A HIMU-like component in Mariana Convergent Margin magma sources during initial arc rifting revealed by melt inclusions.

Compositions of island arc and back-arc basin basalts are often used to trace the recycling of subducted materials. However, the contribution of subducted components to the mantle source during initial arc rifting before back-arc basin spreading is not yet well constrained. The northernmost Mariana arc is ideal for studying this because the transition from rifting to back-arc spreading is happening here. Here we report major and trace element and Pb isotopic compositions of olivine-hosted melt inclusions from lavas erupted during initial rifting at 24°N (NSP-24) and compare them with those in active arc front at 21°N and mature back-arc basin at 18°N. NSP-24 high-K melt inclusions have highly radiogenic Pb compositions and are close to those of the HIMU end-member, suggesting the presence of this component in the magma source. The HIMU-like component may be stored in the over-riding plate and released into arc magma with rifting. HIMU-type seamounts may be subducted elsewhere beneath the Mariana arc, but obvious HIMU-type components appear only in the initial stages of arc rifting due to the low melting degree and being consumed during the process of back-arc spreading.

Transient receptor potential ankyrin 1 channels in the bladder mediate low temperature elicited bladder overactivity in rats.

AIMS: This study aimed to investigate whether pathways involving transient receptor potential ankyrin 1 (TRPA1) channels in the urinary bladder mediate the bladder overactivity elicited by exposure to a low temperature in rats. METHODS: At postnatal week 10, female Sprague-Dawley (SD) rats were intraperitoneally injected with the TRPA1 channel antagonist, HC030031, at room temperature (RT) and subsequently exposed to low temperature (LT). Bladder specimens treated with HC030031 were evaluated for contractions through cumulative addition of the TRPA1 channel agonist trans-cinnamaldehyde. Two days before cystometric investigation, small interfering RNA (siRNA) targeting TRPA1 was transfected into urinary bladders. Then, cystometric investigations were performed on rats subjected to TRPA1 siRNA transfection at both RT and LT. Expression of TRPA1 channels in the urinary bladder was assessed through immunohistochemistry and real-time reverse transcription-polymerase chain reaction. RESULTS: At RT, micturition patterns were unaffected by HC030031 treatment. However, upon exposure to LT, rats treated with HC030031 exhibited a reduction of LT-elicited bladder overactivity, as evidenced by inhibited decreases in voiding interval, micturition volume, and bladder capacity. Additionally, HC030031 inhibited trans-cinnamaldehyde-induced contractions. Immunohistochemical analysis showed the presence of TRPA1 channels in the urinary bladder. Notably, rats with TRPA1 siRNA-transfected bladders could partially inhibit bladder overactivity during LT exposure. CONCLUSIONS: These findings indicate that pathways involving TRPA1 channels expressed in the urinary bladder could mediate the LT-elicited bladder overactivity.

Newspaper Campaign to Promote Deceased Organ Donation: Who Can Appeal to the General Japanese Population?

BACKGROUND: Various interventions are reportedly effective in promoting organ donor registration. However, the identity of those who best serve as presenters to appeal to the general public is not known. METHODS: A campaign for organ donor registration was conducted through a local newspaper advertisement in Japan. The advertisement appeared in 439,733 copies of the newspaper on January 9, 2021. In addition to the main message, 6 different presenters with photos of their faces and quick response codes were listed in the advertisement, namely a urologist, transplant physician, nephrologist, dialysis physician, ophthalmologist, and kidney transplant recipient who was a nephrologist himself (ie, a recipient and nephrologist). Newspaper readers watched each video about deceased organ donation via the quick response codes, and the number of video views acquired 30 days after the appearance was the main outcome, which was assessed using YouTube analytics. The proportions (95% CI) of people who watched each video among 439,733 newspaper readers were compared among the 6 presenters. RESULTS: The analyzed videos were viewed 262 times. The video produced by the recipient and nephrologist had the highest number of views among the 6 presenters (proportion: 0.019% [95% CI, 0.015-0.023]), followed by the one produced by the dialysis physician (0.011% [95% CI, 0.008-0.014]), the nephrologist (0.010% [95% CI, 0.007-0.014]), the urologist (0.008% [95% CI, 0.006-0.012]), the transplant physician (0.006% [95% CI, 0.004-0.009]), and the ophthalmologist (0.005% [95% CI, 0.004-0.008]). CONCLUSIONS: The appeal by the recipient and the nephrologist reached the highest proportion of people who watched the video about deceased organ donation in Japan.

