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1.
Curr Urol ; 14(3): 113-121, 2020 Oct.
Artigo em Inglês | MEDLINE | ID: mdl-33224003

RESUMO

Introduction: There have been a number of reports on dose increase therapy (DI-T) with the alpha 1 adrenoceptor antagonists (α1-blockers) naftopidil and tamsulosin for lower urinary tract symptoms associated with benign prostatic hyperplasia. Methods and Results: The reports on DI-T (naftopidil 75 mg/d, tamsulosin 0.4 mg/d) in non-responders to low-dose initial therapy (LI-T, naftopidil 50 mg/d, tamsulosin 0.2 mg/d) were summarized. In each study, a non-responder was defined as a patient without sufficient improvements on the International Prostate Symptom Score (IPSS), IPSS Quality of Life, maximum flow rate of urine, or treatment satisfaction. These reports showed that 22.4-76.1% of patients were non-responders to LI-T, indicating that a novel treatment strategy for such patients is important. Moreover, 22.5-90.0% of non-responders to LI-T showed a response to DI-T, which achieved the same level of efficacy as low-dose maintenance therapy. Specifically, the improvements of the IPSS voiding symptom sub-score and maximum flow rate of urine were superior. The predictive factors for non-response to α1-blockers LI-T were insufficient improvement of subjective symptoms and objective findings during LI-T. These patients require high-dose initial therapy or DI-T at an early stage, since adverse events associated with naftopidil and tamsulosin do not show a dose-response relationship. Conclusions: DI-T with α1-blockers has high potential as an essential treatment strategy for lower urinary tract symptoms associated with benign prostatic hyperplasia.

2.
Adv Ther ; 2020 Nov 27.
Artigo em Inglês | MEDLINE | ID: mdl-33245533

RESUMO

INTRODUCTION: MATCH was a randomized, double-blind, placebo-controlled study enrolling Japanese and Korean men aged ≥ 40 years who still had overactive bladder (OAB) symptoms while receiving tamsulosin. After a 4-week single-blind screening period in which patients received placebo and tamsulosin, patients were randomized to mirabegron 50 mg + tamsulosin or placebo + tamsulosin for 12 weeks (n = 568). This post hoc analysis investigated the proportion of treatment responders for each treatment group and for subgroups stratified by age based on voiding diaries and patient-reported outcomes (PROs). METHODS: Responders were defined as those achieving normalization or clinically meaningful improvements in efficacy, or clinically important differences in PROs [≥ 10-point improvement in OAB questionnaire (OAB-q) symptom bother or total health-related quality of life (HRQoL) subscales at end of treatment (EoT; minimally important difference [MID]) or OAB symptom score (OABSS) total score decreased by ≥ 3 points at EoT [minimally clinically important change (MCIC)]]. RESULTS: At EoT, micturition frequency normalization was achieved by 30.7% of tamsulosin + mirabegron patients and 18.6% of tamsulosin + placebo patients. Normalization of urgency and incontinence was 19.1% and 60.7% for tamsulosin + mirabegron and 18.2% and 60.0% for tamsulosin + placebo. Normalization of OAB symptoms based on OABSS was 17.1% for tamsulosin + mirabegron and 14.5% for tamsulosin + placebo. Higher proportions of patients in the mirabegron add-on group versus the placebo group reported clinically meaningful improvements in micturitions, urgency, and incontinence and in MCIC for OABSS and MID for the OAB-q subscales. Double- and triple-responder findings were as predicted by the results of single-responder analyses. These results were mirrored in the age groups using cut-offs of 65 and 75 years. CONCLUSION: Mirabegron therapy added on to tamsulosin resulted in a higher frequency of responders in terms of normalization (e.g., micturition frequency normalization), clinically meaningful improvements in efficacy (e.g., ≥ 50% decrease in urgency), and minimally important changes in PROs (e.g., MCIC in OABSS). TRIAL REGISTRATION: ClinicalTrials.gov identifier, NCT02656173.

