Language：English   Publishing type：Research paper (scientific journal)  

Prostaglandin E1 intracavernous injection test is an established method for diagnosing erectile dysfunction. However, the evaluation is non-objective and often influenced by the evaluator's subjectivity. Herein, we measured and objectively evaluated shear wave elastography results of the corpus cavernosum before and after injection in 16 patients who underwent prostaglandin E1 testing. The response score of prostaglandin E1 tests were "1" in 2 cases, "2" in 2 cases, and "3" in 12 cases. The average transmission velocity before the injection and at the time of maximum erection after the injection were 2.21 m/s and 1.57 m/s, respectively. Transmission velocity decreased during erection in 14 of 16 cases (87.5%). The overall rate of change in transmission velocity due to injection was -26.7% and was significantly different between the poor (responses 1 and 2: -16.1%) and good erection (response 3: -30.2%) groups. To the best of our knowledge, this is the first attempt to evaluate erectile phenomenon using percutaneous ultrasonic elastography in Japan. Rate of change in shear wave transmission velocity due to prostaglandin E1 injection in the corpus cavernosum penis was associated with the degree of erection. Therefore, the rate of change in shear wave transmission velocity in the corpus cavernosum penis could be used as an objective index of erectile phenomenon. Percutaneous ultrasonic elastography is a non-invasive and useful test method for diagnosing erectile dysfunction, determining the therapeutic effect, and predicting prognosis.

DOI： 10.18999/nagjms.86.1.104

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Language：English   Publishing type：Research paper (scientific journal)  

DOI： 10.31662/jmaj.2023-0134

PubMed

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Language：Japanese   Publisher：独立行政法人 大学入試センター  

日本の高等教育では，2017 年に 3 つのポリシーの策定・公表が義務化され，アドミッション・ポリシーにおける入学者受け入れの方針の明確化が求められている。医師養成課程においては，将来医師となる人材を育成するため，明確なアドミッション・ポリシーを策定した上で学生選抜を行うことが極めて重要となる。本稿では，医師養成課程におけるアドミッション・ポリシーの内容をテキストマイニングの手法で分析した結果を提示し，今後の在り方を考察する。

DOI： 10.57513/dncjournal.34.0_218

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Language：English   Publishing type：Research paper (scientific journal)  

OBJECTIVES: Double incontinence (DI), which is the co-occurrence of fecal incontinence (FI) and urinary incontinence (UI), increases with age and has a greater negative impact on the quality of life (QOL) than either incontinence alone. We aimed to assess lower urinary tract symptoms (LUTS) in patients with FI to elucidate the prevalence and characteristics of DI. METHODS: This study enrolled consecutive patients who visited our hospital with FI symptoms. FI was evaluated using the Cleveland Clinic Florida Fecal Incontinence Score (CCFIS). LUTS were assessed using the International Prostate Symptom Score (IPSS), QOL score (IPSS-QOL) and Overactive Bladder Symptom Score (OABSS). RESULTS: This study evaluated 140 patients (96 women [mean age: 70.7 years] and 44 men [mean age: 74.4 years]). The mean IPSS was significantly higher in men than in women (12.0 vs. 7.5, p = 0.003). A positive correlation was found between IPSS and CCFIS in women (r = 0.256, p = 0.012) but not in men. For both sexes, the older group (aged ≥70 years) had higher OABSS scores and more urge UI instances than the younger group (aged ≤69 years). Of the 140 patients with FI, 78 (55.7%) had DI, and DI was more common in women than in men (63.5% vs. 38.6%, p = 0.006). CONCLUSIONS: The characteristics of LUTS and UI in patients with FI were comparable to those in the general population for both sexes; however, the prevalence of DI was much higher among patients with FI than that in the general population.

DOI： 10.23922/jarc.2023-040

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Language：Japanese   Publisher：(一社)日本泌尿器内視鏡・ロボティクス学会  

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Language：Japanese   Publisher：(一社)日本排尿機能学会  

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Language：Japanese   Publisher：(一社)日本排尿機能学会  

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Language：Japanese   Publisher：(一社)日本抗加齢医学会  

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Language：English   Publisher：(一社)日本泌尿器科学会総会事務局  

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Language：English   Publisher：(一社)日本泌尿器科学会総会事務局  

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Language：English   Publisher：(一社)日本泌尿器科学会総会事務局  

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Language：Japanese   Publisher：The Japanese Society of Clinical Pharmacology and Therapeutics  

Face-to-face communication during on-site monitoring is important for clinical trial quality assurance. However, with the coronavirus disease early 2020 pandemic, medical institutions placed restrictions on hospital visits to secure their medical systems.

Asahikawa Medical University Hospital similarly established restrictions on outpatient and inpatient visits and legal restrictions on outside vendors. Therefore, the frequency of on-site monitoring of clinical trials conducted at our hospital was reduced. Since there was no sign of convergence at the infection units even after 2 years, we investigated the frequency of on-site monitoring and the frequency of clinical trial deviations in the review of the system.

In addition, although a clinical trial deviation report form (previous form) was prepared in the fiscal year 2019, there were many free descriptions, and many deviation reports were difficult to understand. Similarly, there were cases where deviations were not recorded on the deviation report form but only on article records (source documents), such as electronic medical records after consultation with the sponsor, and deviations were not recorded in a uniform format. Thus, the hospital experienced difficulty tabulating and classifying the number of deviation occurrences. Based on this experience, this report describes the progress of revising the clinical trial deviation report, clarifying the items to be included in the report, and establishing a system to clarify the process related to clinical trial deviation occurrences.

DOI： 10.3999/jscpt.54.2_71

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Other Link： https://search.jamas.or.jp/link/ui/2023156149

Language：English   Publishing type：Research paper (scientific journal)   Publisher：Anticancer Research {USA} Inc.  

DOI： 10.21873/invivo.13203

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Publishing type：Research paper (scientific journal)   Publisher：International Journal of Medical Education  

DOI： 10.5116/ijme.6372.1fce

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Language：Japanese   Publisher：(一社)日本排尿機能学会  

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Language：Japanese   Publisher：東京 : 科学評論社  

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Other Link： https://ndlsearch.ndl.go.jp/books/R000000004-I032401379

Language：Japanese   Publisher：東京 : 科学評論社  

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Other Link： https://ndlsearch.ndl.go.jp/books/R000000004-I032401495

Language：Japanese   Publisher：(公社)日本超音波医学会  

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Language：Japanese   Publisher：東京 : 科学評論社  

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Other Link： https://ndlsearch.ndl.go.jp/books/R000000004-I032133496

Language：Japanese   Publisher：The Japanese Society of Clinical Pharmacology and Therapeutics  

The authors attempted to manufacture an investigational drug using a manufacturing facility within the university without outsourcing it to a contract manufacturing organization (CMO). However, they experienced difficulty in purchasing an exclusive drug as a raw material for the process. The authors made inquiries to the Ministry of Health, Labor and Welfare (MHLW) about the interpretation of the Notice of the Director-General regarding Article 138 of the Act on Securing Quality, Efficacy, and Safety of Products Including Pharmaceuticals and Medical Devices. The response was that the purchase of drugs dedicated to manufacture of investigational products for the purpose of administering them to humans may be possible, even if the manufacturing facilities are in a university that does not have the license for pharmaceutical manufacturing of drugs. Raw materials derived from manufacturing-specific drugs or (non-manufacturing) medical drugs, which are considered to be safer in humans than as research reagents, should consistently meets safety requirements for study subjects. Therefore, the regulatory authorities should consider revising the Act on Securing Quality, Efficacy and Safety of Products Including Pharmaceuticals and Medical Devices or the Notification by the Director-General to allow the purchase of drugs by research institutions for the purpose of manufacturing investigational drugs or test drugs to be used in clinical<b> </b>studies, and that investigational drugs or products be used for clinical research at research institutions, or that “the purpose of research should include clinical trials and clinical research.”

DOI： 10.3999/jscpt.53.27

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Other Link： https://search.jamas.or.jp/link/ui/2023032965

Language：Japanese  

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Other Link： https://ndlsearch.ndl.go.jp/books/R000000004-I032006943

Language：Japanese   Publisher：Japanese Pharmacological Society  

<b><u>Hypothesis.</u></b> Overflow urinary incontinence (OUI) often occurs as a complication after pelvic surgery. Our previous experiment found that bone marrow-derived stem cell lysate (BMSCL) improves neurogenic erectile dysfunction. In this study, we investigated the effectiveness of BMSCL in a model of OUI by bilateral accessory nerve injury (ACNI). 

<b><u>Methods.</u></b> Rat bone marrow-derived stem cells were collected, and BMSCL (lysate of 1×10⁶ cells/PBS) was prepared. Eight-week-old male Wistar-ST rats were divided into sham+PBS (sham, n=7), ACNI+PBS (ACNI, n=10), and ACNI+BMSCL (BMSCL, n=10) groups. Following surgery, PBS or BMSCL (100μl/body) was administered intravenously. Bladder function, bladder weight, and morphology were evaluated after one week. In addition, the response of carbachol (CCh) was assessed.

<b><u>Results.</u></b> While 7 of 10 rats in the ACNI group showed symptoms of OUI, only 3 of 10 rats in the BMSCL group presented symptoms of OUI. Bladder weight in the ACNI group was significantly larger than in the sham group (P&lt;0.01), while bladder weight in the BMSCL group was significantly lower than in the ACNI group (P&lt;0.01). Fibrotic area in the ACNI group was larger than in the sham group, while that in the BMSCL group was smaller than in the ACNI group. The maximum response to CCh in bladder specimens in the ACNI group was higher than that of sham group, while this was lower in the BMSCL group than in the ACNI group.

<b><u>Conclusion.</u></b>  BMSCL improved bladder function and morphology, suggesting that intravenous injection of BMSCL may be a useful treatment for neurogenic bladder dysfunction.

DOI： 10.1254/jpssuppl.95.0_1-ss-47

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Publishing type：Research paper (scientific journal)   Publisher：Scientific Research Publishing, Inc.  

DOI： 10.4236/oju.2022.126035

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Publishing type：Research paper (scientific journal)  

Web of Science

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Language：Japanese   Publisher：Japanese Pharmacological Society  

[Objective] Radical prostatectomy is involved with cavernous nerve (CN) damage which often cause neurogenic erectile dysfunction (ED). Bone marrow derived mesenchymal stem cell (BMSC) transplantation was proven effective in treating a neurogenic ED model rat with bilateral CN injury (BCNI). However, stem cell therapy may induce embolization and immunoreactions. We aimed to investigate the effects of filtrated BMSC lysate (BSCL) which does not contain cells.

[Methods] Rats underwent either sham or BCNI surgery. Phosphate buffered saline (PBS) or BSCL was injected postoperatively into the corpus cavernosum (each group; n=7). Erectile function was evaluated by measuring intracavernosal pressure/mean arterial pressure (ICP/MAP) while the CN was stimulated. After the experiment, penis samples were obtained for histological assessment. Neurite outgrowth was evaluated using major pelvic ganglia (MPG), which were placed on Matrigel^🄬 and incubated with normal medium or medium with either BSCL or vascular endothelial growth factor (VEGF) as a positive control.

[Results] While BCNI significantly decreased ICP/MAP compared to sham surgery (P &lt; 0.05), the injection of BSCL significantly reversed ICP/MAP compared to PBS injection (P &lt; 0.05). In addition, MPG treated with medium containing BSCL or VEGF had longer neurite outgrowth than those treated with normal medium. On the other hand, the penile structures of each group did not differ significantly.

[Discussion] Our results suggest that BSCL improve ED caused by CN injury, which may be due to CN regeneration.