Cold stress-induced bladder overactivity in type 2 diabetic mellitus rats is mitigated by the combination of a M3 -muscarinic antagonist and a ß3 -adrenergic agonist.

OBJECTIVES: Goto-Kakizaki (GK) rats with type 2 diabetes mellitus respond to low temperature (LT) environments with bladder overactivity, including increased voiding frequency and decreased voiding interval and micturition volume. We determined if bladder overactivity could be inhibited by treatment with the combination of a M3 -muscarinic receptor antagonist and a ß3 -adrenergic receptor agonist. METHODS: Ten-week-old female GK rats were fed a high-fat diet for 4 weeks. Cystometric investigations were conducted at room temperature (RT, 27 ± 2°C). The rats were then intraperitoneally administered the vehicle, the M3 -muscarinic receptor antagonist solifenacin, the ß3 -adrenergic agonist mirabegron, or a combination of solifenacin and mirabegron. Ten minutes after the administrations, the rats were transferred to the LT environment (4 ± 2°C), where the cystometric measurements were continued. The expressions of both M3 -muscarinic and ß3 -adrenergic receptors were investigated. RESULTS: After transfer from RT to LT, both voiding interval and bladder capacity of the vehicle-, solifenacin-, or mirabegron-treated rats were significantly decreased. However, the combination of solifenacin and mirabegron significantly mitigated the bladder overactivity. While both M3 -muscarinic and ß3 -adrenergic receptors were detected, the expression of M3 -muscarinic receptor mRNA was significantly higher than that of ß3 -adrenergic receptor mRNA. CONCLUSIONS: The cold stress-induced bladder overactivity was not improved by either the M3 -muscarinic receptor antagonist or the ß3 -adrenergic receptor agonist alone. However, the combined treatment mitigated the cold stress responses. Combined therapy with M3 -muscarinic antagonists and ß3 -adrenergic agonists could reduce side effects and improve the quality of life for diabetic patients with bladder overactivity.

Autologous Bilayered Adipose-Derived Mesenchymal Cell-Gelatin Sheets Reconstruct Ureters in Rabbits.

Repair of ureteral defects or strictures due to disease or trauma is usually dependent upon surgery that often requires either reoperation or an alternative treatment. By taking advantage of tissue engineering and regenerative techniques, it may be possible to define new approaches to ureteral repair. In this study, we fabricated autologous bilayered adipose-derived mesenchymal cell (AMC)-gelatin sheets and transplanted them into rabbits to replace surgically excised ureteral segments. AMCs harvested from abdominal adipose tissues of female New Zealand white rabbits were cultured on collagen-coated dishes and labeled with PKH26, a red fluorescent dye, for later identification. Monolayers of the cultured PKH26-labeled AMCs were detached and applied to gelatin hydrogel sheets. Two gelatin sheets were then united with the AMC monolayers apposed together, forming a bilayered AMC-gelatin sheet. Following each partial ureterectomy, a bilayered autologous AMC-gelatin sheet was transplanted, joining the proximal and distal ends of the remaining ureter (n = 9). Control animals underwent the same procedure except that the transplant was achieved with a bilayered acellular-gelatin sheet (n = 9). At 4 and 8 weeks after transplantation, the proximal regions of ureters treated with the control bilayered acellular-gelatin sheets exhibited flexures and dilations, which are not characteristic of unoperated ureters. In contrast, the bilayered AMC-gelatin sheet-transplanted rabbits did not have ureteral flexures or dilations. About midway between the proximal and distal ends, both the control and experimental reconstructed ureteral walls had smooth muscle layers; however, those in the experimental reconstructed ureteral walls were significantly thicker and better organized than those in the control reconstructed ureteral walls. Some AMCs differentiated into smooth muscle marker-positive cells. The experimental ureteral walls contained smooth muscle cells derived from the PKH26-labeled AMCs and others that were derived through migration and differentiation of cells from the remaining proximal and distal ends of the original ureter. In addition, the lumina of the 8-week reconstructed ureteral tissues in experimental rabbits did not show histological strictures as seen in the control ureters. These results suggest that the bilayered AMC-gelatin sheets have the potential to replace defective tissues and/or reconstruct damaged ureters. Impact Statement To reconstruct ureter tissues following partial ureterectomy, we fabricated bilayered adipose-derived mesenchymal cell (AMC)-gelatin sheets based on cell sheet engineering principles. The bilayered AMC-gelatin sheets were transplanted into rabbits to replace a surgically excised ureteral segment. At 4 and 8 weeks after, the ureters that received bilayered AMC-gelatin sheets did not exhibit severe flexures, dilations, or strictures. The experimental ureteral walls had smooth muscle marker-positive cells that were differentiated from the AMCs, and similar cells were present in the adjacent intact ureteral tissues. Therefore, the bilayered AMC-gelatin sheets have the potential to reconstruct ureters damaged through disease or trauma.

