Detrusor nerve radiofrequency ablation (DENERA): Experimental study of safety and efficacy in an ovine model.

PURPOSE: The subtrigonal perivesical nerve plexus contains a large proportion of the bladder's innervation. A transurethral radiofrequency ablation approach has successfully denervated this region to alleviate overactive bladder symptoms, with some urothelial heat injury. We report a novel transvaginal RFA device (DENERA) and assess its feasibility and efficacy in denervating the perivesical nerve plexus of in vivo sheep. METHODS: In 14 adult female in vivo sheep, pulsed radiofrequency energy was applied transvaginally for three cycles of 4 min, maintaining the tissue temperature at 45°C, with 30 s of rest between each cycle. The control group (n = 4) was sacrificed without ablation, and various groups were sacrificed 1 week (n = 3), 4 weeks (n = 4), and 12 weeks (n = 3) after ablation. The bladder subtrigones were harvested then analyzed with H&E, S100, and TH immunostaining to quantify their neural density and neural vacuolization. RESULTS: The ablation procedure increased the neural vacuolization the most at 1 week and decreased the neural density the most at 4 weeks, with both variables displaying a significant change followed by a slight rebound towards baseline at 12 weeks. The H&E analysis showed that the needles penetrated deep into the subtrigonal detrusor muscle. The sheep recovered from the procedure with no complications or damage in the bladder wall or urothelium. CONCLUSIONS: This study shows that one DENERA treatment can cause subtrigonal denervation with some rebound afterwards and no complications. DENERA may become a promising OAB treatment option that can ablate the perivesical plexus without harming the urothelium.

Unilateral orchiectomy of a testicular adrenal rest tumor: Case report and review of management options.

Testicular adrenal rest tumors are a rare development of patients with congenital adrenal hyperplasia. It is difficult to diagnose due to similarities with Leydig cell tumors. Treatment can be conservative or surgical. We describe the case of a 56 year old male presenting with bilateral testicular pain and irregular growth that was managed with a unilateral orchiectomy. We analyzed the distinguishing factors of testicular adrenal rest tumors compared to Leydig cell tumors, as well as the diagnostic and treatment methods.

Safety and efficacy of polydimethylsiloxane (Macroplastique®) in women with stress urinary incontinence: analysis of data from patients who completed three years follow-up.

INTRODUCTION AND HYPOTHESIS: This study aimed to report 3-year completed follow-up of the safety and efficacy of Macroplastique® (MPQ) in women with stress urinary incontinence (SUI) due to intrinsic sphincter deficiency (ISD). METHODS: This is a retrospective analysis of all women who completed 3-year follow-up post-MPQ injection(s) at ten medical centers. We used the ROSE registry data report of Macroplastique® [Macroplastique® Real-time Observation of Safety and Effectiveness (ROSE) registry P040050/PAS001 on 2017]. Subjective incontinence outcome and adverse effects were assessed. RESULTS: The study included all patients (n = 70) who completed 3-year follow-up after the last MPQ injection. Twenty-four of 70 (34%) patients had two injections; 21/70 (30%) patients reported Stamey grade 0 and 28/70 (40%) reported Stamey grade 1. The overall patient satisfaction was 68% who completed 3-year follow-up. The composite success rate (I-QoL, PGI-S, and Stamey grade improvement) was 51.4%. No serious adverse events (AE) were reported within the completed 3-year follow-up. CONCLUSIONS: MPQ was found to be safe and efficacious for the treatment of SUI secondary to ISD in women. The overall high satisfaction rate was sustained from baseline to 3 years post-injection. Most complications were minor and transient without sequelae.

Assessment of patients with lower urinary tract symptoms where an undiagnosed neurological disease is suspected: A report from an International Continence Society consensus working group.

