Current and Emerging Pharmacological Targets and Treatments of Urinary Incontinence and Related Disorders.

Overactive bladder syndrome with and without urinary incontinence and related conditions, signs, and disorders such as detrusor overactivity, neurogenic lower urinary tract dysfunction, underactive bladder, stress urinary incontinence, and nocturia are common in the general population and have a major impact on the quality of life of the affected patients and their partners. Based on the deliberations of the subcommittee on pharmacological treatments of the 7th International Consultation on Incontinence, we present a comprehensive review of established drug targets in the treatment of overactive bladder syndrome and the aforementioned related conditions and the approved drugs used in its treatment. Investigational drug targets and compounds are also reviewed. We conclude that, despite a range of available medical treatment options, a considerable medical need continues to exist. This is largely because the existing treatments are symptomatic and have limited efficacy and/or tolerability, which leads to poor long-term adherence. SIGNIFICANCE STATEMENT: Urinary incontinence and related disorders are prevalent in the general population. While many treatments have been approved, few patients stay on long-term treatment despite none of them being curative. This paper provides a comprehensive discussion of existing and emerging treatment options for various types of incontinence and related disorders.

Potential Role of Macrophage Polarization in the Progression of Hunner-Type Interstitial Cystitis.

BACKGROUND: Hunner-type interstitial cystitis (HIC) is a chronic inflammatory condition of the bladder. However, it remains unclear whether there is a causal relationship between the presence of Hunner lesions and seemingly normal-appearing areas in the bladder (non-Hunner lesions). This study aimed to investigate the fundamental aspects of HIC by examining potential genetic differences between Hunner and non-Hunner lesions and elucidate their role as potential markers in the progression and suppression of the disease. METHODS: This cross-sectional study enrolled patients with HIC (n = 10) who underwent supratrigonal cystectomy along with augmentation cystoplasty. Full-thickness bladder tissue was collected from Hunner and non-Hunner lesions in the same patient. Normal bladder tissue biopsies were also obtained as controls. Whole transcriptome analysis was performed to analyze the gene expression patterns and immune cell populations. RESULTS: The mucosal layers of patients exhibited similar pathway dysregulation across Hunner and non-Hunner lesions, with immunerelated pathways being prominently affected. In the mucosal layer, genes related to anti-inflammatory and immune suppression were downregulated in Hunner lesions compared to non-Hunner lesions. Moreover, in Hunner lesions, genes related to macrophage differentiation and polarization, such as VSIG4, CD68, MAFB, and LIRB4, were downregulated. The cell fraction of M2 macrophages was found to decrease in Hunner lesions. Immunohistochemical staining revealed an elevated fraction of M1 macrophages and a reduced fraction of M2 macrophages in Hunner lesions compared to those in non-Hunner lesions. In the muscular layer, transcriptomic evidence of muscle thickness was observed in both Hunner and non-Hunner lesions; however, the difference was not significant. CONCLUSION: Hunner lesions showed a reduced expression of anti-inflammatory and immunosuppressive factors compared to non-Hunner lesions, along with alterations in immune cell populations. This study suggests the possibility that macrophage polarization is related to the progression from non-Hunner lesions to Hunner lesions, suggesting its relevance to the characteristics of autoimmune diseases.

A treatment prediction strategy for overactive bladder using a machine learning algorithm that utilized data from the FAITH study.