DOI： 10.1254/jpssuppl.95.0_1-yia-25

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Language：Japanese   Publisher：東京 : 科学評論社  

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Other Link： https://ndlsearch.ndl.go.jp/books/R000000004-I031784256

Language：English   Publishing type：Research paper (scientific journal)   Publisher：Springer Science and Business Media {LLC}  

PURPOSE: We analyzed the annual trends in and initial choice of pharmacotherapy for children with nocturnal enuresis (NE) using a large-scale medical claims database in Japan. METHODS: A retrospective descriptive study performed using data from the Japan Medical Data Center between January 2005 and March 2019 involving 23,814 registrants under 16 years of age. In the first cohort of children with NE, we analyzed the comorbidities and associated annual pharmacotherapy prescribing trends. In the second cohort of only newly diagnosed cases, we analyzed the first prescribed age and initial choice of pharmacotherapy. RESULTS: A total of 3494 children with NE were identified (mean age, 5.1 ± 3.6 years; male, 66.0%). An incremental increase in the proportion of children administered NE medications was observed. The proportion of children treated with desmopressin significantly increased, whereas the prescription of tricyclic antidepressants significantly decreased and that of anticholinergics did not significantly change. Among the newly diagnosed children, 1897 were treated with approximately 90% of the prescribed monotherapy. Sublingual desmopressin monotherapy accounts for more than half of the initial pharmacotherapy from 2016 onward. Regardless of the drug class, pharmacological therapy was commonly initiated at the age of 8.3 ± 2.1 years. CONCLUSIONS: In Japan, the proportion of children treated with pharmacotherapy has been increasing. Furthermore, since the introduction of desmopressin sublingual formulations in 2012, a paradigm shift has occurred and this form of medication is now the most commonly prescribed, both from the annual perspective and as an initial choice among the newly diagnosed.

DOI： 10.1007/s00345-021-03664-y

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Language：Japanese   Publisher：東京 : 科学評論社  

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Language：English   Publishing type：Research paper (scientific journal)   Publisher：Springer Science and Business Media {LLC}  

Purpose Axitinib is an orally active multikinase inhibitor currently used to treat patients with metastatic renal cell carcinoma (RCC). This study examined the pharmacokinetics of axitinib and the relationship between peak drug concentration (Cmax) and clinical outcomes in real-world practice. Methods Twenty patients with metastatic RCC treated with axitinib monotherapy were enrolled. Post-dose (1-4 h) blood samples were obtained, and axitinib Cmax in plasma was measured by liquid chromatography-tandem mass spectrometry. Efficacy endpoints were best overall response (per RECIST 1.1) and progression-free survival (PFS). The safety endpoint was the cumulative incidence of dose-limiting toxicities (DLTs). Results Large inter- and intra-individual variability in dose-adjusted Cmax was observed (0.02-11.2 ng/mL/mg). Axitinib absorption was significantly influenced by glucuronidation activity (P = 0.040). Cmax at steady state was significantly higher in responders than in non-responders (P = 0.013). The optimal Cmax cutoff to predict a clinical response was 12.4 ng/mL. The median PFS was significantly longer in patients who achieved an average steady state Cmax above the threshold than in those who did not (799 vs. 336 days; P = 0.047). The cumulative incidence of DLTs was significantly higher in patients with Cmax ≥ 40.2 ng/mL than in other patients (sub-hazard ratio, 4.13; 95% confidence interval, 1.27-13.5; P = 0.019). Conclusions The potential therapeutic window of axitinib Cmax in metastatic RCC was estimated at 12.4-40.2 ng/mL. Pharmacokinetically guided dose titration using therapeutic drug monitoring may improve the efficacy and safety of axitinib, warranting further investigation in a larger patient population.

DOI： 10.1007/s10637-020-01023-z

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Language：English   Publishing type：Research paper (scientific journal)  

BACKGROUND: Inflammatory bowel disease (IBD) is a chronic, persistent, and intractable enteritis; however, an effective treatment strategy is yet to be established. Mesenchymal stem cells (MSCs) and their paracrine factors exhibit anti-inflammatory actions and have been proposed as a new therapeutic candidate for IBD treatment, although the efficacy of MSC lysate on enteritis is unclear. AIMS: Here, we examined the efficacy and appropriate regimen of filtrated murine adipose-derived mesenchymal stem cell lysate (FADSTL) in an acute colitis mouse model as a novel cell-free MSC therapy. METHODS: To confirm the clinical effects of FADSTL, survival rate, body weight, and disease activity index (DAI) were investigated in the DSS-induced colitis mouse model. Further, differences in efficacy with dosing frequency were assessed to optimize the proper regimen. Colon length, histological findings, gene expression of inflammatory mediators and tight junction proteins in colon tissues, and anti-apoptotic effects were also compared in 3-day continuous FADSTL administration and PBS groups. RESULTS: Three-day continuous FADSTL administration significantly improved weight loss and DAI score compared to those in the PBS-treated group, whereas the effect was not observed with single administration. Additionally, colon shortening and histological inflammation were suppressed in the FADSTL-treated group. Further, this treatment decreased gene expression of inflammatory mediators, maintained expression of tight junction proteins in the colon, and showed anti-apoptotic effects. CONCLUSIONS: FADSTL effects were dependent on its administration frequency, suggesting the requirement of continuous FADSTL administration. FADSTL improved colitis by maintaining the intestinal barrier function through its anti-inflammatory and anti-apoptotic actions.

DOI： 10.1007/s10620-020-06359-3

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Language：English   Publishing type：Research paper (scientific journal)   Publisher：Biomedical Research Press  

We investigated the bladder and urethral function in a rat model lacking the protein lysyl oxidase-like 1 (Loxl1). Female nulliparous rats of Loxl1-/- or age-matched wild type (WT) rats had leak-point pressure testing, cystometry, histopathological analyses of lower urinary tract, and contractile response of isolated detrusor strips to carbachol and electric field stimulation. The Loxl1-/- rats showed increased looseness and redundancy of the skin, the decreased intercontraction interval and voided volume in cystometry, the lower leak-point pressure, thinner elastic fibers of the mesentery, bladder, urethra and vagina, and smaller contractile response of detrusor strips to carbachol when compared to the WT rats. Thus, the insufficient hydrostatic mechanism of urethra via submucosal impaired elastin synthesis might reduce the resting urethral closure pressure and the diminished cholinergic contractile response of detrusor smooth muscle might be involved in bladder activity in the Loxl1-/- rats.

DOI： 10.2220/biomedres.42.23

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Language：English   Publishing type：Research paper (scientific journal)   Publisher：Wiley  

<jats:title>Abstract</jats:title><jats:sec><jats:title>Aims</jats:title><jats:p>To investigate the relationship between lower urinary tract function and the accessory nerve (ACN) arising from the major pelvic ganglion (MPG).</jats:p></jats:sec><jats:sec><jats:title>Methods</jats:title><jats:p>Ten‐week‐old male Wistar/ST rats were randomly divided into eight groups according to the type of treatment (sham or bilateral accessory nerve injury [BACNI]) and the duration of observation (3 days, 1 week, 2 weeks, or 4 weeks: Sham‐3d, Sham‐1w, Sham‐2w, Sham‐4w, BACNI‐3d, BACNI‐1w, BACNI‐2ws, and BACNI‐4w. BACNI was induced in the following manner: the ACN was crushed for 1 min (2 mm away from the MPG) using reverse‐action tweezers. The same procedure was performed on both sides. On the last day of each observation period, the bladder function was measured by awake cystometry, and histological evaluation was performed.</jats:p></jats:sec><jats:sec><jats:title>Results</jats:title><jats:p>All rats in the Sham groups micturated normally. In the BACNI‐3d and BACNI‐1w groups, all rats showed symptoms of overflow urinary incontinence (OUI). This OUI improved gradually over time. The bladder's size in the BACNI group was significantly larger than that in the Sham group (<jats:italic>p</jats:italic> &lt; .01). In addition, fibrosis was observed in the subserosa of the bladder of rats in BACNI groups.</jats:p></jats:sec><jats:sec><jats:title>Conclusion</jats:title><jats:p>The BACNI model rats exhibited OUI, suggesting that ACN is involved in the lower urinary tract function. It might be possible that ACN controls the function of either the bladder, the urethra, or both.</jats:p></jats:sec>

DOI： 10.1002/nau.24612

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Language：Japanese   Publisher：THE JAPANESE UROLOGICAL ASSOCIATION  

(Purpose) Ingestion of hydrogen is said to prevent oxidation in the body, but hydrogen is produced by intestinal bacterial flora and excreted in the exhaled breath. We investigated how breath hydrogen concentrations change with the diurnal cycle and under various conditions, including after consuming food or drink, and in people with urological disease.

(Subjects and methods) Participants were healthy volunteers (40 men, 45 women; 30-83 years old) and urological outpatients (40 men with benign prostatic hyperplasia, 30 women with overactive bladder; 60 years or older). Breath hydrogen levels were measured before and after eating and drinking in three volunteers, and its diurnal variation was examined in one. The relationship between breath hydrogen and age or urological disease status was also analyzed by gender. Additional measurements were taken in the person with the highest breath hydrogen concentration and the person with the lowest; in these two people, breath hydrogen was measured at the same time for 10 or more days to determine the fluctuation range.

(Results) Breath hydrogen concentration increased temporarily after ingestion of tap water, hydrogen water or food. It also increased with food intake and in cases of flatulence with intestinal gas accumulation, but decreased after defecation. In the person with the highest breath hydrogen, concentrations were 11.2-188.6 ppm, whereas in the person with the lowest, they were 0.4-2.3 ppm. Breath hydrogen increased significantly with age in healthy female volunteers. There was no association between breath hydrogen and benign prostatic hyperplasia, overactive bladder or constipation.

(Conclusion) Breath hydrogen concentration increases with eating, drinking and aging, and is not associated with benign prostatic hyperplasia, overactive bladder or constipation. Breath hydrogen concentration varies widely between individuals, which may be due to differences in intestinal flora.

DOI： 10.5980/jpnjurol.112.11

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Language：English   Publishing type：Research paper (scientific journal)   Publisher：Wiley  

OBJECTIVES: The scent of vanilla has a relaxing effect and is used to treat sleep disorders. Sleep disorders can both cause and be caused by nocturia. Therefore, we examined whether vanilla inhalation would reduce the frequency of urination in rats under light urethane anesthesia. METHODS: Twenty-four rats were anesthetized with 0.6 g/kg urethane subcutaneously (half the usual dose) to induce a sleep-like state. In 12 rats, continuous cystometry was performed via a transurethral catheter before, during and after inhalation of vanilla (n = 7) or the citrus fruit shiikuwasa (n = 5) for 60 minutes. The remaining 12 rats did not undergo cystometry but underwent vanilla inhalation treatment for 60 minutes (n = 6), or no inhalation treatment (n = 6); blood was then collected from these two groups and serum monoamine levels were compared. RESULTS: Intervals between bladder contractions were significantly longer after vanilla inhalation than before. However, baseline bladder pressure, maximum bladder contraction pressure, and residual volume remained unchanged. During shiikuwasa inhalation, the body movement of each rat increased but cystometric parameters did not change. Serum concentrations of adrenaline, noradrenaline and dopamine, but not serotonin, were significantly lower in rats that had inhaled vanilla than in those that had not. CONCLUSIONS: Vanilla scent decreased serum catecholamine levels and urination frequency in rats under light urethane anesthesia. These results suggest that the scent of vanilla may reduce nocturia.