AIM: Lower urinary tract symptoms (LUTS) are a common urological referral, which sometimes can have a neurological basis in a patient with no formally diagnosed neurological disease ("occult neurology"). Early identification and specialist input is needed to avoid bad LUTS outcomes, and to initiate suitable neurological management. METHODS: The International Continence Society established a neurological working group to consider: Which neurological conditions may include LUTS as an early feature? What diagnostic evaluations should be undertaken in the LUTS clinic? A shortlist of conditions was drawn up by expert consensus and discussed at the annual congress of the International Neurourology Society. A multidisciplinary working group then generated recommendations for identifying clinical features and management. RESULTS: The relevant conditions are multiple sclerosis, multiple system atrophy, normal pressure hydrocephalus, early dementia, Parkinsonian syndromes (including early Parkinson's Disease and Multiple System Atrophy) and spinal cord disorders (including spina bifida occulta with tethered cord, and spinal stenosis). In LUTS clinics, the need is to identify additional atypical features; new onset severe LUTS (excluding infection), unusual aspects (eg, enuresis without chronic retention) or "suspicious" symptoms (eg, numbness, weakness, speech disturbance, gait disturbance, memory loss/cognitive impairment, and autonomic symptoms). Where occult neurology is suspected, healthcare professionals need to undertake early appropriate referral; central nervous system imaging booked from LUTS clinic is not recommended. CONCLUSIONS: Occult neurology is an uncommon underlying cause of LUTS, but it is essential to intervene promptly if suspected, and to establish suitable management pathways.

Potential Role of Monocyte Chemoattractant Protein-1 in Monitoring Disease Progression and Response to Treatment in Overactive Bladder Patients.

PURPOSE: To compare urinary levels of monocyte chemoattractant protein-1 (MCP-1), an inflammatory cytokine, in healthy controls and overactive bladder (OAB) patients, to correlate changes in urinary MCP-1 with OAB treatment response and symptom severity, and to study the diagnostic potential of MCP-1 for OAB, as well as the efficacy of MCP-1 as a potential biomarker for different phenotypes of OAB. METHODS: We used enzyme-linked immunosorbent assay to measure normalized urinary MCP-1 levels in 56 individuals (43 OAB patients and 13 controls). We assessed the OAB patients at 3 visits with 2 validated symptom severity questionnaires (OAB-V8 and Patient Perception of Bladder Condition). RESULTS: The mean pretreatment urinary MCP-1 level at visit 1 (229.2-pg/mg creatinine) was significantly greater than the MCP-1 levels at visit 3 in both the treatment (107.0-pg/mg creatinine) (P<0.001) and control (52.35-pg/mg creatinine) groups (P<0.001). Average OAB symptom severity decreased significantly from visit 1 (baseline) to visits 2 (4 weeks) and 3 (12-14 weeks) and was significantly correlated with urinary MCP-1 levels. Urinary MCP-1 levels dropped significantly (P=0.002) posttreatment in patients whose symptom severity improved by >30%, whereas nonresponders displayed no significant MCP-1 decrease (P=0.164). The receiver operating characteristic analysis of the OAB visit 1 and control groups produced an area under the curve of 0.891. We found no significant differences in sex, race, or age between the OAB and control groups. CONCLUSION: MCP-1 levels differed significantly between the control and OAB groups and were closely correlated with symptom severity and treatment response. The good diagnostic accuracy of MCP-1 for OAB suggests the potential usage of MCP-1 for OAB diagnosis. The varying response of urinary MCP-1 levels to treatment may indicate at least 2 potential phenotypes of OAB. MCP-1, in combination with other biomarkers and symptom severity questionnaires, could potentially aid in developing a patient-centered OAB treatment approach.

Characterisation of urinary monocyte chemoattractant protein 1: Potential biomarker for patients with overactive bladder.

