Primary Chemoablation of Low-Grade Intermediate-Risk Nonmuscle-Invasive Bladder Cancer Using UGN-102, a Mitomycin-Containing Reverse Thermal Gel (Optima II): A Phase 2b, Open-Label, Single-Arm Trial.

PURPOSE: Low-grade intermediate-risk nonmuscle-invasive bladder cancer (LG IR NMIBC) is a recurrent disease, thus requiring repeated transurethral resection of bladder tumor under general anesthesia. We evaluated the efficacy and safety of UGN-102, a mitomycin-containing reverse thermal gel, as a primary chemoablative therapeutic alternative to transurethral resection of bladder tumor for patients with LG IR NMIBC. MATERIALS AND METHODS: This prospective, phase 2b, open-label, single-arm trial recruited patients with biopsy-proven LG IR NMIBC to receive 6 once-weekly instillations of UGN-102. The primary end point was complete response (CR) rate, defined as the proportion of patients with negative endoscopic examination, negative cytology and negative for-cause biopsy 3 months after treatment initiation. Patients with CR were followed quarterly up to 12 months to assess durability of treatment effect. Safety and adverse events were monitored throughout the trial. RESULTS: A total of 63 patients (38 males and 25 females 33-96 years old) enrolled and received ≥1 instillation of UGN-102. Among the patients 41 (65%) achieved CR at 3 months, of whom 39 (95%), 30 (73%) and 25 (61%) remained disease-free at 6, 9 and 12 months after treatment initiation, respectively. A total of 13 patients had documented recurrences. The probability of durable response 9 months after CR (12 months after treatment initiation) was estimated to be 73% by Kaplan-Meier analysis. Common adverse events (incidence ≥10%) included dysuria, urinary frequency, hematuria, micturition urgency, urinary tract infection and fatigue. CONCLUSIONS: Nonsurgical primary chemoablation of LG IR NMIBC using UGN-102 resulted in significant treatment response with sustained durability. UGN-102 may provide an alternative to repetitive surgery for patients with LG IR NMIBC.

[DOES CHOOSING BETWEEN DUSTING OR FRAGMENTATION DURING LASER LITHOTRIPSY OF URINARY STONES CHANGE THE LONG TERM RESULTS?]

INTRODUCTION: Variations in laser pulse energy and it's frequency during lithotripsy, affect the rate and the method of stone breaking. The main modes of lithotripsy are dusting and fragmentation. AIMS: Comparison between long term results of dusting versus fragmentation, by defining the stone free rate (SFR) for each method and the time period until re-treatment need. METHODS: Clinical and radiological follow-up of 43 patients who underwent laser intervention using dusting or fragmentation. Both groups shared similar demographic features, stone sizes and locations. For each group, the percentage of patients without stones requiring intervention during the follow-up period of 36 months was defined as a success parameter. The incidence of emergency department (ED) admissions and auxiliary interventions were assessed. RESULTS: Thirty-eight patients were included in the study. No difference in the median period of time to clinically significant stone was seen (p=0.213). No difference was found in SFR between the dusting (83.3%) and the fragmentation (84.6%) groups respectively (p=1.000). No statistically significant difference was shown in ED admissions due to renal colic occurring in 31.6% and 10.5% within dusting and fragmentation groups respectively (p=0.116). CONCLUSIONS: No difference in time period until clinically significant stone appearance was seen. No significant difference in SFR was found between the groups at the long term follow-up. DISCUSSION: It seems that within the dusting group, the ED admission rate could be somewhat higher. However, this impression lacks statistical significance. A long term prospective study with a larger population is needed to confirm these results.

A feasibility study with a novel, dynamic, and disposable over-the-counter device for the management of stress urinary incontinence.

