Omega-3 polyunsaturated fatty acids: a modified approach for chemo-prevention of bladder cancer in a rat model and molecular studies of antineoplastic mechanisms.

OBJECTIVES: To test the chemo-preventative effects of omega-3 against bladder cancer (BC) induction in a rat model and its potential antineoplastic mechanisms. MATERIAL AND METHODS: Ninety male Fisher rats were divided into three groups during a 22-week protocol: group 1 (control), group 2 (Placebo + N-butyl-N-4- hydroxybutyl nitrosamine (BBN) for induction of BC and group 3 received omega-3 (1200 mg/kg/day) + BBN. At the end, blood samples and bladder tissues were collected and checked for the presence of malignancy, markers of angiogenesis (VEGF relative gene expression), inflammation (IL-6), proliferation (KI-67 expressions), oxidative stress (serum MDA and serum SOD) and epigenetic control (miRNA-145 level). RESULTS: At the end of the study, 60% and 86.6% rats survived in group 2 and 3 with significant weight loss among rats in group 2 when compared with other groups. In group 2, all rats developed visible bladder lesions of which five and 13 developed squamous cell carcinoma (SCC) and transitional cell carcinoma (TCC). In omega3-treated group, only one developed low grade SCC and one developed high grade non- invasive TCC. Bladders from omega-3-treated rats showed lower expression ofKI-67 (p < 0.05), VEGF (p < 0.001) and IL-6 (p < 0.001) and significant higher expression of mi-RNA (p < 0.001). Also, omega-3-treated group showed statistically significant lower MDA level (p < 0.001). CONCLUSION: Omega-3 inhibits bladder tumor growth in the BBN-induced BC rat model, due to anti-inflammatory, antioxidant, anti-proliferative, and anti-angiogenic properties together with epigenetic control.

Mirabegron for treatment of erectile dysfunction concomitant with lower urinary tract symptoms in patients with benign prostatic obstruction: A randomized controlled trial.

OBJECTIVE: To assess the efficacy of mirabegron in the treatment of erectile dysfunction concomitant with lower urinary tract symptoms in benign prostatic obstruction patients. METHODS: In this randomized controlled trial, 55 sexually active lower urinary tract symptoms/benign prostatic obstruction patients with concomitant erectile dysfunction were randomly allocated in two groups: the first received mirabegron 50 mg plus doxazosin 2 mg once daily (mirabegron group) and the second received tolterodine 4 mg plus doxazosin 2 mg (tolterodine group) for 12 weeks. The evaluation was based on the International Index of Erectile Function questionnaire, Erection Hardness Score questionnaire, International Prostate Symptom Score, quality of life, uroflowmetry and post-voiding residual. The therapeutic outcomes were assessed at 4 and 12 weeks compared with the baseline. RESULTS: Only the mirabegron group achieved significant improvement in sexual functions after 4 and 12 weeks. By using ≥5 points difference from the baseline as a cut-off point of change, there was a significant difference in change of direction of the International Index of Erectile Function-15 total score in favor of the mirabegron group; after 12 weeks, the International Index of Erectile Function-15 total score decreased in 0%, was unchanged in 8.3% and improved in 91.7% in the mirabegron group compared with 8.7%, 65.2% and 26.1%, respectively, in the tolterodine group (P < 0.001). Regarding the urinary characteristics, both groups showed significant improvement in the International Prostate Symptom Score, quality of life, and post-voiding residual after 4 and 12 weeks, with no significant difference among them. CONCLUSION: Mirabegron improves urinary characteristics and the associated sexual dysfunction in patients with lower urinary tract symptoms/benign prostatic obstruction.

Effect of low-energy shock wave therapy on intravesical epirubicin delivery in a rat model of bladder cancer.