3.
Invest New Drugs ; 2020 Oct 23.
Artigo em Inglês | MEDLINE | ID: mdl-33098047

RESUMO

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.

4.
Hinyokika Kiyo ; 66(9): 289-292, 2020 Sep.
Artigo em Japonês | MEDLINE | ID: mdl-32993272

RESUMO

We retrospectively investigated the clinical course of α1 blocker discontinuation in patients who had lower urinary tract symptoms with benign prostate hypertrophy (LUTS/BPH) and received combination therapy ofdutasteride and α1 blocker. Among the patients with LUTS/BPH who had been receiving combination therapy, those who wished to reduce the number ofprescribed drugs and discontinue the use of α1 blocker because ofsymptom improvement were recruited in this study. Symptom scores including International Prostate Symptom Score (IPSS) and overactive bladder symptom score (OABSS), parameters ofuroflowmetry and prostate volume (PV) were evaluated at the time of α 1 blocker discontinuation. Twenty-two patients discontinued the use of α 1 blocker. The mean PV at the time of α 1 blocker discontinuation was 43.2 ml, and the mean duration ofcombination therapy was 39.4 months. In 11 (50%) patients, dutasteride monotherapy without α1 blocker was maintained for a mean follow-up of 10.5 months (9-12 months) after α1 blocker discontinuation (Non-resumption group). In the other 11 patients (50%), α1 blocker was resumed because ofthe patient's request to resume the use of α1 blocker (Resumption group). The mean length ofdutasteride monotherapy was 4. 5 months (1-8 months) in the resumption group. Compared with the non-resumption group, IPSS total score and storage sub-score ofIPSS at the time of α1 blocker discontinuation were significantly higher in the resumption group. Based on the ROC curve, IPSS total score <16, IPSS voiding/storage symptom score <7, OABSS <7 and PV 54 ml or more at the time of α1 blocker discontinuation were predictors ofnon-resumption of α1 blocker. These results suggest that if LUTS is controlled by a long-term combination therapy ofdutasteride and α1 blocker and still PV is large enough, α1 blocker can be discontinued.


Assuntos
Sintomas do Trato Urinário Inferior/tratamento farmacológico , Hiperplasia Prostática/complicações , Hiperplasia Prostática/tratamento farmacológico , Quimioterapia Combinada , Dutasterida/uso terapêutico , Humanos , Masculino , Estudos Retrospectivos , Resultado do Tratamento
5.
Artigo em Inglês | MEDLINE | ID: mdl-32975024

RESUMO

OBJECTIVES: To investigate the cardiovascular safety of mirabegron add-on treatment to tamsulosin in male patients with residual overactive bladder symptoms. METHODS: This was a post hoc analysis of MATCH, the first double-blind, placebo-controlled study comparing mirabegron and placebo as add-on therapy to tamsulosin for treatment of overactive bladder in men with lower urinary tract symptoms. The analysis focused on treatment-emergent adverse events relating to the cardiovascular system or blood pressure, and changes in vital signs during 12 weeks of follow-up. RESULTS: Cardiovascular-related treatment-emergent adverse events were reported by 6/566 patients, although only one serious treatment-emergent adverse event was related to treatment (unstable angina in the tamsulosin + placebo group). Hypertension (two patients) and increased blood pressure (one patient) were reported in the tamsulosin + placebo group, but there were no blood pressure-related treatment-emergent adverse events among tamsulosin + mirabegron patients. There were no clinically meaningful changes from baseline in blood pressure, and changes in pulse rate were small (+1.2 bpm in the tamsulosin + mirabegron group). Increased pulse rate was more frequent with tamsulosin + mirabegron than with tamsulosin + placebo in older patients, although within the normal range. CONCLUSIONS: Cardiovascular-related adverse events were uncommon in both treatment groups. Mirabegron is a well-tolerated add-on therapy to tamsulosin in Japanese and Korean males with residual overactive bladder symptoms.

