Effect of ß3-adrenoceptor agonist on the micromotion of bilateral major pelvic ganglion-excised rat bladder.

AIMS: Micromotion is an autonomous intramural movement of the bladder, and is believed to be an initial step in the generation of urinary urgency. Therefore, controlling micromotion may be a novel target in overactive bladder (OAB) treatment. However, developing micromotion treatment has been limited by the absence of a standardized animal model. We attempted to create a micromotion animal model and investigated the effectiveness of a ß3 -adrenoceptor agonist (CL316,243) on micromotion. METHODS: Bilateral major pelvic ganglia (MPGs) were excised in 18 male Sprague-Dawley rats, resulting in an almost completely denervated bladder. On postoperative Day 7, cystometry was performed. Rats were divided into three treatment groups: CL316,243; ß3- adrenoceptor antagonist (SR59230A) pretreated CL316,243; and a nonselective antimuscarinic agent (oxybutynin). Changes in micromotion were evaluated after the intra-arterial administration of each agent. RESULTS: Low-amplitude oscillations in intravesical pressure (micromotion) were observed 1 week after MPGs excision. Micromotion frequency significantly (p = 0.003) decreased (2.17 ± 3.54 times/5 min) with CL316,243 compared with vehicle (6.33 ± 1.97 times/5 min). Micromotion amplitude also decreased with CL316,243 (1.15 ± 1.93 cmH2 O) compared with vehicle (5.96 ± 5.12 cmH2 O), approaching conventional significance (p = 0.090). No significant decreases in frequency or amplitude were observed with oxybutynin treatment. CONCLUSIONS: Systemic administration of the ß3 -adrenoceptor agonist CL316,243 effectively controlled micromotion in bilateral MPGs-excised, almost completely denervated rat bladders. This result indicates that ß3 -adrenoceptor agonist may affect the bladder directly, suggesting that it might be effective for overall OAB, regardless of the presence or level of neurological deficits. Bilateral MPGs-excised rats are considered a plausible micromotion animal model suitable for future research.

Efficacy and Safety of DA-8010, a Novel M3 Antagonist, in Patients With Overactive Bladder: A Randomized, Double-Blind Phase 2 Study.

PURPOSE: DA-8010 is a novel muscarinic M3 receptor antagonist with significant selectivity for bladder over salivary gland in preclinical studies. We evaluated the clinical efficacy and safety of DA-8010 in overactive bladder (OAB) patients. METHODS: This phase 2, randomized, double-blind, parallel-group, active reference- and placebo-controlled trial was conducted at 12 centers in South Korea (NCT03566134). Patients aged ≥19 years with OAB symptoms for ≥3 months were enrolled. Three hundred six patients (30.07% male) were randomized to 12 weeks of treatment among 4 groups; 2 experimental groups (DA-8010 2.5 or 5 mg), an active reference group (solifenacin 5 mg), and a placebo group. The change from the baseline of (=∆) 24-hour frequency at 12 weeks (primary endpoint), episodes of urgency, overall/urgency urinary incontinence, average/ maximum voided volume, nocturia, and patients' subjective responses were analyzed. RESULTS: In the full analysis set, the mean (standard deviation) [median] values for ∆ 24-hour frequency at 12 weeks were -1.01 (2.44) [-1.33] for placebo, -1.22 (2.05) [-1.33] for DA-8010 2.5 mg, and -1.67 (2.25) [-1.67] for DA-8010 5 mg; DA-8010 5 mg showed a significant decrease compared with placebo (P=0.0413). At 4 and 8 weeks, both DA-8010 2.5 mg (P=0.0391 at 4 weeks, P=0.0335 at 8 weeks) and DA-8010 5 mg (P=0.0001 at 4 weeks, P=0.0210 at 8 weeks) showed significant decrease in ∆ 24-hour frequency compared with placebo. DA-8010 5 mg achieved a significant decrease in ∆ number of urgency episodes, compared with placebo at 4 (P=0.0278) and 8 (P=0.0092) weeks. Adverse drug reactions (ADRs) were observed in 3.95% of placebo, 6.67% of DA-8010 2.5 mg, 18.42% of DA-8010 5 mg, and 17.33% of solifenacin 5 mg groups. No serious ADRs were observed in any patient. CONCLUSION: Both DA-8010 2.5 mg and 5 mg showed therapeutic efficacy for OAB without serious ADRs. Therefore, both dosages of DA-8010 can advance to a subsequent large-scale phase 3 trial.