DOI： 10.1111/luts.12346

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Language：Japanese   Publisher：Japanese Pharmacological Society  

<b>Hypothesis</b> Interstitial cystitis (IC) is a chronic inflammatorydisease characterized by pain in the bladder and voiding symptoms. To date,there are no effective treatments for IC. We investigated whether filteredadipose-derived stem cell lysate (FADSCL) alleviates IC in a rat model ofHCl-induced cystitis.

<b>Materials and methods</b> Rat adipose-derived stem cells were collectedfrom the subcutaneous fat of rats, and FADSCL (lysate of 1×107 cells/PBS) wasprepared. Female Fisher 344 rats, aged eight weeks, were divided into thesham+PBS (sham, n=10), HCl+PBS (HCl, n=12), and HCl+FADSCL (FADSCL, n=9) groups.Saline or 0.1 M HCl (250μl/body) was intravesically administered from atransurethral catheter. Bladder function was investigated after one week bycystometrography. A sample of bladder tissue was used for RNA-seq analysis.

<b>Results</b> The intercontraction intervals (ICIs) in the HCl group weresignificantly shorter than those in the sham group (P<0.01), while the ICIsof the FADSCL group were significantly longer than those of the HCl group(P<0.01). There was no significant difference between the groups with respectto the maximum voiding pressure and bladder weight. RNA-Seq analysis revealed anincrease in immune and inflammatory signaling in the HCl group compared to thatin the sham group, and these signals were suppressed in the FADSCL group.

<b>Conclusion</b> FADSCL might alleviate IC via anti-inflammatory actionsand suppress the immune response. Thus, FADSCL could serve as a noveltherapeutic agent for IC.

DOI： 10.1254/jpssuppl.94.0_2-o-d3-5

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Language：English   Publishing type：Research paper (scientific journal)  

BACKGROUND: Cell-free DNA (cfDNA) shed from tumors into the circulation offers a tool for cancer detection. Here, we evaluated the feasibility of cfDNA measurement and utility of digital PCR (dPCR)-based assays, which reduce subsampling error, for diagnosing pancreatic ductal adenocarcinoma (PDA) and surveillance of intraductal papillary mucinous neoplasm (IPMN). METHODS: We collected plasma from seven institutions for cfDNA measurements. Hot-spot mutations in KRAS and GNAS in the cfDNA from patients with PDA (n = 96), undergoing surveillance for IPMN (n = 112), and normal controls (n = 76) were evaluated using pre-amplification dPCR. RESULTS: Upon Qubit measurement and copy number assessment of hemoglobin-subunit (HBB) and mitochondrially encoded NADH:ubiquinone oxidoreductase core subunit 1 (MT-ND1) in plasma cfDNA, HBB offered the best resolution between patients with PDA relative to healthy subjects [area under the curve (AUC) 0.862], whereas MT-ND1 revealed significant differences between IPMN and controls (AUC 0.851). DPCR utilizing pre-amplification cfDNA afforded accurate tumor-derived mutant KRAS detection in plasma in resectable PDA (AUC 0.861-0.876) and improved post-resection recurrence prediction [hazard ratio (HR) 3.179, 95% confidence interval (CI) 1.025-9.859] over that for the marker CA19-9 (HR 1.464; 95% CI 0.674-3.181). Capturing KRAS and GNAS could also provide genetic evidence in patients with IPMN-associated PDA and undergoing pancreatic surveillance. CONCLUSIONS: Plasma cfDNA quantification by distinct measurements is useful to predict tumor burden. Through appropriate methods, dPCR-mediated mutation detection in patients with localized PDA and IPMN likely to progress to invasive carcinoma is feasible and complements conventional biomarkers.

DOI： 10.1007/s00535-020-01724-5

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Language：English   Publishing type：Research paper (scientific journal)   Publisher：American Society of Clinical Oncology ({ASCO})  

PURPOSE: Nivolumab dosage was initially selected on the basis of body weight, often resulting in leftover drug after sterile compounding. This study sought to investigate the real-world wastage of nivolumab and assess the long-term stability of leftover nivolumab within vials to facilitate drug vial optimization (DVO). METHODS: We collected all discarded vials after preparation from 17 regional hospitals in Japan over a 6-month period preceding the adoption of a fixed dose of 240 mg per administration. The actual amount of waste was measured for each preparation. Stability assessment was performed under different storage conditions. RESULTS: A total of 2,789 100-mg vials and 4,069 20-mg vials were collected. Overall, the drug cost associated with the expenditure of nivolumab alone was $12.1 million, whereas the total cost due to drug wastage was $0.735 million (rate of wastage, 6.1%). Furthermore, the immunoglobulin G concentrations of nivolumab remaining within vials, as well as binding activity to programmed death-1 protein, did not change significantly over 4 weeks of storage at either 4°C or room temperature. CONCLUSION: Significant drug wastage occurs during sterile preparation of nivolumab according to body weight-based dosing. Although nivolumab dosing has been changed to a fixed dose in Japan, body weight-based dosing is still applied in some other countries, as well as in combination therapy with ipilimumab. Our findings regarding the long-term stability of leftover nivolumab within the vials should motivate hospitals to implement DVO for cost savings.

DOI： 10.1200/JOP.19.00813

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Language：Japanese   Publisher：東京 : 科学評論社  

北海道内の参加協力が得られた17施設を対象に、2017年10月から2018年3月までの6ヵ月間の腎細胞癌(RCC)に対するニボルマブ廃棄量について解析した。その結果、RCCの病名登録が確認できたのは9施設であった。ニボルマブの廃棄率は、すべてのがん腫で約6.1%に対し、RCCでは約5.5%とやや低値を示した。廃棄額に関しては、すべてのがん腫での廃棄額は8017万円であったのに対し、RCCでは約1273万円で、廃棄額全体に対する割合は15.9%であった。

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Other Link： https://ndlsearch.ndl.go.jp/books/R000000004-I030668690

Language：English   Publishing type：Research paper (scientific journal)   Publisher：Wiley  

AIM: In this study, we investigated self-measured voiding time in the Japanese population. METHODS: A survey questionnaire was used to determine self-measured voiding time in Japanese participants aged ≥20 years. In addition to demographic data such as age and sex, relevant medical conditions, including hypertension, diabetes mellitus, renal impairment and other disorders, were also recorded. Voiding time was measured whenever the participant had the urge to void. RESULTS: In total, 2493 healthy individuals (1347 men, mean ± SD, age 60.50 ± 12.16 years, and 1146 women, 51.16 ± 12.97 years) participated in the survey. Self-measured voiding time was 27.71 ± 20.25 s for men, and 17.49 ± 11.87 s for women. Additionally, 1227 participants with certain diseases were included (1026 men, aged 67.12 ± 9.93 years, and 201 women, 60.26 ± 11.02 years). In this group, self-measured voiding time was significantly longer at P < 0.01 (30.71 ± 20.98 s in men, 21.28 ± 15.56 s in women). In men whose international prostate symptom score (IPSS) was >7, voiding time was significantly longer (healthy men: IPSS ≤7 n = 868, 23.9 ± 14.88 s, IPSS ≥8 n = 479, 34.6 ± 26.05 s, P < 0.05, men with comorbidities: IPSS ≤7: n = 504, 25.64 ± 15.63 s, IPSS ≥8: n = 522, 35.6 ± 24.11 s, P < 0.05). CONCLUSIONS: This self-reported internet survey revealed that self-measured voiding time was longer in men than women regardless of age, and was significantly prolonged with age regardless of sex. Furthermore, self-measured voiding time could be a good screening tool to predict urinary function and health status. Geriatr Gerontol Int ••; ••: ••-•• Geriatr Gerontol Int 2020; ••: ••-••.

DOI： 10.1111/ggi.13933

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In vitro fertilization (IVF) is an established technology that is widely used in reproductive engineering. However, in rats, successful application of IVF is difficult to achieve, and it has had poor reproducibility. In a previous study on the critical issues associated with successful IVF in Wistar rats, we investigated the influence of oocyte collection duration on fertilization rates by dividing the procedure into three steps (oviduct extraction from euthanized animals, oocyte collection from the ampullae of oviducts, and oocyte preincubation until insemination), and identified the appropriate times for each. Here we show that use of the same defined duration for oviduct extraction from superovulated Wistar rats and for oocyte collection from the oviducts also produced highly reproducible fertilization rates of more than 90% in other rat strains. Furthermore, the versatility of these criteria was demonstrated using another IVF protocol. Thus, this simple procedure has enabled the standardization of IVF in rats and will enhance further experimental studies.

DOI： 10.1016/j.theriogenology.2020.01.006

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OBJECTIVES:To evaluate the short-term efficacy and safety of two α1-adrenoceptor (AR) antagonists, tamsulosin and silodosin, in treating patients with untreated lower urinary tract symptoms suggestive of benign prostatic hyperplasia (LUTS/BPH), with a focus on stool form. METHODS:This study was a non-blinded, open-label, prospective randomized comparative study. Tamsulosin or silodosin was administered to patients with untreated LUTS/BPH, and their efficacy and safety in the early stage of treatment were compared using the questionnaire of International Prostate Symptom Score (IPSS)/quality of life (QOL), the Gastrointestinal Symptom Rating Scale (GSRS), and the Bristol Stool Form Scale (BSFS). RESULTS:The per protocol set consisted of 22 patients in tamsulosin group (mean age, 70.15 ± 5.70 years) and 20 patients in silodosin group (73.00 ± 6.48 years). The total IPSS and QOL score improved within 2 weeks in both groups. Although the overall GSRS score showed no significant change in either group, "hard stools" score was significantly decreased in silodosin first at week 2, then in both groups at week 4. Furthermore, the subscale score for "constipation" was significantly decreased only in silodosin at week 4. BSFS was significantly increased at week 4 in silodosin alone. CONCLUSIONS:This study suggests that silodosin was associated with increased digestive symptoms such as diarrhea and loose stools. Therefore, oral drugs for BPH need to be selected by taking into consideration the possibility of digestive symptoms including both the state and type of stools.

DOI： 10.1111/luts.12289

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Language：English   Publishing type：Research paper (scientific journal)   Publisher：Japanese Society for Medical and Biological Engineering  

DOI： 10.14326/abe.9.167

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Language：Japanese   Publisher：大阪 : メディカルレビュー社  

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Language：Japanese   Publisher：南江堂  

DOI： 10.15106/j_naika124_1873

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Other Link： https://search.jamas.or.jp/default/link?pub_year=2019&ichushi_jid=J00974&link_issn=&doc_id=20190902130058&doc_link_id=10.15106%2Fj_naika124_1873&url=https%3A%2F%2Fdoi.org%2F10.15106%2Fj_naika124_1873&type=%E5%8C%BB%E6%9B%B8.jp_%E3%82%AA%E3%83%BC%E3%83%AB%E3%82%A2%E3%82%AF%E3%82%BB%E3%82%B9&icon=https%3A%2F%2Fjk04.jamas.or.jp%2Ficon%2F00024_2.gif

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11歳男児。2年前より陰茎基部に腫瘤性病変が出現した。病変は腫脹と軽快を繰り返し、今回、徐々に増大したため近医の皮膚科を受信後、精査加療目的で当科へ紹介となった。初診時、陰茎基部を逆U字型に取り囲む淡紅色の腫瘤が認められ、病理組織学的所見より原発性陰嚢内硬化性脂肪肉芽腫の診断された。治療としてロキシスロマイシンおよびトラニラストの内服を行ったところ、開始1ヵ月の時点で腫瘤は消退傾向を示した。開始3ヵ月後に内服を中止するも、最終的に腫瘤は自然消退した。

DOI： 10.18888/hi.0000001623

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Other Link： https://search.jamas.or.jp/default/link?pub_year=2019&ichushi_jid=J04290&link_issn=&doc_id=20191111160008&doc_link_id=%2Fai1aamdd%2F2019%2F001505%2F011%2F0582-0587%26dl%3D0&url=https%3A%2F%2Fwww.medicalonline.jp%2Fjamas.php%3FGoodsID%3D%2Fai1aamdd%2F2019%2F001505%2F011%2F0582-0587%26dl%3D0&type=MedicalOnline&icon=https%3A%2F%2Fjk04.jamas.or.jp%2Ficon%2F00004_2.gif

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Language：Japanese   Publisher：東京 : 科学評論社  

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When trying to sense and transmit intra-corporeal biological signal(s), unpowered passive telemetry is known solution for simplicity, size and weight and complexity reduction, and longer lifetime of sensor device, in spite of variety of design restriction. In our prior researches for encapsulated intra-corporeal pressure and/or soundscape telemetry sensor we used both powered (active) and unpowered (passive) methods, such as primary cell, secondary cell, body-fluid fuel cell, electromagnetic feeding, optical feeding, etc., however, all having its intrinsic pros and cons to prevent more extensive development for actual clinical use devising. In this study we use passive (non-power fed) sensor device on site with either ultrasonic or optical excitation and electromagnetic response reception. The method and system have unique affordable characteristics such that, unlike bidirectional electromagnetic coupling, system do not need T-R (transmission and reception) separation within a same kind of signal energy.

