (70%) and 31 (33%) had daytime continence, night-time continence and CUR at the last follow-up visit, respectively. RF deterioration events occurred in 74 patients throughout the follow-up and chronic kidney disease (CKD) stage III-V developed in 80 patients. Patients' age (hazard ratio [HR] 1.41, 95% confidence interval [CI]1.06-1.89; P = 0.02) and serous-lined extramural tunnel diversion (HR 0.43, 95% CI 0.19-0.86; P = 0.02) were the independent predictors of RF deterioration. Among patients with >10 years of follow-up, RF deteriorated in 46 patients (49%) and CKD stage III-V developed in 40 (42%). CONCLUSION: Women surviving more than 10 years after RC and ONB maintained acceptable continence status, apart from having a higher CUR rate, compared to those followed for <10 years. However, RF deterioration developed in nearly half of them.

Identification of Epigenetic Interactions between miRNA and Gene Expression as Potential Prognostic Markers in Bladder Cancer.

Purpose: To identify the role of a set of microRNAs and their target genes and protein expression levels in the pathogenesis of bladder cancer with a muscular invasion (T2−T4) and non-muscular invasion (T1). Methods: In 157 patients, bladder specimen was examined for the expression of a set of miRNAs including let-7a-5p, miRNA-449a-5p, miRNA-145-3P, miRNA-124-3P, miRNA-138-5p, and miRNA-23a-5p and their targeted genes; ß-catenin, WNT7A, IRS2, FZD4, SOS1, HDAC1, HDAC2, HIF1α, and PTEN using the qRT-PCR technique. The prognostic effect of miRNAs and their targeted genes on cancer-specific survival (CSS) was evaluated in pT2−pT4 stages. Results: pT1 was found in 40 patients while pT2−4 was found in 117 patients. The expression of let-7a-5P, miR-124-3P, miR-449a-5P, and miR-138-5P significantly decreased in pT2−4 compared with pT1 (p < 0.001), in contrast, miR-23a-5P increased significantly in pT2−pT4 compared with pT1 (p < 0.001). Moreover, the expression of miR-145 did not show a significant change (p = 0.31). Higher expression levels of WNT7A, ß-catenin, IRS2, FZD4, and SOS1 genes were observed in pT2−pT4 compared with pT1, whereas HDAC1, HDAC2, HIF1α, and PTEN genes were downregulated in pT2−pT4 compared with pT1. Lower CSS was significantly associated with lower expression of let-7a-5P, miR-124-3P, miR-449a-5P, and miR-138-5P. Higher expression of ß-catenin, FZD4, IRS2, WNT7a, and SOS1 was significantly associated with worse CSS. In contrast, lower levels of HDAC1, HDAC2, HIF1α, and PTEN were associated with lower CSS. Conclusion: Our results support let-7a-5P, miR-124-3P, miR-138-5P, and their target genes can be developed as accurate biomarkers for prognosis in bladder cancer with a muscular invasion.

Prediction of recurrence of non-muscle invasive bladder cancer: The role of androgen receptor and miRNA-2909.