Prospective randomized controlled trial comparing fulguration versus fulguration and hydrodistension for Hunner-type interstitial cystitis/bladder pain syndrome.

PURPOSE: In Hunner-type interstitial cystitis/bladder pain syndrome (IC/BPS), it is unclear whether suburothelial afferents underlying normal-appearing background areas contribute to symptom development. We examined whether adding hydrodistension (HD) to transurethral fulguration (TUF) of Hunner lesions, for the purpose of treating the background areas, is superior to TUF alone. METHODS: This randomized controlled trial included 52 patients with Hunner-type IC/BPS allocated at a 1:1 (TUF:TUF+HD) ratio. HD was performed at 80 cmH2O for 8 min before TUF in the TUF+HD group. Thirty-three patients remained until the end of the 6-month observational period. The primary endpoint was the visual analogue scale (VAS) pain score at 1 month. Major secondary endpoints were the treatment-failure rate, VAS pain scores at ≥ 2 months, and frequency-volume chart parameters. RESULTS: Both TUF and TUF+HD showed significant improvement in VAS pain score at 1 month (95% confidence interval [CI]: - 1.62 to 0.16, P = 0.106). VAS pain scores were significantly lower in TUF+HD than TUF at 2 (95% CI: - 1.97 to - 0.28, P = 0.011), 4 (95% CI: - 2.83 to - 0.72, P = 0.002), and 6 (95% CI: - 3.11 to - 0.07, P = 0.040) months. Treatment-failure rate was higher in TUF (36.4%) than TUF+HD (17.4%), without significance (odds ratio: 2.714, 95% CI: 0.68 to 10.84, P = 0.189). Functional capacity and urgency were not significantly different between groups. CONCLUSION: The addition of HD to TUF tended to be superior to TUF monotherapy for controlling pain in Hunner-type IC/BPS. This indicates that not only Hunner lesions but also normal-appearing background areas may have a role in the pain of IC/BPS. TRIAL REGISTRATION: ClinicalTrials.gov Identifier: NCT03987594, date of registration: 2019-06-17 (retrospectively registered).

Lower Urinary Tract Symptoms are Common After Artificial Urinary Sphincter Implantation.

OBJECTIVE: To investigate lower urinary tract symptoms (LUTS) observed after artificial urinary sphincter (AUS) implantation for post-radical prostatectomy urinary incontinence (PRPUI). MATERIALS AND METHODS: Cases of AUS for PRPUI were evaluated. Stress urinary incontinence (SUI) was assessed using the Sandvik-incontinence severity index. Other LUTS were evaluated using the overactive bladder symptom score and international prostate symptom score. The prevalence and predictive risk factors for post-AUS LUTS were analyzed. RESULTS: Of 129 patients evaluated (mean follow-up = 42.3 months, mean age = 76.7 years), 8.5% had very severe SUI, 78.4% had moderately to severely symptomatic LUTS (IPSS = 8-35 points), and 45.2% were dissatisfied with their urinary condition. Nocturia was the most prevalent (48.0%). Maximum cystometric capacity (rho = -0.236, P = .007) and involuntary detrusor contraction (P = .002) were significantly related to the severity of post-AUS urgency urinary incontinence (UUI). Multivariable linear regression analysis indicated that involuntary detrusor contraction was more associated with post-AUS urgency (P <.001) and UUI (P = .006) than any other preoperative parameter. Age significantly correlated with the severity of post-AUS urgency (rho = 0.309, P <.001), UUI (rho = 0.196, P = .026), and the need for straining to void (rho = 0.240, P = .007). CONCLUSION: Even after successful placement of an AUS, many patients were dissatisfied with various LUTS, ranging from the most frequent nocturia to the need for straining to void. Attention should be paid not only to SUI but also to non-SUI LUTS, which are observed in the general population in this age group and change over time. Counseling to educate patients about expected outcomes and continuous monitoring and treatment for LUTS should be provided for the PRPUI-AUS population.

