Review: Lower urinary tract dysfunction in animal models of Parkinson's disease (PD): Translational aspects for the treatment of PD patients with overactive bladder.

Although the loss of dopaminergic neurons in the substantia nigra and consequent motor symptoms are the hallmarks of Parkinson's disease (PD), several non-motor symptoms may appear prior to these typical motor symptoms. While a variety of non-motor symptoms have emerged as the primary predictor of PD patients' quality of life, even though motor symptoms are undoubtedly distressing. According to a study, the prevalence of lower urinary tract symptoms (LUTS) varies between 27% and 64%, suggesting that PD-related lower urinary tract dysfunction may be affected by the disease stage, the presence of concomitant conditions affecting the lower urinary tract, and other autonomic dysfunctions. Animal models can serve as a platform for research into the causes of PD-related dysfunction and the evaluation of cutting-edge therapeutic approaches although the majority of animal research have been directed toward motor symptoms of PD. At present, the cause of lower urinary tract dysfunction in PD has not been fully clarified although the increasing evidence showing the multiple mechanisms underlying PD-related LUTS has emerged. In this chapter we summarize the findings of basic research in the studies of the lower urinary tract dysfunction using with different animal PD models and we try to shed light on the translational aspects for the development of future treatment modalities in PD patients with LUTS.

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.

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.

[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.

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.

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.

Vorticity in lower urinary tract can be assessed and associates with urinary tract morphology in men.

OBJECTIVES: The aim of this study is to develop a method to evaluate the fluid dynamics of urine flow in the lower urinary tract (LUT), especially that of vorticity. MATERIALS AND METHODS: This investigation included three sub-studies to demonstrate urine flow in the entire LUT. First, we attempted to observe vorticity generation in the urinary bladder during spontaneous voiding using transabdominal color Doppler ultrasonography (CDUS). Second, we performed transrectal CDUS to evaluate the vorticity of urine flow in the prostatic urethra. Patients with prostate cancer were enrolled before robotic surgery and divided into the vorticity and non-vorticity groups based on CDUS findings for comparisons of longitudinal urethral diameter and prostatic urethral angle. Third, the vorticity of the voided urine stream was observed using a high-speed video-camera. Micturition was done in a standing position while synchronously monitored for urine flow using uroflowmetry. RESULTS: Vorticity formation could be dynamically demonstrated in the urinary bladder and prostatic urethra using CDUS. The prostatic urethral angle of the vorticity group was more than that of the non-vorticity group. High-speed video recording could clearly capture vorticity and spiral shape generation in voided urine. The distance from the external urethral orifice to the first twist changed in accordance with urine flow rate. CONCLUSIONS: In a series of sub-studies, this investigation proved vorticity generation in the LUT and voided urine. Vorticity was detectable in the LUT and in voided urine using CDUS and a high-speed video-camera. Vorticity generation might be associated with urethral morphology.

Nicotine-induced hypoxia in rat urothelium deteriorates bladder storage functions.

AIMS: To measure the effects of nicotine on lower urinary tract symptoms (LUTS), bladder blood flow, and the urothelial markers hypoxia-inducible factor 1α (HIF1α), uroplakin III (UPIII), and aquaporin 3 (AQP3). METHODS: Ten-week-old female Sprague Dawley rats were subcutaneously injected with 2 mg/kg nicotine (n = 17) or vehicle (control, n = 18) twice daily for 13 days. Some nicotine-treated rats (n = 10) were injected daily with 1 mg/kg tadalafil for the last 6 days of nicotine treatment. One day before cystometry, the bladders of some nicotine-treated and control rats were instilled with 0.08% acetic acid. Urinary frequency and volume were measured 1 day after treatment. Blood flow in the bladder neck was measured, and the urothelia were immunochemically assayed for HIF1α, UPIII, and AQP3. RESULTS: Following acetic acid treatment, both voiding interval and micturition volume of the nicotine-treated rats were significantly lower than controls. Nicotine-treated rats had lower blood flow than controls, and the urothelial expression of HIF1α was higher than controls. Simultaneously, the expressions of UPIII and AQP3 were decreased. Tadalafil treatment increased bladder blood flow, and nicotine-treated rats had increased voiding interval and micturition volume. Further, the expression of HIF1α decreased, and both UPIII and AQP3 levels increased. CONCLUSIONS: Nicotine-treated rats stimulated by intravesicular acetic acid instillation exhibited deterioration of bladder storage functions. Changes in tissue markers in the nicotine-treated rats were consistent with hypoxia and loss of urothelial function. Restoration of blood flow reversed the nicotine effects. Nicotine may induce LUTS through reduced bladder blood flow and urothelial hypoxia.

Intestinal Injury by Heat Conduction from Surgical Sealing Devices.