Successful management of testicular primitive neuroectodermal tumor with multiple bone metastases.

Introduction: Germ cell tumor with malignant transformation is extremely rare. We present a case of testicular primitive neuroectodermal tumor with multiple metastases that was effectively managed by surgery, irradiation, and second-line chemotherapy. Case presentation: A 22-year-old man was diagnosed as having teratoma including primitive neuroectodermal tumor with lymph node and multiple bone metastases. Five months afterwards the first-line therapy, his skull metastasis recurred. Vincristine, doxorubicin, and cyclophosphamide therapy followed by vincristine, actinomycin D, and cyclophosphamide therapy was given as second-line chemotherapy. Computed tomography revealed no disease progression 3 months after the treatments. Conclusion: Metastatic primitive neuroectodermal tumor may be successfully managed by multidisciplinary cancer treatment.

Petrogenesis of isotopically enriched Quaternary magma with adakitic affinity associated with subduction of old lithosphere beneath central Myanmar.

We present a model for the petrogenesis of magma with adakitic affinity in an old subduction zone, which does not involve slab melting and is constrained by new geochronological and geochemical data for Mt. Popa, the largest of three Quaternary volcanoes in central Myanmar (Popa, Monywa and Singu). The edifice is composed of Popa Plateau (0.8-0.6 Ma) with high-K rocks and a stratovolcano (< 0.33 Ma) predominantly composed of medium-K rocks with adakitic affinity (Mg# 45-63, Sr/Y > 40). The distinct K contents indicate that the adakitic magmas cannot be derived from Popa high-K rocks, but they share trace-element signatures and Sr-Nd isotope ratios with medium-K basalts from Monywa volcano. Our estimation of water contents in Popa magma reveals that primary magma for medium-K basalts was generated by partial melting of wedge mantle with normal potential temperature (TP 1330-1340 °C) under wet conditions (H2O 0.25-0.54 wt%). Its melting was probably induced by asthenospheric upwelling that is recognized by tomographic images. Mafic adakitic magma (Mg# ~ 63, Sr/Y ~ 64) was derived from the medium-K basaltic magma in fractional crystallization of a garnet-bearing assemblage at high pressure, and felsic adakitic rocks (Mg# ~ 45, Sr/Y ~ 50) were produced by assimilation-fractional crystallization processes at mid-crustal depths.

Influence of background characteristics in responders of regenerative therapy by periurethral injection of adipose-derived regenerative cells for male stress urinary incontinence.

OBJECTIVES: To determine if the male responders with post-prostatectomy incontinence in the ADRESU study, which is a clinical trial of regenerative therapy by periurethral injection of adipose-derived regenerative cells, are influenced by any background characteristics. METHODS: Briefly, autologous adipose-derived regenerative cells isolated from abdominal adipose tissue and a mixture of adipose-derived regenerative cells with fat tissue were transurethrally injected into the rhabdosphincter and submucosal space of the urethra, respectively. Sixteen out of 43 patients (37.2%) responded to treatment (responders) and exhibited improvement in the urine leakage volume, defined as >50% reduction from baseline determined by the 24-hour pad test at 52 weeks of treatment (or last visit within 52 weeks). Background data such as age, body weight, method of prostatectomy, baseline frequency of leaks, number of leaks, number of pad changes, International Consultation on Incontinence Questionnaire-Short Form, King's Health Questionnaire, urodynamic urethral function including functional profile length and maximum urethral closure pressure, and abdominal leak point pressure were collected and compared between responders and nonresponders. RESULTS: None of the background factors influenced improvement in the responders as compared with the nonresponders. However, a significant between-group difference in the rates of decrease in urine leakage volume was noted in patients of younger age (<70 years), compared with those of older age (≥70 years) from 2 to 26 weeks of treatment. CONCLUSION: A greater decrease in urine leakage volume was noted in the younger patient group than in the older patient group.

