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HASHIMOTO Mamoru

    Department of Medicine　Lecturer in Medical School
Last Updated :2024/05/15

Researcher Information

Degree

  • Doctor of Philosophy（2024/03 Kindai University）

Research funding number

  • 60716463

J-Global ID

Research Areas

  • Life sciences / Urology

Academic & Professional Experience

  • 2013/04 - Today  Kindai UniversityFaculty of Medicine助教
  • 2022/05 - 2023/08  Department of Urology, University of Pittsburgh
  • 2011/04 - 2013/03  三重県立総合医療センター研修医

Education

  • 2005/04 - 2011/03  Mie University  Faculty of Medicine  School of Medecine

Published Papers

  • Kang Jun Cho; Mamoru Hashimoto; Sergei Karnup; Kanako Matsuoka; Tadanobu Kamijo; Joon Chul Kim; Jun Sung Koh; Naoki Yoshimura
    Neurourology and urodynamics 2024/03 
    AIMS: Activation of the endocannabinoid system by monoacylglycerol lipase (MAGL) blockade may affect the lower urinary tract function. We investigated the effect of an MAGL inhibitor, MJN110, on neurogenic lower urinary tract dysfunction (LUTD) in the mouse model of spinal cord injury (SCI). METHODS: Female C57BL/6 mice that underwent spinal cord transection at T8-10 level were divided into three groups consisting of (1) vehicle-treated SCI mice, (2) 5 mg/kg, or (3) 10 mg/kg of MJN110-treated SCI mice. MJN110 and vehicle were administered intraperitoneally for 7 days from 4 weeks after spinal cord transection. We then conducted awake cystometrograms and compared urodynamic parameters between three groups. The expression of cannabinoid (CB) receptors, TRP receptors, and inflammatory cytokines in L6-S1 dorsal root ganglia (DRG) or the bladder mucosa were evaluated and compared among three groups. Changes in the level of serum 2-arachidonoylglycerol (2-AG) and bladder MAGL were also evaluated. RESULTS: In the cystometrogram, detrusor overactivity (DO) parameters, such as the number of nonvoiding contraction (NVC), a ratio of time to the 1st NVC to intercontraction interval (ICI), and NVC integrals were improved by MJN110 treatment, and some effects were dose dependent. Although MJN110 did not improve voiding efficiency, it decreased bladder capacity, ICI, and residual urine volume compared to vehicle injection. MJN110 treatment groups had lower CB2, TRPV1, TRPA1, and inflammatory cytokines mRNA levels in DRG and bladder mucosa. Serum 2-AG was increased, and bladder MAGL was decreased after MAGL inhibitor treatment. CONCLUSIONS: MAGL inhibition improved LUTD including attenuation of DO after SCI. Thus, MAGL can be a therapeutic target for neurogenic LUTD after SCI.
  • Joonbeom Kwon; Duk Yoon Kim; Kang Jun Cho; Mamoru Hashimoto; Kanako Matsuoka; Tadanobu Kamijo; Zhou Wang; Sergei Karnup; Anne M Robertson; Pradeep Tyagi; Naoki Yoshimura
    International neurourology journal 28 (Suppl 1) 12 - 33 2024/02 
    Overactive bladder (OAB) is a symptom-based syndrome defined by urinary urgency, frequency, and nocturia with or without urge incontinence. The causative pathology is diverse; including bladder outlet obstruction (BOO), bladder ischemia, aging, metabolic syndrome, psychological stress, affective disorder, urinary microbiome, localized and systemic inflammatory responses, etc. Several hypotheses have been suggested as mechanisms of OAB generation; among them, neurogenic, myogenic, and urothelial mechanisms are well-known hypotheses. Also, a series of local signals called autonomous myogenic contraction, micromotion, or afferent noises, which can occur during bladder filling, may be induced by the leak of acetylcholine (ACh) or urothelial release of adenosine triphosphate (ATP). They can be transmitted to the central nervous system through afferent fibers to trigger coordinated urgency-related detrusor contractions. Antimuscarinics, commonly known to induce smooth muscle relaxation by competitive blockage of muscarinic receptors in the parasympathetic postganglionic nerve, have a minimal effect on detrusor contraction within therapeutic doses. In fact, they have a predominant role in preventing signals in the afferent nerve transmission process. β3-adrenergic receptor (AR) agonists inhibit afferent signals by predominant inhibition of mechanosensitive Aδ-fibers in the normal bladder. However, in pathologic conditions such as spinal cord injury, it seems to inhibit capsaicin-sensitive C-fibers. Particularly, mirabegron, a β3-agonist, prevents ACh release in the BOO-induced detrusor overactivity model by parasympathetic prejunctional mechanisms. A recent study also revealed that vibegron may have 2 mechanisms of action: inhibition of ACh from cholinergic efferent nerves in the detrusor and afferent inhibition via urothelial β3-AR.
  • Yasunori Akashi; Yutaka Yamamoto; Mamoru Hashimoto; Shogo Adomi; Kazutoshi Fujita; Keisuke Kiba; Takafumi Minami; Kazuhiro Yoshimura; Akihide Hirayama; Hirotsugu Uemura
    Cancers 15 (24) 2023/12 
    INTRODUCTION: Immune checkpoint inhibitor (ICI) therapy has significantly improved the prognosis of some patients with advanced urothelial carcinoma (UC), but it does not provide high therapeutic efficacy in all patients. Therefore, identifying predictive biomarkers is crucial in determining which patients are candidates for ICI treatment. This study aimed to identify the predictors of ICI treatment response in patients with platinum-refractory advanced UC treated with pembrolizumab. METHODS: Patients with platinum-refractory advanced UC who had received pembrolizumab at two hospitals in Japan were included. Univariate and multivariate analyses were performed to identify biomarkers for progression-free survival (PFS) and overall survival (OS). RESULTS: Forty-one patients were evaluable for this analysis. Their median age was 75 years, and the vast majority of the patients were male (85.4%). The objective response rate was 29.3%, with a median overall survival (OS) of 17.8 months. On multivariate analysis, an Eastern Cooperative Oncology Group performance status (ECOG-PS) ≥ 2 (HR = 6.33, p = 0.03) and a baseline neutrophil-to-lymphocyte ratio (NLR) > 3 (HR = 2.79, p = 0.04) were significantly associated with poor OS. Antibiotic exposure did not have a significant impact on either PFS or OS. CONCLUSIONS: ECOG-PS ≥ 2 and baseline NLR > 3 were independent risk factors for OS in patients with platinum-refractory advanced UC treated with pembrolizumab. Antibiotic exposure was not a predictor of ICI treatment response.
  • Eisuke Tomiyama; Kazutoshi Fujita; Mamoru Hashimoto; Hirotsugu Uemura; Norio Nonomura
    International journal of urology : official journal of the Japanese Urological Association 2023/11 
    Bladder cancer is a common urological cancer with a high recurrence rate that requires long-term follow-up, and early detection positively affects prognosis. To date, the initial diagnosis and follow-up for bladder cancer rely on cystoscopy, which is an invasive and expensive procedure. Therefore, urinary markers for the detection of bladder cancer have attracted research attention for decades to reduce unnecessary cystoscopies. Urine, which is in continuous contact with bladder cancer, is considered a suitable fluid for providing tumor information. Urinary cytology is the only widely used urinary marker in clinical practice; however, it has poor sensitivity for low-grade tumors; indicating the need for novel urinary markers. Considerable research has been conducted on this topic over the years, resulting in a complex landscape with a wide range of urinary markers, including protein-, exfoliated cell-, RNA-, DNA-, and extracellular vesicle-based markers. Although some of these markers have been approved by the U.S. Food and Drug Administration and are commercially available, their use in clinical practice is limited. To facilitate clinical application, potential urinary markers must withstand prospective clinical trials and be easy for patients and clinicians to understand and utilize in a clinical context. This review provides a comprehensive overview of currently available and recently reported promising urinary markers for bladder cancer. Additionally, the challenges and the prospects of these urinary markers for clinical implementation in bladder cancer treatment were discussed.
  • Mamoru Hashimoto; Sergei Karnup; Stephanie L Daugherty; Kang Jun Cho; Eri Banno; Nobutaka Shimizu; Kazutoshi Fujita; Akihide Hirayama; Hirotsugu Uemura; William C de Groat; Jonathan M Beckel; Naoki Yoshimura
    Neurourology and urodynamics 2023/11 
    OBJECTIVES: We examined sex differences of lower urinary tract function and molecular mechanisms in mice with and without spinal cord injury (SCI). METHODS: SCI was induced by Th8-9 spinal cord transection in male and female mice. We evaluated cystometrograms (CMG) and electromyography (EMG) of external urethral sphincter (EUS) at 6 weeks after SCI in spinal intact (SI) and SCI mice. The mRNA levels of Piezo2 and TRPV1 were measured in L6-S1 dorsal root ganglia (DRG). Protein levels of nerve growth factor (NGF) in the bladder mucosa was evaluated using an enzyme-linked immunosorbent assay. RESULTS: Sex differences were found in the EUS behavior during voiding as voiding events in female mice with or without SCI occurred during EUS relaxation periods without EUS bursting activity whereas male mice with or without SCI urinated during EUS bursting activity in EMG recordings. In both sexes, SCI decreased voiding efficiency along with increased tonic EUS activities evident as reduced EUS relaxation time in females and longer active periods of EUS bursting activity in males. mRNA levels of Piezo2 and TRPV1 of DRG in male and female SCI mice were significantly upregulated compared with SI mice. NGF in the bladder mucosa showed a significant increase in male and female SCI mice compared with SI mice. However, there were no significant differences in Piezo2 or TRPV1 levels in DRG or NGF protein levels in the bladder mucosa between male and female SCI mice. CONCLUSIONS: We demonstrated that female and male mice voided during EUS relaxation and EUS bursting activity, respectively. Also, upregulation of TRPV1 and Piezo2 in L6-S1 DRG and NGF in the bladder could be involved in SCI-induced lower urinary tract dysfunction in both sexes of mice.
  • Nobutaka Shimizu; Tetsuichi Saito; Naoki Wada; Mamoru Hashimoto; Takahiro Shimizu; Joonbeom Kwon; Kang Jun Cho; Motoaki Saito; Sergei Karnup; William C. de Groat; Naoki Yoshimura
    International Journal of Molecular Sciences MDPI AG 24 (9) 7885 - 7885 2023/04 
    This article provides a synopsis of current progress made in fundamental studies of lower urinary tract dysfunction (LUTD) after spinal cord injury (SCI) above the sacral level. Animal models of SCI allowed us to examine the effects of SCI on the micturition control and the underlying neurophysiological processes of SCI-induced LUTD. Urine storage and elimination are the two primary functions of the LUT, which are governed by complicated regulatory mechanisms in the central and peripheral nervous systems. These neural systems control the action of two functional units in the LUT: the urinary bladder and an outlet consisting of the bladder neck, urethral sphincters, and pelvic-floor striated muscles. During the storage phase, the outlet is closed, and the bladder is inactive to maintain a low intravenous pressure and continence. In contrast, during the voiding phase, the outlet relaxes, and the bladder contracts to facilitate adequate urine flow and bladder emptying. SCI disrupts the normal reflex circuits that regulate co-ordinated bladder and urethral sphincter function, leading to involuntary and inefficient voiding. Following SCI, a spinal micturition reflex pathway develops to induce an overactive bladder condition following the initial areflexic phase. In addition, without proper bladder–urethral-sphincter coordination after SCI, the bladder is not emptied as effectively as in the normal condition. Previous studies using animal models of SCI have shown that hyperexcitability of C-fiber bladder afferent pathways is a fundamental pathophysiological mechanism, inducing neurogenic LUTD, especially detrusor overactivity during the storage phase. SCI also induces neurogenic LUTD during the voiding phase, known as detrusor sphincter dyssynergia, likely due to hyperexcitability of Aδ-fiber bladder afferent pathways rather than C-fiber afferents. The molecular mechanisms underlying SCI-induced LUTD are multifactorial; previous studies have identified significant changes in the expression of various molecules in the peripheral organs and afferent nerves projecting to the spinal cord, including growth factors, ion channels, receptors and neurotransmitters. These findings in animal models of SCI and neurogenic LUTD should increase our understanding of pathophysiological mechanisms of LUTD after SCI for the future development of novel therapies for SCI patients with LUTD.
  • Takafumi Minami; Kazutoshi Fujita; Mamoru Hashimoto; Mitsuhisa Nishimoto; Shogo Adomi; Eri Banno; Masahiro Nozawa; Kazuhiro Nose; Kazuhiro Yoshimura; Masahiro Inada; Masaki Yokokawa; Kiyoshi Nakamatsu; Hirotsugu Uemura
    World journal of urology 2023/04 
    PURPOSE: To investigate the risk of bladder cancer (BCa) in patients treated with brachytherapy for prostate cancer (PCa). METHODS: We retrospectively analyzed 583 patients with PCa who underwent brachytherapy with or without external beam radiotherapy (EBRT). We analyzed the disease-free survival (DFS) of BCa in patients with PCa who underwent brachytherapy with or without EBRT. We performed multivariate Cox regression analyses of DFS using age, EBRT, and Brinkman index (BI) score (number of cigarettes smoked per day × number of years smoking) ≥ 200 as variables for BCa after brachytherapy. RESULTS: Fourteen patients (2.4%) developed BCa after brachytherapy with or without EBRT. The percentage of high-grade urothelial carcinoma (UC) was 63.6%. A total of 85.7% of patients had non-muscle invasive BCa, and 14.3% of patients had muscle invasive BCa. DFS was longer in brachytherapy monotherapy than in combination therapy (brachytherapy + EBRT). Multivariate Cox regression analysis showed that a BI score ≥ 200 (Hazard Ratio (HR 8.61; 95% Confidence Interval (CI) 1.12-65.98) and EBRT combination (HR 3.29; 95% CI 1.03-10.52) were significantly associated with BCa development in patients with PCa treated with brachytherapy. Furthermore, patients with BI score ≥ 200 and EBRT combination had a significantly higher risk of BCa compared with patients with BI score < 200 (HR Log-rank test P = 0.010). CONCLUSION: Most cases of BCa after brachytherapy with or without EBRT are high grade and invasive. We hypothesized that the EBRT combination might be a risk factor for BCa in patients with PCa who underwent brachytherapy.
  • Anirban Ganguly; Shachi Tyagi; Christopher Chermansky; Anthony Kanai; Jonathan Beckel; Mamoru Hashimoto; Kang Jun Cho; Michael Chancellor; Jonathan Kaufman; Naoki Yoshimura; Pradeep Tyagi
    Drugs & aging 2023/03 