DOI： 10.11239/jsmbe.annual56.s91

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Language：Japanese   Publisher：The Oto-Rhino-Laryngological Society of Japan, Inc.  

DOI： 10.3950/jibiinkoka.121.169

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[Purpose] The aim of this study was to examine the relationship between physical activity (PA) in elderly people as preventive exercise for lower urinary tract symptoms (LUTS) or overactive bladder (OAB), and how PA in primary preventive care can impact change upon LUTS. [Subjects and Methods] An interview sheet featuring LUTS domains (IPSS/QOL and OABSS questionnaire) was distributed to all participants (104 males and 494 females) who attended the public elderly people's physical exercise class "Muscle Enhancing Club 2010" in Asahikawa city. [Results] The interview sheet was collected from 65 males (75.4 ± 5.79 years of age) and 304 females (72.7 ± 5.23 years of age). In all cases, there was a statistically significant difference of QOL. In 77 LUTS cases, there was a statistically significant difference in the change of the following LUTS domains: incomplete bladder emptying, frequency, nocturia, QOL, urgency, and OABSS total score. In 61 OAB cases, there was a statistically significant difference in the change of the following LUTS domains: QOL, urgency, and OABSS total score. [Conclusion] PA, as a preventative exercise for elderly people, led to improvements in LUTS, especially storage symptoms and QOL. Our data show that gross movement and education was beneficial. From the point of preventive medicine, various exercise classes, organized by the local government and others, also indicated that these classes increase the possibility of improvement to LUTS.

DOI： 10.1589/jpts.29.1167

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DOI： 10.11477/mf.1413205855

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Language：Japanese   Publisher：公益社団法人 日本生体医工学会  

DOI： 10.11239/jsmbe.55annual.424

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高齢者によくみられる泌尿器科疾患として、排尿障害:下部尿路機能障害(lower urinary tract dysfunction:LUTD)がある。加齢とともに様々な下部尿路症状(lower urinary tract symptoms:LUTS)が出現し、高齢者にとって著しくQOL(quality of life)に影響する。LUTSを呈するLUTDの原因の1つとして血流障害が大いに関係していることが、近年盛んに議論されている。本稿では排尿障害(LUTS/LUTD)の病態として、高血圧や動脈硬化などに伴う血流低下(虚血)障害や、再灌流障害に伴う酸化ストレス障害などの血流障害を中心に解説する。(著者抄録)

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OBJECTIVES: To investigate urodynamic efficacy and safety of mirabegron add-on treatment with tamsulosin for Japanese male patients with overactive bladder (OAB). METHODS: A prospective study was conducted in 26 consecutive male patients with OAB who had been taking tamsulosin. OAB was diagnosed by overactive bladder symptom score (OABSS). Before and 8 weeks after mirabegron add-on treatment with preceding tamsulosin, we assessed OABSS, International Prostate Symptom Score (IPSS), free uroflowmetry (UFM), filling cystometry and pressure-flow study (PFS). RESULTS: Mean age and prostate volume of the study patients were 75 ± 7 years and 32 ± 19 mL, respectively. Mirabegron significantly improved OABSS (from 8.5 ± 2.3 to 4.7 ± 2.5, P < 0.001). On free UFM, mirabegron significantly increased voided volume (from 135 ± 47 to 182 ± 102 mL, P = 0.01), maximum (from 10.7 ± 3.7 to 13.5 ± 6.4 mL/sec, P < 0.01) and average flow rate (from 5.5 ± 1.9 to 7.1 ± 3.3 mL/sec, P < 0.01), while postvoid residual urine volume did not change significantly (from 47 ± 38 to 63 ± 61 mL, P = 0.23). Before mirabegron, 24 patients (92%) had detrusor overactivity (DO). After mirabegron add-on, maximum cystometric capacity significantly increased from 170 ± 98 to 212 ± 95 mL (P = 0.01) and DO disappeared in six patients (25%). In the other 18 patients with persistent DO, amplitude of involuntary contraction decreased and bladder volume at first involuntary contraction increased with statistical significance. On PFS, detrusor pressure at maximum flow rate (from 79 ± 31 to 68 ± 19 cmH2 O, P = 0.10) or bladder contractility index (from 126 ± 39 to 120 ± 27, P = 0.45) did not change significantly. CONCLUSIONS: Mirabegron add-on treatment with tamsulosin has efficacy and safety because it improves storage symptom without impairment of bladder contractility during voiding in male patients with OAB.

DOI： 10.1111/luts.12091

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OBJECTIVES: To investigate the efficacy of combination treatment of degarelix and antiandrogen in patients with prostate cancer. METHODS: We prospectively investigated the efficacy of combination treatment of degarelix and antiandrogen in 12 patients with treatment-naive prostate cancer. We surveyed PSA, LH, FSH and testosterone at day 3, 7, 14 and 28 during the initial month and thereafter once a month for 1 year. In cases with bone metastasis, we analyzed serum bone markers such as alkaline phosphatase(ALP), bone-type ALP and carboxyterminal telopeptide of type- I collagen once a month. Skeletal related events (SREs) were also monitored. RESULTS: PSA progression free survival was 65%. PSA was reduced from baseline by 80% at day 14 and by 93% at day 28. In all patients serum testosterone immediately reached castrate level at day 3 and was maintained for 1 year without breakthrough escape. Both LH and FSH were reduced to within normal range at day 3. In contrast, all bone markers temporarily increased at day 28, and thereafter decreased. Although 2 patients had suffered from SREs before treatment, there were no SREs after combination treatment. CONCLUSIONS: The present study showed that combination of degarelix and antiandrogen could lead to favorable PSA reduction and immediate castrate level at an earlier phase. However, further study is needed to compare the difference between degarelix monotherapy and these combinations.

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Language：Japanese   Publisher：東京 : 科学評論社  

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An 81-year-old man was referred to our hospital because of a right renal tumor with vena cava thrombus and multiple lung metastases that were detected by computed tomography (CT) scan during evaluation of respiratory discomfort. We started medical treatment with sunitinib at a dose of 50 mg daily in a 2-weekon, 1-week-off schedule after confirming clear cell renal cell carcinoma by tumor biopsy. After 2-week sunitinib treatment, thrombocytopenia continued and platelet count decreased to 1.8×109/l at day 11 after stopping sunitinib. We needed to administer a total of 60 units platelet transfusion because of persistent thrombocytopenia. Bone marrow aspiration did not reveal myelosuppression or carcinoma invasion to bone marrow. Under the clinical diagnosis of drug-induced thrombocytopenia secondary to sunitinib, we started immunoglobulin therapy at day 23 after stopping sunitinib. Platelet count returned to normal 10 days after starting immunoglobulin. The patient developed exacerbating lung metastasis and carcinomatous lymphangiosis during subsequent course and died of renal cell carcinoma 79 days after starting sunitinib. Thrombocytopenia after sunitinib therapy is often encountered but prolonged thrombocytopenia is rare after stopping sunitinib. This case suggests that immunoglobulin therapy is effective for drug-induced prolonged thrombocytopenia through immunological mechanism.

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Other Link： http://id.ndl.go.jp/bib/027165931

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A 66-year-old male patient was referred to our hospital for bilateral renal pelvic tumors. Ureteroscopic biopsy revealed urothelial carcinoma (UC) of low grade (G1) of the renal pelvis. Renal sparing treatment with systemic chemotherapy and percutaneous tumor resection was performed. However, during subsequent follow up, a recurrent tumor was foundon the left ureter. After ureteroscopic laser ablation of the tumor, Bacillus Calmette-Guerin (BCG) perfusion therapy (once a week, total 6 weeks) was performed via a single J ureteral catheter with no adverse events. Later, another recurrent recurrence was found on the right ureter, and was managed by ureteroscopic laser ablation followed by BCG perfusion therapy via a single J ureteral catheter. However, the patient developed high fever with chill from the day after initial BCG perfusion therapy on the right side. Although we started antibiotics, high fever continued. Then antituberculous drugs were administered and his condition was improved. Computed tomographic scan revealeda right renal mass 57 mm in diameter, which was consistent with tuberculous granuloma. The tuberculous granuloma persisted despite the continuation of anti-tuberculous drugs. In exceptional cases of upper tract UC such as single kidney andbilateral tumor, BCG perfusion therapy has been usedas adjunctive treatment to cure or prevent UC. However, dosages and administration methods of BCG perfusion therapy for upper tract UC still remain to be standardized. Serious adverse events after BCG perfusion therapy require prompt and proper management including the use of anti-tuberculous drugs.

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When two flat ring coils are layed on a plane in free space, overlapping about 20%, there can be found a null-coupling point where mutual flux coupling is cancelled to make zero transmission to each other. On such setup we can detect nearby interrupting magnetic material and/or LC-resonant tank circuit which causes extra transmission via cross-coupling to the interrupter. Such detection capabikity would depend on accuracy of null-point setup, driving signal design, gain and bandwidth of detecting amplifier and the size of the interrupter to be detected. Adequate design can detect a similar size tank circuit having Q0=70 or more at several times distance of interlogating coil pair diameter. In this study we aimed to use this for extrra corporeal sensing of intra corporeal passive sensing device. In our model experiment 5cm interlogating coil pair can steadily sense 1cm dia. x 1cm length ferrite cored LC tank circut, at 1 to 2 MHz frequency band.

DOI： 10.11239/jsmbe.54annual.1t5-4-5-1

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DOI： 10.11477/mf.1413205527

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Conventional uroflowmetry (UFM) performs an observation of time-serial urinary flow pattern, together with measurements for voided volume, flow rate, etc. Although it's a relatively simple and non-invasive examination, it is based on a urine receiving container like a toilet device equipped with various sensors in hospital. It also causes an unnatural urination due to such unnatural environment, and hence improper understanding of patient status. Our new UFM device aims to abolish the concept of equipping the toilet bowl with various sensors while satisfying the need of measuring urination anytime, anywhere in an easy, natural and repeated manner. We developed two new wearable finger-tip mounted continuous-wave Doppler UFM devices, one with 40KHz airborne ultrasound and the other with K-band (24GHz) millimeter wave. They provide time-series pattern of frequency spectrogram of the Doppler shifted echo of a urination. The Doppler spectrogram gives qualitatively and diagnostically equivalent impression to the urinary flow curve derived from conventional UFM devices. Furthermore, the system can estimate same parameters as conventional UFM devices by integrating locally weighted frequency spectra. It was confirmed that there is a potential for the clinical application of the new UFM devices.