AIMS: To use machine learning algorithms to develop a model to accurately predict treatment responses to mirabegron or antimuscarinic agents in patients with overactive bladder (OAB), using real-world data from the FAITH registry (NCT03572231). METHODS: The FAITH registry data included patients who had been diagnosed with OAB symptoms for at least 3 months and were due to initiate monotherapy with mirabegron or any antimuscarinic. For the development of the machine learning model, data from patients were included if they had completed the 183-day study period, had data for all timepoints and had completed the overactive bladder symptom scores (OABSS) at baseline and end of study. The primary outcome of the study was a composite outcome combining efficacy, persistence, and safety outcomes. Treatment was deemed "more effective" if the composite outcome criteria for "successful," "no treatment change," and "safe" were met, otherwise treatment was deemed "less effective." To explore the composite algorithm, a total of 14 clinical risk factors were included in the initial data set and a 10-fold cross-validation procedure was performed. A range of machine learning models were evaluated to determine the most effective algorithm. RESULTS: In total, data from 396 patients were included (266 [67.2%] treated with mirabegron and 130 [32.8%] treated with an antimuscarinic). Of these, 138 (34.8%) were in the "more effective" group and 258 (65.2%) were in the "less effective" group. The groups were comparable in terms of their characteristic distributions across patient age, sex, body mass index, and Charlson Comorbidity Index. Of the six models initially selected and tested, the decision tree (C5.0) model was chosen for further optimization, and the receiver operating characteristic of the final optimized model had an area under the curve result of 0.70 (95% confidence interval: 0.54-0.85) when 15 was used for the min n parameter. CONCLUSIONS: This study successfully created a simple, rapid, and easy-to-use interface that could be further refined to produce a valuable educational or clinical decision-making aid.

The Asia-Pacific AMS800 artificial urinary sphincter consensus statement.

This Asia-Pacific (AP) AMS 800™ artificial urinary sphincter (AUS) consensus statement aims to provide a set of practical recommendations to assist surgeons with the AMS 800 device surgery. The AP consensus committee consisted of key opinion leaders with extensive experience with AMS 800 surgery across several AP countries. The panel reviewed and discussed relevant findings with emphasis on locoregional and specific clinical challenges relevant to the AP region. Recommendations were made in key areas namely (1) patient selection and informed consent process; (2) preoperative assessment; (3) dealing with co-existing urological disorders; (4) surgical principles and intraoperative troubleshooting; (5) postoperative care; (6) special populations; and (7) cost analysis and comparative review. The AMS 800 device should be offered to males with moderate to severe stress urinary incontinence (SUI). Full informed consent should be undertaken, and emphasis is placed on surgical contraindications and high-risk candidates. The presence of a surgical mentor or referral to experts is recommended in complex AUS candidates. Preoperative cystoscopy with or without multichannel urodynamic study is necessary and patients with pre-existing urological disorders should be treated adequately and clinically stable before surgery. Adherence to strict patient selection and safe surgical principles are critical to ensure excellent clinical outcomes and minimize complications. Given that InhibiZone-coated device is not available in many AP countries, the use of prophylactic antibiotics pre-and post-operatively are recommended. The AMS 800 device should be prepared according to the manufacturer's guidelines and remains a cost-effective treatment for male SUI. The AMS 800 device remains the surgical benchmark for male SUI but is associated with certain mechanical limitations and a unique set of complications.

The impact of Hunner lesion-type interstitial cystitis/bladder pain syndrome on health-related quality of life and the effects of transurethral ablation.

PURPOSE: Interstitial cystitis/bladder pain syndrome (IC/BPS) has a negative impact on quality of life. We compared health-related quality of life (HRQoL) of patients with IC/BPS with patients having other diseases using the EuroQol five-dimension (EQ-5D) and evaluated whether the HRQoL is improved after surgery. METHODS: We compared EQ-5D of patients with Hunner lesion type IC/BPS with patients who had other diseases that cause chronic and severe pain including arthritis and cancer from a cross-sectional analysis of responses to the 2012-2016 Korea National Health and Nutrition Examination Survey. Changes in EQ-5D after transurethral coagulation (TUC) or resection (TUR) were measured in the IC/BPS participants. RESULTS: Compared to the EQ-5D index of normal population, patients with arthritis, cancer and IC/BPS had - 0.07 (95% CI - 0.07, - 0.06), - 0.01 (95% CI - 0.02, - 0.01), and - 0.21 (95% CI - 0.23, - 0.20) lower scores, respectively. Patients with IC/BPS were 35.9, 9.24, and 9.05 times more likely to have "extreme problem" in pain/discomfort, anxiety/depression, and usual activities EQ-5D domains, respectively, than patients without arthritis/cancer. After TUC or TUR, EQ-5D index was 0.90 in the TUC group and 0.92 in the TUR group. CONCLUSION: IC/BPS patients have worse HRQoL than healthy individuals. However, after surgical treatment, HRQoL is restored to a level close to normal.