    This article provides an overview of the diagnosis and the treatment of lower urinary tract symptoms in older adults complicated by the neurodegenerative changes in the micturition reflex and further confounded by age-related decline in hepatic and renal clearance raising the propensity of adverse drug reactions. The first-line drug treatment for lower urinary tract symptoms, orally administered antimuscarinics, fails to reach the equilibrium dissociation constant of muscarinic receptors even at their maximum plasma concentration and tends to evoke a half-maximal response at a muscarinic receptor occupancy of just 0.206% in the bladder with a minimal difference from exocrine glands, which raises the adverse drug reaction risk. On the contrary, intravesical antimuscarinics are instilled at concentrations 1000-fold higher than the oral maximum plasma concentration and the equilibrium dissociation constant erects a downhill concentration gradient that drives passive diffusion and achieves a mucosal concentration around ten-fold lower than the instilled concentration for a long-lasting occupation of muscarinic receptors in mucosa and sensory nerves. A high local concentration of antimuscarinics in the bladder triggers alternative mechanisms of action and is supposed to engage retrograde transport to nerve cell bodies for neuroplastic changes that underlie a long-lasting therapeutic effect, while an intrinsically lower systemic uptake of the intravesical route lowers the muscarinic receptor occupancy of exocrine glands to lower the adverse drug reaction relative to the oral route. Thus, the traditional pharmacokinetics and pharmacodynamics of oral treatment are upended by intravesical antimuscarinics to generate a dramatic improvement (~ 76%) noted in a meta-analysis of studies enrolling children with neurogenic lower urinary tract symptoms on the primary endpoint of maximum cystometric bladder capacity as well as the secondary endpoints of filling compliance and uninhibited detrusor contractions. The therapeutic success of intravesical multidose oxybutynin solution or oxybutynin entrapped in the polymer for sustained release in the pediatric population bodes well for patients with lower urinary tract symptoms at the other extreme of the age spectrum. Though generally used to predict oral drug absorption, Lipinski's rule of five can also explain the ten-fold lower systemic uptake from the bladder of positively charged trospium over oxybutynin, a tertiary amine. Chemodenervation by an intradetrusor injection of onabotulinumtoxinA is merited for patients with idiopathic overactive bladder discontinuing oral treatment because of a lack of efficacy. However, age-related peripheral neurodegeneration potentiates the adverse drug reaction risk of urinary retention that motivates the quest of liquid instillation, delivering larger fraction of onabotulinumtoxinA to the mucosa as opposed to muscle by an intradetrusor injection can also probe the neurogenic and myogenic predominance of idiopathic overactive bladder. Overall, the treatment paradigm of lower urinary tract symptoms in older adults should be tailored to individual's overall health status and the risk tolerance for adverse drug reactions.
  • Mamoru Hashimoto; Kazutoshi Fujita; Eisuke Tomiyama; Saizo Fujimoto; Shogo Adomi; Eri Banno; Takafumi Minami; Tetsuya Takao; Masahiro Nozawa; Hiroaki Fushimi; Kazuhiro Yoshimura; Norio Nonomura; Hirotsugu Uemura
    Anticancer research 43 (1) 167 - 174 2023/01 
    BACKGROUND/AIM: Upper urinary tract urothelial carcinoma (UTUC) is a rare disease, often discovered at an advanced stage at diagnosis. Nectin-4 is expressed in a broad range of patients with UTUC and is associated with poor progression-free survival. The receptors of the erythroblastosis oncogene B (ErbB) family are potential therapeutic targets for urothelial carcinoma. Herein, we aimed to investigate the relationship of nectin-4 and ErbB family receptors, namely epidermal growth factor receptor (EGFR) and human epidermal growth factor receptor 2 (HER2) in patients with UTUC. Targeted therapies for these receptors could be used in sequence or in combination for increasing treatment efficiency. PATIENTS AND METHODS: We performed immunohisto-chemical analysis for HER2, EGFR, and nectin-4 using tissue microarrays. A total of 98 UTUC patients were included in the study. We investigated the impact of EGFR and HER2 expression status on recurrence-free survival (RFS) and cancer-specific survival (CSS) of all patients. RESULTS: The percentages of patients positive for HER2, EGFR, and nectin-4 were 97%, 70%, and 65%, respectively. The co-expression rates of HER2-EGFR, HER2-nectin-4, and EGFR-nectin-4 were 69%, 64%, and 47%, respectively. The number of patients positive for all three receptors was 47%. Higher HER2 levels were significantly associated with worse CSS and RFS. Higher EGFR levels were associated with a worse CSS. CONCLUSION: HER2, EGFR, and nectin-4 were highly expressed in UTUC. Combination of HER2-, EGFR-, and nectin-4-targeted therapy may be an effective option for the treatment of patients with UTUC.
  • Mamoru Hashimoto; Nobutaka Shimizu; Saizo Fujimoto; Ken Kuwahara; Mitsuhisa Nishimoto; Shogo Adomi; Eri Banno; Takafumi Minami; Kazutoshi Fujita; Kazuhiro Yoshimura; Akihide Hirayama; Hirotsugu Uemura
    International urology and nephrology 2022/09 
    PURPOSE: In this study, we aimed to elucidate the pathophysiology of post-micturition dribble (PMD) through analyzing several variables including pressure flow study (PFS) findings and symptoms questionnaire. METHODS: We retrospectively analyzed male patients who visited our department between 2010 and 2020. We used modified international prostate symptom score (m-IPSS), which consists of eight sub-score related to lower urinary tract symptoms (Incomplete Emptying, Frequency, Intermittency, Urgency, Weak Stream, Straining, Nocturia, and PMD) and one question related to quality of life (QOL). Multivariate regression analysis was conducted to evaluate the relationship between PMD and the variables, including age, prostate volume (PV), body mass index, bladder outlet obstruction index (BOOI), bladder contractility index, and bladder voiding efficiency, which were obtained by PFS. RESULTS: A total of 143 male patients were analyzed. The patients with PMD showed significantly larger PV and higher BOOI, and worse IPSS total and QOL score than those without PMD. Multivariate regression analysis showed that large PV and BOOI were significantly associated with PMD. In Spearman's correlation analysis, PMD and each m-IPSS sub-score except nocturia had significant positive correlation. Furthermore, Spearman's correlation analysis showed that PMD and QOL had significant strong positive correlation. CONCLUSION: PMD was significantly associated with large PV and BOO evaluated by PFS. Furthermore, PMD significantly exacerbated QOL. The severity of PMD and the other m-IPSS sub-score except nocturia could have intercorrelation with each other.
  • Saizo Fujmoto; Kazutoshi Fujita; Mitsuhisa Nishimoto; Mamoru Hamaguchi; Ken Kuwahara; Mamoru Hashimoto; Shogo Adomi; Takafumi Minami; Masahiro Nozawa; Kazuhiro Yoshimura; Hirotsugu Uemura
    Cancer medicine 2022/08 
    Enzalutamide, apalutamide, and darolutamide are currently recommended for patients with non-metastatic castration-resistant prostate cancer (nmCRPC), but cross-resistance of androgen receptor-axis-targeted therapies (ARAT) occurs. Because darolutamide has a distinct chemical structure to other non-steroidal antiandrogens, it may be effective for nmCRPC patients resistant to enzalutamide or apalutamide. We retrospectively evaluated the efficacy of switching to darolutamide in patients with nmCRPC. We included nine nmCRPC patients who experienced biochemical progression on enzalutamide or apalutamide and were switched over to darolutamide. Five patients (55.5%) had a PSA response >50% decline after starting darolutamide, with an average of 73% PSA decline. Median progression-free survival was 6 months. In conclusion, an ARAT switch from enzalutamide or apalutamide to darolutamide might be effective for nmCRPC. Although the validation in a large-scale cohort is necessary, the switch to darolutamide could be a promising therapeutic option after the progression of 1st line ARAT in nmCRPC patients.
  • Mitsuhisa Nishimoto; Kazutoshi Fujita; Yutaka Yamamoto; Mamoru Hashimoto; Shogo Adomi; Eri Banno; Yoshitaka Saito; Nobutaka Shimizu; Yasunori Mori; Takafumi Minami; Masahiro Nozawa; Kazuhiro Nose; Akihide Hirayama; Kazuhiro Yoshimura; Hirotsugu Uemura
    Translational cancer research 11 (8) 2681 - 2687 2022/08 
    Background: Several therapeutic agents are available for metastatic castration-resistant prostate cancer (CRPC). However, prognosis is still not well developed. The Gleason score (GS) is a prognostic factor available for patients with metastatic CRPC. GSs ranging from 6 to 10 and GSs ≥8 are usually categorized as single prognostic factors. In this study, we evaluated the prognosis of high-GS metastatic CRPC in Japanese men. Methods: Overall, 105 patients with metastatic CRPC with a GS ≥8 were retrospectively analyzed. Multivariate analyses of patient age, GS, and Eastern Cooperative Oncology Group performance status (ECOG-PS) were performed using Cox proportional hazards analysis to predict overall survival (OS). Results: GS 8 had all Gleason patterns of 4+4. Thirty patients (28.6%) had GS of 8, and 75 (71.4%) had GS of 9 or 10. As a first-line treatment for metastatic CRPC, 42 patients (40%) received abiraterone, 35 (33.3%) received enzalutamide, and 26 (24.8%) received docetaxel. The 5-year OS in patients with GS of 8 was 65.0% [95% confidence interval (CI): 43.07-86.82%], while the 5-year OS in patients with GS of 9 or 10 was 37.0% (95% CI: 24.41-56.11%). There was a significant difference in OS between the GS 8 and GS 9-10 groups (log-rank test, P=0.038). Multivariate analysis showed that GS and ECOG-PS were significant prognostic factors for OS. Conclusions: Patients with metastatic CRPC with GS 9-10 had poor prognoses, suggesting the need for additional treatment options.
  • Eisuke Tomiyama; Kazutoshi Fujita; Kyosuke Matsuzaki; Ryohei Narumi; Akinaru Yamamoto; Toshihiro Uemura; Gaku Yamamichi; Yoko Koh; Makoto Matsushita; Yujiro Hayashi; Mamoru Hashimoto; Eri Banno; Taigo Kato; Koji Hatano; Atsunari Kawashima; Motohide Uemura; Ryo Ukekawa; Tetsuya Takao; Shingo Takada; Hirotsugu Uemura; Jun Adachi; Takeshi Tomonaga; Norio Nonomura
    British journal of cancer 127 (7) 1312 - 1323 2022/07 
    BACKGROUND: Urinary extracellular vesicles (uEVs) secreted from bladder cancer contain cancer-specific proteins that are potential diagnostic biomarkers. We identified and evaluated a uEV-based protein biomarker for bladder cancer diagnosis and analysed its functions. METHODS: Biomarker candidates, selected by shotgun proteomics, were validated using targeted proteomics of uEVs obtained from 49 patients with and 48 individuals without bladder cancer, including patients with non-malignant haematuria. We developed an enzyme-linked immunosorbent assay (ELISA) for quantifying the uEV protein biomarker without ultracentrifugation and evaluated urine samples from 36 patients with and 36 patients without bladder cancer. RESULTS: Thirteen membrane proteins were significantly upregulated in the uEVs from patients with bladder cancer in shotgun proteomics. Among them, eight proteins were validated by target proteomics, and Ephrin type-A receptor 2 (EphA2) was the only protein significantly upregulated in the uEVs of patients with bladder cancer, compared with that of patients with non-malignant haematuria. The EV-EphA2-CD9 ELISA demonstrated good diagnostic performance (sensitivity: 61.1%, specificity: 97.2%). We showed that EphA2 promotes proliferation, invasion and migration and EV-EphA2 promotes the invasion and migration of bladder cancer cells. CONCLUSIONS: We established EV-EphA2-CD9 ELISA for uEV-EphA2 detection for the non-invasive early clinical diagnosis of bladder cancer.
  • Kazutoshi Fujita; Koji Hatano; Mamoru Hashimoto; Eisuke Tomiyama; Eiji Miyoshi; Norio Nonomura; Hirotsugu Uemura
    International journal of molecular sciences 22 (24) 2021/12 
    Fucosylation is an oligosaccharide modification that plays an important role in immune response and malignancy, and specific fucosyltransferases (FUTs) catalyze the three types of fucosylations: core-type, Lewis type, and H type. FUTs regulate cancer proliferation, invasiveness, and resistance to chemotherapy by modifying the glycosylation of signaling receptors. Oligosaccharides on PD-1/PD-L1 proteins are specifically fucosylated, leading to functional modifications. Expression of FUTs is upregulated in renal cell carcinoma, bladder cancer, and prostate cancer. Aberrant fucosylation in prostate-specific antigen (PSA) could be used as a novel biomarker for prostate cancer. Furthermore, elucidation of the biological function of fucosylation could result in the development of novel therapeutic targets. Further studies are needed in the field of fucosylation glycobiology in urological malignancies.
  • Eisuke Tomiyama; Kazutoshi Fujita; Mamoru Hashimoto; Hiroshi Miyamoto; George J Netto; Norio Nonomura
    International journal of urology : official journal of the Japanese Urological Association 29 (1) 89 - 90 2021/09
  • Mamoru Hashimoto; Takahito Nakayama; Saizo Fujimoto; Shunsuke Inoguchi; Mitsuhisa Nishimoto; Takashi Kikuchi; Shogo Adomi; Eri Banno; Marco A. De Velasco; Yoshitaka Saito; Nobutaka Shimizu; Yasunori Mori; Takafumi Minami; Kazutoshi Fujita; Masahiro Nozawa; Kazuhiro Nose; Kazuhiro Yoshimura; Hirotsugu Uemura
    Anti-Cancer Drugs Ovid Technologies (Wolters Kluwer Health) Publish Ahead of Print (1) e818-e821  0959-4973 2021/08 
    Recently, combination therapy including immune checkpoint inhibition (ICI) has proven to be effective as first-line therapy for patients with metastatic renal cell carcinoma. Although the first-line combination therapies with ICI have shown clinical benefit, a number of patients require second-line treatment. We report a 60-year-old man with metastatic renal cell carcinoma who was treated with pazopanib soon after nivolumab plus ipilimumab combination therapy. He experienced Grade 3 disseminated intravascular coagulation (DIC). We suspect that this was caused by an interaction between pazopanib and nivolumab even though ICI therapy was discontinued. He was treated with thrombomodulin and platelet transfusion and recovered from DIC. Treatment with pazopanib was subsequently restarted. No evidence of DIC was observed thereafter. This severe adverse reaction may have been induced by an interaction between activated proinflammatory immune cells and cytokines from an exacerbated inflammatory state and pazopanib. This report highlights the need to perform careful monitoring of patients who receive molecular targeted therapy after ICI-based immunotherapy.
  • Mamoru Hashimoto; Nobutaka Shimizu; Mitsuhisa Nishimoto; Takafumi Minami; Kazutoshi Fujita; Kazuhiro Yoshimura; Akihide Hirayama; Hirotsugu Uemura
    Research and Reports in Urology 2021 (13) 557 - 563 2021/08 [Refereed]
     