DOI： 10.11239/jsmbe.54annual.s29

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Quadrivalent influenza vaccines were newly available and distributed in Japan from the 2015–16 influenza season. Adverse drug reactions to influenza vaccines among adults are rarely reported, so we carried out a questionnaire survey of adverse drug reaction following quadrivalent influenza vaccination coverage of our medical university and university hospital workers. Overall, 75.3% of adverse drug reactions, mainly solicited injection-site symptoms such as redness, swelling and pain, etc. were reported. No severe adverse drug reactions were reported. The type and frequency of adverse drug reaction were similar to previous reports, and quadrivalent influenza vaccination was well tolerated in adults.<br>

DOI： 10.4058/jsei.31.397

DOI： 10.1248/yakushi.18-00160_references_DOI_WBh1um9bb1EKbs6oTZINj0GtSTj

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Trpm7 is a divalent cation-permeable channel that has been reported to be involved in magnesium homeostasis as well as cellular adhesion and migration. We generated urothelium-specific Trpm7 knock-out (KO) mice to reveal the function of Trpm7 in vivo. A Trpm7 KO was induced by tamoxifen and was confirmed by genomic PCR and immunohistochemistry. By using patch clamp recordings in primary urothelial cells, we observed that Mg(2+)-inhibitable cation currents as well as acid-inducible currents were significantly smaller in Trpm7 KO urothelial cells than in cells from control mice. Assessment of voiding behavior indicated a significantly smaller voided volume in Trpm7 KO mice (mean voided volume 0.28 ± 0.08 g in KO mice and 0.36 ± 0.04 g in control mice, p < 0.05, n = 6-8). Histological analysis showed partial but substantial edema in the submucosal layer of Trpm7 KO mice, most likely due to inflammation. The expression of proinflammatory cytokines TNF-α and IL-1β was significantly higher in Trpm7 KO bladders than in controls. In transmission electron microscopic analysis, immature intercellular junctions were observed in Trpm7 KO urothelium but not in control mice. These results suggest that Trpm7 is involved in the formation of intercellular junctions in mouse urothelium. Immature intercellular junctions in Trpm7 knock-out mice might lead to a disruption of barrier function resulting in inflammation and hypersensitive bladder afferent nerves that may affect voiding behavior in vivo.

DOI： 10.1074/jbc.M115.667899

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INTRODUCTION: We studied the effect of dutasteride on bone mineral density (BMD) in aging male patients with lower urinary tract symptoms (LUTS) and prostatic enlargement. METHODS: We prospectively studied 17 patients with LUTS and prostatic enlargement. Before and 1 year after dutasteride (0.5 mg daily), we assessed International Prostate Symptom Score (IPSS), prostatic volume (PV), serum prostatic-specific antigen (PSA) and testosterone. BMD in the lumbar and femur was measured by DEXA method. RESULTS: Dutasteride significantly reduced PV (from 51 ± 24 to 34 ± 17 ml, p < 0.001) and improved IPSS (from 15.1 ± 9.8 to 11.7 ± 10.3, p < 0.05). Serum PSA was significantly decreased (from 3.2 ± 2.6 to 1.0 ± 0.8 ng/ml, p < 0.001), while serum testosterone "was not changed" significantly. BMD of the lumbar "was not changed" significantly after dutasteride. BMD of the femur was significantly improved (from 0.75 ± 0.14 to 0.82 ± 0.16 g/cm(2), p < 0.01). In nine patients whose testosterone was increased after dutasteride, BMD of the lumbar (from 1.18 ± 0.26 to 1.22 ± 0.25 g/cm(2), p < 0.05) and femur (from 0.76 ± 0.12 to 0.84 ± 0.16 g/cm(2), p < 0.05) was significantly improved. CONCLUSIONS: Dutasteride has a potential to improve BMD with elevation of serum testosterone in aging male patients with LUTS and prostatic enlargement.

DOI： 10.3109/13685538.2015.1072155

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Other Link： http://amcor.asahikawa-med.ac.jp/modules/xoonips/detail.php?id=26225793

Language：Japanese   Publisher：東京 : 医学図書出版  

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Other Link： https://ndlsearch.ndl.go.jp/books/R000000004-I026857144

Authorship：Lead author   Language：Japanese   Publishing type：Research paper (scientific journal)  

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OBJECTIVES: To evaluate the correlation of clinical and urodynamic parameters with bladder vascular resistance before and after dutasteride treatment in patients with lower urinary tract symptoms associated with benign prostatic enlargement. METHODS: A prospective study was conducted in 30 consecutive patients with benign prostatic enlargement who had not been satisfied with alpha-adrenergic antagonist monotherapy. Before and 24 weeks after dutasteride add-on treatment, we assessed International Prostate Symptom Score (IPSS), prostate volume (PV), urodynamic study and contrast-enhanced color Doppler ultrasonography to measure bladder vascular resistive index (RI). RESULTS: Twenty-four weeks after dutasteride, PV significantly decreased from 68 ± 29 to 48 ± 28 mL (P < 0.001), and there was significant improvement of IPSS (from 18.8 ± 7.7 to 13.4 ± 7.2, P < 0.001). Urgency score of IPSS was also significantly improved from 2.3 ± 1.9 to 1.4 ± 1.4 (P < 0.01) after dutasteride. On pressure-flow study, bladder outlet obstruction index (BOOI) (from 58 ± 36 to 38 ± 27, P < 0.001) and detrusor pressure at Qmax (PdetQmax) (from 73 ± 34 to 54 ± 25 cmH2 O, P < 0.001) were significantly improved. RI significantly decreased after dutasteride (from 0.548 ± 0.069 to 0.486 ± 0.064, P < 0.001). In 20 patients with persistent urgency after dutasteride, RI was less improved than in another 10 patients without urgency (change of RI 0.045 ± 0.091 vs. 0.096 ± 0.042, P < 0.05). Post-treatment BOOI and PdetQmax in patients with persistent urgency was significantly higher than in those without urgency after dutasteride (BOOI: 46 ± 28 vs. 24 ± 20, P < 0.05, PdetQmax: 62 ± 26 vs. 40 ± 17 cmH2 O, P < 0.01). CONCLUSIONS: Reduction of obstruction and improvement of bladder ischemia might play an important role in a beneficial impact of dutasteride on overactive bladder symptoms.

DOI： 10.1111/luts.12047

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Other Link： http://amcor.asahikawa-med.ac.jp/modules/xoonips/detail.php?id=26663650

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To investigate the relationship between chronic periodontal disease (CPD) and lower urinary tract symptoms (LUTS) in both sexes.The interview sheet of the CPD self-checklist and LUTS was distributed to 600 adult men and women (300 each) who visited the first dental examination at dental clinics. The International Prostate Symptom Score (IPSS) questionnaire/Quality Of Life (IPSS/QOL) and Overactive Bladder Symptom Score (OABSS) were used to assess LUTS. The relationship between the CPD score and LUTS or OAB was examined.The interview sheet was collected from 88 men (50.9 ± 16.6 years old) and 97 women (51.1 ± 15.5 years old). There was no statistically significant correlation between the CPD score and age, or between the CPD score and the presence of LUTS in either men or women. However, urgency and weak stream score of IPSS were significantly correlated with the severity of CPD in both sexes. Significant correlation between the severity of CPD and the presence of OAB was only noted in men but not in women.The present study demonstrated for the first time that some storage and voiding symptoms were significantly associated with CPD in both sexes. Thus, although CPD and LUTS seem to have common pathophysiological factors, the interrelationship between CPD and LUTS is slightly different between men and women.

DOI： 10.1111/luts.12042

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Language：Japanese   Publishing type：Research paper (bulletin of university, research institution)  

Using a videourodynamic study, we examined the efficacy of combination therapy with mirabegron for anticholinergic-resistant neurogenic bladder. We retrospectively studied 7 patients with neurogenic bladder (5 males and 2 females) who had detrusor overactivity (DO) or low compliance bladder (＜10 ml/cmH2O) despite taking anticholinergic medication. Bladder deformity was categorized from G0 to G3 by Ogawa’s classification. Mean age of study patients was 51 years (25-76). Underlying diseases were spinal cord injury in 3 patients, spina bifida in 2, spinal cord infarction in 1, and post-radical hysterectomy in 1. Preceding anticholinergic medication was solifenacin 5 mg in 1 patient, solifenacin 10 mg in 5, and tolterodine 4 mg in 1. Before mirabegron, bladder deformity was G1 in 4 patients, G2 in 1 and G3 in 2, and vesicoureteral reflux (VUR) was detected in 3 patients. Five and 4 patients had detrusor overactivity and low compliance bladder, respectively. Videourodynamic study was reevaluated at a mean of 7 months (2- 12 months) after mirabegron. After mirabegron, urinary incontinence was improved in all patients. G3 bladder deformity was improved to G2 and G1 in one patient each, and VUR disappeared in all 3 patients. DO disappeared in 2 of the 5 patients, and bladder compliance was improved in all 4 patients with low compliance bladder. In conclusion, combination therapy of mirabegron is effective and beneficial for anticholinergic-resistant neurogenic bladder.

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Other Link： http://id.ndl.go.jp/bib/026062885

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Language：Japanese   Publishing type：Research paper (scientific journal)   Publisher：The Japanese Pharmacological Society  

DOI： 10.1254/fpj.147.40

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Language：Japanese   Publisher：Japanese Society for Medical and Biological Engineering  

The study presented here relates a tissue hardness (stiffness) measurement system, or more precisely for example, external labor transducer for monitoring of gravidae, including possible cases of fetal and maternal combined signal transducer. As a theory of measurement, suction cup is applied on subject body surface where the tissue hardness thereon or shallow depth, is to be measured. Unlike conventional “pushing” type measurement, our method is to apply negative pressure (sucking) thereon by suction cup. Response of the body surface to this negative pressure is measured for external labor for example. The advantage of this method is that the suction cup can hold it on body surface for itself, to allow belt-less labor (and fetal signal by the way) transducer, for easier operation.Keywords: external labor sensing, suction cup, transducer, belt, fetal, maternal

DOI： 10.11239/jsmbe.53.s272_03

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DOI： 10.1016/J.JURO.2015.02.2165

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DOI： 10.1016/J.JURO.2015.02.1815

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DOI： 10.1016/J.JURO.2015.02.1366

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DOI： 10.1016/J.JURO.2015.02.1295

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When one need measurement, signal acquisition and wireless transmission, the electronics inevitably needs an adequate supply of operating power. In case of intra-corporeal telemetry device, unless fed extra-corporeally by other means, the operating power must be supported by a local battery there. In this study we devised an intra-corporeal battery system using body fluid available there as presiding electrolyte, to make obvious electronic component “battery” unnecessary in a capsule type sensor-telemeter transmitter. It employs a pair of electrode, magnesium for negative and silver-silver-chloride or carbon positive, placed across the surface of the plastic capsule. Their electrochemical potential difference causes an in-situ primary battery, for example, 1.2V～1.7V, 10～20 microampere capability. A model capsule about 6mm dia. and 12mm length having such electrode cylinders pair electrically separated over core plastic material (poly-oxymethylene(POM), also called poly-acetal or Delrin). In physiological saline water or human urea, the model device operated successfully for more than 24 hours continuously, to conclude a positive feasibility for practical use.

