Open Label, Pilot Evaluation of the Safety and Efficacy of Intravesical Sustained Release System of Lidocaine and Oxybutynin (TRG-100) for Patients With Interstitial Cystitis/Bladder Pain Syndrome, Overactive Bladder and Patients With Retained Ureteral Stents Following Endourological Interventions.

BACKGROUND: Intravesical instillation of analgesic and anticholinergic drugs have shown efficacy in the treatment of pain and voiding symptoms. Unfortunately, drug loss with urination and dilution in the bladder limit their durability and clinical usefulness. We have recently developed and tested in vitro, a sustained delivery system (TRG-100) of fixed-dose combination of lidocaine and oxybutynin designed to allow for a longer exposure of the urinary bladder to the drugs. OBJECTIVE: To asses the safety and efficacy of TRG-100 in Interstitial Cystitis/Bladder Pain Syndrome (IC/BPS), overactive bladder (OAB), and endourological intervention stented (EUI) patients in an open-label, prospective study. METHODS: Thirty-six patients were enrolled: 10 IC/BPS, 10 OAB, and 16 EUI. EUI patients received a once-weekly installation until stent removal, OAB and IC/BPS patient received weekly installations for 4 consecutive weeks. Treatment effect was assessed by visual analog scale (VAS) score for the EUI group, voiding diaries for OAB group and VAS score, voiding diaries and O'Leary Sant Questionnaires for the IC/BPS group. RESULTS: The EUI group showed a mean 4-point improvement in their VAS score. The OAB group showed 33.54% reduction in frequency of urination and IC/PBS group showed a mean of 3.2-point improvement in their VAS score, 25.43% reduction in frequency of urination, and a mean 8.1-point reduction in O'Leary Sant Questionnaires score. All changes were statistically significant. CONCLUSION: Intravesical instillation of TRG-100 was found to be safe and efficient in reducing pain and irritative bladder symptoms in our study population. TRG-100 efficacy and safety should be further assessed in a large, randomized control trial.

'What goes in, could come out' - A case report: Endoscopic extraction of a giant foreign body from a female urinary bladder.

Foreign bodies in the urinary tract are quite rare. The etiology for this phenomenon is variable. The extraction of those objects should be done in endoscopic manner whenever possible. The larger the object's diameter, the harder it will be to extract. According to recent literature the female urethra can calibrate up to 54 Fr (1.8 cm). The case which presented here demonstrates an endoscopic extraction of an object of 2.5 cm diameter (75 Fr.). Our paper aims to suggest strategies for successful endoscopic extraction and to shed more light on the skills and inter-specialty collaboration that these cases needed.

Surgical Treatment of Meatal Stenosis: Lessons Learned from the Pediatric Urology Practice.

OBJECTIVE: To evaluate the indications for surgery and outcome of meatotomy and meatoplasty in a big cohort of children. METHODS: We retrospectively evaluated 2211 children who underwent either meatotomy or meatoplasty between 2009 and 2020 utilizing the same operative setup. For continuous data, we performed t-test and Mann-Whitney U test. For categorical data, chi-squared test or Fisher's exact test was used. A binary logistic regression model was used to compare the indications for surgery between the groups. RESULTS: Of 2211 children, 1906 underwent meatotomy and 305 meatoplasty. The mean age was 5 years (range: 1m-15y) and there was no age difference between the groups. There was no difference between duration of surgery, recovery time, or complication rates between the groups. Deviated stream was the most frequent indication for treatment 1477 (67%). On Univariate logistic regression children with the following indications: dysuria, meatitis, and urinary retention had increased odds toward meatoplasty, while the indication of deviated stream had increased odds toward meatotomy. On Multivariate Logistic regression only deviated stream (Odd-ratios 1.47, P: .005) and urinary retention (Odds-ratio 4.5, P: .027) remained significant for meatotomy and meatoplasty respectively. Eleven (0.58%) children who underwent meatotomy developed recurrent Urethral Meatal Stenosis and underwent another surgery. Sixty-nine children (3.6%) after meatotomy required manual opening of the meatus on the first post-operative visit. None of the children, who underwent meatoplasty needed reoperation. CONCLUSION: Meatotomy had a higher reoperation rate and frequently required manual meatal spreading in early postoperative period. We believe meatoplasty is a preferable surgery for pediatric UMS.