    Purpose: This study aimed to elucidate the relationship of psoas muscle atrophy and visceral obesity with lower urinary tract symptoms in geriatric female patients. Patients and Methods: We retrospectively reviewed the medical records of female patients aged ≥65 years. The psoas muscle index was defined, using computed tomography, as the cross-sectional area of the psoas muscle at the third lumbar vertebral level divided by the body surface area. We also measured visceral fat area at the umbilical level using computed tomography. We used logistic regression analysis to examine the relationships between the International Prostate Symptom Score (total score, voiding subscore, and storage subscore) and variables, such as age, body mass index, psoas muscle index, and visceral fat area. The International Prostate Symptom Score was categorized as mild, moderate, or severe. Results: One hundred thirty-nine patients were included in our study. In the logistic regression analysis, we found statistically significant relationships between severe (versus mild-to-moderate) International Prostate Symptom Score storage subscore and variables, including low and high levels of psoas muscle index and visceral fat area, respectively. We could not find any significant relationships between the International Prostate Symptom Score total score and voiding subscore and the variables. Conclusion: Psoas muscle atrophy and visceral fat accumulation are potential risk factors for severe storage symptoms in female patients aged ≥65 years.
  • Nobutaka Shimizu; Daisuke Gotoh; Mitsuhisa Nishimoto; Mamoru Hashimoto; Tetsuichi Saito; Kazutoshi Fujita; Akihide Hirayama; Naoki Yoshimura; Hirotsugu Uemura
    International journal of urology : official journal of the Japanese Urological Association 28 (10) 1068 - 1072 2021/07 
    OBJECTIVES: To investigate the effect of vibegron, a new clinically approved β3-adrenoceptor agonist in lower urinary tract dysfunction in mice with spinal cord injury. METHODS: Investigators performed cystometry under awake conditions in 4-week spinal cord injury female mice. Two weeks after spinal cord injury, saline or vibegron (30 mg/kg) was orally administered for 2 weeks prior to the urodynamic study. Investigators removed L6-S1 dorsal root ganglia from the saline- or vibegron-treated spinal cord injury mice as well as from saline-treated normal (spinal intact) mice to evaluate the levels of transient receptor potential cation channel subfamily V member 1, transient receptor potential cation channel subfamily A member 1, activating transcription factor 3, and inducible nitric oxide synthase transcripts using real-time polymerase chain reaction. RESULTS: In vibegron-treated spinal cord injury mice, nonvoiding contractions during bladder filling, which were increased in spinal cord injury compared to spinal intact mice, were significantly decreased. Micturition pressure or voiding efficiency was not significantly increased in comparison to measurements in saline-treated spinal cord injury mice. The expression of transient receptor potential cation channel subfamily V member 1, transient receptor potential cation channel subfamily A member 1, activating transcription factor 3, and inducible nitric oxide synthase messenger RNA was increased in spinal cord injury mice compared to spinal intact mice, but significantly decreased after vibegron treatment. CONCLUSIONS: Vibegron improves spinal cord injury-induced detrusor overactivity in addition to significantly reducing C-fiber afferent receptors such as transient receptor potential cation channel subfamily V member 1, transient receptor potential cation channel subfamily A member 1, and inflammatory cytokines/markers, such as activating transcription factor 3 and inducible nitric oxide synthase, in spinal cord injury mice. Thus, vibegron might be effective in the treatment of storage lower urinary tract dysfunction induced by C-fiber afferent activation after spinal cord injury.
  • Remon Kunishige; Takayuki Ozeki; Mamoru Hamaguchi; Shingo Toyoda; Mamoru Hashimoto; Takashi Kikuchi; Mitsuhisa Nishimoto; Nobutaka Shimizu; Yasunori Mori; Takafumi Minami; Masahiro Nozawa; Kazuhiro Nose; Kazuhiro Yoshimura; Hirotsugu Uemura
    Hinyokika kiyo. Acta urologica Japonica 67 (2) 63 - 66 2021/02 
    A 67-year-old man underwent open radical left nephrectomy for left renal cell carcinoma [pT4N0M1 (right lower lobe of lung)] and thoracoscopic partial right lung resection for lung metastasis. The patient subsequently developed a solitary lung metastasis at 10 months and then at 26 months postoperatively. He underwent partial lung resection on each occasion. During the 28 months postoperatively, he was found to have a 12 mm middle mediastinal lymph node metastasis and a 30 mm splenic metastasis, which gradually increased in size. Three months after discovery, sunitinib was initiated at 37.5 mg 2 weeks on/1 week off. Twelve days later, the patient presented with complaints of fever. A gas-producing splenic abscess was diagnosed and he was admitted on the same day. His condition improved with antibiotics and splenic drainage. On day 35 of hospitalization, he underwent laparoscopic splenectomy. The patient's postoperative clinical course was uneventful and he was discharged 7 days after the surgery.
  • Eisuke Tomiyama; Kazutoshi Fujita; Mamoru Hashimoto; Shogo Adomi; Atsunari Kawashima; Takafumi Minami; Kazuhiro Yoshimura; Hirotsugu Uemura; Norio Nonomura
    Translational Andrology and Urology AME Publishing Company 11 (12) 1747 - 1761 2223-4683 2021/01 
    BACKGROUND AND OBJECTIVE: Although upper tract urothelial carcinoma (UTUC) shares the histological appearance of urinary bladder cancer (UBC), molecular studies suggest that UTUC and UBC represent two distinct disease entities. However, treatment approaches for UTUC are virtually extrapolated from the evidence on UBC. As targeted drugs-immune-checkpoint inhibitors, fibroblast growth factor receptor inhibitors, and antibody-drug conjugates-target specific molecules, gaining more knowledge about the target-molecular profiles of each drug can help formulate optimal treatment strategies for UTUC. METHODS: This narrative review summarized the subgroup analyses of clinical trials of FDA-approved targeted drugs to explore the differential effects of each targeted drug when administered for UTUC compared to UBC. We focused on the differences in mutation frequency, RNA expression subtype, and therapeutic target protein expressions (specifically PD-L1, Nectin-4, and Trop-2) between UTUC and UBC and discussed their relationship with the efficacy of each targeted drug. KEY CONTENT AND FINDINGS: A clinical trial of nivolumab in an adjuvant setting (CheckMate 274) implied that immune-checkpoint inhibitors might be less efficacious in UTUC than in UBC. Genomic and transcriptomic studies suggest that UTUC has a high frequency of FGFR3 mutations and predominantly shows the luminal papillary subtype, which is immunologically cold with low T-cell infiltration. These findings are consistent with a possible lower response rate to immunotherapy in UTUC than that in UBC. Clinical trials of enfortumab vedotin in a third-line setting (EV201 and EV301) implied that enfortumab vedotin might be less efficacious in UTUC than in UBC. Previous immunohistochemical analyses suggest that UTUC might have a slightly lower rate of Nectin-4 positivity than UBC, indicating that enfortumab vedotin was less efficacious in UTUC than in UBC. CONCLUSIONS: Clinical differences in the effects of targeted drugs for UTUC and UBC may highlight the molecular differences between these diseases. The treatment strategy should be optimized based on further investigation of the molecular characteristics of UTUC.
  • Mamoru Hashimoto; Kazutoshi Fujita; Takahito Nakayama; Saizo Fujimoto; Mamoru Hamaguchi; Mitsuhisa Nishimoto; Takashi Kikuchi; Shogo Adomi; Eri Banno; Marco A. De Velasco; Yoshitaka Saito; Nobutaka Shimizu; Yasunori Mori; Takafumi Minami; Masahiro Nozawa; Kazuhiro Nose; Kazuhiro Yoshimura; Hirotsugu Uemura
    Translational Andrology and Urology AME Publishing Company 10 (7) 2838 - 2847 2223-4683 2021/01 [Refereed]
     