Urological presentations of adult primary tethered cord syndrome.

AIMS: To investigate the urological presentations of patients initially diagnosed with closed spinal dysraphism in adulthood: adult primary tethered cord syndrome (ApTCS). METHODS: Patients with ApTCS who underwent subsequent untethering were studied. Urological presentations were evaluated grouped by symptom onset period of either after (group 1) or before (group 2) the completion of physical growth. RESULTS: Of the 43 patients, median age at diagnosis and initial untethering was 35.5 (18.4-67.2) years. At diagnosis, 90.7% (39/43) had urological symptoms and 18.6% (8/43) initially consulted a urologist without noticeable neurological symptoms. Enuresis was observed in 16.3% (7/43) and common among patients without significant neurological symptoms (62.5%, 5/8). Urgency urinary incontinence and frequency prevailed in group 1. Stress urinary incontinence and straining to void prevailed in group 2. Among 26 patients with pre- and post-operative urodynamics, detrusor overactivity predominated in group 1 and acontractile detrusor predominated in group 2. Glomerular filtration rate ≥90 mL/min/1.73m2 was noted in 86.0% (37/43) and 84.9% (73/86) of renal units were morphometrically intact. More patients in group 2 (93.3%) relied on assisted emptying than in group 1 (53.6%). CONCLUSIONS: In ApTCS, enuresis was prevalent among patients without noticeable neurological symptoms. Over 80% in both groups had favorable renal function. Bladder conditions were different based on symptom onset period. Significantly more patients whose symptoms developed before completion of growth relied on assisted emptying. Proper discerning might be crucial in ApTCS which has a potential of misdiagnosis even in the modern developed era.

Autonomic response during bladder hydrodistention reflects the severity of symptoms in patients with bladder pain syndrome/interstitial cystitis.

AIMS: To evaluate the correlation between symptom severity of bladder pain syndrome/interstitial cystitis (BPS/IC) and autonomic nervous system activity, we examined autonomic responses during bladder hydrodistention. METHODS: Medical records were collected from a prospective database for patients who underwent bladder hydrodistention with a fixed protocol from March 2012 to December 2013. A total of 40 patients (16 males, 24 females) were included for the analysis. Hydrodistention was performed under general anesthesia (31 patients), spinal anesthesia (six patients), and both types of anesthesia (three patients) at different times. Twenty-five patients who underwent holmium laser enucleation of the prostate served as controls. Pulse rate (PR), systolic (SBP), and diastolic blood pressure (BP) were measured pre-hydrodistention, during hydrodistention, and after drainage. RESULTS: The spinal anesthesia and control groups exhibited little change in BP and PR during hydrodistention, while a significant increase was demonstrated in the general anesthesia group (e.g., ΔSBP 4.89 ± 4.80, 10.40 ± 19.03, and 56.26 ± 30.38 mm Hg, respectively, P < 0.001). Under general anesthesia, autonomic response during hydrodistention was more prominent in patients with preoperative visual analogue scale (VAS) pain score ≥7, Hunner's lesion, and glomerulation grade 4. Preoperative maximal cystometric capacity negatively correlated with changes in SBP during hydrodistention (R2 = 0.294, P = 0.009), while VAS score and interstitial cystitis problem index demonstrated a positive correlation with the changes (R2 = 0.208, P = 0.012; R2 = 0.173, P = 0.015). CONCLUSIONS: Under general anesthesia, exaggerated autonomic responses to bladder hydrodistention were demonstrated in BPS/IC patients, which reflected the severity of symptoms. These results support the hypothesis of altered activity of autonomic system in BPS/IC. Neurourol. Urodynam. 36:677-682, 2017. © 2016 Wiley Periodicals, Inc.