AIM: The exact role of androgen receptor (AR) and miR-2909 in non-muscle invasive bladder cancer (NMIBC) remains controversial. Our aim is to assess the relationship between NMIBC recurrences with AR expression and miRNA-2909. PATIENTS AND METHODS: This prospective controlled cohort study included 99 male patients with NMIBC (Ta-T1) who were treated by transurethral resection and 50 male patients as healthy control. We quantified blood AR messenger RNA variants 1 and 2 (AR1, AR2) and plasma miRNA-2909 with real-time quantitative polymerase chain reaction and the full length AR (AR-FL) using enzyme-linked immunosorbent assay in serum samples. In addition, AR1 and AR2 expression in tumor as well as normal tissues were analyzed. Kaplan-Meier survival curves and multivariate Cox analysis were used to identify independent predictors of recurrence-free survival. RESULTS: In comparison to control group, blood AR1, AR2, and serum AR-FL expression were significantly lower in the NMIBC group compared to plasma miRNA-2909 expression that was significantly higher in the control group. Blood AR1, AR2, and serum AR-FL were significantly correlated with higher tumor stage (pT1) while plasma miRNA-2909 was not. The median survival time (months) was significantly better for higher blood AR1 (34 vs. 21; P = 0.03), lower plasma miRNA-2909 (29 vs. 8; P <0.001), lower AR2 in normal tissues (32 vs. 22; P = 0.007). On multivariate analysis, serum free testosterone (hazards ratio [HR]: 8.9; 95% CI: 1.8-45.1; P = 0.008), serum AR1 (HR: 0.5; 95% CI: 0.3-0.9; P = 0.02), and plasma miRNA-2909 (HR: 5.8; 95% CI: 2.3-14.7; P = 0.0002), and tissue AR2 (HR: 2.6; 95% CI: 1.4-4.7; P = 0.002) were independent predictor for NMIBC recurrence. CONCLUSIONS: Blood and tissue levels of AR expression have a potential significant effect on NMIBC recurrence. Further studies are recommended to establish its exact role.

Oncologic Outcomes of Squamous Cell Carcinoma Versus Urothelial Carcinoma With Squamous Differentiation After Radical Cystectomy for Bladder Carcinoma.

INTRODUCTION: In this study we aim to compare clinicopathological characteristics and cancer specific survival between patients treated with radical cystectomy for pure squamous cell carcinoma (SCC) and urothelial carcinoma with squamous differentiation (SqD). PATIENTS AND METHODS: We reviewed data of 1737 consecutive patients treated with radical cystectomy and urinary diversion between January 2004 and February 2014. Only patients with pure SCC or SqD were included in the analysis. Squamous differentiation was defined as intercellular bridges or keratinization in the tumor. Clinicopathological data and recurrence free survival (RFS) were compared between patients diagnosed with SCC and SqD. RESULTS: SCC and SqD were found in 318 and 223 patients, respectively. Mean age was 57 ± 8.3 years in SCC and 58.8 ± 7.8 in SqD (P = .008). A higher proportion of female patients was observed in SCC group compared to SqD (31.8% vs. 22% P < .0001). Patients with SqD were more likely to have extravesical (58.3% vs. 46.2%: P = .006) and nodal positive disease (34.5% vs. 14.5%: P < .0001) than pure SCC patients. Bilharzial eggs were found in 61% of SCC vs. 46% of SqD (P = .001).; The median (IQR) follow up period for SCC and SqD was 63 (12-112) months and 23 months (9-74.7), respectively. The 5-year RFS for SCC and SqD were 77% and 59.8 %, respectively (P < .0001).; Multivariate cox regression analysis identified advanced pT stage (OR: 1.9, 95% CI: 1.3-2.86, P = .0001), nodal positive disease (OR: 1.6, 95% CI: 1.1-2.48, P = .01) and SqD histology (OR: 1.6, 95% CI: 1.14-2.31, P = .007 as independent predictors of 5-year RFS. CONCLUSION: Patient with SCC had significantly higher 5-year RFS in comparison to SqD. The higher rate of extravesical disease and lymph node metastasis in SqD patients is indicative of aggressive behavior of this histologic type.

Predictors and survival benefit of achieving pentafecta in a contemporary series of open radical cystectomy.