    Background: Inflammatory cytokines and immature myeloid derived suppressor cells (MDSCs), which increase during cancer progression, could lead to a neutrophil increase and lymphocyte reduction. Thus, the neutrophil-lymphocyte ratio (NLR) was used to predict survival of patients suffering from urological cancers including upper urinary tract carcinoma. We further determined whether the NLR during the first cycle of first-line chemotherapy could predict cancer specific survival. Methods: We recruited patients with locally advanced or metastatic upper urinary tract urothelial carcinoma (UTUC) who received chemotherapy between January 2014 and July 2019. We investigated the impact of various clinical variables, including age, sex, performance status, and estimated creatinine clearance (CCr), and NLR before and after the first cycle of the first-line chemotherapy on prognosis. Results: A total of 41 patients were included in our study. Cancer specific survival of the patients with lower NLR was significantly better than that of the patients with higher NLR measured after the first cycle of the first-line chemotherapy (log-rank test P=0.005, median 29.2 vs. 11.9 months, respectively). Cox proportional regression analysis showed that higher NLR after the first cycle of the first-line chemotherapy was a significant predictor of cancer specific survival. Conclusions: The NLR after the first cycle of the first-line chemotherapy could be an indication for patients with locally advanced or metastatic UTUC to maintain their first-line chemotherapy treatment.
  • Nobutaka Shimizu; Naoki Wada; Takahiro Shimizu; Takahisa Suzuki; Masahiro Kurobe; Anthony J Kanai; William C de Groat; Mamoru Hashimoto; Akihide Hirayama; Hirotsugu Uemura; Naoki Yoshimura
    Neurourology and urodynamics 39 (1) 108 - 115 0733-2467 2020/01 [Refereed]
     