AIMS: This study aimed to evaluate the initial efficacy, safety, and usability of a novel, dynamic, and disposable intravaginal device in women suffering from stress urinary incontinence (SUI). METHODS: Twenty-six women with SUI were recruited to perform a modified 1-h Pad Weight Gain (PWG) test. In this test, women drank 250-500 ml of water, were given a pre-weighed pad, and asked to perform a set of incontinence-inducing activities. At the end of the activities session, the pad was removed and weighed. This test was performed both with and without the Nolix device. Three efficacy endpoints measured were continuous percent reduction in urine leakage, dryness (defined as pad weight increase by no more than 1 g), and improvement in pad weight (measured as continuous percent reduction in PWG ≥ 50%). Any adverse events, reported by subjects during the device use were recorded. The usability and user's satisfaction were assessed using the Benefit, Satisfaction, and Willingness to Continue and Nolix Satisfaction questionnaires. RESULTS: The average reduction in PWG was 79.4%. The average reduction in urine leakage while using the device was at least 70%. In addition, in 79.5% of tests, the clinically meaningful level of improvement in PWG was achieved. Use of the device produced substantial improvement in the patient's perceived quality of life. No adverse events were reported during the study. CONCLUSION: The Nolix device served as a noninvasive, effective, and well-tolerated treatment option for reducing SUI in a modified 1-h PWG test with a set of incontinence-inducing activities.

Comparison of Partial and Radical Laparascopic Nephrectomy: Perioperative and Oncologic Outcomes for Clinical T2 Renal Cell Carcinoma.

INTRODUCTION: Nephron-sparing surgery has emerged as the treatment of choice for small renal masses. However, its role in larger tumors remains controversial. In this study, we compare the outcomes of laparoscopic partial nephrectomy (LPN) vs those of laparoscopic radical nephrectomy (LRN) for T2 renal tumors. MATERIALS AND METHODS: Thirteen patients who had LPN and 16 patients who had LRN for T2 renal tumors were retrospectively analyzed for preoperative factors (age, gender, comorbidities, hemoglobin, and creatinine levels and estimated glomerular filtration rate [eGFR]), operative and perioperative characteristics (tumor characteristics, operative time [OT], warm ischemia time [WIT], estimated blood loss [EBL], length of stay [LOS], and postoperative complications), histopathologic results, and follow-up data (eGFR and recurrences). RESULTS: Tumor size was comparable between groups; however, tumors in the LRN group were more endophytic, central, and closer to the collecting system. There were no cases of positive surgical margins. Median OT was 160 minutes vs 230 minutes (p = 0.0029) and EBL was 25 mL vs 100 mL ([p = 0.0027], LRN vs LPN). Median WIT in the LPN group was 27 minutes, with three zero ischemias. Minor postoperative complications (≤Clavien-Dindo III) were noted in 6.25% and 23% (LRN vs LPN). Median LOS was 4.56 and 5.77 days (LRN vs LPN), respectively. Mean postsurgery eGFR was significantly lower for the LRN group (54.5 cc/[min ·1.73 m2] vs 76.3 cc/[min ·1.73 m2], p = 0.019). Within mean follow-up of 44.5 months, one tumor recurrence in the contra lateral kidney was observed in the LPN group and two cases of metastasis in the LRN group. CONCLUSIONS: We show that LPN is technically feasible for T2 tumors, with acceptable intra- and perioperative outcomes. Furthermore, our results show a significant advantage in preservation of renal function for LPN without compromising oncologic results. Taken together, we believe that LPN should be considered for larger tumors based on technical feasibility rather than only tumor size.

Fibroid surgery and improvement in bladder symptoms: The FAB study.

AIMS: Uterine fibroids are the most common tumor of the female reproductive tract [Baird et al Am J Obstet Gynecol. 188:100-107, 2003] and bladder symptoms are more prevalent in these women [Pron et al Fertil Steril. 79:112-119, 2003; Volkers et al Am J Obstet Gynecol. 196:519.e1-e11, 2007] However, the effect of various fibroid debulking surgeries on different types of urinary incontinence symptoms is poorly understood. Our primary objective was to determine whether surgical debulking of uterine fibroids affects urinary symptoms. Secondary objectives were: to define the baseline prevalence of bladder symptoms in women undergoing fibroid surgery; to explore links between fibroid characteristics, size of debulked fibroids, type of surgery, and postoperative changes in bladder function. MATERIALS AND METHODS: Prospective cohort study (2011-2016) of women undergoing vaginal or abdominal myomectomy or hysterectomy. Baseline demographics were obtained. All women underwent a detailed pelvic ultrasound preoperatively. The Urinary Distress Inventory (UDI) questionnaire of the validated Pelvic Floor Distress Inventory (PFDI) was administered before and 6 weeks after surgery. Score changes were assessed using Wilcoxon signed rank test. RESULTS: Sixty-one women completed the study. At baseline, regardless of fibroid characteristics, 96.6% of women had various bothersome urinary symptoms including storage, voiding, and incontinence. Following surgical fibroid debulking, median improvement in the UDI total score was clinically and statistically significant at 39.9 (P < 0.001). All urinary subscale scores were also significantly improved. 11/17 women (64.7%) and 11/18 women (61.1%) were cured of moderately to severely bothersome symptoms of urge and stress urinary incontinence respectively. CONCLUSIONS: Urinary symptoms are common in women undergoing surgery for uterine fibroids. Fibroid debulking may be offered as treatment for bladder symptoms in symptomatic women.