BACKGROUND: Pentafecta provides a comprehensive approach for standardized reporting of surgical and oncologic outcomes after radical cystectomy and urinary diversion. We aimed to report the rate, predictors of achieving pentafecta and its impact on long-term survival in a contemporary series of open radical cystectomy (ORC). METHODS: A retrospective analysis of a computerized database of patients treated with ORC between 2004 till 2014 was performed. Pentafecta criteria included negative soft tissue surgical margin (STSM), retrieval of ≥16 lymph nodes, absence of clinical recurrence within 12 months after surgery, absence of high-grade complication (GIII-V) within 90 days after surgery, and absence of urinary diversion related complications at 12 months follow-up. Multivariate analysis was used to identify predictors of achieving pentafecta. RESULTS: Pentafecta was achieved in 545 (33.6%) patients out of 1624 included in the study. Absence of ≥16 LN yield was the first cause of missing pentafecta (49.5%). Multivariate analysis identified: ASA Score grades ≥III (OR=0.7, 95%CI 0.6-0.9, P=0.04), BMI≥35 (OR=0.5, 95%CI 0.3-0.8, P=0.007), perioperative blood transfusion (≥4 units) (OR=0.5, 95%CI 0.3-0.7, P=0.001), and ileal conduit (OR=0.7, 95%CI 0.5-0.9, P= 0.01) as independent predictors of missing pentafecta. Patients who achieved pentafecta had higher estimated 5-year RFS than their counterparts (81.7% vs. 62.5%; P<0.0001). CONCLUSIONS: Pentafecta was achieved in nearly one third of patients after ORC. Achievement of pentafecta was associated with better long-term recurrence-free survival. Obesity (class II, III), perioperative blood transfusion (>4 units), associated comorbidities, and ileal conduit were independent predictors of missing pentafecta.

Prognostic influence of microsatellite alterations of muscle-invasive bladder cancer treated with radical cystectomy.

OBJECTIVE: To examine the prognostic effect of microsatellite instability (MSI) and loss of heterozygosity (LOH) on cancer-specific survival (CSS) in patients with muscle-invasive bladder cancer (MIBC). PATIENTS AND METHODS: The liquid nitrogen-preserved specimens of 220 patients between March 2009 and December 2012 were analyzed for the presence of MSI and LOH in 12 loci (ACTBP2, D16S310, D16S476, D18S51, D4S243, D9S162, D9S171, D9S747, FGA, INF-α, MBP, MJD) using polymerase chain reaction. MSI was defined as MSI-stable, MSI-Low, or MSI-High if instability was detected in 0, 1, or 2 or more of the examined markers, respectively. The association between MSI-High and LOH and CSS was analyzed using uni- and multivariate analyses and the degree of agreement between tumor and urine samples were determined. RESULTS: MSI were found in 1030 (39%) and 1148 (43.5%) in tumor and urine specimens, respectively (Kappa = 0.77). On the other hand, LOH was found in 163 (6.2%) of tumor tissues and 44 (1.7%) in urine specimens (Kappa = 0.34). Microsatellite alterations were significantly associated with worse CSS at 1- and 5-year in tumor tissue (95% and 83.7% vs. 65.8% and 3.5%, respectively; P < 0.001) and in urine sample (90% and 64% vs. 46.5% and 9.3%, respectively; P < 0.001). MSI and/or LOH was an independent predictor of CSS (HR: 9.8; 95%CI: 5.1-18.9; P < 0.001). CONCLUSIONS: Microsatellite alterations were potentially an independent predictor of CSS in patients with MIBC. The agreement was good between tumor and urine MSI but weak for LOH.

Parastomal hernia after ileal conduit urinary diversion: re-visiting the predictors radiologically and according to patient-reported outcome measures.

PURPOSE: To evaluate the predictors of post-ileal conduit (IC) parastomal hernia (PSH) based on a standard grading methodology and according to the patients reported outcome measures (PROM). METHODS: A prospective evaluation for patients with IC attending their scheduled follow-up was conducted between December 2013 and October 2015. The hernia stage was determined according to the European Hernia Society (EHS) classification as types I and II included defect size < 5 cm without and with a concomitant incisional hernia, respectively. Types III and IV included defect size > 5 cm without and with a concomitant incisional hernia (high-grade hernia). The evaluation was performed by a non-contrast CT scan. PROM were defined as symptomatic if there were hernia-related abdominal discomfort, appliance problems, and/or bowel complications. Perioperative parameters were modeled for prediction of high-grade and PROM outcomes. RESULTS: PSH was diagnosed in 138 (39.9%) patients, symptomatic in 119 (34.4%) and high-grade in 59 (17%). Independent predictors of radiologically diagnosed PSH were hypoalbuminemia (odds ratio [OR]: 1.7; 95% Confidence interval [CI]: 1.1-2.7; p = 0.02), localised disease (OR: 0.6; 95% CI: 0.3-0.9; p = 0.04) and negative lymphadenopathy (OR: 0.4; 95%CI: 0.2-0.8; p = 0.004). Predictors of symptomatic PSH were hypoalbuminemia (OR: 2; 95%CI: 1.2-2.3: p = 0.003) and previous hernia surgery (OR: 2.1; 95%CI: 1.1-4.2; p = 0.024). CONCLUSIONS: Only a small proportion of patients with PSH were asymptomatic. Preoperative hypoalbuminemia was the most significant factor contributing to the development and symptomatizing of PSH. Previous hernia surgery further contributed to the patient complaint.