OBJECTIVES: To study the efficacy of low-energy shock wave therapy (LESW) on enhancing intravesical epirubicin (EPI) delivery in a rat model of bladder cancer (BCa). MATERIALS AND METHODS: A total of 100 female Fischer rats were randomly allocated into five groups: control; BCa; LESW; EPI; and EPI plus LESW. After BCa induction by N-butyl-N-(4-hydroxybutyl)nitrosamine, EPI (0.6 mg/0.3 mL of EPI diluted in 0.3 mL saline) or saline (0.6 mL) was administered and retained in the bladders for 1 h with or without LESW treatment (300 pulses at 0.12 mJ/mm2 ). This was repeated weekly for 6 weeks. Survival was then calculated, rats were weighed and their bladders were harvested for bladder/body ratio estimation, histopathological examination, p53 immunostaining, miR-210, hypoxia-inducible factor (HIF)-1α, tumour necrosis factor (TNF)-α and interleukin (IL)-6 relative gene expression and fluorescence spectrophotometric drug quantification. Heart and blood samples were also collected for assessment of the safety profile and toxicity. RESULTS: The EPI plus LESW group had significantly lower mortality rates, loss of body weight and bladder/body ratio. Histopathological results in terms of grossly visible bladder lesions, mucosal thickness, dysplasia formation and tumour invasion were significantly better in the combined treatment group. The EPI plus LESW group also had statistically significant lower expression levels of p53 , miR-210, HIF-1α, TNF-α and IL-6. LESW increased urothelial concentration of EPI by 5.7-fold (P < 0.001). No laboratory variable exceeded the reference ranges in any of the groups. There was an improvement of the indicators of EPI-induced cardiomyopathy in terms of congestion, hyalinization and microvesicular steatosis of cardiomyocytes (P = 0.068, 0.003 and 0.046, respectively) in the EPI plus LESW group. CONCLUSIONS: The combined use of intravesical EPI and LESW results in less BCa invasion and less dysplasia formation, as LESW increases urothelial permeability of EPI and enhances its delivery into tumour tissues, without subsequent toxicity.

The alternating bidirectional versus the standard approach during shock wave lithotripsy for upper lumbar ureteric stones: a randomized controlled trial.

PURPOSE: To compare the outcome of shock wave lithotripsy (SWL) for upper lumbar ureteric stones using the alternating bidirectional approach versus the standard approach during the first session. METHODS: Our study was a randomized controlled trial including patients with single radio-opaque stone < 1 cm located in the upper lumbar ureter (from the ureteropelvic junction till the level medial to the lower margin of the kidney). SWL was conducted using electromagnetic Dornier Gemini Lithotripter. In group 1, patients were treated with the alternating under and over-table approach during the first session only and if other sessions were needed, the standard under-table approach was used. In group 2, patients were treated with the standard under-table approach during all sessions. Stone disintegration after the first session was assessed by kidney-ureter-bladder X-ray, renal ultrasonography and noncontrast computed tomography. Moreover, the incidence and severity of postoperative complications were evaluated. RESULTS: Forty-eight patients in each group completed the study. Patient demographics and stone characteristics were comparable in both groups. Complete disintegration was achieved in 41.7% of patients in group 1 versus 18.8% in group 2 (P = 0.021). Stone-free rate (SFR) was 58.3% and 20.8% in group 1 and 2 respectively (P = 0.001). The mean session time was 56.42 min in group 1 versus 46.35 min in group 2 (P < 0.001). There was no significant difference in postoperative complications. CONCLUSION: Stone disintegration and SFR after the first SWL session are higher when using the alternating bidirectional approach for upper lumbar ureteric stones at the expense of longer procedural duration. TRIAL REGISTRATION: ClinicalTrials identifier (ID: NCT03243682), clinicaltrials.gov.

Optimal non-invasive treatment of 1-2.5 cm radiolucent renal stones: oral dissolution therapy, shock wave lithotripsy or combined treatment-a randomized controlled trial.