    AIM: To investigate the role of p38 MAP kinase in lower urinary tract dysfunction in mice with spinal cord injury (SCI). METHODS: Cystometry and external urethral sphincter-electromyography were performed under an awake condition in 4-week SCI female mice. Two weeks after SCI, a catheter connected to an osmotic pump filled with a p38 mitogen-activated protein kinase (MAPK) inhibitor or artificial cerebrospinal fluid (CSF) was implanted into the intrathecal space of L6-S1 spinal cord for continuous intrathecal instillation at infusion rate of 0.51 μL/h for 2 weeks before the urodynamic study. L6 dorsal root ganglia were then removed from CSF and p38 MAPK inhibitor-treated SCI mice as well as from CSF-treated normal (spinal intact) mice to evaluate the levels of transient receptor potential cation channel subfamily V member 1 (TRPV1), tumor necrosis factor-α (TNF-α), and inducible nitric oxide synthase (iNOS) transcripts by real-time polymerase chain reaction. RESULTS: In p38 MAPK inhibitor-treated SCI mice, nonvoiding contractions during bladder filling, bladder capacity, and post-void residual volume were significantly reduced while micturition pressure and voiding efficiency were significantly increased in comparison to these measurements in CSF-treated SCI mice. The expression of TRPV1, TNF-α, and iNOS messenger RNA was increased in SCI mice compared with expression in spinal intact mice and significantly decreased after p38 MAPK inhibitor treatment. CONCLUSIONS: The p38 MAPK signaling pathway in bladder sensory neurons or in the spinal cord plays an important role in storage and voiding problems such as detrusor overactivity and inefficient voiding after SCI.
  • Mamoru Hashimoto; Takafumi Minami; Mamoru Hamaguchi; Saizo Fujimoto; Tomoki Takahashi; Takashi Kikuchi; Shogo Adomi; Eri Banno; Takayuki Ohzeki; Nobutaka Shimizu; Yasunori Mori; Masahiro Nozawa; Kazuhiro Nose; Kazuhiro Yoshimura; Hirotsugu Uemura
    Medicine 98 (51) e18436  0025-7974 2019/12 [Refereed]
     