Can Hypertrophy of the Contralateral Testis Predict the Absence of a Viable Testis in Infancy with Cryptorchidism: A Prospective Analysis.

This prospective study aimed to evaluate whether Contralateral compensatory testicular hypertrophy (CTH) is valid as a predictive tool for a non-viable testis in children aged between 6 and 18 months, and whether CTH is affected by mini-puberty. Seventy-two testes from 60 boys aged between 6 and 18 months were categorized into three groups: 24 testes contralateral to surgically removed non-viable testes (NVTs), 24 testes contralateral to surgically corrected undescended testes (UDTs), and 24 testes from a normal controls. Contralateral testicular length and volume were measured with ultrasonography and compared among the groups. Group 1 (NVT) had a significantly longer length and larger volume than group 2 (UDT). The length and volume of each group among three developmental periods (6-10, 10-14, and 14-18 months) were also analyzed. In the controls, the length was significantly larger at 6-10 months than at 10-14 months in accordance with previously reported changes in testicular size due to the effect of "mini-puberty." The volume of controls showed a similar pattern, though without statistical significance. However, this pattern was not observed in the NVT and UDT groups. A receiver operating curve revealed that a testicular length of 16.1 mm or a volume of 0.59 ml had the highest sensitivity and specificity for predicting NVTs. The CTH was also found to be valid as a predictive tool for a NVT in children of ages 6 to 18 months, as the effect of mini-puberty appeared to be absent in the NVT and UDT groups. However, the cut-off values were less than those of previous reports. The proper cut-off level according to the age and measurement method should be applied in this developmental period.

Ureteral stent failure in pediatric patients under 10 years: occurrence and risk factors.

OBJECTIVE: To examine the occurrence of ureteral stent failure in pediatric patients aged <10 years and to determine risk factors for failure. METHODS: We performed a retrospective cohort analysis of 100 patients who underwent ureteral stent insertion between January 2006 and December 2013. All patients were aged <10 years and were followed up until ureteral stent removal. Information regarding patient demographics, reason for stent insertion, duration of stent maintenance, stent diameter and length, and postoperative results was collected. Risk factors for stent failure were analyzed. RESULTS: Ureteral stenting was performed in 114 ureter units. The median age at stenting was 34.1 months (interquartile range [IQR], 8.1-71.2 months), and the median duration of stent maintenance was 35.0 days (IQR, 21.0-44.3 days). A 3-Fr stent was used in 39.5% of patients. Stent failure was observed in 11 ureter units (9.6%) at a median of 11.5 days (IQR, 7.8-24.5 days) after insertion, and the stent was subsequently removed. Use of a 3-Fr ureteral stent was the only risk factor for the development of stent failure; the failure rate was 20.0% with this stent diameter. CONCLUSION: Ureteral stenting was a useful procedure with a high success rate, even in patients aged <10 years. A 3-Fr ureteral stent was the only risk factor for stent failure; its substantial failure rate should be considered when deciding whether to insert a stent. Also, short-term re-evaluation after ureteral stent insertion is mandatory, especially with 3-Fr ureteral stents.

Which Patients Should We Follow up beyond 5 Years after Definitive Therapy for Localized Renal Cell Carcinoma?

PURPOSE: Up to 10% of recurrences develop beyond 5 years after curative treatment of localized renal cell carcinoma (RCC). Clinicopathologic features were evaluated to determine which factors are associated with late recurrence. MATERIALS AND METHODS: A total of 753 patients were diagnosed with localized RCC from January 2000 to June 2008. We enrolled 225 patients who were treated surgically and had a minimal recurrence-free survival of 60 months. Patients who had recurrence beyond 5 years after nephrectomy were defined as the late recurrence group and the remaining patients as the recurrence-free group. Multivariate logistic regression analyses and the Cox proportional hazard model were used for determination of features associated with late recurrence. RESULTS: In multivariate analyses, age older than 60 (p=0.030), Fuhrman grade ≥ 3 (p=0.042), and pT stage ≥ pT2 (p=0.010) showed statistical association with late recurrence. The Cox proportional hazard model showed significant differences in recurrence-free survival when we classified the patients based on pT2 (p=0.007) and on patient age ≥ 60 years (p=0.039). CONCLUSION: Patient age greater than 60 years, Fuhrman grade ≥ 3, and tumor stage ≥ pT2 are independent risk factors of recurrence more than 5 years after surgery in patients with RCC. Therefore, close lifelong follow-up is recommended for patients with these risk factors.