PURPOSE: To evaluate the efficacy of oral dissolution therapy (ODT), shock wave lithotripsy (SWL), and combined SWL and ODT for medium-sized radiolucent renal stone (RLS). METHODS: A randomized controlled trial for patients with medium-sized RLS, 1-2.5 cm, ≤ 500 Hounsfield unit (HU). The ODT patients were counseled for oral potassiumsodium-hydrogen citrate (Uralyt-U®). The 2nd group underwent SWL and the last group had combined SWL and ODT. The primary outcome, stone-free rate (SFR) at 3 months, was assessed by non-contrast computed tomography (NCCT). We defined complete response (success) if no residual fragment were detected by NCCT; partial response (failure) if there was a decrease in stone size, but presence of residual stones; no response if there was no change or increase in stone size (failure). RESULTS: 150 patients completed follow-up. The SFR at 1st month and 3rd month were, respectively; 16% and 50% in the ODT group, 10% and 46% in the SWL group, and 35% and 72% patients in combined group with (p = 0.03 and 0.003, respectively. The overall SFR for all groups was 66%. Combined treatment and initial response in first month follow-up were independent factors predicting SFR. In addition, combined treatment significantly decreased the overall stone volume (p = 0.03) and the need for additional stone management procedures after 3 months (p = 0.01). CONCLUSION: Combined ODT and SWL treatment constitutes the most rapid and effective therapeutic approach for medium-sized RLS, decreasing overall stone volume as well as the number of SWL sessions needed in comparison to SWL therapy, alone.

Prospective Assessment of Learning Curve of Holmium Laser Enucleation of the Prostate for Treatment of Benign Prostatic Hyperplasia Using a Multidimensional Approach.

PURPOSE: Despite being endorsed in most guidelines, wide adoption of holmium laser enucleation of the prostate is hindered by learning difficulties. We prospectively assessed the learning curve using a multidimensional approach. MATERIALS AND METHODS: We prospectively report all perioperative safety and efficacy outcome measures as well as the need for reoperation and continence status. Case difficulty and learning curve characterization variables were considered, looking for predictors of different outcome measures. Our analysis included the first 313 procedures done by a total of 3 surgeons. RESULTS: Prostate volume and the number of previously performed cases independently predicted operative and enucleation efficiency (mean ± SD 0.76 ± 0.36 and 1.2 ± 0.6 gm per minute, respectively). Both measures plateaued only after the first 40 procedures. The mean percent reduction in postoperative prostate specific antigen was 80% ± 19%. A significantly lower decrease was independently predicted by the transrectal ultrasound depiction of a grossly multinodular prostate (p = 0.000, R2 = 0.59). Perioperative safety measures showed significant improvement after the first and second 20 procedures apart from hospital stay and catheter time. Urinary incontinence was reported in 89 (28.5%), 26 (8.3%) and 7 cases (2.2%) at 1, 4 and 12 months, respectively. Only the number of previously performed cases predicted urinary incontinence at 1 month, which was significantly reduced following the first 20 procedures (plateau) (OR 0.99, 95% CI 0.98-0.999, p = 0.03). The I-PSS (International Prostate Symptom Score) preoperative storage subdomain (OR 0.7, 95% CI 0.4-0.9, p = 0.04), case density (OR 0.3, 95% CI 0.2-0.6, p = 0.01) and number of previously performed cases (OR 0.97, 95% CI 0.98-0.999, p = 0.02) predicted urinary incontinence at 4 months, which was significantly reduced after the first and second 20 procedures. Persistent urinary incontinence at 12 months was significantly associated with fewer previously performed cases (median 60, range 0 to 211 vs 20, range 0 to 99, p = 0.04) with no plateauing through the curve. CONCLUSIONS: Plateauing through the learning curve of holmium laser enucleation of the prostate is a moving target. Looking at different outcome measures, different levels of experience are needed to reach the plateau. Preoperative prostate volume, the number of previously performed cases and case density are the main influential factors in the curve. Urinary incontinence is the most relevant clinical outcome that was significantly affected by learning, although its transient nature is assuring.