The role of apparent diffusion coefficient as a predictive factor for tumor recurrence in patients with cerebellopontine angle epidermoid tumor.

Intracranial epidermoid tumors are slowly growing benign tumors, but due to adjacent critical neurovascular structures, surgical resection is challenging, with the risk of recurrence. The apparent diffusion coefficient (ADC) has been used to evaluate the characteristics of brain tumors, but its utility for intracranial epidermoid tumors has not been specifically explored. This study analyzed the utility of preoperative ADC values in predicting tumor recurrence for patients with intracranial epidermoid tumors. Between 2008 and 2019, 21 patients underwent surgery for cerebellopontine angle (CPA) epidermoid tumor, and their preoperative ADC data were analyzed. The patients were divided into two groups: the recurrence group, defined by regrowth of the remnant tumor or newly developed mass after gross total resection on magnetic resonance imaging (MRI); and the stable group, defined by the absence of growth or evidence of tumor on MRI. Receiver operating characteristic (ROC) analysis was used to obtain the ADC cutoff values for predicting tumor recurrence. The prognostic value of the ADC was assessed using Kaplan-Meier curves. The minimum ADC values were significantly lower in the recurrence group than in the stable tumor group (P = 0.020). ROC analysis showed that a minimum ADC value lower than 804.5 × 10-6 mm2/s could be used to predict higher recurrence risk of CPA epidermoid tumors. Non-total resection and mean and minimum ADC values lower than the respective cutoffs were negative predictors of recurrence-free survival. Minimum ADC values could be useful in predicting the recurrence of CPA epidermoid tumors.

Identification and Characterization of a Novel Large-Conductance Calcium-Activated Potassium Channel Activator, CTIBD, and Its Relaxation Effect on Urinary Bladder Smooth Muscle.

The large-conductance calcium-activated potassium channel (BKCa channel) is expressed on various tissues and is involved in smooth muscle relaxation. The channel is highly expressed on urinary bladder smooth muscle cells and regulates the repolarization phase of the spontaneous action potentials that control muscle contraction. To discover novel chemical activators of the BKCa channel, we screened a chemical library containing 8364 chemical compounds using a cell-based fluorescence assay. A chemical compound containing an isoxazolyl benzene skeleton (compound 1) was identified as a potent activator of the BKCa channel and was structurally optimized through a structure-activity relationship study to obtain 4-(4-(4-chlorophenyl)-3-(trifluoromethyl)isoxazol-5-yl)benzene-1,3-diol (CTIBD). When CTIBD was applied to the treated extracellular side of the channel, the conductance-voltage relationship of the channel shifted toward a negative value, and the maximum conductance increased in a concentration-dependent manner. CTIBD altered the gating kinetics of the channel by dramatically slowing channel closing without effecting channel opening. The effects of CTIBD on bladder muscle relaxation and micturition function were tested in rat tissue and in vivo. CTIBD concentration-dependently reduced acetylcholine-induced contraction of urinary bladder smooth muscle strips. In an acetic acid-induced overactive bladder (OAB) model, intraperitoneal injection of 20 mg/kg CTIBD effectively restored frequent voiding contraction and lowered voiding volume without affecting other bladder function parameters. Thus, our results indicate that CTIBD and its derivatives are novel chemical activators of the bladder BKCa channel and potential candidates for OAB therapeutics. SIGNIFICANCE STATEMENT: The novel BKCa channel activator CTIBD was identified and characterized in this study. CTIBD directly activates the BKCa channel and relaxes urinary bladder smooth muscle of rat, so CTIBD can be a potential candidate for overactive bladder therapeutics.

Impact of COVID-19 on medical education: introducing homo digitalis.