Laparoscopic Excision of an Extra-Adrenal Pheochromocytoma (Paraganglioma) of the Organ of Zuckerkandl.

Background: Paraganglioma of the organ of Zuckerkandl (OZ) is a rare surgically challenging tumor because of its critical location and the nature of catecholamine secretion. We describe the technique of laparoscopic excision as well as provide a literature review to confirm its feasibility. Case Presentation: In a 23-year-old male patient, laparoscopic excision of a 5 × 4 cm tumor located at the aortic bifurcation and indenting the vertebral column was performed. Preoperatively, the patient received α- and ß-adrenergic blockers as well as underwent sperm banking. The patient was put in the lateral position, five ports were used: four in the midline and one in the left iliac fossa. The tumor was approached by the reflection of the colon. Ureter, gonadal vein, and sympathetic chain were preserved. Dissection of the tumor from the inferior mesenteric artery was done followed by control of three feeding arteries and two draining veins posteriorly and inferiorly. The procedure was completed laparoscopically with minimal blood loss. Intraoperatively, three episodes of hypertension developed and required stoppage and the administration of vasodilators. The patient recovered on the second day postoperatively and all antihypertensive medications were stopped. At 1 year of follow-up, the patient is tumor-free but developed anejaculation for which he is under current treatment. Conclusion: Laparoscopic excision of paraganglioma located at the OZ is safe and feasible.

Diagnostic performance and predictive capacity of early urine cytology after transurethral resection of nonmuscle invasive bladder cancer: A prospective study.

OBJECTIVES: To prospectively evaluate the value of early urine cytology (EUC) after the primary transurethral resection of bladder tumor (TURBT) of nonmuscle invasive bladder cancer (NMIBC) for the prediction of positive biopsy findings on repeat TURBT. METHODS: After approval of institutional review board, patients who underwent TURBT for NMIBC between February 2014 and July 2018 were included in the study. Patients with concomitant Carcinoma in Situ (CIS), upper tract urothelial tumors, biopsy proven muscle invasion, or low-risk NMIBC (single, primary, Ta, and G1 tumor) were excluded. Forty-eight hours after primary TURBT, EUC was retrieved and patients were scheduled for repeat TURBT 2 to 6 weeks later according to the predetermined protocol. The primary outcome was to determine the role of positive EUC to predict positive biopsy findings on repeat TURBT. RESULTS: During the study period, 198 patients fulfilled the study inclusion criteria of which 49 (25%) had recurrent NMIBC. Primary TURBT pathology results showed T1 stage in 195 (98.5%) patients and high-grade malignancy in 158 (79.8%). Intermediate- and high-risk NMIBC were defined in 49 (25%) and 149 (75%) patients, respectively. EUC was positive in 114 patients; of whom 78 (68.4%) showed positive biopsy findings on repeat TURBT (P = 0.001). The sensitivity, specificity, negative, and positive predictive values of EUC for biopsy findings at repeat TURBT were 90% (95%CI: 87-94), 75% (95%CI: 71-79), 89% (95%CI: 85-94), and 68% (95%CI: 62-74), respectively. On mean (±SD) follow-up of 42(±13) months, tumor recurrence was encountered in 101 (53%) patients. On multivariate Cox regression analysis, EUC was significantly associated with tumor recurrence (HR = 4.6, 95%CI: 2.37-8.9, P < 0.001). CONCLUSIONS: Positive EUC after primary TURBT for NMIBC is significantly associated with positive repeat TURBT for malignancy. EUC is an independent predictor of tumor recurrence. EUC might be implemented after primary TURBT to help refining indications of repeat biopsy and planning of further intervention.