Residual stones after percutaneous nephrolithotomy: comparison of intraoperative assessment and postoperative non-contrast computerized tomography.

OBJECTIVES: To compare the intraoperative surgeon perspective for detection of residual fragments (RFs) after percutaneous nephrolithotomy (PNL) with postoperative NCCT. METHODS: A prospective study of adult patients who underwent PNL between March and September 2014 was conducted. Stone complexity was evaluated using the Guy's stone score (GSS). All patients were evaluated by pre- and postoperative NCCT. After the procedure, the surgeon had been asked whether there were residual stones or not. The sensitivity, specificity and predictive values were tested against postoperative NCCT. Predictors of accurate intraoperative assessment were determined using univariate and multivariate statistical analyses. RESULTS: The study included 306 consecutive patients. The surgeons reported no residual stones in 236 procedures; of whom 170 (72%) were reported stone-free by NCCT. On the other hand, 65 out of 70 procedures (93%) reported with residual stones by the surgeons were true by NCCT. The sensitivity was 50% and the NPV was 72%, while the specificity was 97% and the PPV was 93%. On multivariate analysis, only lower GSS (p < 0.001) was independently associated with true negative surgeon opinion. CONCLUSIONS: Although there was a high surgeon ability to detect post-PNL residual stones, postoperative imaging is mandatory because of the high false negative rates and low NPV. The surgeon opinions can be judged only in stones with lower GSS. The NPV could be enhanced if a consistent definition of clinically significant RFs is introduced.

Percutaneous nephrolithotomy for staghorn stones: a randomised trial comparing high-power holmium laser versus ultrasonic lithotripsy.

OBJECTIVE: To compare high-power holmium laser lithotripsy (HP-HLL) and ultrasonic lithotripsy (US-L) for disintegration of staghorn stones during percutaneous nephrolithotomy (PCNL). PATIENTS AND METHODS: A non-inferiority randomised controlled trial was conducted between August 2011 and September 2014. Inclusion criteria were patients' aged >18 years who had complete staghorn stones (branching to the three major calyces), without contraindications to PCNL. Eligible patients were randomised between two groups: HP-HLL and US- . A standard PCNL in the prone position was performed for all patients. The only difference between the treatment groups was the method of stone disintegration. In the first group (HP-HLL), a laser power of 40-60 W (2 J, 20-30 Hz) was used to pulverise the staghorn stone into very small fragments, which could pass through the Amplatz sheath with the irrigation fluid. US-L,with suction of the fragments, was used in the second group. The primary outcome (stone-free rate) was evaluated with non-contrast computed tomography after 3 months. Secondary outcomes of complications, blood transfusion, operative time, and haemoglobin deficit were compared. The outcome assessor was 'blinded' to the treatment arm. RESULTS: The study included 70 patients (35 in each group). The baseline characteristics (age, sex, body mass index, side, stone volume, and density) and operative technique (number, size of tracts, and need for second PCNL session) were comparable for both groups. Operative time was significantly shorter in US-L group, at a mean (SD) of 130 (34) vs 148.7 (35) min (P = 0.028). The haemoglobin deficit was significantly more with in the US-L group, at a mean (SD) of 1.7 (0.9) vs 1.3 (0.6) g/dL (P = 0.037). The differences in blood transfusion (17% for US-L vs 11% for HP-HLL) and the complication rates (34% for US-L vs 23% for HP-HLL) were not significant (P = 0.495 and P = 0.290, respectively). The stone-free rates at 3 months were comparable (60% for US-L and 66% for HPL-L; P = 0.621). CONCLUSIONS: Compared with US-L for intracorporeal lithotripsy of staghorn stones during PCNL, HP-HLL showed comparable safety and efficacy with a lower haemoglobin deficit but longer operative time.

Holmium laser enucleation of the prostate for treatment for large-sized benign prostate hyperplasia; is it a realistic endourologic alternative in developing country?