PURPOSE: To determine how members of the Société Internationale d'Urologie (SIU) are continuing their education in the time of COVID-19. METHODS: A survey was disseminated amongst SIU members worldwide by email. Results were analyzed to examine the influence of age, practice region and settings on continuing medical education (CME) of the respondents. RESULTS: In total, 2494 respondents completed the survey. Internet searching was the most common method of CME (76%; all ps < 0.001), followed by searching journals and textbook including the online versions (62%; all ps < 0.001). Overall, 6% of the respondents reported no time/interest for CME during the pandemic. Although most urologists report using only one platform for their CME (26.6%), the majority reported using ≥ 2 platforms, with approximately 10% of the respondents using up to 5 different platforms. Urologists < 40 years old were more likely to use online literature (69%), podcasts/AV media (38%), online CME courses/webinars (40%), and social media (39%). There were regional variations in the CME modality used but no significant difference in the number of methods by region. There was no significant difference in responses between urologists in academic/public hospitals or private practice. CONCLUSION: During COVID-19, urologists have used web-based learning for their CME. Internet learning and literature were the top frequently cited learning methods. Younger urologists are more likely to use all forms of digital learning methods, while older urologists prefer fewer methods.

Mirabegron has longer treatment persistence than antimuscarinics: Real-world data from a Korean national cohort database.

AIMS: To descriptively evaluate treatment persistence among adults who received mirabegron or antimuscarinics in South Korea. METHODS: This study involved a retrospective analysis of the Health Insurance Review and Assessment (HIRA) database. Patients (≥18 years) who had a new prescription for an overactive bladder (OAB) target medication (mirabegron/antimuscarinic) within an 8-month index period (July 1, 2015-February 29, 2016) were included. The date when the target (index) medication was dispensed was the index date. The 6-month period before the index date was used to assess patient eligibility. A 12-month post-index period was used to assess medication persistence, which was defined as the time to discontinuation. Overall data were analyzed and the results were also stratified by age group (≤65, >65 years), sex, or prior OAB medication experience. Persistence rates were calculated after the 1st, 3rd, 6th, 9th, and 12th months. RESULTS: A data set of 52 722 cases was obtained (mirabegron: 11 424, antimuscarinics: 41 298). The mean age was 60.9 ± 16.1 years and the majority of the patients were female (30 862 [58.5%] patients). Median persistence was longer with mirabegron (51 days) versus antimuscarinics (25 days). The persistence rate with mirabegron was higher throughout the study compared with all the antimuscarinics (12-month data: 13.5% and 4.9%, respectively). Longer treatment persistence was noted in older, male, and treatment-experienced patients. CONCLUSION: The results from the HIRA database showed that persistence was longer with mirabegron than with antimuscarinics in South Korea. This finding may help inform clinical decision-making within the South Korean healthcare system.

A multicenter prospective study for overactive bladder patient treatment satisfaction with mirabegron after being unsatisfied with antimuscarinic therapy (FAVOR study).

AIM: We investigated the satisfaction and efficacy of mirabegron in patients with overactive bladder (OAB) symptoms who were unsatisfied with previous antimuscarinic treatment. METHODS: This was a 12-week, open-label study of adults with OAB who had been treated with antimuscarinics within 2 years of screening and expressed dissatisfaction over poor efficacy or adverse events of antimuscarinics. All enrolled patients have received mirabegron 50 mg once daily for 12 weeks. The primary outcome was the percentage of patients reporting treatment satisfaction questions (TSQ) at week 12 ("very satisfied" or "somewhat satisfied"). Patients completed voiding diaries, Overactive Bladder Questionnaire short form (OAB-q-SF), Overactive Bladder Symptom Score (OABSS), and the global response assessment (GRA) at baseline, Week 4, and Week 12. At 12-weeks, patients were assessed for willingness to continue treatment. RESULTS: The response rate of treatment satisfaction at 12 weeks was 69.3% (275/397) (95% confidence interval 64.7-73.8). Significant improvements from baseline to weeks 4 and 12 were observed in the frequency, urgency due to urinary incontinence, and urgency episodes per 24 h (all p < .0001). Both OAB-q-SF and OABSS were significantly improved compared to baseline. At 4 and 12 weeks, 27.5% and 41.8% of patients, respectively, responded to the GRA as being moderately or markedly improved. At 12 weeks, 80.8% of patients were willing to continue mirabegron. CONCLUSIONS: Mirabegron improved the rates of treatment satisfaction and symptoms in patients with OAB who were unsatisfied with prior antimuscarinic treatment.