Evaluation of serum fatty acid binding protein-4 (FABP-4) as a novel biomarker to predict biopsy outcomes in prostate biopsy naïve patients.

OBJECTIVES: To investigate the role of serum fatty acid-binding protein-4 (FABP-4) as a surrogate of obesity and metabolic syndrome in the prediction of the outcome of prostate biopsy. METHODS: A prospective pilot study was conducted for patients undergoing prostate needle biopsy (PNB) for clinically suspected prostate cancer (PCa) between June 2016 and August 2017. Fifty consecutive patients with biopsy-proven PCa were included as study group and 50 consecutive patients with negative biopsy were included as a control group. Receiver Operating Characteristic (ROC) curve was used to calculate the area under the curve (AUC) to compare the accuracy of the different parameters in the diagnosis as well as the presence of high-grade PCa (Gleason score 8-9) at PNB. Predictors of the outcome were analyzed using univariate and multivariate logistic regression analysis. RESULTS: FABP-4 (AUC: 0.75; P < 0.001) and PSA-density (AUC: 0.84; P < 0.001) were the most accurate to detect PCa at PNB. On multivariate analysis, FABP-4 > 22.5 ng/ml (OR: 16.6; 95% CI 2.8-98; P = 0.002) and PSA-density > 0.38 ng/ml/ml OR: 17.7; 95% CI 5.3-59; P < 0.001) were independent predictors of PCa detection. Regarding high-grade PCa at PNB, FABP-4 (AUC: 0.79; P < 0.001) and %Free-PSA (AUC: 0.75; P < 0.001) were the most accurate. Independent predictors of high-grade PCa were FABP-4 > 32.3 ng/ml OR: 9.2; 95% CI 1.8-45; P = 0.006) and %Free-PSA ≤ 21.9 (OR: 5.5; 95% CI 1.1-27; P = 0.03). CONCLUSIONS: FABP-4 is an independent predictor for both the diagnosis and high-grade Gleason score at PNB. This novel biomarker might have a promising role in optimizing PNB outcomes.

Single Versus Maintenance Intravesical Chemotherapy for the Prevention of Bladder Recurrence after Radical Nephroureterectomy for Upper Tract Urothelial Carcinoma: A Randomized Clinical Trial.

INTRODUCTION: The objective of this study was to determine the efficiency of 1-year maintenance intravesical chemotherapy (MIC) in reducing bladder recurrence (BR) after radical nephroureterectomy (RNU) for upper tract urothelial carcinoma compared with single intravesical instillation (SIC). PATIENTS AND METHODS: Between January 2015 and May 2017, patients who underwent RNU were randomized to receive SIC (epirubicin 50 mg) or MIC (once weekly for 6 weeks plus once monthly for 1 year). The primary outcome was the rate of histologically proven BR. The secondary outcomes included chemotherapy-related toxicities and disease-specific survival (DSS). Thirty-five patients in each arm were required to achieve a power of 80%. RESULTS: A total of 38 (SIC) and 36 (MIC) patients were analyzed. In SIC, BR developed in 5 (13.2%) over a median follow-up of 3 months (range, 3-6 months) compared with 9 (25%) patients over 12 months (range, 3-28 months) in MIC (P = .08). The 6- and 12-month BR-free survivals were the same (86.8%) in SIC versus 88.9% and 83.3% in MIC, respectively (P = .2). Lymphovascular invasion was significantly associated with BR (P = .04). Post-RNU intravesical chemotherapy regimens did not alter DSS. Blood transfusion and advanced tumor stage were independent predictors for DSS. No significant medication toxicity was reported. CONCLUSIONS: Following RNU, MIC did not change the natural course of BR beyond a single instillation apart from potentially delaying its occurrence. Lymphovascular invasion and blood transfusion were associated with worse BR and DSS outcomes, respectively.