    RATIONALE: Latent tuberculosis infection (LTBI) describes the dormant state of tuberculosis (TB), in which persistent immune-related interaction between TB and T-cells maintain its state. Cabazitaxel (CBZ) is reported to improve overall survival in patients with castration-resistant prostate cancer (CRPC) after progression observed in regimens including docetaxel. CBZ is known for severe myelosuppression; however there is no recommendation for the treatment of LTBI before CBZ treatment. To the authors' knowledge, this is the first report to describe reactivation of LTBI induced by CBZ. PATIENT CONCERNS: A 75-year-old Japanese male with a medical history of TB since 16 years of age had been treated for prostate cancer (PC) (initial prostate-specific antigen 532 ng/ml; cT4N1M1b; Gleason score4+4) with androgen deprivation therapy, abiraterone, and docetaxel. Calcified nodules and radiological findings of LTBI were present in the upper right lobe since the diagnosis of PC. After progression was observed during these treatments, CBZ was administered combined with pegfilgrastim, long-acting granulocyte colony-stimulating factor (G-CSF). Seven days after the third course of CBZ, he was admitted to the authors' hospital to treat febrile neutropenia (FN). High fever persisted even after myelosuppression had recovered. Computed tomography (CT) revealed distribution of small nodules in the bilateral lungs, for which miliary TB was included in the differential diagnosis. T-Spot, interferon-gamma-release assay, and bronchoscopy yielded no significant findings; however, sputum and urine culture confirmed the diagnosis of TB. DIAGNOSIS: CT, sputum and urine culture confirmed the diagnosis of miliary TB. INTERVENTIONS: The patient was treated with anti-bacterial therapy (cefepime) on hospital admission, which was not effective. After the diagnosis of miliary TB was confirmed, anti-TB drugs, including isoniazid, rifampicin, pyrazinamide and ethambutol, were administered. OUTCOMES: Despite anti-TB therapy, high fever persisted and radiological findings worsened. Fifty days after the third course of CBZ, the patient died of respiratory dysfunction caused by progression of miliary TB. LESSONS: Management of LTBI is needed in cases of radiographic findings of LTBI and medical history of TB before CBZ treatment, despite the rarity of LTBI reactivation in patients with PC.
  • Nobutaka Shimizu; Naoki Wada; Takahiro Shimizu; Takahisa Suzuki; Ei-Ichiro Takaoka; Anthony J Kanai; William C de Groat; Akihide Hirayama; Mamoru Hashimoto; Hirotsugu Uemura; Naoki Yoshimura
    Neuroscience letters 683 100 - 103 0304-3940 2018/09 [Refereed]
     
    Nerve growth factor (NGF) is reportedly involved in the changes in C-fiber bladder afferent pathways that induce detrusor overactivity (DO) following spinal cord injury (SCI). This study examined the roles of NGF in TRP channel expression in bladder afferent neurons in mice with SCI using laser-capture microdissection (LCM) methods. Spinal intact (SI) and SCI mice were divided into 3 groups: (1) SI with vehicle treatment; (2) SCI with vehicle treatment; and (3) SCI with anti-NGF antibody. Two weeks after SCI, an osmotic pump was placed subcutaneously into the back of the mice and vehicle or anti-NGF antibody was administered at a rate of 10 μg/kg per hour for two weeks. Four weeks after SCI, the L6 dorsal root ganglia (DRG) were removed. Expression of the TRPV1, TRPC1, TRPC3, and TRPC6 genes was analyzed using real-time polymerase chain reaction (PCR) following LCM of the bladder afferent neurons, which were labeled by Fast Blue injected into the bladder wall 1 week prior to tissue removal. The mRNA expression of TRPV1 was found to be higher in vehicle-treated SCI mice than in SI mice. The expression level of TRPC3 and TRPC6 in vehicle-treated SCI mice was lower than in SI mice. However, in SCI mice treated with anti-NGF antibody, the mRNA expression of TRPV1 was lower, and the mRNA levels of TRPC3 and TRPC6 were higher than in vehicle-SCI mice. These results suggest that the NGF-dependent changes in specific TRP channel genes, such as TRPV1, TRPC3, and TRPC6, could be involved in SCI-induced afferent hyperexcitability and DO.
  • Shimizu Nobutaka; Takaoka Ei-ichiro; Suzuki Takahisa; Kwon Joonbeom; Hashimoto Mamoru; Uemura Hirotsugu; Hirayama Akihide; Kanai Anthony J; de Groat William C; Yoshimura Naoki
    JOURNAL OF UROLOGY ELSEVIER SCIENCE INC 199 (4) E396 - E397 0022-5347 2018/04 [Refereed]
  • Hashimoto, Mamoru; Shimizu, Nobutaka; Takahashi, Tomoki; Sugimoto, Koichi; Minami, Takafumi; Uemura, Hirotsugu; Hirayama, Akihide
    JOURNAL OF UROLOGY ELSEVIER SCIENCE INC 199 (4) E1085 - E1086 0022-5347 2018/04 [Refereed]
  • Inhibition of phosphodiesterase type 9 (PDE9) improves storage and voiding dysfunction in mice with spinal cord injury
    Shimizu N; Hashimoto M; Suzuki T; Takaoka E; Kwon J; Shimizu T; Wada N; Hirayama A; Uemura H; Kanai AJ; de Groat WC; Yoshimura N
    Neurourol. Urodyn. 37 S96 - S97 2018 [Refereed]
  • Mamoru Hashimoto; Naoki Matsumura; Takayuki Ohzeki; Sachiko Hongo; Koichi Sugimoto; Nobutaka Shimizu; Yasunori Mori; Takafumi Minami; Masahiro Nozawa; Kazuhiro Nose; Hideo Tahara; Kazuhiro Yoshimura; Hirotsugu Uemura
    Urologia internationalis 101 (1) 74 - 79 0042-1138 2018 [Refereed]
     
    INTRODUCTION: We investigated whether the change in the neutrophil lymphocyte ratio (NLR) from the first to the last repeat prostate biopsy (ΔNLR) could be the diagnostic tool or not for prostate cancer (PCa) detection. MATERIALS AND METHODS: We retrospectively evaluated medical records of men who had undergone repeat prostate biopsy. The investigated parameters were white blood cell, neutrophil, lymphocyte counts, NLR at the last prostate biopsy, ΔNLR, prostate-specific antigen (PSA), PSA density (PSAD), and PSA velocity. Exclusion criteria were the presence of cancers other than prostate origin, medication, and diseases which induce the change of NLR. RESULTS: A total of 301 men who had undergone repeat prostate biopsy were selected for this study. After applying exclusion criteria, 223 patients were included. Of these patients, 94 were diagnosed with PCa (Group I) and 129 with no malignancy (Group II). Only a single patient had metastasis. On evaluating the area under the receiver operating characteristic curve of all study parameters, ΔNLR was the most accurate marker, followed by PSAD and then NLR measured at the last biopsy. CONCLUSIONS: ΔNLR was the most accurate marker to improve the total predictive value in repeat prostate biopsy for diagnosing PCa.
  • Hashimoto, Mamoru; Shimizu, Nobutaka; Sugimoto, Koichi; Hongoh, Sachiko; Minami, Takafumi; Nozawa, Masahiro; Yoshimura, Kazuhiro; Hirayama, Akihide; Tahara, Hideo; Uemura, Hirotsugu
    LUTS-LOWER URINARY TRACT SYMPTOMS WILEY 9 (3) 157 - 160 1757-5664 2017/09 [Refereed]
     