The timing of fusion surgery for clival chordoma with occipito-cervical joint instability: before or after tumor resection?

Clival chordoma with occipito-cervical (OC) joint invasion can result in preoperative and postoperative instability. The authors investigate the appropriate timing of OC fusion to prevent instability-, fusion-, and surgery time-related morbidity. Twenty-two consecutive patients underwent surgery for clival chordoma from December 2008 to September 2014. OC fusion was performed for patients with OC joint invasion and instability due to preoperative destruction of the occipital condyle or extensive postoperative condylectomy. The data in relation to OC joint instability, fusion, and surgery time were analyzed retrospectively and compared between OC fusion before and after tumor resection. Of the 22 patients, 8 with tumor invasion of the OC joint underwent OC fusion. OC fusion was performed after tumor resection in one-stage for four patients and before tumor resection in two-stage for four patients. There was OC joint instability from tumor destruction of the occipital condyle in seven patients (87.5%). Patients with OC fusion after tumor resection encountered complications such as surgery site wound dehiscence, encephalitis, and cardiac arrest with consequent mortality in one patient. These complications were avoided in subsequent patients where OC fusion was performed before tumor resection. There were no differences in the extent of tumor resection between OC fusion before and after tumor resection. Two-stage OC fusion before tumor resection can reduce instability-, fusion-, and surgery time-related morbidity and achieve feasible tumor resection when OC joint instability is expected. The extent of tumor invasion and brain stem compression should be considered when fusion precedes tumor resection.

Radiosurgery vs. microsurgery for newly diagnosed, small petroclival meningiomas with trigeminal neuralgia.

Trigeminal neuralgia (TN) is an excruciating pain that can occur with petroclival meningiomas (PCMs). Gamma knife radiosurgery (GKRS) is an appealing option for small PCMs, but the role of microsurgery (MS) compared to GKRS is not well defined for small PCMs with regard to TN relief. From January 2009 to September 2019, 70 consecutive patients were treated by GKRS or MS for newly diagnosed, small (< 3.5 cm) PCMs with TN. GKRS or MS were performed for 35 patients each. The surgical outcome and TN control according to Barrow Neurological Institute (BNI) score were retrospectively analyzed and compared between GKRS and MS. The predominant origin of PCMs was upper clival (49%) with trigeminal nerve compression at the medial dorsal root entry zone. Tumor control rates were equally 94% with GKRS or MS for a mean tumor size and volume of 2.3 cm and 5.3 cm3, respectively. The preoperative BNI scores were mostly II (40%) and IV (37%) with GKRS and MS, respectively. TN relief without medications (BNI scores I and II) was achieved in 13 of 35 patients (37%) with GKRS and 32 of 35 patients (91%) with MS during a mean follow-up of 50.5 months. The most common complications after GKRS and MS were dysesthesia (23%) and diplopia (9%), respectively. MS could be more effective than GKRS in providing prompt, medication-free pain relief from TN for small PCMs. The risks of MS have to be considered carefully in experienced hands, especially for small PCMs.

Lateral supraorbital versus pterional approach for parachiasmal meningiomas: surgical indications and esthetic benefits.

The lateral supraorbital (LSO) approach is a minimally invasive modification of the pterional approach. The authors assess the surgical indications and esthetic benefits of the LSO approach in comparison with the pterional approach for parachiasmal meningiomas. From April 2013 to May 2017, a total of 64 patients underwent surgery for parachiasmal meningiomas. Among them, tumor resection was performed with the LSO approach for 34 patients and pterional approach for 30 patients. A retrospective analysis was done on tumor characteristics, surgical outcome, approach-related morbidity, and esthetic outcome between the two approaches. Gross total resection was achieved in 33 of 34 patients (97.1%) with the LSO approach. There were no differences in tumor size, origin, consistency, internal carotid artery encasement, cranial nerve adhesion, and optic canal invasion between the two approaches. The most common tumor origin was the tuberculum sellae for both the LSO and pterional approaches. For tumors with preoperative visual compromise, immediate visual outcome improved or remained stable in 76% and 80.9% with the LSO and pterional approaches, respectively. Surgery time, surgical bleeding, hospital length of stay, and esthetic outcome were significantly shorter and superior with the LSO approach. There were no differences in surgical morbidity and brain retraction injury between the two approaches. The LSO approach can provide a safe, rapid, and minimally invasive exposure for parachiasmal meningiomas compared with the pterional approach. Surgeons must consider tumor size, origin, and extent in determining the resectability of the tumor rather than the extent of exposure.