OBJECTIVES: To assess the functional outcome and cumulative health-resource-related cost of holmium laser enucleation of the prostate (HoLEP) in comparison with transvesical open prostatectomy (TVOP) in a developing country. METHODS: Matching of 92 HoLEP and 91 TVOP procedures was performed using resected prostate tissue weight as a sole matching criterion. Safety, efficacy, and accordingly health-related cost-efficiency of both procedures were statistically compared. RESULTS: Preoperative criteria and mean prostate size (166.7 ± 49.7, 161.4 ± 35.7 ml) were similar in HoLEP and TVOP, respectively; however, HoLEP treated more comorbid patients. Blood transfusion was 2.1 and 26.1 % after HoLEP and TVOP, respectively (P = 0.001). Median time to catheter removal and hospital stay was 2 days after HoLEP and 5 and 9 days, respectively, after TVOP (P < 0.001). On modified Clavien scale, grade per grade, there was no statistically significant difference between the two groups apart from local wound complications in TVOP group. High-grade complications (≥ grade 3) were reported in 3.2 and 6.5 % in HoLEP and TVOP, respectively (P = 0.49). Resected prostate tissue weight was independently associated with high-grade periprocedure complications (OR[95 %CI] 1.22[1.02:1.49], P = 0.03). Last follow-up symptom score, peak urine flow rate, residual urine, % PSA reduction, and need for reoperation were comparable between the two groups. HoLEP costs the hospital in the first 3 months 4111.8EP (575US$) versus 4305.4EP (602US$) for TVOP (P = 0.09). CONCLUSION: In high-volume hospital, HoLEP procedure seems to be equally safe and effective as TVOP with the advantages of minimally invasive procedures. Two years after adopting the technique, HoLEP equally costs the hospital as TVOP. Significant hospital cost savings are anticipated in subsequent cases.

Impact of the type of ureteroileal anastomosis on renal function measured by diuretic scintigraphy: long-term results of a prospective randomized study.

OBJECTIVE: To determine the long-term effects of the direct refluxing-type ureteroileal anastomosis technique with those of an antireflux technique on individual renal units, using diuretic scintigraphy in a prospectively randomized study. PATIENTS AND METHODS: Between 2002 and 2006, a prospective randomized study was conducted on 102 patients undergoing radical cystectomy and urinary diversion. In every patient, both ureters were randomized to be implanted using a direct refluxing technique or an antireflux, serous-lined extramural tunnel (SLET) technique. Renal function (RF) was evaluated using (99m)Tc-MAG-3 diuretic scintigraphy. The serial changes in corrected glomerular filtration rate (cGFR) for each technique and for each side were compared. RESULTS: Over a median follow-up of 6 years, the patients in both the direct refluxing and the SLET technique groups were found to have a significant reduction in mean (SD) cGFR between baseline and last follow-up: cGFR decreased from 59.4 (12.4) to 45.6 (15.3) mL/min (P < 0.001) and from 54.3 (11.2) to 46.3 (12.8) mL/min (P = 0.002), respectively. Five patients (4.9%) in the SLET group developed obstruction (four left-sided and one right-sided) compared with one (0.9%) in the direct refluxing group (right-sided). The onset of obstruction was noted 1-7 months after radical cystectomy. There was no significant difference between the groups in reductions in cGFR across the timepoints. Comparison of the two techniques according to the side of ureter implantation showed that the direct refluxing technique trended towards better functional outcomes on the left side. CONCLUSIONS: There was no observed difference in the RF of individual renal units between the SLET and the direct refluxing groups in the long term. The need to incorporate an antireflux technique should be questioned and tailored according to the surgeon's experience and confidence.

Renal function evaluation in patients undergoing orthotopic bladder substitution: a systematic review of literature.