Objective: To investigate urinary monocyte chemoattractant protein 1 (MCP-1) as a potential marker for idiopathic overactive bladder (OAB). This is a quantitative measurement of urinary MCP-1 to establish baseline normal values that could help in future index studies. Normalised urinary MCP-1 levels are measured in female patients with OAB and aged-matched controls. Severity of OAB symptoms is correlated to normalised urinary MCP-1 levels. Patients and methods: Urinary MCP-1 levels were measured in 29 female patients with OAB and 10 normal female controls. The patients with OAB were either newly diagnosed or off any OAB oral therapy for at least 2 weeks. OAB symptoms were assessed using validated OAB questionnaires. Urinary MCP-1 levels were measured using enzyme-linked immunosorbent assay and normalised by urinary creatinine (Cr) levels. Results: The baseline urinary MCP-1 levels in female patients with OAB were significantly higher than those of the controls, at a mean of 210.25 vs 48.02 pg/mg Cr (P < 0.001). Patients who had severe OAB bother symptoms had higher levels of urinary MCP-1 (r = 0.03), also patients with OAB-wet had higher levels of urinary MCP-1, at a mean (SEM) of 209.25 (30.5) vs OAB-dry 185.25 (10) pg/mg Cr (P < 0.001). Conclusion: Urinary MCP-1 levels were higher in female patients with idiopathic OAB. The close association of urinary MCP-1 and OAB bother severity symptoms and OAB-wet suggest that inflammation plays a major role in the pathophysiological mechanisms underlying the sensitisation of bladder afferent nerves. Establishing urinary MCP-1 levels in patients with OAB hopefully will help future studies to confirm the correlation as a baseline and changes with treatments. Abbreviations: BMI: body mass index; Cr: creatinine; MCP-1: monocyte chemoattractant protein 1; OAB: overactive bladder; OAB-q: Overactive Bladder Questionnaire; PPBC: Patient Perception of Bladder Condition; UI: urinary incontinence.

Face, Content, and Construct Validations of Endoscopic Needle Injection Simulator for Transurethral Bulking Agent in Treatment of Stress Urinary Incontinence.

INTRODUCTION AND OBJECTIVES: Endoscopic injection of urethral bulking agents is an office procedure that is used to treat stress urinary incontinence secondary to internal sphincteric deficiency. Validation studies important part of simulator evaluation and is considered important step to establish the effectiveness of simulation-based training. The endoscopic needle injection (ENI) simulator has not been formally validated, although it has been used widely at University of California, Irvine. We aimed to assess the face, content, and construct validity of the UC, Irvine ENI simulator. METHODS: Dissected female porcine bladders were mounted in a modified Hysteroscopy Diagnostic Trainer. Using routine endoscopic equipment for this procedure with video monitoring, 6 urologists (experts group) and 6 urology trainee (novice group) completed urethral bulking agents injections on a total of 12 bladders using ENI simulator. Face and content validities were assessed by using structured quantitative survey which rating the realism. Construct validity was assessed by comparing the performance, time of the procedure, and the occlusive (anatomical and functional) evaluations between the experts and novices. Trainees also completed a postprocedure feedback survey. Effective injections were evaluated by measuring the retrograde urethral opening pressure, visual cystoscopic coaptation, and postprocedure gross anatomic examination. RESULTS: All 12 participants felt the simulator was a good training tool and should be used as essential part of urology training (face validity). ENI simulator showed good face and content validity with average score varies between the experts and the novices was 3.9/5 and 3.8/5, respectively. Content validity evaluation showed that most aspects of the simulator were adequately realistic (mean Likert scores 3.9-3.8/5). However, the bladder does not bleed, and sometimes thin. Experts significantly outperformed novices (p < 001) across all measure of performance therefore establishing construct validity. CONCLUSION: The ENI simulator shows face, content and construct validities, although few aspects of simulator were not very realistic (e.g., bleeding).This study provides a base for the future formal validation for this simulator and for continuing use of this simulator in endourology training.

Are Electronic and Paper Questionnaires Equivalent to Assess Patients with Overactive Bladder?