Does the use of ureteral stents with extraction strings increase urinary infection rates?

PURPOSE: To assess the effect of ureteral stents with extraction string on the rate of postoperative UTI after ureteroscopies. METHODS: Retrospective analysis of patient records who underwent ureteroscopy from January 2011 to August 2014 was performed. Patients were grouped into three groups according to postoperative stent status: non-stented or ureteral catheter for up to 24 h (NS), ureteral stent without extraction string (US) and ureteral stent with an extraction string (US-E). RESULTS: There were 144, 133 and 282 cases in the NS, US and US-E groups, respectively. Overall infection rate was 4.7%; NS-2.1%, US-3.0% and US-E-6.7% (p = 0.057). Four percentage of men and 6.6% of women had postoperative UTI (p = 0.22). Within the group of men infection rates were 0, 2.4 and 6.4% for the NS, US and US-E groups, respectively (p = 0.01). For women, UTI rates were 7.5, 4.0 and 8.5% in the NS, US and US-E groups, respectively (p = 0.6). Infection rates were 20 and 3.9% (p = 0.001) for patients with extraction strings for >8 and <8 days. In multivariate analysis the presence of an extraction string was found to be a risk factor for infection OR 7.7 (1.01-58.9, 95% CI, p = 0.049) along with renal stone location OR 5.09 (2.1-12.05, 95% CI, p < 0.001). CONCLUSIONS: No statistically significant difference was found between overall infections rates for patients with and without extraction strings, and such difference was found within the male group, suggesting extraction strings in men may increase the risk of infection.

Positional pelvic organ prolapse (POP) evaluation using open, weight-bearing magnetic resonance imaging (MRI).

INTRODUCTION: Magnetic resonance imaging (MRI) of patients with pelvic organ prolapse (POP) is completed in the supine position. Open magnetic resonance imaging (MRO) uses vertical magnets, allowing imaging in a variety of upright postures. This pilot study used MRO to evaluate the change of prolapse in different positions compared to non-prolapsed images. METHODS: In total, 11 women (6 POP, 5 controls) aged 24 to 65 years had 12 MRO images (midline sagittal pelvic line) consecutively when supine, sitting and standing with a full and empty bladder. Lengths between the lowest point of the bladder to the pubococcygeal (PC) and pubopromontoreal (PP) lines in each image were compared, and the ratio of bladder area under the PC and PP lines to the total bladder area. RESULTS: Significant elongation between the PC line and lowest point of the bladder was evident in subjects with POP comparing supine and standing images (p = 0.03), but not controls (p = 0.07). Similarly, this axis was significantly longer in cystocele subjects versus controls only in the standing position. Bladder area under the PC line was significantly increased between supine and standing positions only among subjects with cystocele (p < 0.01), and significantly larger among the study group in the standing position (p < 0.005), less significant in the supine position (p = 0.015), and not significant in the sitting position (p = 0.3). CONCLUSIONS: MRO imaging allows us to investigate the effects of upright position and weight bearing on the staging of POP. Imaging patients when sitting and standing identified that significant changes occur in the maximal descent of the bladder.

Risk factors for the development of stress urinary incontinence in women.