DOI： 10.11239/jsmbe.53.s202_03

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OBJECTIVES: To examine urinary nerve growth factor before and after dutasteride treatment, and to analyze correlations between clinical parameters and change of urinary nerve growth factor in patients with benign prostatic enlargement. METHODS: We prospectively studied 30 patients with benign prostatic enlargement who had not been satisfied with α-adrenergic antagonist monotherapy for more than 3 months. Before and 24 weeks after dutasteride add-on treatment, we assessed International Prostate Symptom Score, prostatic volume, filling cystometry and pressure-flow study. Urinary nerve growth factor was measured by enzyme-linked immunosorbent assay, and normalized to the urinary creatinine (nerve growth factor/creatinine) before and 24 weeks after dutasteride add-on treatment. RESULTS: In baseline characteristics before dutasteride, there was no significant correlation between urinary nerve growth factor/creatinine and any clinical parameters including age, International Prostate Symptom Score, prostatic volume, presence of detrusor overactivity, detrusor pressure at maximum flow rate, bladder outlet obstruction index or bladder contractility index. Dutasteride significantly reduced prostatic volume (from 68 ± 31 mL to 49 ± 28 mL) and improved International Prostate Symptom Score (from 17.2 ± 8.7 to 13.1 ± 6.8), storage (from 8.0 ± 4.3 to 6.0 ± 2.9) and voiding symptom subscore of International Prostate Symptom Score (from 9.3 ± 5.7 to 7.1 ± 4.5). In urodynamic study, detrusor pressure at maximum flow rate (from 77 ± 32 cmH2 O to 59 ± 24 cmH2 O) and bladder outlet obstruction index (from 62 ± 32 to 42 ± 27) were significantly decreased after dutasteride treatment. Urinary nerve growth factor/creatinine was significantly decreased after dutasteride from 2.61 ± 2.50 to 1.64 ± 1.68. The change of urinary nerve growth factor/creatinine significantly correlated only with the change of prostatic volume (r = 0.38) and bladder outlet obstruction index (r = 0.36). CONCLUSIONS: Urinary nerve growth factor decreases in association with reduction of prostatic volume and relief of bladder outlet obstruction. Urinary nerve growth factor might be useful as a biomarker to monitor the improvement of bladder outlet obstruction in patients with benign prostatic enlargement.

DOI： 10.1111/iju.12570

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Language：Japanese   Publishing type：Research paper (bulletin of university, research institution)  

We examined perioperative complications of transurethral resection of bladder tumor (TURBT) in patients receiving antithrombotic therapy. We retrospectively studied 276 patients who underwent TURBT in our institute from January 2007 to March 2013. The study group consisted of 105 patients (38%) who were receiving antithrombotic agents, and the other 171 patients (62%) without antithrombotic agents were assigned to the control group. The period of discontinuation of antithrombotic agents complied with our institutional rule. The most frequently used agent was aspirin (69 patients : 66%), followed by warfarin (25 patients : 24%). Fourteen patients receiving warfarin (56%) needed heparin bridging therapy. There was no significant difference in average operative time (51 minutes versus 54 minutes), or average days to removal of urethral catheter (3.7 days versus 3.3 days) between the study and control groups. Hemorrhagic and ischemic complications were noted in 11 (10.5%) and 2 (1.9%) patients in the study group and 11 (6.4%) and none (0%) of the patients in the control group, respectively, with no significant difference between the 2 groups. However, prevalence of hemorrhagic complications in patients receiving heparin bridging therapy (21.4%) was significantly higher than that in the control group. Ischemic complications in the study group included chest pain suggestive of angina in one patient and acute myocardial infarction leading to death in another patient. We should pay attention to hemorrhagic complications in patients receiving heparin bridging therapy and keep in mind the possibility of lethal ischemic complications after discontinuation of antithrombotic agents.

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Other Link： http://id.ndl.go.jp/bib/025935601

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To investigate the impact of abdominal aortic calcification and visceral fat area (VFA) on lower urinary tract symptoms (LUTS) and clinical parameters in patients with benign prostatic hyperplasia (BPH).We retrospectively studied 250 patients with LUTS associated with BPH. Each participant was examined with routine examination including measurement of various data; (1) voided volume (VV), maximum urinary flow rate on free uroflowmetry, (2) postvoid residual urine volume and prostate volume using transabdominal ultrasound, (3) International Prostate Symptom Score (IPSS) and Overactive Bladder Symptom Score (OABSS), and (4) aortic calcification index (ACI) and VFA were measured by abdominal CT.Mean age of the patients was 72.4 ± 9.6 years. ACI significantly correlated with VV (P = 0.0392) and tended to correlate with maximum urinary flow rate, while ACI did not correlate with subjective symptoms. VFA significantly correlated with nocturia score of IPSS (P = 0.0177) and frequency score of OABSS (P = 0.0166) and tended to correlate with urgency score of IPSS and maximum urinary flow rate.Aortic calcification index (ACI) correlated with only objective parameters, while VFA correlated with only storage symptoms. This study suggested that abdominal aortic calcification and VFA have certain influence on LUTS and clinical parameters in patients with BPH.

DOI： 10.1007/s11255-014-0757-3

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Other Link： http://amcor.asahikawa-med.ac.jp/modules/xoonips/detail.php?id=24908284

Language：Japanese   Publisher：東京 : 医学図書出版  

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Other Link： https://ndlsearch.ndl.go.jp/books/R000000004-I026857425

Publisher：株式会社医学書院  

DOI： 10.11477/mf.1413103668

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Language：English   Publishing type：Research paper (scientific journal)   Publisher：Elsevier {BV}  

OBJECTIVE: To investigate whether bladder dysfunction after bladder outlet obstruction (BOO) could be altered by treatment with cilostazol, a phosphodiesterase 3 inhibitor (PDE3i). METHODS: Twelve-week-old female Sprague-Dawley rats were divided into 5 groups: groups 1 and 2, sham-operated rats and groups 3-5, BOO rats. Group 1 and 3 rats were given normal diet, group 2 and 5 rats were given high-dose PDE3i diet, and group 4 rats were given low-dose PDE3i diet. PDE3i was given within diet from the day of surgery. Four weeks after BOO, the bladder was excised and dissected into 4 longitudinal strips for isometric organ-bath assay. Contractile responses of bladder strips to electrical field stimulation (EFS), carbachol, and potassium chloride (KCl) were determined for each group. RESULTS: BOO induced a significant increase in bladder weight in groups 3-5 compared with groups 1 and 2. PDE3i treatment did not affect bladder weight in sham or BOO rats. Contractile forces in response to EFS, carbachol, and KCl in group 3 were about 20%-40% of those in group 1. Contractile responses to EFS or KCl in PDE3i-treated BOO rats were not significantly different from those in group 3. Only high dose of PDE3i treatment in BOO rats caused a statistically significant increase in the response to carbachol compared with group 3. CONCLUSION: PDE3i has a small but significant protective effect on the contractile dysfunction induced by a 4-week BOO in rats, although the increase in bladder mass was not altered. PDE3i could be a useful protection against contractile dysfunction of the obstructed bladder.

DOI： 10.1016/j.urology.2013.11.030

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Other Link： http://amcor.asahikawa-med.ac.jp/modules/xoonips/detail.php?id=24581543

Language：Japanese   Publishing type：Research paper (bulletin of university, research institution)  

An 11-year-old girl visited the emergency room of our hospital with complaints of pain, nausea and gross hematuria after abdominal injury due to a fall from a fence. Computed tomography (CT) showed ruptured right kidney, hematoma, urinoma, and slight liver damage in S7 area. According to the Classification of Renal Injury by the Japanese Association for the Surgery of Trauma, this case was Type IIIb, but according to the American Association for the Surgery of Trauma Organ Injury Severity Scale for the Kidney, it was Type V. Because her vital signs were stable after admission, conservative management was initiated. There was no progression of anemia, and blood transfusion was not required. Right ureteral stenting was performed on the 4th hospital day because of an increase in fluid accumulation around the right kidney. Percutaneous drainage was performed on the 9th hospital day because of a further increase in fluid accumulation around the right kidney. After percutaneous drainage, fluid accumulation around the kidney was improved, and the drainage tube was removed on the 20th hospital day. The patient was discharged on the 22nd day. Although the decreased blood flow in the ruptured portion of the right kidney was observed in a subsequent CT scan, renal scintigraphy showed a relatively well maintained function of the right kidney (split renal function ; right 38% and left 62%). She had no increase in blood pressure one year after renal injury.

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Other Link： https://ndlsearch.ndl.go.jp/books/R000000004-I025399179

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OBJECTIVES: To evaluate the clinical efficacy of transurethral resection of the prostate on nocturia and sleep disorders in patients with lower urinary tract symptoms suggestive of benign prostatic obstruction. METHODS: A prospective multicenter study including lower urinary tract symptoms suggestive of benign prostatic obstruction patients with nocturia (twice or more) undergoing transurethral resection of the prostate was carried out. All patients were assessed using the International Prostate Symptom Score and the Pittsburgh Sleep Quality Index at baseline, and 6 months after transurethral resection of the prostate. RESULTS: Overall, 49 patients were included in the study. A total of 20 of them (41%) had a sleep disorder defined as a score of 5.5 or more on the Pittsburgh Sleep Quality Index global score. The nocturia score significantly correlated with component 4 of the Pittsburgh Sleep Quality Index (habitual sleep efficiency). Nocturia significantly decreased after transurethral resection of the prostate from 3.0 ± 1.2 to 1.9 ± 0.8, whereas the global Pittsburgh Sleep Quality Index score did not. In 20 patients with a sleep disorder before transurethral resection of the prostate, subjective sleep quality (component 1) and habitual sleep efficiency (component 4) significantly decreased after transurethral resection of the prostate, but this was not the case for the global Pittsburgh Sleep Quality Index score. In 16 patients with a persistent sleep disorder after transurethral resection of the prostate, International Prostate Symptom Score, voiding and storage symptoms score were higher than those of patients without a sleep disorder, although the nocturia score improved equivalently in both groups. CONCLUSIONS: Transurethral resection of the prostate diminishes nocturnal urinary frequency and partly improves sleep quality in patients with nocturia and lower urinary tract symptoms suggestive of benign prostatic obstruction. A persistent sleep disorder after transurethral resection of the prostate is associated with persistent voiding and storage symptoms.

DOI： 10.1111/iju.12185

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Other Link： http://id.ndl.go.jp/bib/028506242

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DOI： 10.1016/J.JURO.2014.02.702

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DOI： 10.1016/J.JURO.2014.02.1981

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AIMS: We prospectively investigated the effect of dutasteride on clinical and urodynamic parameters in patients with benign prostatic enlargement (BPE). MATERIALS AND METHODS: A prospective study was conducted in consecutive 52 patients with BPE who had not been satisfied with alpha-adrenergic antagonist monotherapy. Inclusion criteria were prostate volume (PV) ≥30 ml and the International Prostate Symptom Score (IPSS) ≥8 or QOL index ≥3 under administration of an alpha-adrenergic antagonist without anticholinergic agent. Before and 24 weeks after dutasteride (0.5 mg daily) add-on treatment with preceding alpha-adrenergic antagonist, we assessed IPSS, uroflowmetry (UFM), filling cystometry, and pressure-flow study (PFS). RESULTS: Dutasteride add-on treatment significantly improved IPSS (from 18.4 ± 7.5 to 13.8 ± 7.3) and maximum flow rate (from 11.4 ± 5.6 to 13.0 ± 6.8 ml/sec). Maximum cystometric capacity on filling cystometry did not change significantly by dutasteride add-on treatment (221 ± 97 and 240 ± 104 ml before and after dutasteride add-on, respectively). All of the 41 patients with detrusor overactivity (DO) before dutasteride add-on treatment showed apparent reduction in the amplitude of involuntary detrusor contraction after dutasteride add-on treatment, including seven in whom DO disappeared. Dutasteride significantly reduced PV from 66.4 ± 31.9 to 47.6 ± 26.1 ml. In PFS, detrusor pressure at maximum flow rate (PdetQmax) significantly decreased from 71.5 ± 30.1 to 59.1 ± 24.9 cmH2O after dutasteride add-on treatment. Bladder outlet obstruction index (BOOI) also decreased significantly from 55.2 ± 31.9 to 42.3 ± 27.9, and obstruction grade assessed by the Schäfer nomogram significantly improved. CONCLUSIONS: Dutasteride can improve lower urinary tract symptoms by improving storage bladder function and relieving obstruction.