Clinical guidelines for interstitial cystitis/bladder pain syndrome.

The clinical guidelines for interstitial cystitis and related symptomatic conditions were revised by updating our previous guidelines. The current guidelines define interstitial cystitis/bladder pain syndrome as a condition with chronic pelvic pain, pressure or discomfort perceived to be related to the urinary bladder accompanied by other urinary symptoms, such as persistent urge to void or urinary frequency in the absence of confusable diseases. The characteristic symptom complex is collectively referred as hypersensitive bladder symptoms. Interstitial cystitis/bladder pain syndrome is divided into Hunner-type interstitial cystitis and bladder pain syndrome; Hunner-type interstitial cystitis and bladder pain syndrome represent interstitial cystitis/bladder pain syndrome with Hunner lesions and interstitial cystitis/bladder pain syndrome without Hunner lesions, respectively. So-called non-Hunner-type interstitial cystitis featured by glomerulations or bladder bleeding after distension is included in bladder pain syndrome. The symptoms are virtually indistinguishable between Hunner-type interstitial cystitis and bladder pain syndrome; however, Hunner-type interstitial cystitis and bladder pain syndrome should be considered as a separate entity of disorder. Histopathology totally differs between Hunner-type interstitial cystitis and bladder pain syndrome; Hunner-type interstitial cystitis is associated with severe inflammation of the urinary bladder accompanied by lymphoplasmacytic infiltration and urothelial denudation, whereas bladder pain syndrome shows little pathological changes in the bladder. Pathophysiology would also differ between Hunner-type interstitial cystitis and bladder pain syndrome, involving interaction of multiple factors, such as inflammation, autoimmunity, infection, exogenous substances, urothelial dysfunction, neural hyperactivity and extrabladder disorders. The patients should be treated differently based on the diagnosis of Hunner-type interstitial cystitis or bladder pain syndrome, which requires cystoscopy to determine the presence or absence Hunner lesions. Clinical studies are to be designed to analyze outcomes separately for Hunner-type interstitial cystitis and bladder pain syndrome.

Efficacy and Safety of Tolterodine and Pilocarpine in Patients with Overactive Bladder.

PURPOSE: We evaluated the efficacy and safety of a combination of 2 mg tolterodine and 9 mg pilocarpine, vs tolterodine monotherapy in patients with overactive bladder. MATERIALS AND METHODS: We enrolled patients with overactive bladder symptoms in a multicenter, randomized, double-blind, parallel, active control study. Patients were randomized to the combination or 2 mg tolterodine twice daily for 12 weeks. After the double-blind period finished all patients were started on the combination for 12 weeks. Study co-primary end points were the change from baseline in the mean number of daily micturitions and cumulative incidence of dry mouth at the end of 12 weeks. Secondary end points were other overactive bladder symptoms, the total xerostomia inventory score and results of a visual analogue scale for dry mouth at the end of 12 and 24 weeks. RESULTS: The mean change in the number of daily micturitions from baseline to 12 weeks was -1.49 and -1.74 in the combination and tolterodine monotherapy groups, respectively. The mean difference was -0.26 (95% CI -0.79-0.27), confirming noninferiority. At 12 weeks the incidence of dry mouth was lower in the combination group than in the tolterodine monotherapy group (30.0% vs 42.9%, p = 0.009). All secondary and other efficacy outcomes related to overactive bladder symptoms improved in each group with no significant differences between the groups at 12 weeks. Changes from baseline in the total xerostomia inventory score and the visual analogue scale for dry mouth were significantly lower in the combination group than in the tolterodine monotherapy group. CONCLUSIONS: Tolterodine and pilocarpine alleviated dry mouth in patients with overactive bladder while maintaining anticholinergic efficacy similar to that of tolterodine.