Serum lipids might improve prostate-specific antigen sensitivity in patients undergoing transrectal ultrasonography-guided biopsy for suspected prostate cancer: A pilot study.

Objectives: To investigate the potential use of body mass index (BMI) and serum lipids in improving prostate-specific antigen (PSA) sensitivity in patients undergoing biopsy for suspicion of prostate cancer, as there is an established relationship between metabolic syndrome, obesity and serum lipids with prostate cancer. Patients and methods: A pilot study was conducted in a tertiary referral centre between June 2016 and August 2017 of patients undergoing transrectal ultrasonography (TRUS)-guided biopsy. After the result of TRUS-biopsy, the first 50 patients diagnosed with prostate cancer (study group) and those with no prostate cancer (control group) were enrolled. BMI, serum PSA level, fasting blood sugar and lipid profile (e.g. cholesterol, triglycerides, low-density lipoprotein [LDL] and high-density lipoprotein [HDL]), were compared between the groups. Results: Higher BMI, cholesterol, LDL and lower HDL together with PSA were significantly associated with a positive biopsy. On multivariate analysis, LDL (odds ratio [OR] 5.3, 95% confidence interval [CI] 1.2-24.9; P = 0.03) and total PSA level (OR 12.9, 95% CI 4.7-35; P < 0.001) were independent predictors of a positive biopsy. A combination of LDL <80 mg/dL and PSA level <26 ng/mL threshold values determined by receiver operating characteristic curve analysis, had a sensitivity and specificity of 94% and 28%, respectively; whilst, the negative (NPV) and positive predictive values were 82.4% and 56.6%, respectively. The sensitivity and NPV of the combination was significantly higher than that of PSA level alone (94% vs 72% and 82.4% vs 75%, respectively; P < 0.001). Conclusions: Serum lipids might have a role in the diagnosis of prostate cancer and could be used as an adjunct to PSA measurement to improve sensitivity and avoid unnecessary biopsies. Abbreviations: AUC: area under the curve; BMI: body mass index; FBS: fasting blood sugar; HDL: high-density lipoprotein; LDL: low-density lipoprotein; LOX-1: lectin-like oxidised LDL receptor-1; OR: odds ratio; ROC: receiver operating characteristic; RP: radical prostatectomy; TG: triglyceride.

The short-term effects of tolterodine on nocturnal incontinence after ileal orthotopic neobladder: a randomised crossover placebo-controlled study.

OBJECTIVES: To assess the effect of tolterodine in the treatment of nocturnal urinary incontinence (NUI) after ileal orthotopic neobladder (ONB). PATIENTS AND METHODS: This is a prospective randomised placebo-controlled crossover study (clinicaltrials.gov: NCT02877901). Patients with NUI after ONB were randomly allocated into two equal groups. Group T received 4 mg extended-release tolterodine at bed-time and Group P received placebo for 4 weeks followed by 2 weeks of washout, then crossed over to the alternate therapy for 4 weeks. Patients were assessed by the number of pads used per night (PPN) and with the Arabic version of the International Consultation on Incontinence Modular Questionnaire-Short Form (ICIQ-SF) at both phases of the study. The outcomes were the rate of NUI improvement and medication adverse events. RESULTS: Out of 172 patients, 150 and 122 patients were evaluated at both phases of the study. The mean ICIQ-SF scores and PPN were significantly decreased in Group T compared to Group P in both study phases (P < 0.001). In Group T, 15 (10%) and 11 (9%) patients became dry after the first allocation and crossover, respectively. In Group T, 60 (77.9%) patients reported improvement vs four (5.5%) in Group P (P < 0.001) after the first allocation. Similarly, 46 (73%) and seven (11.9%) patients showed improvement in groups T and P after the crossover, respectively (P < 0.001). Dry mouth occurred in 31 (20.8%) patients. CONCLUSIONS: Tolterodine seems to be a good choice for treatment of NUI after radical cystectomy and ONB. However, further studies are needed to delineate the long-term effects and the associated urodynamic characteristics.