DOI： 10.1002/nau.22349

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Language：Japanese   Publisher：東京 : 電子情報通信学会  

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Other Link： https://ndlsearch.ndl.go.jp/books/R000000004-I024925930

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AIMS: Ischemia-reperfusion injury is an important factor in the development of lower urinary tract symptoms (LUTS) that is partly mediated by the generation of free radicals. We investigate the effect of the phytotherapeutic agent Eviprostat, a treatment for benign prostatic hyperplasia (BPH) that has antioxidant and anti-inflammatory activity, on urinary bladder blood flow (BBF), and function in a rat model of bladder overdistension and emptying (OE). METHODS: For 8 days before surgery, OE rats received daily oral Eviprostat (36 mg/kg/day) or vehicle, while sham-operated animals received vehicle. The bladder was distended by infusion of saline over a period of 2 hr (overdistension) and then emptied. After 24 hr, BBF was measured with a laser speckle blood flow imager. The oxidative-stress marker malondialdehyde (MDA), proinflammatory cytokines, and myeloperoxidase were determined in the isolated bladder, and histological analysis was performed. Functional contractile responses of bladder strips to electrical field stimulation, carbachol, and KCl were measured. RESULTS: Twenty-four hours after bladder OE, a significant decrease in BBF and significant increases in bladder weight, malondialdehyde, proinflammatory cytokines, and myeloperoxidase were observed. Eviprostat almost completely prevented these changes. Histological analysis of the bladder of OE rats showed hemorrhage, accumulation of leukocytes, desquamation of epithelium, and edema, and Eviprostat suppressed these changes. The reduction in functional contractile forces in the bladder of OE rats was also prevented by Eviprostat. CONCLUSION: Eviprostat-mediated suppression of increased bladder oxidative stress and inflammation caused by bladder OE may contribute to the improvement of BBF and bladder function by Eviprostat.

DOI： 10.1002/nau.22350

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To examine the relationship between chronic periodontal disease (CPD) and ED, the interview sheet including the CPD self-checklist (CPD score) and the five-item version of the International Index of Erectile Function (IIEF-5) was distributed to 300 adult men who received a comprehensive dental examination. Statistical analyses were performed by the Spearman's rank correlation coefficient and other methods. Statistical significance was accepted at the level of P<0.05. The interview sheets were collected from 88 men (response rate 29.3%, 50.9±16.6 years old). There was a statistically significant correlation between the CPD score and the presence of ED (P=0.0415). The results in the present study suggest that ED is related to the damage caused by endothelial dysfunction and the systematic inflammatory changes associated with CPD. The present study also suggests that dental health is important as a preventive medicine for ED.International Journal of Impotence Research advance online publication, 4 July 2013; doi:10.1038/ijir.2013.30.

DOI： 10.1038/IJIR.2013.30

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To investigate bladder function in a model of nonbacterial prostatitis (NBP) induced in castrated rats by 17β-estradiol injection.Ten-month-old male Wistar rats were divided into two groups, sham and NBP (both N = 8). NBP was induced by castration followed by daily subcutaneous injection of 17β-estradiol for 30 days. On the 31st day after surgery, we investigated (1) voiding behavior, (2) bladder blood flow (BBF), (3) prostate and bladder weight, and proinflammatory cytokines (TNF-α and CXCL1) levels and (4) bladder contractile responses to electrical field stimulation (EFS), carbachol and KCl.(1) Voiding behavior (average micturition volume, total urine volume and number of micturitions) and (2) BBF were not significantly different between the sham and NBP groups. (3) NBP led to a significant decrease in prostatic weight and increase in proinflammatory cytokine levels in the prostate, but NBP did not cause a significant change in bladder weight or proinflammatory cytokine levels in the bladder. (4) Bladder contractile forces in response to EFS, carbachol and KCl were not significantly affected by NBP.In this rat model, NBP did not cause a significant change in the level of proinflammatory cytokines in the bladder and affect bladder function.

DOI： 10.1007/s11255-013-0442-y

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UNLABELLED: WHAT'S KNOWN ON THE SUBJECT? AND WHAT DOES THE STUDY ADD?: There is known to be an association between overactive bladder (OAB) and irritable bowel syndrome (IBS). The study investigates the association between OAB and IBS using an internet-based survey in Japan. It is the first to investigate the prevalence and severity of OAB in the general population using the OAB symptom score questionnaire. OBJECTIVE: To investigate the association between overactive bladder (OAB) and irritable bowel syndrome (IBS) by using an internet-based survey in Japan. SUBJECTS AND METHODS: Questionnaires were sent via the internet to Japanese adults. The overactive bladder symptom score was used for screening OAB, and the Japanese version of the Rome III criteria for the diagnosis of IBS was used for screening this syndrome. RESULTS: The overall prevalence of OAB and IBS was 9.3% and 21.2%, respectively. Among the subjects with OAB, 33.3% had concurrent IBS. The prevalence of OAB among men was 9.7% and among women it was 8.9%, while 18.6% of men and 23.9% of women had IBS. Concurrent IBS was noted in 32.0% of men and 34.8% of women with OAB. CONCLUSION: Taking into account a high rate of concurrent IBS in patients with OAB, it seems to be important for physicians to assess the defaecation habits of patients when diagnosing and treating OAB.

DOI： 10.1111/j.1464-410X.2012.11591.x

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OBJECTIVE: To investigate the efficacy of hydrogen-rich water for the treatment of patients with interstitial cystitis/painful bladder syndrome (IC/PBS). METHODS: We conducted a prospective, randomized, double-blind, placebo-controlled clinical trial of hydrogen-rich water in patients with IC/PBS. Inclusion criteria were stable symptoms of IC/PBS for ≥ 12 weeks after bladder hydrodistension, Interstitial Cystitis Symptom Index score of ≥ 7 and bladder pain (question 4 on Interstitial Cystitis Symptom Index) of ≥ 4. They were randomized by a 2:1 ratio to receive hydrogen-rich water or placebo water for 8 weeks. The symptoms were assessed using the Interstitial Cystitis Symptom Index, Interstitial Cystitis Problem Index, Parsons' Pelvic Pain and Urgency/Frequency Patient Symptom Scale, visual analog scale bladder pain scores, and a standard 3-day voiding diary. The primary outcome was improvement of patient-reported symptoms evaluated after treatment. RESULTS: A total of 30 participants (29 women and 1 man, age 64.0 ± 14.8 years) were enrolled in the present study, and 2 patients (both women) were withdrawn from the study. The score of bladder pain was significantly reduced in both groups. However, the effect of hydrogen-rich water on symptoms was not significantly different from that of placebo, although supplementation with hydrogen-rich water was extremely effective in improving the bladder pain score in 11% of the patients. CONCLUSION: The results of the present study do not support the use of supplementation with hydrogen-rich water for treating patients with IC/PBS.

DOI： 10.1016/j.urology.2012.10.026

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OBJECTIVES: To investigate the effect of intrathecal administration of E-series prostaglandin 1 antagonist in cyclophosphamide-induced murine cystitis. METHODS: Female Wistar rats were used for this experimental study. Intrathecal administration of E-series prostaglandin 1 antagonist (ONO-8711; 0.5, 5 and 50 µg) in sham controls and rats with cystitis induced by a single intraperitoneal injection of cyclophosphamide (300 mg/kg) was assessed by evaluating micturition pressure and intercontraction interval using a conscious-filling cystometry at 48 h after cyclophosphamide or saline injection. In both groups, prostaglandin E2 concentrations and the expression of E-series prostaglandin 1 receptor in the spinal cord were measured by enzyme-linked immunosorbent assay and reverse transcription polymerase chain reaction, respectively. RESULTS: Rats with cyclophosphamide-induced cystitis showed a shorter intercontraction interval compared with controls, where the cumulative intrathecal administration of ONO-8711 did not significantly change micturition pressure or intercontraction interval compared with the baseline. In rats with cyclophosphamide-induced cystitis, each dose of ONO-8711 significantly increased the intercontraction interval compared with the baseline (46% increase at 50 µg intrathecally). Polymerase chain reaction revealed the expression of E-series prostaglandin 1 receptor in the spinal cord of both sham and cyclophosphamide-induced cystitis rats. In rats with cyclophosphamide-induced cystitis, PGE2 concentration in the dorsal horn of the L5-6 spinal cord was significantly higher than that in controls (3.55 ± 1.24 vs 0.99 ± 0.06 pg/mg tissue). CONCLUSIONS: In rats with cyclophosphamide-induced cystitis, urinary frequency seems to be caused by prostaglandin E2 acting on E-series prostaglandin 1 receptor at the level of the spinal cord. Blockade of the spinal E-series prostaglandin 1 receptor by ONO-8711 might have a therapeutic potential in the control of interstitial cystitis/bladder pain syndrome.

DOI： 10.1111/j.1442-2042.2012.03126.x

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DOI： 10.1111/j.1442-2042.2012.03199.x

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DOI： 10.1016/J.JURO.2013.02.649

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DOI： 10.1093/ANNONC/MDT460.23

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過活動膀胱は尿意切迫感を主体とする蓄尿症状を呈する症状症候群である。小児の過活動膀胱はself-esteemの確立やQOLに多大な影響を与えるため、適切な診断方法および有効な治療体系の確立が望まれる。機能的脳画像により、蓄尿に重要な中枢は、島、視床、前帯状回、被殻、中脳中心灰白質、橋、小脳などであり、特に前帯状回は行動を調節する部位としても重要であることが判明している。脳の機能異常が膀胱機能に影響する一方、膀胱の機能異常は蓄尿に対する脳の反応を変化させ、脳波の変化をもたらし、睡眠中の覚醒の亢進をもたらす。健常成人では睡眠は膀胱容量を増大させるが、過活動膀胱患者では睡眠による膀胱容量の増大効果が低下し、夜間頻尿につながる。夜尿症のない健常児においても、夜間の機能的膀胱容量は日中の1.6〜2.1倍に達するとされているが、小児の治療抵抗性の夜尿症では夜間の機能的膀胱容量の減少が認められている。抗コリン薬を用いて過活動膀胱を治療すると、蓄尿症状の改善とともに睡眠障害が改善し、また夜間多尿指数が改善する可能性があることが報告されている。今後は、小児を対象とした機能的脳画像や睡眠の質の解析などを行うことで、過活動膀胱が睡眠に及ぼす影響を小児患者で解析することが求められており、このような研究は夜尿症の病態解明やより有効な治療法の確立にも貢献することが期待される。
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DOI： 10.11477/mf.1413103250

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We investigated the add-on effect of dutasteride (0.5 mg once a day) on lower urinary tract symptoms (LUTS), prostate volume (PV), and serum prostate specific antigen (PSA) and testosterone level in 72 patients with benign prostatic hyperplasia (BPH) who had been treated with alpha-blocker monotherapy. Inclusion criteria were men with BPH who had PV ≧30 ml and international prostate symptom score (IPSS) ≧8 or quality of life (QOL) index ≧3 under alpha-blocker monotherapy for more than 3 months. At the baseline, 12 and 24 weeks after dutasteride add-on, we assessed IPSS, overactive bladder symptom score (OABSS), PV, serum PSA and testosterone. Among 47 patients (65%) with OAB diagnosed by OABSS, responders were defined as those with urgency score of OABSS ＜2 or total score of OABSS ＜3. At the 24th week, dutasteride significantly improved IPSS (−4.2) and OABSS (−1.9) and reduced PV (−29%) compared with the baseline. Furthermore, dutasteride significantly decreased serum PSA (−45%) and increased testosterone (36%). Among OAB patients, dutasteride significantly improved urgency and urgency incontinence but not nocturia. Responders had lower OABSS, urgency incontinence score and serum testosterone at the baseline than non-responders. In conclusion, dutasteride add-on therapy is beneficial in patients with BPH who do not show enough improvement with alpha-blocker monotherapy.