Factors affecting the time to recurrence after radical nephrectomy for localized renal cell carcinoma.

PURPOSE: The objective of this study was to determine the factors affecting the time to recurrence after radical nephrectomy for localized renal cell carcinoma. MATERIALS AND METHODS: We retrospectively evaluated 321 patients who received radical nephrectomies for localized renal cell carcinoma (pT1a-pT2b N0M0). Of 29 patients with disease recurrence, 9 had recurrence more than 5 years after radical nephrectomy. We evaluated the clinicopathological factors, with the use of a retrospective study design. RESULTS: Tumor necrosis was statistically different between the late recurrence group and the recurrence free group (Fisher exact test, p=0.046). Hematuria at diagnosis (chi-square test, p=0.045) was statistically significant in early recurrence. In the univariate logistic regression analysis, tumor necrosis (odds ratio [OR], 4.629; 95% confidence interval [CI], 1.106 to 19.379; p=0.036) and pT stage>1 (OR, 7.232; 95% CI, 1.727 to 30.280; p=0.007) were risk factors of late recurrence. In the multivariable logistic regression analysis, pT stage>1 (OR, 7.143; 5% CI 1.706 to 29.912, p=0.007) was associated with late recurrence. Regarding early recurrence, initial symptoms at diagnosis and pathologic T stage>1 were statistically significant in both univariate and multivariable logistic regression analysis. In terms of recurrence site, patients with late recurrence tended to have unusual metastasis sites other than lung, liver or bone (chi-square test, p=0.012). CONCLUSIONS: These data suggest that tumor necrosis may affect late disease recurrence. Patients with initial symptoms and hematuria at diagnosis are vulnerable to recurrence in a shorter period after nephrectomy. Patients with late recurrence showed a tendency to have unusual metastasis site other than lung, liver or bone.

The unidirectional barbed suture for renorrhaphy during laparoscopic partial nephrectomy: Stanford experience.

PURPOSE: Using barbed suture represents a novel technical modification in the performance of minimally invasive partial nephrectomy. Our purpose of this study was to evaluate the safety and efficacy of this suture for renorrhaphy during laparoscopic partial nephrectomy (LPN). PATIENTS AND METHODS: Thirteen consecutive patients underwent LPN using V-Loc™ 180 (Covidien, Dublin, Ireland) suture, and a nonconsecutive control group of 24 patients, matched according to tumor size and R.E.N.A.L. nephrometry score, underwent LPN using absorbable polyglactin suture. All 37 patients underwent LPN performed by a single surgeon. Perioperative and postoperative indicators of morbidity, estimated blood loss, and warm ischemia time (WIT) were compared between the groups. RESULTS: Baseline characteristics including age, body mass index, American Society of Anesthesiologists score, tumor size, laterality, and R.E.N.A.L nephrometry score were identical between the groups. On multivariable analysis, there were no significant differences between the two groups with regard to operative time, estimated blood loss, transfusion rates, rates of surgical complications, and length of hospital stay. However, mean WIT was significantly shorter in the V-Loc group compared with the control group (24.5±5.3 minutes versus 31.9±8.9 minutes, P=.01). CONCLUSIONS: The use of V-Loc sutures for renorrhaphy during LPN is safe and feasible and, in our series, significantly reduces WIT. Further studies are needed to corroborate these findings, but these results indicate a promising development in reducing WIT during minimally invasive partial nephrectomy.