Intravesical sustained release system of lidocaine and oxybutynin results from in vitro and animal study.

PURPOSE: Interstitial cystitis/bladder pain syndrome (IC/BPS) is a chronic debilitating condition of unknown etiology. Intravesical lidocaine demonstrated pain relief in patients with IC/BPS. Intravesical oxybutynin has shown therapeutic efficacy in patients with urinary bladder disorders. However, loss of drug with urination requiring multiple administrations and immediate dilution of drug concentration by residual urine in the bladder mitigated intravesical use of both drugs in clinical practice. The aim of this study was to evaluate the efficacy and safety of fixed-dose combination of lidocaine and oxybutynin, forming in the urine a sustained delivery system named TRG-042. MATERIAL AND METHODS: In-vitro, we have quantitatively tested the concentration of lidocaine and oxybutynin released from TRG-042 in artificial urine. Following the successful in-vitro study weekly formulation of TRG-042 was instilled intravesically to six pigs. All pigs were followed with cystoscopy to assess the gradual degradation of the delivery system and to evaluate bladder response over 7 days. Daily blood samples were tested for drug quantization. RESULTS: In-vitro studies have demonstrated oxybutynin and lidocaine sustained release over 1-week period coupled with full degradation of the matrix. None of the animals demonstrated any side effects following instillation. Cystoscopy examination observed gradual disintegration of TRG-042 over 1-week with no adverse reaction to the mucosa. Plasma concentrations of oxybutynin and lidocaine were uniformly stable over the 1-week period [1.46 ± 0.176 ng/ml and 4.29 ± 2.48 ng/ml respectively(mean ± SEM)] with almost undetectable concentration of N-desethyloxybutynin (NDO)[0.032 ± 0.068 ng/ml]. CONCLUSIONS: The in-vitro and animal data demonstrated that TRG-042 can safely be used for intravesical sustained release of lidocaine and oxybutynin in the treatment of BPS/IC.

[OBTAINING A PROSTATE MPMRI BEFORE THE FIRST PROSTATE BIOPSY - IS IT THE TIME TO CHANGE THE INDICATIONS IN ISRAEL?]

INTRODUCTION: Transrectal ultrasound is utilized as an auxiliary tool when performing a prostate biopsy, but its sensitivity and specificity are low. Performing prostate multiparametric magnetic resonance imaging (mp-MRI) before prostate biopsy can increase the probability to detect aggressive prostate cancer while decreasing the probability to detect indolent prostate cancer, thereby assisting in the selection of patients before the biopsy. The Israel Basket of Health Services does not include prostate mpMRI prior to the first prostate biopsy. Our objective was to examine the significance of performing mpMRI before prostate biopsy. METHODS: We retrospectively evaluated the demographic, clinical, and pathological data from men who underwent transrectal biopsy of the prostate in the last 30 months in our institute. In all men with suspicious findings on mpMRI, targeted biopsies were taken in addition to systematic biopsies. We considered cancer as clinically significant if the Gleason sum was 7 or above. Fisher's Exact test was performed for categorical variables and student t-test for continuous variables. RESULTS: Five hundred and sixteen men underwent prostate biopsy; 163(32%) performed prostate mpMRI before the biopsy; 101(25%) performed mpMRI before the first prostate biopsy and 62(59%) before the second or more prostate biopsies. Prostate cancer was detected in 46% of all men (61% in men after mpMRI versus 38% in men without, p<0.0001). In men for whom this was the first prostate biopsy, prostate cancer was detected in 47% (73% in men after mpMRI versus 39% in men without, p<0.0001); and after second or more biopsies 38% (42% in men after mpMRI versus 33% in men without, p=0.4147). Also, there was a statistically significant difference in the detection of clinically significant prostate cancer with mpMRI versus without. CONCLUSIONS: Performing prostate mpMRI before prostate biopsy significantly increases the detection rate of prostate cancer and clinically significant prostate cancer. It should be recommended to perform mpMRI before any prostate biopsy in accordance with the European and American Urology Association, and NCCN guidelines.