Large-scale population-based surveys published in the past decade give new insights regarding risk factors for stress urinary incontinence (SUI) in women. Age plays a significant role in the development of all forms of urinary incontinence, but findings regarding the role of hormonal changes are inconsistent. Obesity is an increasingly prevalent health condition that was shown to have detrimental impact on SUI development, while weight reduction was proven to reduce SUI. Other modifiable risk factors, such as diabetes, also are related to SUI. Pregnancy, delivery, and pelvic floor surgery are risk factors discussed in the review. Recent genetic studies identified several genes encoding components of the extracellular matrix, which could be related to a predisposition to SUI. Identifying risk factors for SUI can facilitate prevention strategies in an aim to reduce SUI prevalence among women.

Oxybutynin for treatment of nocturnal enuresis in children.

QUESTION: A 7-year-old child and his parents visit my clinic owing to the child's frequent bed-wetting. During the day, he has no problem controlling his urination. The family has tried behavioural methods but has failed to achieve dryness during the night. They ask to begin medical treatment. Is oxybutynin a safe and effective drug for treating nocturnal enuresis? ANSWER: Oxybutynin is an anticholinergic drug that has not been proven to be effective for treatment of nocturnal enuresis not accompanied by daytime symptoms, such as urgency. It can be added as a second-line drug and is effective for treating children with both daytime and nighttime wetting. Nevertheless, its common adverse effects, which can involve the central nervous system, should be considered when deciding whether or not to use it, especially in young children.

Predominant expression of CCL2 at the tumor site of prostate cancer patients directs a selective loss of immunological tolerance to CCL2 that could be amplified in a beneficial manner.

We have previously shown that, during inflammatory autoimmune diseases in humans, the immune system develops a neutralizing auto-Ab-based response to a very limited number of inflammatory mediators, and that amplification of each response could be beneficial for the host. Our working hypothesis has been that this selective breakdown of immunological tolerance is due to a predominant expression of an inflammatory mediator at an immune-restricted site undergoing a destructive process. All three conditions also take place in cancer diseases. In this study, we delineate this hypothesis for the first time in a human cancer disease and then explore its clinical implications. We show that in primary tumor sections of prostate cancer subjects, CCL2 is predominantly expressed at the tumor site over other chemokines that have been associated with tumor development, including: CXCL12, CXCL10, CXCL8, CCL3, and CCL5. Subsequently, the immune response selectivity mounts an Ab-based response to CCL2. These Abs are neutralizing Abs. These findings hold diagnostic and therapeutic implications. The current diagnosis of prostate cancer is based on prostate-specific Ag measurements that do not distinguish benign hypertrophy from malignancy. We show in this study that development of anti-CCL2 Abs is selective to the malignant stage. From a clinically oriented perspective, we show, in an experimental model of the disease, that DNA-based amplification of this response suppresses disease, which has implications for a novel way of therapy in humans.

[Prostatic abscess--diagnosis and treatment].

Prostatic abscess is an uncommon condition, often difficult to discern clinically from acute prostatitis. It results from focal accumulation of pus within the prostate gland. Historically, the common infecting organisms were Neisseria gonorrheae, Staphylococcus aureus and Mycobacterium tuberculosis. However, more recently, gram negative bacteria, such as Escherichia coli, are causative species. Prostatic abscess mainly affects diabetic and immunosuppressed patients. In the past, transurethral drainage was the first choice for therapy. Today, percutaneous transperineal or transrectal drainage under transrectal sonography is the first choice for therapy because of the low risk of complication. This is a case history of 47-year old male patient who was admitted due to prostatic abscess. On admission he complained of severe dysuria and high fever lasting 10 days after antibiotic treatment for urinary tract infection. On rectal examination the prostate was enlarged and very tender. Both the CT-scan and transrectal ultrasound revealed well defined fluid collection areas compatible with an abscess in the right lobe of the prostate. Under general anesthesia and transrectal ultrasound guidance the abscess was aspirated transperineally. A 12-F drain was left for 6 days with complete remission in clinical and CT findings. Once an abscess of the prostate is diagnosed, anaerobic antimicrobial therapy should be added and transrectal or percutaneous transperineal aspiration and drainage is required. The authors consider the percutaneuos transperineal drainage to be the most effective and safest solution.