Renal function (RFn) after orthotopic bladder substitution (OBS) is a critical point to be assessed. We performed a systematic review of MEDLINE for full length peer reviewed English articles from the year 2000 till January 2013. We included only original articles and excluded reviews, editorials and replies and abstracts presented in conferences. The outcome is formulated in research questions; what is the status of RFn after OBS? Which is better, the direct free-refluxing or anti-refluxing ureteroileal anastomosis (UIA) techniques? Studies reporting RFn as secondary outcome were also reported. A total of 129 publications were reviewed for full text and only 41 were included in this review. All studies were of low level of evidence and grade of recommendations. Only 3 randomized controlled trials were included and were of poor quality. Renal function after OBS was poorly described in the literature with no universal definition about RFn deterioration or outcome with no consensus on the best evaluation method. Urinary obstruction, chemotherapy and pyelonephritis appeared significant factors but with insufficient evidence. There is a universal trend to use the free refluxing technique for UIA to avoid complications of anti-refluxing techniques. However, the anti-reflux technique proved acceptable outcome in experienced hands. There is marked heterogeneity and underestimation of RFn evaluation among reported outcomes after OBS with most publications reporting the incidence of UIA and pyelonephritis with paucity reporting absolute figures about RFn measurements. In conclusion, urinary tract obstruction remains the main factor of RFn deterioration after OBS. Methods evaluating RFn, definitions of RFn outcome and factors predicting it are poorly studied in the literature and the current evidence is relatively weak to draw solid conclusions. Further well-designed studies and consensus about method of assessment and definitions of RFn are warranted.

Are there long-term effects of extracorporeal shockwave lithotripsy in paediatric patients?

UNLABELLED: WHAT'S KNOWN ON THE SUBJECT? AND WHAT DOES THE STUDY ADD?: Extracorporeal shockwave lithotripsy is effective for the treatment of paediatric renal stones with favourable short-term safety. Extracorporeal shockwave lithotripsy for treatment of paediatric renal stones is also safe for the kidney and the child on long-term follow-up. OBJECTIVE: To evaluate the long-term effects of extracoporeal shockwave lithotripsy (SWL) for treatment of renal stones in paediatric patients. PATIENTS AND METHODS: A database of paediatric patients who underwent SWL monotherapy for treatment of renal stones from September 1990 through to January 2009 was compiled. This study included only patients with follow-up for more than 2 years. The long-term effects of SWL were evaluated at the last follow-up with measurement of patients' arterial blood pressure, estimation of random blood sugar and urine analysis. The results of diastolic blood pressure were plotted against a standardized age reference curve. The treated kidney was examined by ultrasonography for measurement of renal length and detection of stones. The measured renal lengths were plotted against age-calculated normal renal lengths in healthy individuals. RESULTS: The study included 70 patients (44 boys (63%) and 26 girls) with mean age at the time of SWL 6.5 ± 3.6 years (range 1-14). The mean follow-up period was 5.2 ± 3.6 years (range 2.1-17.5). The mean age at last follow-up was 11.7 ± 5.3 years (range 4.4-27.5). No patients developed hypertension or diabetes. Only one treated kidney was smaller than one standard deviation of the calculated length. The cause of this was obstruction by a stone in the pelvic ureter 3 years after SWL. CONCLUSION: The long-term follow-up after SWL for treatment of renal stones in paediatric patients showed no effect on renal growth and no development of hypertension or diabetes.

Extracorporeal shockwave lithotripsy for renal stones in pediatric patients: a multivariate analysis model for estimating the stone-free probability.

OBJECTIVES: To define factors affecting the stone-free rate of extracorporeal shockwave lithotripsy in the treatment of pediatric renal calculi, and to establish a regression model for pretreatment prediction of stone-free probability. METHODS: From January 1999 through February 2012, 207 children with mean age 6.4 ± 3.8 years underwent shockwave lithotripsy with Dornier Lithotripter S for treatment of renal stones. The stone-free rate was evaluated 3 months after the last shockwave lithotripsy session with non-contrast computed tomography. Treatment success was defined as complete clearance of the stones with no residual fragments. Multivariate logistic regression analysis was used to identify independent risk factors and to predict the probability of being stone free. RESULTS: The mean length of the stone was 11.6 ± 4 mm. The stone-free rate was 71%. Independent factors that adversely affect stone-free rate were increasing stone length and calyceal site of the stone. Relative risks for not being free of stones were 1.123 for stone length, 2.673 for stones in the upper or middle calyx and 4.208 for lower calyx stones. CONCLUSION: Stone length and location are prognostic factors determining stone-free rate after shockwave lithotripsy for renal calculi in pediatric patients. Based on our analysis, shockwave lithotripsy should be recommended for renal pelvis stones up to 24 mm, upper or middle calyceal stones up to 15 mm and lower calyceal stones up to 11 mm.