Endoscopic Correction of Reflux Utilizing Polyacrylate Polyalcohol Bulking Copolymer (Vantris) as a Tissue Augmenting Substance: Lessons Learned Over the 10 Years of Experience.

Objectives: To prove the hypothesis that modifying the endoscopic correction of vesicoureteral reflux (VUR) technique (STING procedure) and sharpening its contraindications, lead to increased success rate and decline in the complication rate. Materials and Methods: All patients that underwent endoscopic correction of VUR utilizing Vantris were divided into two groups according to procedure date; before 2015 and 2015-2019. Indication for treatment included persistent high-grade VUR or breakthrough infections. Contraindications included voiding dysfunction, active infection and since 2015 suspicion for obstructive/refluxing ureterovesical junction (UVJ) presented by "beak" sign on voiding cystourethrography (VCUG). Follow-up regiment included ultrasound and VCUG at predetermined intervals. Results: The first group included 215 (158 girls and 57 boys) children with mean age of 4.8 ± 2.8 years who underwent endoscopic correction between 2009 and 2015 and the second group included 42 children (28 girls and 14 boys) with mean age of 3.9 ± 2.1 years who underwent surgery between 2015 and 2019. In the first group, VUR was unilateral in 74 patients and bilateral in 132 comprising 338 renal refluxing units. In the second group, VUR was unilateral in 14 patients and bilateral in 30 comprising 74 RRUs. In the first group reflux was corrected in 317 (94.9%) RRUs after a single injection, after the second in 7 (2.1%) RRUs. In seven (2.1%) RRUs, reflux downgraded to Grade I-II. Three RRUs (0.9%) failed endoscopic correction and required ureteral reimplantation. Nine (2.7%) RRUs developed UVJ obstruction. In the second group reflux was corrected in 61 (82.4%) RRUs after a single injection, after the second in 12 (16.2%) RRUs. In one (1.4%) RRU, endoscopic correction failed and required ureteral reimplantation. None of the patients developed UVJ obstruction. Reflux correction has led to the significant decrease of febrile urinary tract infection (UTI) in both groups. Conclusions: Our data indicate that endoscopic injection utilizing Vantris is safe and long durable procedure. Although utilizing the proper technique and contraindication criteria, the rates of post procedural VUJ obstruction is null.

Learning curve of robotic-assisted laparoscopic pyeloplasty (RALP) in children: how to reach a level of excellence?

It has been suggested that up to 40 cases of RALP are required to reach the operative results equal to open surgery. We have hypothesized that previous experience in open and laparoscopic surgeries might shorten the learning curve of robotic surgery. We have retrospectively evaluated the data of all children who underwent pyeloplasty in our institute by a single surgeon since 2003. The children were divided into three groups: open pyeloplasty (OP) of 72 children, laparoscopic pyeloplasty (LAP) of 22, and RALP of 33 patients subsequently. The data included: demographics, duration of surgery, length of stay, success of surgery, and complication rate according to the Clavien-Dindo score. The groups were ordered chronologically by the operation date and each group was divided into two different phases: early and late. A comparison was made between the data of the early and the late phase. There was no difference in the demographic data between the groups; however, the patients who underwent laparoscopic surgery were significantly older compared with the patients from the other groups. The median duration of surgery in the RALP group was significantly shorter than the OP group (65 min vs 72.5 min P < 0.01), while the first RALP case was already shorter than the median duration of surgery in OP group. There was no significant decrease in the duration of surgery of the RALP group over the study period, though there was a significant trend of decreasing operative time in the OP and LAP groups. There was no difference in the length of stay in the early vs late phases in the RALP group. There was no difference in the complication and success rate between the RALP and OP group, as well as the early and late phases of the RALP group. Our data show that previous experience in OP and LAP surgery may contribute to a shorter learning curve of robotic surgery required for the surgeon to achieve a similar outcome to that of OP.