PURPOSE: Overactive bladder syndrome is defined as urinary urgency, usually accompanied by frequency and nocturia, with or without urgency urinary incontinence in the absence of urinary tract infection or another obvious pathological condition. Electronic questionnaires have been used in a few specialties with the hope of improving treatment outcomes and patient satisfaction. However, they have not been widely used in the urological field. When treating overactive bladder, the main outcome is to improve patient quality of life. The primary objective of this study was to evaluate whether electronic questionnaires would be equally accepted as or preferred to paper questionnaires. The secondary objective was to look at the preference in relation to patient age, education and iPad® tablet familiarity. MATERIALS AND METHODS: We prospectively evaluated the iList® electronic questionnaire application using a friendly iPad tablet in patients with overactive bladder who presented to the urology clinic at our institution. Each of the 80 patients who were recruited randomly completed the validated OABSS (Overactive Bladder Symptom Score) and the PPBC (Patient Perception of Bladder Condition) questionnaires in paper and electronic format on the tablet. Variables potentially associated with the outcomes of interest included demographic data, questionnaire method preference, patient response rate and iPad familiarity. We used the 2-sided Z-test to determine whether the proportion of patients who considered the tablet to be the same, better or much better than paper was significantly greater than 50%. The 2-sided chi-square test was applied to assess whether the intervention effect significantly differed among the demographic subgroups. RESULTS: A total of 80 patients 21 to 87 years old were enrolled in the study from November 2015 to August 2016. Of the patients 53% were female and 49% were 65 years or younger. The incidence of those who considered the tablet to be the same or better than paper was 82.5% (95% CI 74.2-90.8, p <0.001). The incidence of patients who considered the tablet to be the same or better than paper ranged from 76% to 97% regardless of age, gender and education subgroup as well as in those with any familiarity with the tablet (each p <0.001). Of the 20 patients who were not familiar with the tablet 45% preferred the electronic questionnaire (p = 0.654). CONCLUSIONS: We found that the proportion of patients who considered electronic questionnaires to be equivalent to or better than paper versions was higher than those who preferred paper questionnaires regardless of age, gender or education level.

Surgical technique for removal of tined lead for InterStim.

INTRODUCTION: We aimed to introduce our technique describing the removal of a chronic implanted tined-lead in patients with a sacral neuromodulator implant. MATERIALS AND METHODS: We performed a retrospective review of patients who had chronic sacral neuromodulator (InterStim) implanted by a single surgeon from 2001 through 2015. This simple surgical technique was developed and successfully performed to remove the leads. Primary reasons for removal were elective due to poor symptoms control and failure to maintain response or lead migration. Patient demographics, indication for implantation, as well as installation and removal complications were recorded and analyzed. RESULTS: Twenty-five patients were included [mean age: 60.4 years (32-86), 17 females]. Primary indications for sacral nerve stimulation were overactive bladder in 16 (64%), mixed incontinence in 6 (24%), urinary retention in 2 (8%), and interstitial cystitis 3 (12%). Mean implant duration was 24.2 (0.5-90) months. The existing tined lead was removed and replaced in 11 (44%) patients while the remaining 14 (56%) underwent complete removal of the unit without subsequent replacement. Successful lead removal without complications was achieved in 24 (96%) patients. CONCLUSIONS: This minimally invasive technique is a simple, safe, and effective method of removing chronic implanted tined leads en bloc.

Squamous cell carcinoma of the urinary bladder: Systematic review of clinical characteristics and therapeutic approaches.

OBJECTIVE: To highlight the current understanding of the epidemiology, clinicopathological characteristics, and management of squamous cell carcinoma (SCC) of the bladder, as it accounts for 2-5% of bladder tumours, with a focus on non-bilharzial-associated SCC (NB-SCC). The standard treatment for bladder SCC remains radical cystectomy (RC). We present an updated clinical profile of bladder SCC and a review of NB-SCC therapeutic approaches, including RC, neoadjuvant and adjuvant treatments, radiotherapy, chemotherapy, and immunotherapy. METHODS: Using search terms relating to SCC, urinary bladder, and treatment modalities, we performed a search of the PubMed and Embase databases to identify NB-SCC treatment approaches and outcomes. Peer-reviewed English language reports from 1975 to present assessing SCC management were included. Two authors independently screened and extracted the data. RESULTS: Of the 806 articles screened, 10 met the pre-defined inclusion criteria. RC was performed in seven of the 10 studies. Although radiotherapy alone yielded poor outcomes, preoperative radiotherapy and RC were associated with improved survival. There is little evidence supporting the use of chemotherapy in NB-SCC, and its efficacy in relation to RC is not known. CONCLUSION: Based on current literature, there is insufficient evidence to provide a treatment recommendation for NB-SCC. Whilst RC is the standard of care, the role of preoperative radiotherapy should be revisited and compared to RC alone. Additional studies incorporating multimodal approaches, contemporary radiation techniques, and systemic therapies are warranted. Immunotherapy as a treatment for bladder SCC has yet to be investigated.