    ObjectivesTo assess the efficacy of dutasteride add-on therapy for patients with benign prostatic hyperplasia (BPH) and lower urinary tract symptoms (LUTS) with small prostates who have been treated with -blocker therapy for >3 months.MethodsA total of 110 men with clinical BPH were enrolled. There were 17 and 93 subjects with a prostate volume (PV) <30 and 30 mL, respectively. All subjects had been treated with -blocker therapy for >3 months. Subjective and objective clinical variables were assessed using the total International Prostate Symptom Score (IPSS-T), IPSS quality of life (IPSS-QoL), IPSS voiding subscore (IPSS-V), IPSS storage subscore (IPSS-S), overactive bladder symptom score (OABSS), PV, prostate specific antigen (PSA) level, post-void residual (PVR), and maximum flow rate (Qmax). These variables were assessed at baseline and every 3 months for 1 year.ResultsIn the small prostate group, IPSS-T and IPSS-V showed improvements from baseline at 6 and 9 months, storage subscore at 6 months, and OABSS at 3 months, but no sustained improvements were observed. During the study period, only the IPSS QoL scores did not show any improvement. Conversly, dutasteride was significantly effective at improving IPSS-T, IPSS-V, IPSS-S, and IPSS-QoL scores throughout the study period in the large prostate BPH group. PSA levels and PV significantly decreased in both groups throughout the study.ConclusionsBenign prostatic hyperplasia in LUTS patients with small prostates did not show a sustainable benefit from the addition of dutasteride to -blocker therapy.
  • Koichi Sugimoto; Takahiro Akiyama; Nobutaka Shimizu; Naoki Matsumura; Mamoru Hashimoto; Takafumi Minami; Kazuhiro Nose; Masahiro Nozawa; Kazuhiro Yoshimura; Hirotsugu Uemura
    Research and reports in urology 9 141 - 143 2017 [Refereed]
     
    Acute urinary retention is the most common urological emergency. To resolve this emergency, urethral catheterization is performed. If the procedure fails and permanent transurethral catheterization is required, the patient's quality of life is significantly affected. Therefore, catheter-free treatment is the ideal goal of therapy for patients with acute urinary retention. Especially, for women, placement of a catheter poses a cosmetic problem. Therefore, the aim of this study was to treat female patients who had already received urapidil/distigmine bromide with acotiamide. Acotiamide was administered at a dose of 100 mg three times daily for 2 weeks, and the outcome of trial without catheter was evaluated. Only female patients were enrolled for this study. Treatment proved successful and all patients become catheter free.
  • Yasuharu Nagai; Nobutaka Shimizu; Takafumi Minami; Shingo Toyoda; Mamoru Hashimoto; Mitsuhisa Nishimoto; Takashi Kikuti; Yoshitaka Saitou; Yutaka Yamamoto; Taiji Hayashi; Hidenori Tsuji; Masahiro Nozawa; Kazuhiro Yoshimura; Hirotsugu Uemura
    Hinyokika kiyo. Acta urologica Japonica 61 (10) 383 - 7 0018-1994 2015/10 [Refereed]
     
    OBJECTIVES: We compared sexual function by the expanded prostate cancer index composite (sexual domains of EPIC), health-related quality of life (SF-8), and International Prostate Symptom Score (I-PSS) inpatients using tadalafil after prostate brachytherapy (PB). Forty-five patients who underwent PB between April 2011 and January 2014 were included in this study. Patients were divided into the tadalafil (20 mg,once/week or once/two weeks) treated and non-treated (NT) groups. Sexual function was assessed prior to PB treatment and followed up to 24 weeks after PB. SF-8, sexual domains of EPIC, IPSS and subjective symptoms were assessed pre-PB and at 4, 8, 16, and 24 weeks post-PB. Patients in the tadalafil group achieved higher sexual function scores compared to NT group at all time points. For SF8, the patients in the tadalafil group significantly improved in mental health by the eighth week, and significantly worsened in the NT group (8 w ; p = 0.04). The voiding domains of EPIC score were found to worsen significantly after 4 weeks from PB in both groups, but the score tended to improve over 24 weeks. There was no significant difference between two groups. The I-PSS total score was found to worsen significantly in both groups post-PB, but the tadalafil group had a tendency to worsen less. PB treatment of localized prostate cancer is preferred for the preservation of sexual function. Management of sexual dysfunction with tadalafil after PB does not worsen sexual functions. We concluded that tadalafil might be applicable to mental health care in the treatment of patients with a high interest in sexual function before PB.
  • Shingo Toyoda; Takafumi Minami; Mamoru Hashimoto; Mitsutaka Saito; Nobutaka Shimizu; Yutaka Yamamoto; Taiji Hayashi; Hidenori Tsuji; Masahiro Nozawa; Kazuhiro Yoshimura; Tokumi Ishii; Hirotsugu Uemura
    Hinyokika kiyo. Acta urologica Japonica 61 (6) 223 - 6 0018-1994 2015/06 [Refereed]
     
    The aim of our study was to identify risk factors that may influence outcomes for patients presenting with Fournier gangrene. Twelve patients hospitalized and treated between August 2007 and August 2013 were included in this study. Distinct features were noted after one or two weeks of hospitalization. We did not observe a significant correlation between death risk and the extent of necrosis in this patient set. However, the extent of necrosis tended to correlate with the duration of hospitalization in the survivors. We also compared the results of blood biochemical analyses between the surviving and non-surviving groups. A significant difference was noted in the levels of glucose (Glu) after two weeks. In the non-surviving group, Glu levels were increased. These findings suggest a relationship between glycemic control after the initiation of therapy and death. We also examined the results of blood biochemical analyses according to the duration of hospitalization. The lactate dehydrogenase (LDH) levels at admission and LDH levels after two weeks were significantly higher in the patients with a duration of hospitalization longer than the median duration of 61.5 days. These findings suggest a relationship between the duration of hospitalization and the extent of necrosis at diagnosis.
  • Mamoru Hashimoto; Nobutaka Shimizu; Shingo Toyoda; Yoshitaka Saito; Yutaka Yamamoto; Takafumi Minami; Taiji Hayashi; Hidenori Tsuji; Masahiro Nozawa; Kazuhiro Yoshimura; Tokumi Ishii; Hirotsugu Uemura
    Hinyokika kiyo. Acta urologica Japonica 60 (6) 269 - 73 0018-1994 2014/06 [Refereed]
     
    We report a case of a patient with a fistula between the right ureter and external iliac artery. The patient was a 75-year-old woman who had undergone abdominal radical hysterectomy for uterine cancer, and whole pelvis radiotherapy for right external iliac lymph node metastasis. Her post-operative course was complicated by hydronephrosis of the right kidney, which was treated by the insertion of a double-J stent. While removing the frequently obstructed double-J stent after percutaneous nephrostomy, arterial hemorrhage occurred from the external urethral meatus. Computed tomographic scan demonstrated right ureteral external iliac artery fistula formation located adjacent to the pseudoaneurysm. The patient was treated successfully with endovascular stent grafting and has showed no episode of hematuria since then.