[IMPACT OF GENERAL FATIGUE ON TREATMENT PERIOD AFTER INDUCTION OF ENZALUTAMIDE FOR CASTRATION-RESISTANT PROSTATE CANCER].

(Objectives) Enzalutamide is an effective therapeutic options for castration resistant prostate cancer (CRPC). General fatigue is a major adverse event after commencing of enzalutamide in CRPC patients; however, its precise impact remains uncertain, especially on the duration of enzalutamide therapy. This study evaluated the relationship of general fatigue with patient age and enzalutamide treatment duration using real-world clinical data. (Patients and methods) This investigation retrospectively included patients who received enzalutamide therapy for CRPC between 2014 and 2018 at Shinshu University School of Medicine or Nagano Municipal Hospital. We classified the patients into the general fatigue group and the non-general fatigue group, and analyzed the groups in with regard to age and the duration of enzalutamide treatment. (Results) Of the 98 patients with CRPC were enrolled, 40 (40.8%) complained of general fatigue after enzalutamide induction. The median age of the study group was 78.0 years (71.0 years in the general fatigue group and 75.0 years in the non-general fatigue group), with no significant difference between the groups. Mean treatment duration was also comparable at 265.9 days in the general fatigue group and 266.5 days in the non-general fatigue group. (Conclusions) General fatigue after commencing enzalutamide was not impacted by age and did not remarkably influence the duration of therapy for CRPC.

Functional and histologic imaging of urinary bladder wall after exposure to psychological stress and protamine sulfate.

To quantify the urinary bladder wall T1 relaxation time (T1) before and after the instillation contrast mixture in rats previously subjected to water avoidance stress (WAS) and/or acute exposure to protamine sulfate (PS). Female Wistar rats were randomized to receive either sham (control) or 1 h of WAS for ten consecutive days before the evaluation of nocturnal urination pattern in metabolic cages. T1 mapping of urinary bladder wall at 9.4 T was performed pre- and post- instillation of 4 mM Gadobutrol in a mixture with 5 mM Ferumoxytol. Subsequently, either T1 mapping was repeated after brief intravesical PS exposure or the animals were sacrificed for histology and analyzing the mucosal levels of mRNA. Compared to the control group, WAS exposure decreased the single void urine volume and shortened the post-contrast T1 relaxation time of mucosa- used to compute relatively higher ingress of instilled Gadobutrol. Compromised permeability in WAS group was corroborated by the urothelial denudation, edema and ZO-1 downregulation. PS exposure doubled the baseline ingress of Gadobutrol in both groups. These findings confirm that psychological stress compromises the paracellular permeability of bladder mucosa and its non-invasive assay with MRI was validated by PS exposure.

Effect of oxybutynin patch versus mirabegron on nocturia-related quality of life in female overactive bladder patients: A multicenter randomized trial.

OBJECTIVES: To investigate the effect of oxybutynin patch versus ß3-adrenoceptor agonist mirabegron on nocturia-related quality of life in female overactive bladder patients. METHODS: In the present study, female overactive bladder patients were enrolled. The patients were randomly allocated into two groups: the oxybutynin patch group and the mirabegron group. Each of the drugs was given for 8 weeks. The changes in the total Nocturia Quality of Life Questionnaire score were evaluated. Parameters on a frequency volume chart were also evaluated. RESULTS: In total, 100 patients (51 oxybutynin patch, 49 mirabegron) were treated with oxybutynin patch or mirabegron. The changes in the Nocturia Quality of Life Questionnaire score 4 weeks after administration were 3.8 ± 18.6 and 8.7 ± 13.1 with the oxybutynin patch group and the mirabegron group, respectively, which were significantly higher than those at the baseline. Furthermore, the changes in the Nocturia Quality of Life Questionnaire score 8 weeks after administration were 4.3 ± 16.5 and 7.7 ± 12.3, respectively. A statistical difference was seen only in the mirabegron group. Regarding the Nocturia Quality of Life Questionnaire subscores, oxybutynin patch and mirabegron significantly improved the Nocturia Quality of Life Questionnaire bother/concern subscore 4 and 8 weeks after administration, whereas the Nocturia Quality of Life Questionnaire sleep/energy subscore was not significantly improved in each period. Eight weeks after administration, 24-h frequency, 24-h urinary urgency and mean voided urine volume were improved in both groups statistically. CONCLUSIONS: The oxybutynin patch improves quality of life, focusing mainly on nocturia by improving the bother/concern subscores of the Nocturia Quality of Life Questionnaire in the short term.