The challenges in the diagnosis of detrusor underactivity in clinical practice: A mini-review.

OBJECTIVE: To review the current definitions, terminology, epidemiology and aetiology of detrusor underactivity (DU), with specific attention to the diagnostic criteria in use. In addition, we address the relation and the overlap between DU and bladder outlet obstruction (BOO). In this mini-review, we hope to help identify DU patients and facilitate structured clinical evaluation and research. METHODS: We searched the English literature using ScienceDirect and PubMed for relevant articles. We used the following terms: 'detrusor underactivity', 'underactive bladder', 'post voiding residual', 'post micturition residual', 'acontractile bladder', 'detrusor failure', and 'detrusor areflexia'. RESULT: DU is one of the most common conditions causing lower urinary tract symptoms (LUTS). Unfortunately, it is also the most poorly understood bladder dysfunction with scant research. To our knowledge there is no clear definition and no non-invasive method to characterise this important clinical condition. DU may result from the normal ageing process; however, it has multiple aetiologies including neurogenic and myogenic dysfunction. In many cases the symptoms of DU are similar to those of BOO and it usually requires invasive urodynamic study (UDS) for diagnosis to differentiate the two diagnoses. A number of diagnostic tests may be used including: UDS testing, the Schafer pressure/flow nomogram, linear passive urethral resistance relation, Watts factor, and the bladder contractility index. Of these, UDS testing is the most practical as it determines both the maximum urinary flow rate and the pressure exerted by the detrusor muscle relative to the maximal flow of urine, allowing for precise characterisation of detrusor function. CONCLUSION: Currently, the diagnosis of DU is based on invasive urodynamic parameters as defined by the International Continence Society in 2002. There is no consensus for the definition of DU prior to 2002. As there is significant overlap between the symptoms of DU and BOO, it is difficult to diagnose DU clinically.

Transvaginal Excision of Bilateral Single Ureteral Stumps of Refluxing Ectopic Ureters in an Adult Female With Urinary Incontinence.

OBJECTIVE: To report a novel surgical technique of transvaginal excision of bilateral refluxing single ureteral stumps in an adult female, with emphasis on the technique, the difficulties of the procedure, and other surgical consideration such as bladder neck reconstruction and use of pubovaginal sling in patients with these congenital anomalies. METHODS: The procedure starts with cystoscopy for identification and catheterization of the orifices of remnant ectopic ureters. This is important to facilitate close dissection of ureteral stumps without the risk of vascular and visceral injury. A wide inverted U incision is made in the anterior vaginal wall to complete the dissection and excision for the remnants of ectopic ureters followed by water-tight closure for each ureterourethral junction. The procedure is completed with bladder neck reconstruction and pubovaginal sling with autologous rectus fascia. RESULTS: The operative time was 3 hours, estimated blood loss was 50 mL, and hospital stay was 1 day. There were no intraoperative complications, and the patient went home on catheter drainage for 10 days with prophylactic antibiotics and anticholinergic medications. One-year follow-up showed her global satisfaction of 80%, and she uses one small pad per day as needed. She reported no more recurrent urinary tract infections, no difficulty of voiding, and no pain. CONCLUSION: Transvaginal approach for excision of bilateral infravesical remnant of ectopic ureters in an adult female is feasible. Successful surgical outcomes require bladder neck reconstruction and use of autologous rectus fascia in patient with bilateral single-system ectopic ureters, as the sphincteric mechanism of the bladder neck is absent.