Conference Activities & Talks

  • Gender differences in spinal neural circuits in the control of external urethral sphincter (EUS) function and lower urinary tract dysfunction after spinal cord injury (SCI) in mice
    M. HASHIMOTO; N. YOSHIMURA; J. M. BECKEL; W. C. DE GROAT; S. KARNUP
    Neuroscience2022  2022
  • The relationship between urodynamic study findings and post micturition dribble in male patients.  [Not invited]
    Hashimoto M; Shimizu N; Nishimoto M; Minami T; Fujita K; Yoshimura K; Hirayama A; Hirotsugu U
    ICS2021  2021
  • The impact of psoas muscle atrophy on lower urinary tract symptoms in elderly female patients
    Hashimoto M; Nishimoto M; Banno E; Saito Y; Shimizu N; Mori Y; Minami T; Fujita K; Nozawa M; Nose K; Yoshimura K; Hirayama A; Uemura H
    ICS2020  2020
  • NOCTURNAL ANTIDIURESIS AFTER ADMINISTRATION OF IMIDAFENACIN IS INDUCED BY CONCENTRATION OF URINE OSMOLALITY  [Not invited]
    Hashimoto Mamoru; Shimizu Nobutaka; Takahashi Tomoki; Sugimoto Koichi; Minami Takafumi; Uemura Hirotsugu; Hirayama Akihide
    AUA2018  2018/04
  • Imidafenacin mediates nocturnal antidiuresis through concentration of urine osmolality.
    Hashimoto M; Shimizu N; Ohzeki T; Minami T; Nozawa M; Yoshimura K; Uemura H; Tahara H; Hirayama A
    ICS2018  2018
  • Effects of withdrawing dutasteride on serum testosterone and lower urinary tract symptoms  [Not invited]
    Mamoru Hashimoto; Nobutaka Shimizu; Naoki Matsumura; Sachiko Hongoh; Koichi Sugimoto; Takafumi Minami; Masahiro Nozawa; Kazuhiro Yoshimura; Hirotsugu Uemura; Hideo Tahara; Akihide Hirayama
    THE INTERNATIONAL CONTINENCE SOCIETY  2017/09
  • What outcome is expected for BPH patients after withdrawal of dutasteride?  [Not invited]
    Hashimoto M; Shimizu N; Sugimoto K; Minami T; Nozawa M; Yoshimura K; Uemura H; Tahara H; Hirayama A
    ICS2015  2015/10

MISC

  • 前立腺癌Ptenノックアウトマウスを用いたCD73とA2aR阻害の効果について(Efficacy of combined CD73 and A2aR blockade in mouse Pten-deficient prostate cancer)
    デベラスコ・マルコ; 倉 由吏恵; 坂井 和子; 藤田 和利; 橋本 士; 坂野 恵里; 西本 光寿; 野澤 昌弘; 吉村 一宏; 西尾 和人; 植村 天受  日本泌尿器科学会総会  110回-  OP76  -02  2023/04
  • アンドロゲン受容体シグナル阻害を標的とした分子および免疫応答を評価可能とする前臨床前立腺癌マウスモデルの活用について(Use of a preclinical prostate cancer model to assess molecular and immune responses to androgen receptor signaling axis blockade)
    植村 天受; 倉 由吏恵; 藤田 和利; 坂井 和子; 橋本 士; 西本 光寿; 吉村 一宏; 野澤 昌弘; 西尾 和人; デベラスコ・マルコ  日本泌尿器科学会総会  110回-  OP76  -03  2023/04
  • 橋本士; 清水信貴; 國重玲紋; 豊田信吾; 西本光寿; 大關孝之; 南高文; 野澤昌弘; 吉村一宏; 田原秀男; 平山暁秀; 植村天受  日本排尿機能学会誌  29-  (1)  230  -230  2018/09
  • 前立腺癌患者の予後不良に関わる遺伝子群の同定(Identification of a gene set associated with poor clinical outcomes in prostate cancer patients)
    橋本 士; デベラスコ・マルコ; 倉 由吏恵; 坂井 和子; 清水 信貴; 森 康範; 野澤 昌弘; 吉村 一宏; 吉川 和宏; 西尾 和人; 植村 天受  日本癌学会総会記事  77回-  792  -792  2018/09
  • MRIを用いた健常女性骨盤底の検討
    本郷 祥子; 橋本 士; 松村 直紀; 大関 孝之; 杉本 公一; 清水 信貴; 森 康範; 南 高文; 野澤 昌弘; 能勢 和宏; 吉村 一宏; 植村 天受; 上島 成也  日本泌尿器科学会総会  106回-  OP  -429  2018/04
  • 限局性前立腺癌に対する放射線療法後膀胱癌発症例の検討
    南 高文; 橋本 士; 松村 直紀; 大關 孝之; 本郷 祥子; 杉本 公一; 清水 信貴; 森 康範; 野澤 昌弘; 能勢 和宏; 吉村 一宏; 植村 天受  日本泌尿器科学会総会  106回-  PP1  -212  2018/04
  • 中長期デュタステリド投与中の前立腺肥大症患者に対するデュタステリド休薬の影響
    橋本 士; 清水 信貴; 本郷 祥子; 杉本 公一; 南 高文; 野澤 昌弘; 田原 秀男; 吉村 一宏; 平山 暁秀; 植村 天受  日本排尿機能学会誌  28-  (1)  272  -272  2017/09
  • 排尿筋低活動患者に対する排尿時間の検討
    杉本 公一; 清水 信貴; 橋本 士; 西本 光寿; 本郷 祥子; 安富 正悟; 大關 孝之; 齋藤 允孝; 南 高文; 能勢 和宏; 野澤 昌弘; 吉村 一宏; 植村 天受  日本泌尿器科学会総会  105回-  OP31  -5  2017/04
  • 経会陰的前立腺再生検における好中球/リンパ球比の有用性の検討
    橋本 士; 松村 直紀; 大關 孝之; 本郷 祥子; 齋藤 允孝; 杉本 公一; 清水 信貴; 南 高文; 能勢 和宏; 野澤 昌弘; 田原 秀男; 吉村 一宏; 植村 天受  日本泌尿器科学会総会  105回-  PP17  -11  2017/04
  • 夜間頻尿合併不眠患者に対するエスゾピクロンの検討
    西本 光寿; 杉本 公一; 清水 信貴; 橋本 士; 松村 直紀; 林 泰司; 西岡 伯; 南 高文; 野澤 昌弘; 吉村 一宏; 平山 暁秀; 植村 天受  日本排尿機能学会誌  27-  (1)  270  -270  2016/12
  • 腎癌に対する分子標的薬によるPresurgical療法の検討
    大関 孝之; 明石 泰典; 橋本 士; 安富 正悟; 齋藤 允孝; 清水 信貴; 山本 豊; 南 高文; 野澤 昌弘; 能勢 和宏; 吉村 一宏; 植村 天受  泌尿器科紀要  62-  (3)  149  -149  2016/03
  • アビラテロン投与にて重篤な低カリウム血症を起こした2例
    明石 泰典; 橋本 士; 西野 安紀; 安富 正悟; 大關 孝之; 齋藤 允孝; 清水 信貴; 山本 豊; 南 高文; 野澤 昌弘; 能勢 和宏; 吉村 一宏; 植村 天受  泌尿器科紀要  61-  (12)  527  -527  2015/12
  • 下大静脈腫瘍塞栓が認められた後腹膜原発Extraskeletal Ewing's sarcomaの1例
    豊田 信吾; 橋本 士; 齋藤 允孝; 清水 信貴; 南 高文; 山本 豊; 林 泰司; 辻 秀憲; 野澤 昌弘; 吉村 一宏; 石井 徳味; 植村 天受; 中居 卓也; 北山 仁士  泌尿器科紀要  60-  (5)  255  -255  2014/05

Awards & Honors

  • 2023 2023 DIOKNO - LAPIDES ESSAY CONTEST on Urodynamics and Neurourology Research, Second Place
     
    受賞者: Mamoru Hashimoto;University of Pittsburgh School of Medicine
  • 2017 一般社団法人日本排尿機能学会 河邉賞
     
    受賞者: 橋本 士
  • 2015 一般社団法人大阪泌尿器科臨床医会 大阪泌尿器科臨床医会学術奨励賞
     
    受賞者: 橋本 士

Research Grants & Projects

  • 脊髄損傷モデル動物における下部尿路機能障害の分子メカニズムの解明
    公益財団法人大阪難病研究財団 国際交流助成：
    Date (from‐to) : 2022/05 -2023/03 
    Author : 橋本士

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