BACKGROUND: There have been no investigations of intestinal injury induced by surgical sealing devices, especially focusing heat conduction from the back of active blades during laparoscopic surgery. OBJECTIVE: This study of damage to the small intestine by heat conduction from the back of active blades both physically and histopathologically was performed to establish safe usage of surgical sealing devices. MATERIALS AND METHOD: We compared seven types of bipolar sealing device and two types of ultrasonic coagulating shear in an animal model simulating laparoscopic surgery. Time-dependent changes in heat conduction from the back of active blades were measured using a direct contact thermometer during intracorporeal activation. Histopathological damage to the small intestine by the back of active blades in laparoscopic surgical application was evaluated. The backs of active blades were activated while attached to the serosa of the small intestine. The depths of histopathological changes were measured to evaluate the thermal effects of surgical sealing devices. RESULTS: Most devices generated temperatures >70°C even on the back of active blades. There were no significant differences in duration for cooling to ≤50°C among these devices. All devices induced histopathological heat damage in the submucosal layer or deeper. CONCLUSIONS: Regardless of type, the backs of active blades of surgical sealing devices conduct high temperatures and can induce heat damage in the small intestine. Surgical sealing devices should not be activated while attached to surrounding tissue or organs in laparoscopic surgery.

Recent Developments in Imaging in BPS/IC.

Purpose of review: In this review, the current literature of imaging of bladder pain syndrome and interstitial cystitis (BPS/IC) will be addressed. Topics include BPS/IC, cystoscopy, computed tomography, and magnetic resonance image (MRI). Recent findings: There are no randomized clinical trials on imaging of BPS/IC. Recently, contrast-enhanced MRI could detect the brain alterations and the changes in bladder permeability, and detection of the latter is enhanced by intravesical injection of contrast agents. Summary: MRI could advance the understanding of pathological changes in the brain and the bladder of BPS/IC patients. Especially, contrast-enhanced MRI has a potential to become a diagnostic tool although more evidences are necessary for clarifying the efficacy.

[EFFECTIVENESS OF HOCHUEKKITO (JAPANESE HERBAL MEDICINE) FOR GENERAL FATIGUE AFTER INTRODUCTION OF ENZALUTAMIDE IN THREE CASES OF CASTRATION-RESISTANT PROSTATE CANCER].

(Purpose) Enzalutamide is one of the therapeutic options for castration-resistant prostate cancer (CRPC). However, general fatigue is frequently observed in patients after introduction of enzalutamide. Here, we used the Cancer Fatigue Scale (CFS) to monitor general fatigue after introduction of enzalutamide, and administered the Japanese herbal medicine (Kampo) drug, Hochuekkito, for management of general fatigue. (Materials and methods) Three patients with CRPC were enrolled in this retrospective observational study. The patients were all male, 72, 69, and 88 years old, respectively, and had received previous hormone therapy for CRPC. They complained of general fatigue 2-5 weeks after introduction of enzalutamide. The CFS was divided into three subcategories: physical fatigue, affective fatigue, and cognitive fatigue. Hochuekkito was prescribed for management of general fatigue. Moreover, 31 previous CRPC cases treated in our hospital were divided into a general fatigue group and a non-general fatigue group. The period of enzalutamide prescription was compared among the previous groups and the present three cases to determine the usefulness of Hochuekkito. (Results) In this series, CFS was useful to monitor general fatigue after introduction of enzalutamide. General fatigue after introduction of enzalutamide mainly consisted of physical fatigue, and improved in two of the three cases included in this study. However, enzalutamide was discontinued in one patient due to general fatigue. Fourteen of our 31 previous CRPC cases developed general fatigue after introduction of enzalutamide. The mean periods of enzalutamide prescription were 265.6, 173.2, and 193.0 days in the non-general fatigue, general fatigue, and the present three cases, respectively. The differences among the groups were not significant. (Conclusions) The CFS is useful to monitor general fatigue, including its subcategories, after introduction of enzalutamide in patients with CRPC. The Kampo medicine Hochuekkito may be useful for management of general fatigue in such cases.

Morphological and clinical evaluation of prostatic urethra using modified sonourethrography with retrograde jelly injection.

OBJECTIVE: Using modified sonourethrography (mSUG) with retrograde jelly injection to precisely measure the morphological characteristics of the prostatic urethra, we assessed prostatic urethral morphology associated with clinical parameters of benign prostatic hyperplasia (BPH). METHODS: BPH patients (n = 43) and control patients with localized prostate cancer (PC; n = 57) were imaged by mSUG before surgery. Using the seminal colliculus as a landmark, prostatic urethral angulation (PUA), sagittal urethral diameter, and anterior or posterior prostatic urethral length were measured. The International Prostatic Symptoms Score (IPSS) was also evaluated in all patients. The Bladder Outlet Obstruction Index (BOOI) was measured in BPH patients that could void in a pressure-flow study. Parameters were compared between BPH and PC patients, and correlations among morphological and clinical parameters were evaluated. RESULTS: Prostatic urethras were clearly observed in all patients by mSUG. PUA, sagittal urethral diameter, and posterior urethral length were all greater in BPH than PC patients (P < .05). Among all parameters examined, PUA had the strongest correlation with IPSS (r = 0.56). Longitudinal urethral diameter showed the strongest correlation with BOOI, whereas PUA was not correlated with BOOI. CONCLUSIONS: Prostatic urethral morphology can be imaged precisely by mSUG. Morphometric measurements showed that increased PUA was strongly correlated with problematic urinary symptoms, and a flattened shape of the posterior urethra, such as extension of the sagittal urethral diameter, was correlated with urinary tract obstruction by BPH.