Time-dependent progression of neurogenic lower urinary tract dysfunction after spinal cord injury in the mouse model.

This study evaluated the time-course changes in bladder and external urinary sphincter (EUS) activity and the expression of mechanosensitive channels in lumbosacral dorsal root ganglia (DRG) after spinal cord injury (SCI). Female C57BL/6N mice in the SCI group underwent transection of the Th8/9 spinal cord. Spinal intact mice and SCI mice at 2, 4, and 6 wk post-SCI were evaluated by single-filling cystometry and EUS-electromyography (EMG). In another set of mice, the bladder and L6-S1 DRG were harvested for protein and mRNA analyses. In SCI mice, nonvoiding contractions were confirmed at 2 wk post-SCI and did not increase over time to 6 wk. In 2-wk SCI mice, EUS-EMG measurements revealed detrusor sphincter dyssynergia, but periodic EMG reductions during bladder contraction were hardly observed. At 4 wk, SCI mice showed increases of EMG activity reduction time with increased voiding efficiency. At 6 wk, SCI mice exhibited a further increase in EMG reduction time. RT-PCR of L6-S1 DRG showed increased mRNA levels of transient receptor potential vanilloid 1 and acid-sensing ion channels (ASIC1-ASIC3) in SCI mice with a decrease of ASIC2 and ASIC3 at 6 wk compared with 4 wk, whereas Piezo2 showed a slow increase at 6 wk. Protein assay showed SCI-induced overexpression of bladder brain-derived neurotrophic factor with a time-dependent decrease post-SCI. These results indicate that detrusor overactivity is established in the early phase, whereas detrusor sphincter dyssynergia is completed later at 4 wk with an improvement at 6 wk post-SCI, and that mechanosensitive channels may be involved in the time-dependent changes.NEW & NOTEWORTHY This is the first paper to evaluate the time-course changes of bladder dysfunction associated with mechanosensitive channels in a mouse model.

Pleural and pulmonary metastases from nonseminomatous germ cell tumors successfully managed by extrapleural pneumonectomy.

INTRODUCTION: Surgery for postchemotherapy residual nonseminomatous germ cell tumors may be difficult due to exceptional lesion size and location. CASE PRESENTATION: A 47-year-old man presented with swelling and pain in the left scrotum. Computed tomography revealed a solid occupied lesion in the left scrotum with huge metastases in the left lung and pleura. Results of a left high inguinal orchiectomy indicated a pathological diagnosis of germ cell tumors of several histological types. The patient declined postoperative chemotherapy but returned to our department 10 months later with dyspnea. Serum tumor marker levels were restored to normal range by adjuvant chemotherapy. Thereafter, an extrapleural pneumonectomy was performed for the remaining tumors. He has since been asymptomatic without recurrence or dyspnea for over 5 years. CONCLUSION: Extrapleural pneumonectomy is a valid treatment option for the management of huge pleural and pulmonary metastases of nonseminomatous germ cell tumors.

Clinical Guidelines for Female Lower Urinary Tract Symptoms (second edition).

The present article is an abridged English translation of the Japanese Clinical Guidelines for Female Lower Urinary Tract Symptoms (second edition), published in September 2019. These guidelines consist of a total of 212 pages and are unique worldwide in that they cover female lower urinary tract symptoms other than urinary incontinence. They contain two algorithms for "primary treatment" and "specialized treatment," respectively. These guidelines, consisting of six chapters, address a total of 26 clinical questions including: (i) treatment algorithms; (ii) what are female lower urinary tract symptoms?; (iii) epidemiology and quality of life; (iv) pathology and illness; (v) diagnosis; and (vi) treatment. When the patient's symptoms mainly involve voiding and post-micturition symptoms, specialized treatment should be considered. In the event of voiding symptoms concurrent with storage symptoms, residual urine should be measured; if the residual urine volume is <100 mL, then diagnosis and treatment for storage symptoms is prioritized, and if the volume is ≥100 mL, then specialized treatment should be considered. When storage symptoms are the primary condition, then the patient is subject to the primary treatment algorithm. Specialized treatment for refractory overactive bladder includes botulinum toxin injection and sacral nerve stimulation. For stress urinary incontinence, surgical treatment is indicated, such as urethral slings. The two causes of voiding symptoms and post-micturition symptoms are lower urinary tract obstruction and detrusor underactivity (underactive bladder). Mechanical lower urinary tract obstruction, such as pelvic organ prolapse, is expected to improve with surgery.