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AIMS: To evaluate bladder vascular resistance before and after transurethral resection of the prostate (TURP). METHODS: Thirty-three patients with lower urinary tract symptoms (LUTS) suggestive of benign prostatic obstruction were prospectively studied. We analyzed correlations of bladder vascular resistance with various factors including age, vascular risk factors, symptom score, prostate volume (PV), and urodynamic parameters before and 3 months after TURP. Using contrast-enhanced color Doppler ultrasonography for measuring bladder vascular resistance, resistive index (RI) of vesical arteries was calculated. RESULTS: Compared with healthy young male (n = 10) and age-matched controls (n = 10), the study patients had a higher preoperative RI (0.403 ± 0.100, 0.436 ± 0.042, and 0.561 ± 0.089, respectively; P < 0.01). Preoperative RI was significantly higher in patients with PV ≥ 60 ml versus <60 ml (0.604 ± 0.078 vs. 0.525 ± 0.082; P < 0.01), and in patients with severe obstruction versus mild/moderate obstruction (0.615 ± 0.087 vs. 0.534 ± 0.078; P = 0.017). Overall RI decreased significantly after TURP (from 0.561 ± 0.089 to 0.450 ± 0.086; P < 0.001). In patients with persistent urgency after TURP, RI was less improved than in those without urgency after TURP (change of RI 0.068 ± 0.098 vs. 0.135 ± 0.090; P < 0.05). This study was limited by a small sample size. CONCLUSIONS: Bladder vascular resistance in patients with LUTS was elevated in correlation with PV and severity of obstruction. Although bladder vascular resistance decreased significantly after TURP in overall patients, less reduction of vascular resistance was related to persistent urgency after TURP, implying that persistent urgency after TURP might be caused by persistent bladder ischemia.

DOI： 10.1002/nau.21201

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The association between metabolic syndrome and lower urinary tract symptoms has been attracting enormous interest and attention. This enthusiasm is based on the presence of many common risk factors being involved in both metabolic syndrome and lower urinary tract symptoms, as shown by various epidemiological studies. Metabolic syndrome and lower urinary tract symptoms have many pathophysiological features in common, particularly overactive bladder. Herein, we analyze the pathophysiological relationship between metabolic syndrome and lower urinary tract symptoms with a special emphasis on bladder blood flow. We also propose a new treatment strategy for treating lower urinary tract symptoms from the viewpoint of bladder blood flow.

DOI： 10.1111/j.1442-2042.2011.02903.x

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Solitary fibrous tumor (SFT) is a neoplasm of pleura and its occurrence in the retroperitoneal space is rare. We report a case of SFT of the adrenal gland associated with ipsilateral renal cell carcinoma (RCC) and angiomyolipoma (AML).A48-year-old woman was referred to our hospital for a left renal AML. Computed tomography (CT) in our hospital showed a left adrenal mass (25×20 mm). Because the adrenal tumor was nonfunctioning, she was followed at outpatient clinic. Four years later, CT showed an increase in the left adrenal tumor size (42×30 mm) and a left RCC. Left adrenectomy and partial nephrectomy for RCC and AML were simultaneously performed. Histological examination revealed adrenal SFT and clear cell carcinoma and AML of the kidney.We present a brief review on histological characteristics of retroperitoneal SFT and its occurrence in the adrenal grand region.

DOI： 10.5980/jpnjurol.103.573

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高齢化に伴い、下部尿路機能障害(LUTD)を有する人が増加しているが、その多くが「歳のせい」等の理由で受診していない。(株)セガの「トイレッツ」は、既存の男性用トイレに設置する広告機能付きゲーム機で、おおよその尿量が主に表記される。その結果により多くの人が排尿を身近に感じ、受診のきっかけになる可能性があると思われる。今回、「トイレッツ」を体験した中高年男性を対象に、LUTDの啓発として有効なツールになり得る可能性があるか否かをアンケートにより調査をした。その結果、81.5%が「トイレッツを体験して排尿状態を意識した」と回答しており、「トイレッツ」にて自分の排尿を知るきっかけになり、LUTDの啓発ツールに利用できる可能性が示唆された。
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下部尿路機能障害(LUTD)の診断や治療法の選択には、尿流動態検査(UDS)は必要不可欠である。現状のUDSのさまざまな問題点を克服するため、侵襲性の少ないUDSが発案・開発されており、またより快適な新しい発想の尿流測定装置も出現してきている。近年の工学技術の向上もあり、「アメニティのあるUDS」への追及は、UDSを取り巻く環境の改善も含めて、新たなステージに入りつつあると思われ、より快適なUDSの登場を期待したい。
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OBJECTIVE: To evaluate the efficacy of imidafenacin on nocturia and sleep disorder in patients with overactive bladder (OAB). PATIENTS AND METHODS: A prospective multicenter study of imidafenacin 0.1 mg twice daily for patients with OAB and nocturia was conducted. At baseline and at week 4 and 8, patients were assessed using the overactive bladder symptom score (OABSS), frequency volume charts (FVC) and the Pittsburgh Sleep Quality Index (PSQI). RESULTS: Treatment with imidafenacin significantly improved OAB symptoms. Imidafenacin also improved PSQI, especially subjective sleep quality, sleep latency and daytime dysfunction. In FVC, the number of daytime voids and nighttime voids significantly decreased and average voided volume significantly increased after imidafenacin. Subanalysis of FVC based on the patients' age revealed that nocturnal polyuria was more often found in patients aged 75 years or over than in those aged under 75 years (79 vs. 55%, p < 0.05). Treatment with imidafenacin significantly reduced the nocturnal polyuria index only in patients aged 75 years or over. CONCLUSIONS: Imidafenacin can improve nocturia and sleep disorder in patients with OAB. The efficacy of imidafenacin on nocturia is attributable to an increase in bladder capacity and a decrease in nocturnal urine volume. We conclude that imidafenacin is an effective and safe drug for nocturia in patients with OAB.

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PURPOSE: Decreased bladder blood flow was the subject of a recent study as a pathophysiological cause of bladder overactivity. We developed a rat model of bladder over distention/emptying induced bladder overactivity and investigated the effect of the α(1)-adrenoceptor antagonist tamsulosin on bladder blood flow and bladder function in this model. MATERIALS AND METHODS: The bladder was distended with 2 ml saline using anesthesia for 2 hours (over distention) and then emptied. Bladder blood flow was measured using a perfusion imager. Micturition behavior and parameters were observed using a metabolic cage and a cystometry method, respectively, from 2 hours after bladder emptying. After model establishment was confirmed we examined the participation of afferent C-fibers and the effects of tamsulosin in rats pretreated with capsaicin (Sigma-Aldrich®) (125 mg/kg) and tamsulosin (1 μg/kg per hour), respectively, using a metabolic cage. RESULTS: Decreased bladder blood flow was observed upon over distention with partial recovery at emptying. Bladder over distention/emptying increased micturition frequency and decreased mean voided volume in the micturition recording study, and decreased the intercontraction interval and voided volume without affecting micturition pressure, threshold pressure or post-void residual volume in the cystometry study. Capsaicin pretreatment did not affect bladder overactivity. However, 1-week continuous treatment with tamsulosin increased bladder blood flow after bladder emptying, resulting in decreased micturition frequency and increased voided volume. CONCLUSIONS: Bladder over distention/emptying induced bladder blood flow decrease/partial recovery and caused bladder overactivity via a mechanism other than capsaicin sensitive C-fiber activation. Findings in tamsulosin treated rats confirmed the potency of tamsulosin to increase bladder blood flow and ameliorate bladder overactivity.

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DOI： 10.24492/use.32.0_449

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The patient is a 69-year-oldmale. His chief complaint was chest pain. Because imaging studies suggestedpleural mesothelioma associatedwith multiple bone metastases, right pleural tumor resection was performed. Pathological diagnosis was metastatic pleural tumor, and renal cell carcinoma (RCC) was suspectedas its origin. Dynamic computedtomography showeda small tumor in the right kidney. The tumor was 15 mm in diameter and consistent with RCC. Laparoscopic radical nephrectomy was performed for the right kidney. Pathological diagnosis was RCC, clear cell carcinoma with sarcomatoid component, T1aN0M1, stage IV. Sorafenib therapy was started46 days after the operation as a systemic therapy, and stable disease has been maintained. Generally, small RCC is assumed to have a good prognosis. However, a small percentage of patients with small RCC have distant metastasis at the time of diagnosis, and the prognosis is reportedto be poor. We report this case, anda review of the literature.

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膀胱外反症の根治手術の際に使用した非吸収性テープにより発生した再発性尿道肉芽腫の男児例につき報告する。2004年10月体外受精・胚移植による妊娠後37週2020gで出生。出生時に膀胱外反症と診断され、生後6日目に他院にて膀胱尿道閉鎖術が施行されたが、尿道組織に余裕がなく、外尿道口は陰茎陰嚢部に位置し、尿道下裂の状態となった。同時に整形外科医により離開した恥骨結合の修復が施行された。その後当院を通院し始めるが、術後1年過ぎより外尿道口から腫瘤の出現を認め、出血を起こすため内視鏡的に切除した。膀胱頸部12時方向に茎があり、病理組織学的には炎症性肉芽組織であった。初回切除から22ヵ月の間に3回の再発があり、経尿道的また経膀胱瘻的に腫瘍を再切除した。4回目の経膀胱瘻的切除の際、切除した腫瘤の根部に白色の繊維性物質を認めた。膀胱外反症の手術時、離開した恥骨結合はダクロンテープを両側閉鎖孔に通して引き寄せることで修復されており、ダクロンテープが異物となって発生した尿道肉芽腫と診断した。2009年3月、恥骨部の皮膚を正中切開し、恥骨結合下縁で結び目のあるダクロンテープを確認後、ダクロンテープを切断して摘出した。尿道前壁がやや欠損する形となったため、周囲組織をあわせて前壁を閉じた。その後尿道肉芽腫の再発は認めていない。尿路に近接する部位に非吸収糸やテープを用いると、異物反応が惹起されることが再確認された。膀胱外反症に付随する恥骨結合の離開に対しては、太い吸収糸を用いて左右恥骨の結節縫合を行うなど、術式に留意すべきである。
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前立腺肥大症(BPH)は、中高齢男性の排尿障害として最もよくみられる前立腺疾患である。BPHの有病率は高く、加齢とともに増加し、昨今の高齢化社会でその患者数はさらに増加していると推察される。BPH治療薬も多く発売され、一般臨床医もBPHの薬物療法の一役を担っているのが現状である。今回、われわれは旭川市および周辺地域の一般臨床医を対象に「前立腺肥大症診療アンケート調査」を実施し、BPH診療に関する実態調査を施行した。その結果、一般臨床医はBPH診療に関して併存疾患として取り組んでいることが示された。今後、泌尿器科専門医との連携がより進めば、一般臨床医はBPH診療により積極的に取り組む可能性が示唆された。
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