Analysis of patterns of failure and appraisal of postoperative radiation field for grade II-III meningioma.

PURPOSE: To analyze patterns of failure according to treatment modalities and evaluate the adequacy of an institution's current volume of postoperative radiotherapy (PORT) for World Health Organization (WHO) grade II or III meningiomas. PATIENTS AND METHODS: Data of 98 patients treated by either surgery and PORT (PORT group, n = 53) or surgery alone (surgery group, n = 45) between March 2000 and December 2013 were reviewed. Clinical target volume of PORT was delineated as a 1.5-2-cm expansion from the tumor bed. Local failure (LF) was defined as recurrence within a 2-cm margin from the tumor bed. Failures other than LF were defined as out-field failure (OFF). Median total dose of PORT was 59.4 (range 45.0-69.0) Gy. RESULTS: The PORT group had larger proportions of grade III meningiomas (18/53, 34.0%) than the surgery group (8/46, 15.6%) (p = 0.037). After a median 73.4-month follow-up, 29 patients experienced LF and 5 developed OFF. The actuarial 5-year local control (LC) rates were 86.7% and 59.3% in the PORT and surgery groups, respectively (p = 0.002). PORT was a significant factor of LC in the univariate (p = 0.003, hazard ratio [HR] 3.449, 95% confidence interval [CI] 1.516-7.846) and multivariate analyses (p < 0.001, HR 5.486, 95% CI 2.178-13.820). CONCLUSIONS: Despite the larger proportion of grade III meningiomas in the PORT group, PORT reduced LF in patients with WHO grade II or III meningiomas compared with the surgery group. The current PORT field seems reasonable because LF was the dominant pattern of failure in patients treated by surgery alone.

Patterns of failures after surgical resection in olfactory neuroblastoma.

INTRODUCTION: Patterns of failure in patients with olfactory neuroblastoma (ONB) according to two surgical approaches, craniofacial resection (CFR) and endoscopic surgery (ENDO), have yet to be analyzed. METHODS: We retrospectively reviewed 28 patients with surgically treated ONB between January 1995 and October 2017. Fourteen (50.0%) patients underwent CFR (9 CFR alone, 5 ENDO-assisted CFR) and 14 (50.0%) underwent ENDO. Nineteen (67.9%) patients underwent post-operative radiotherapy (RT). RESULTS: At a median follow-up of 53.8 months (range 10.4-195.3), the 5-year progression-free survival (PFS) and 10-year overall survival were 37.3% and 57.5%, respectively. Patients with adjuvant RT had a 5-year PFS of 46.7%, whereas those treated with surgery alone had a 5-year PFS of 19.4% (p = 0.01). Locoregional failure (LRF) occurred in ten patients (median 59.6 months after initial diagnosis; range 12.7-59.7). Neck node metastasis occurred in 25.0% (7 of 28). Five patients with ENDO showed LRF and underwent proper subsequent treatments with either surgery or adjuvant RT. Approximately 35.7% patients (five patients) in the CFR group experienced distant metastasis in the intracranial dura region (median 116.4 months after initial diagnosis; range 2.6-142.4). Three of four patients who developed LRF after CFR developed dura-based metastasis. CONCLUSIONS: Both dura-based and neck node metastasis in the delayed phase were distinct patterns of failure in ONB. Patterns of recurrence differed based on surgical approach; dura-based metastases were common after CFR. LRF was the distinct failure pattern in ENDO, but could be successfully salvaged. Treatment outcome was improved considerably with RT following surgical resection.

Silicon membrane filter designed by fluid dynamics simulation and near-field stress analysis for selective cell enrichment.