Basalt derived from highly refractory mantle sources during early Izu-Bonin-Mariana arc development.

The magmatic character of early subduction zone and arc development is unlike mature systems. Low-Ti-K tholeiitic basalts and boninites dominate the early Izu-Bonin-Mariana (IBM) system. Basalts recovered from the Amami Sankaku Basin (ASB), underlying and located west of the IBM's oldest remnant arc, erupted at ~49 Ma. This was 3 million years after subduction inception (51-52 Ma) represented by forearc basalt (FAB), at the tipping point between FAB-boninite and typical arc magmatism. We show ASB basalts are low-Ti-K, aluminous spinel-bearing tholeiites, distinct compared to mid-ocean ridge (MOR), backarc basin, island arc or ocean island basalts. Their upper mantle source was hot, reduced, refractory peridotite, indicating prior melt extraction. ASB basalts transferred rapidly from pressures (~0.7-2 GPa) at the plagioclase-spinel peridotite facies boundary to the surface. Vestiges of a polybaric-polythermal mineralogy are preserved in this basalt, and were not obliterated during persistent recharge-mix-tap-fractionate regimes typical of MOR or mature arcs.

Impact of low-dose tadalafil on adverse events after low-dose-rate brachytherapy for prostate cancer: A bi-center randomized open-label trial.

OBJECTIVE: To study the efficacy of phosphodiesterase-5 inhibitor tadalafil in attenuating adverse events after low-dose-rate brachytherapy for prostate cancer. METHODS: This was a randomized open-label trial, conducted at two institutions. Prostate cancer patients undergoing low-dose-rate brachytherapy were randomly assigned to receive tadalafil (study group) or tamsulosin (control group). The primary endpoint was International Prostate Symptom Score for subjective evaluation of lower urinary tract symptoms. Uroflowmetry, postvoid residual urine volume, and Sexual Health Inventory for Men score were the secondary endpoints. Each clinical variable was evaluated during a follow-up period of 1 year after low-dose-rate brachytherapy. RESULTS: A total of 107 patients were enrolled in this study, with a final total of 96 patients analyzed. The mean total International Prostate Symptom Score changes at 1, 3, 6, 9, and 12 months after low-dose-rate brachytherapy were +7.4, +7.1, +4.7, +1.5, and +0.8, respectively, in the tamsulosin group, and +8.5, +9.2, +6.4, +4.1, and +1.6, respectively, in the tadalafil group. There were no statistically significant differences in International Prostate Symptom Score with the exception of the score at 9-month follow-up. Moreover, there were no statistically significant differences in any of the uroflowmetry or postvoid residual urine volume findings. The Sexual Health Inventory for Men score in the tadalafil group was significantly higher than that in the tamsulosin group at 6, 9, and 12 months after low-dose-rate brachytherapy. CONCLUSIONS: Tadalafil could be an effective option for the management of lower urinary tract symptoms after low-dose-rate brachytherapy.

Regenerative treatment for male stress urinary incontinence by periurethral injection of adipose-derived regenerative cells: Outcome of the ADRESU study.

OBJECTIVES: To report the outcome of the ADRESU study, a multicenter, single-arm, investigator-initiated clinical trial to confirm the efficacy and safety of regenerative treatment for male patients with stress urinary incontinence. METHODS: The participants were male patients with mild-to-moderate stress urinary incontinence persisting for >1 year after prostatectomy. Autologous adipose-derived regenerative cells were isolated using the Celution system from adipose tissue obtained by liposuction. Adipose-derived regenerative cells and mixture of adipose-derived regenerative cells with adipose tissue were transurethrally injected into the rhabdosphincter and submucosal space of the urethra, respectively. The primary end-point was the proportion of patients with improvement of the urine leakage volume at 52 weeks (or last visit within 52 weeks). Improvement of leakage volume was defined as a decrease from baseline >50% by the 24-h pad test. A total of 10 secondary end-points were set. RESULTS: A total of 45 patients satisfying the eligibility criteria were enrolled. The primary end-point was met; the proportion of patients with improvement in leakage volume at 52 weeks was 37.2% (95% confidence interval 23.0-53.3%). No serious adverse events with causal relationships to the adipose-derived regenerative cells were encountered. There was a progressive improvement in secondary end-points. In the King's Health Questionnaire, improvement of quality of life scores showed greater improvement in responders, as compared with non-responders. CONCLUSIONS: Findings from the ADRESU study suggest the efficacy and safety of regenerative treatment for male patients with mild-to-moderate stress urinary incontinence.