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.

Radiological diagnosis of vesicouterine fistula: role of magnetic resonance imaging.

PURPOSE: To retrospectively assess the value of magnetic resonance imaging (MRI) in the diagnosis of vesicouterine fistula (VUF). MATERIALS AND METHODS: Between January 2003 and January 2011, 12 patients with a diagnosis of VUF were surgically managed at our center; among them, eight patients had MRI among their preoperative radiological investigations and those were included in our study. The clinical presentation, radiological investigations, and surgical findings of the patients were reviewed. RESULTS: The mean age of the patients was 31 years. Seven of the eight patients had complaints of cyclic hematuria and the remaining patient complained of urinary leakage through the vagina. The etiology of VUF was cesarean section in all patients. The preoperative radiological investigations included conventional cystography in five patients, intravenous urography in two, computed tomography (CT) urography in two, and MRI in eight. The sensitivities of diagnosis for these investigations were 40%, 0%, 50%, and 100%, respectively. CONCLUSION: In our small retrospective series, pelvic MRI was reliable and sensitive for diagnosis of VUF. It should be considered in the work-up of patients with suspected VUF.

Diffusion-weighted magnetic resonance imaging in follow-up of superficial urinary bladder carcinoma after transurethral resection: initial experience.

UNLABELLED: What's known on the subject? and What does the study add? Diffusion-weighted (DW) MRI is a non-invasive technique measuring the microscopic mobility of water molecules in the tissues without contrast administration. It provides information on perfusion and diffusion simultaneously in any organ, so it can be used to differentiate normal and abnormal tissue structure, and it might help in the characterization of various abnormalities. In recent years, DW-MRI has been applied in the evaluation of urinary tract lesions, such as malignant renal, prostatic and bladder tumours; however, it has not previously been tested on its ability to distinguish residual cancer from fibrotic and inflammatory changes secondary to transurethral resection (TUR) and intravesical chemotherapy, both of which manifest as bladder-wall thickening on T2-weighted MRI. This is the first study to show the feasibility of DW-MRI in follow-up of patients with superficial bladder tumours after TUR. DW-MRI was highly reliable in differentiating post-TUR inflammatory changes from bladder tumours, with results similar to those of conventional cystoscopy. This non-invasive method could be used efficiently in future for follow-up of this patient group and may obviate the need for routine cystoscopy. OBJECTIVE: • To study the feasibility of using diffusion-weighted (DW) magnetic resonance imaging (MRI) in bladder cancer follow-up after transurethral resection (TUR). PATIENTS AND METHODS: • Included in the study were 47 patients with a history of TUR of superficial bladder carcinoma, who were admitted to our centre between January and December 2011 for follow-up cystoscopy. • Before cystoscopy, DW-MRI was performed and the apparent diffusion coefficient (ADC) value was measured in a circular region of interest within the carcinoma and normal bladder wall. • Two radiologists, blinded to the results of cystoscopy, independently interpreted the DW images. • A comparison of imaging findings with those of cystoscopy was performed using the McNemar test. RESULTS: • In our 47 patients, cystoscopy identified 34 bladder lesions in 24 patients and in the remaining 23 the bladder looked normal. • In the 24 patients with malignant bladders, DW-MRI detected 32/34 tumours with two false-negative findings of lesions in two patients. • In 23 patients with non-malignant bladders, the DW-MRI data were accurate for 21 patients, as two patients were misdiagnosed as malignant. • The sensitivity, specificity, accuracy, positive and negative predictive values of DW-MRI for identifying bladder tumours were 91.6% (22/24), 91.3% (21/23), 91.5% (43/47), 91.6 (22/24) and 91.3 (21/23), respectively. • Using the McNemar test there was no significant difference between DW-MRI and cystoscopy. CONCLUSIONS: • DW-MRI has a high reliability in differentiating post-TUR inflammatory changes from bladder tumours, which is similar to that of cystoscopy. • DW-MRI could be a first-line diagnostic test in follow-up of patients after TUR.