Selective cell enrichment technologies can play an important role in both diagnostic and therapeutic areas. However, currently used cell sorting techniques have difficulties in rapidly isolating only the desired target cells from a large volume of body fluids. In this work, we developed a filtering system that can quickly separate and highly concentrate cells from a large volume of solution, depending on their size, using a silicon membrane filter. To overcome the problems caused by material limitations of the brittle silicon, we designed a novel membrane filter with various pore designs. From these designs, the most optimal design with high pore density, while preventing crack formation was derived by applying fluid dynamics simulation and near-field stress analysis. The membrane filter system using the selected design was fabricated, and cell filtration performance was evaluated. The LNCaP cell in horse blood was recovered up to 86% and enriched to 187-fold compared to initial cell populations after filtration at a flow rate of 5 mL/min. The results demonstrate that the filter presented in this study can rapidly and selectively isolate target cells from a large volume of body fluid sample.

Therapeutic effects of endoscopic ablation in patients with Hunner type interstitial cystitis.

OBJECTIVE: To investigate the efficacy of endoscopic ablation of Hunner lesions (HLs) in patients with interstitial cystitis (IC) and to find predictors of early recurrence of HLs. PATIENTS AND METHODS: A prospective study was performed of patients with Hunner type IC who underwent transurethral ablation. We repeated endoscopic ablation when symptoms and HLs recurred during the follow-up period. The primary endpoint was recurrence-free time. Secondary endpoints were a change in frequency, nocturia, and urgency episodes, and changes in visual analogue scale (VAS) pain scores and other symptom indices at follow-up visits. RESULTS: A total of 72 patients were analysed. The median (range) follow-up period was 29.5 (12.0-50.0) months. After primary ablation treatment, HLs recurred in 75.0% (54/72) of patients, and the median (sd) recurrence-free time was 12.0 (1.6) months. Amongst the 54 patients with recurrence, 50 underwent a second ablation treatment. HLs occurred in 44.0% (22/50) of individuals after the second operation, and the median (sd) recurrence-free time was 18.0 (5.1) months. Lower maximal cystometric capacity (odds ratio 1.01, 95% confidence interval 1.001-1.013) was the predictive factor for early recurrence. There were significant improvements in the VAS pain scores, O'Leary-Sant Interstitial Cystitis Symptom Index and Problem Index, Pelvic Pain and Urgency/Frequency Patient Symptom Scale after treatment (all, P < 0.05). CONCLUSIONS: Endoscopic ablation is an effective treatment option for HLs and significantly reduces pain and improves voiding symptoms. Repeat ablation upon recurrence could help symptom control and bladder preservation only if the bladder capacity is maintained.

The prevalence and risk factors of nocturia in China, South Korea, and Taiwan: results from a cross-sectional, population-based study.

PURPOSE: To examine the prevalence, symptomatology, and risk factors for nocturia using data from an internet-based questionnaire conducted in China, South Korea, and Taiwan. METHODS: Data from a cross-sectional, population-representative, internet-based study conducted among men and women aged ≥ 40 years were analysed post hoc. Nocturia prevalence and bother were analysed by sex and age group, and with regard to comorbid conditions and lower urinary tract symptoms (LUTS). Multivariate and univariate logistic regression models to identify risk factors for nocturia were constructed, with nocturia involving ≥ 2 nocturnal voids as the dependent variable. RESULTS: Among the 8284 participants, the prevalence of nocturia involving ≥ 1, ≥ 2, or ≥ 3 voids was slightly higher for women (76.1, 37.3, and 17.5%, respectively) compared with men (74.0, 34.5, and 15.5%, respectively). The prevalence and associated bother of nocturia increased with age. Greater proportions of patients with comorbid conditions or wet/more severe overactive bladder syndrome (OAB) experienced nocturia than those without. Multivariate analysis identified that female sex, age > 60 years, diabetes, cardiac disease, body mass index, International Prostate Symptom Score (IPSS) voiding score, stress urinary incontinence, wet OAB, and Hospital Anxiety And Depression Scale (HADS) anxiety score were associated with ≥ 2 nocturnal voids. Hypertension was associated with ≥ 2 nocturnal voids in women but not men, and alcohol consumption in men but not women. CONCLUSIONS: Nocturia is a common and bothersome condition affecting a large proportion of men and women aged ≥ 40 years in China, South Korea, and Taiwan. Factors associated with nocturia included age, sex, comorbid conditions, and LUTS. TRIAL REGISTRATION: This study is registered at ClinicalTrials.gov: NCT02618421.