Safety and efficacy of cabazitaxel in Japanese patients with castration-resistant prostate cancer.

BACKGROUND: Several studies have reported the efficacy of cabazitaxel in cancer therapy; however, investigations of its safety are few. The aim of this study was to retrospectively analyze the efficacy and safety of cabazitaxel based on treatment outcome data. METHODS: A questionnaire form on the use of cabazitaxel was mailed to hospitals associated with the Shinshu University. Responses were received from 11 institutions regarding 55 cases. RESULTS: Patients received a median of 4 courses of cabazitaxel treatment. Decreases in prostrate-specific antigen (PSA) were observed in 61.5% of cases with declines of 30%, 50%, and 90% in 36.5%, 23.0%, and 7.6% of cases, respectively. PSA progression-free survival was 5.0 months, and overall survival after the start of cabazitaxel was 13.0 months. Forty-five patients received postcabazitaxel treatment; 17 showed decreased PSA. Safety assessment indicated that white blood cell and neutrophil counts were significantly higher in the second than in the first course of treatment and Grade 3 to 4 leukopenia and neutropenia significantly decreased. Twenty-four subjects were aged ≥75 years; 79% of them had their doses reduced at the first administration. The mean dose was 20 mg/m2. However, there was no significant difference in the PSA progression-free survival between the ≥75-year-old and <75-year-old groups. Patients in the ≥75-year-old group, particularly those whose doses were not reduced, experienced several Grade 3 to 4 adverse effects. Ten patients discontinued treatment owing to adverse effects and systemic worsening. CONCLUSIONS: To use cabazitaxel effectively, starting administration as early as possible before disease progression is important, and even if Grade 3 to 4 leukopenia and neutropenia are observed during the first course, it is important to carefully maintain the dose. Even when treating elderly patients, reducing the dose does not reduce therapeutic efficacy. However, because this cohort experienced several ≥ Grade 3 adverse effects, a great deal of caution is required.

Therapeutic effects of Choreito, a traditional Japanese (Kampo) medicine, on detrusor overactivity induced by acetic acid in rats.

Choreito (CRT), a traditional Japanese (Kampo) medicine, is widely used for the treatment of overactive bladder (OAB) and other lower urinary tract symptoms in Japan. This study aimed to identify the effects and therapeutic mechanism of CRT on the improvement of detrusor overactivity (DO) using an experimental rat model. Forty-five female Sprague-Dawley rats were equally divided into three groups: intravesical saline instillation with normal food (normal group), intravesical acetic acid (AA) instillation with normal food (AA group), and intravesical AA instillation with CRT (AA with CRT group). To induce a decrease in bladder capacity, instillation of 0.2% AA was used based on prior studies. Cystometric investigation was employed to clarify the effects of AA and CRT. Microcirculation was performed using a laser blood flowmeter, and the localization of hypoxia-inducible factor 1α (HIF1α) was assessed by immunohistochemistry. The bladder capacities of the normal, AA, and AA with CRT groups were 1.2 ± 0.3 mL, 0.4 ± 0.1 mL, and 0.8 ± 0.1 mL, respectively. CRT significantly attenuated AA irritation of the urinary bladder and exerted protective effects on basal pressure, micturition pressure, micturition interval, and micturition volume. Furthermore, CRT could prevent the excess blood flow and edematous change under the urothelium induced by intravesical AA instillation. No obvious changes in immunohistochemical HIF1α staining were observed among the groups. CRT attenuated DO induced by intravesical AA instillation in a rat experimental model. CRT might impart therapeutic effects on OAB via the mitigation of urothelial damage and regulation of excess blood flow.