Comparison of urinary telomerase, CD44, and NMP22 assays for detection of bladder squamous cell carcinoma.

Background: Squamous cell carcinoma (SCC) of the bladder is common in many regions around the world. Prognosis is very poor, as most cases are diagnosed at an advanced stage due to a lack of affordable and valid screening markers for this type of cancer. The diagnostic accuracy of urinary nuclear matrix protein-22 (NMP22), telomerase activity, and CD44 were evaluated in urine samples of patients with bladder SCC. Materials and methods: We conducted a case-control study comprised of 60 consecutive newly diagnosed bladder SCC patients diagnosed by cystoscopy and histopathological examination, and controls were 60 outpatients with benign urologic conditions and healthy clinic visitors. Urine samples collected from each subject underwent testing for NMP22, telomerase activity, and CD44. Descriptive and correlational statistical analysis of cases and controls were carried out and receiver operating characteristic curve analysis was used to determine optimal cut-off points for the three assays. Results: Area under the curve was calculated at 0.96, 0.93, and 0.62 for NMP22, telomerase, and CD44, respectively. Urine levels of NMP22 and telomerase activity were significantly higher in the SCC group compared to controls (p < 0.001). Urine CD44 levels were not significantly higher in the SCC group compared to controls (p = 0.111). The overall sensitivity of NMP22, telomerase, and CD44 was 96.7%, 87%, and 45%, respectively, while the specificity was 85%, 88.6%, and 86.7%, respectively. Conclusions: Urinary telomerase activity, followed by NMP22 urine levels, showed high diagnostic yield and could hold potential promise as urinary biomarkers for the diagnosis of bladder SCC.

A randomized trial of adjuvant tamsulosin as a medical expulsive therapy for renal stones after shock wave lithotripsy.

Adjuvant medical expulsive therapy (MET) for shock wave lithotripsy (SWL) is controversial. With limited use of the computed tomography (CT), the stone free rate (SFR) become overestimated. Herein we evaluate tamsulosin post-SWL for renal stone using the CT to assess SFR. A randomized controlled trial (NCT05032287) was carried out for renal stone patients amenable for SWL. Patients were allocated after 1st session of SWL to receive tamsulosin 0.4 mg or placebo once daily from the 1st day of SWL and for 3-months or becoming stone free. The primary outcome was SFR, defined by presence of residual fragments (RF) ≤ 3 mm (3C-SFR). The 3C-SFR were 73.8% and 59.6% in tamsulosin and placebo groups, respectively (p = 0.03). The median (IQR) pain scores were 3 (3, 5) and 5 (3, 6) in tamsulosin and placebo groups, respectively (p = 0.04), However, the post-SWL complication and add-on analgesia needed showed no significance differences between groups. The median time for stone free were 30 days (95% CI: 27.29-32.71) in tamsulosin arm, and 36 days (95% CI: 31.01-40.99) in placebo arm, HR = 1.42 (95% CI: 1.02-1.98). Tamsulosin has more reversible adverse effect, compared to placebo (p = 0.03). In our study, the use of tamsulosin as MET following SWL facilitates expulsion of retained residual fragments. Tamsulosin shortens time to reach stone free, decreases pain scores. However, tamsulosin does not affect the add-on IV analgesics and have more reversible adverse effect, compared to placebo.

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.

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.