6.
Hinyokika Kiyo ; 66(7): 221-224, 2020 Jul.
Artigo em Japonês | MEDLINE | ID: mdl-32723976

RESUMO

We present 2 cases of penile cancer in which the inguinal lymph node was not palpable and inguinal lymph node dissection (ILND) could be safely avoided by conducting dynamic sentinel lymph node biopsy (DSNB). The first case was in a 54-year-old man complaining of penile tumor for at least 3 months. We performed partial penectomy and DSNB. The pathological diagnosis was squamous cell carcinoma (SCC), pT2-3. There was no cancer metastasis in sentinel nodes (0/2). There has been no recurrence for 6 years after operation. The second case was 65-year-old man suffering from penile tumor for at least 6 months. We performed partial penectomy and DSNB. The pathological diagnosis was SCC,pT2. There was no cancer metastasis in sentinel nodes (0/3). There has been no recurrence for 1 year after operation. ILND has been recommended for intermediate and high-risk penile cancer even in patients with non-palpable inguinal lymph nodes. However,the complication of ILND is very high. DSNB has the potential to avoid ILND if there is no cancer metastasis in sentinel nodes.


Assuntos
Neoplasias Penianas , Biópsia de Linfonodo Sentinela , Idoso , Humanos , Excisão de Linfonodo , Linfonodos , Masculino , Pessoa de Meia-Idade , Recidiva Local de Neoplasia , Estadiamento de Neoplasias
7.
Neurourol Urodyn ; 39(5): 1345-1354, 2020 06.
Artigo em Inglês | MEDLINE | ID: mdl-32394603

RESUMO

AIMS: We examined the time course of urodynamic changes and the effect of the short or long-term inhibition of brain-derived neurotrophic factor (BDNF) from the early phase after spinal cord injury (SCI) in mice. METHODS: The spinal cord of female C57BL/6N mice was completely transected. We examined filling cystometry and bladder BDNF levels at 10, 20, and 30 days after SCI, with an additional day-5 measurement of BDNF. In a separate group of mice, anti-BDNF antibody (Ab) (10 µg/kg/h) was subcutaneously administered using osmotic pumps from day 3 after SCI, and single-filling cystometry was performed at 10 and 30 days (7 and 27 days of treatment, respectively) after SCI. RESULTS: Compared to spinal intact mice, bladder mucosal BDNF was increased at each time point after SCI with the maximal level at day 5 after SCI. Voiding efficiency was lower at each time point after SCI than that of spinal intact mice. The number of non-voiding contractions (NVC) during bladder filling was gradually increased with time. In both 10- and 30-day SCI groups treated with anti-BDNF Ab, voiding efficiency was improved, and the duration of notch-like intravesical pressure reductions during voiding bladder contractions was prolonged. The number of NVC was significantly decreased only in 30-day SCI mice with 27-day anti-BDNF treatment. CONCLUSIONS: Overexpression of BDNF is associated with the deterioration of voiding efficiency after SCI. The early-started, long-term inhibition of BDNF improved voiding dysfunction and was also effective to reduce the later-phase development of detrusor overactivity after SCI.

8.
Urol Int ; 104(5-6): 373-377, 2020.
Artigo em Inglês | MEDLINE | ID: mdl-32348992

RESUMO

OBJECTIVES: We examined the persistence rate with tadalafil for treatment of male lower urinary tract symptoms (LUTS) and explored the factors relevant to withdrawal. PATIENTS AND METHODS: We retrospectively collected the data of male patients who received tadalafil treatment for LUTS. The persistence rate and the reason for withdrawal were investigated. RESULTS: A total of 155 patients were examined. Mean age and mean observation period were 71.9 (48-93) years and 15.1 (1-52) months, respectively. During the observation period, 74 patients (48%) withdrew tadalafil. The Kaplan-Meier curve indicated a 58% persistence rate at 1 year. The reasons for withdrawal included insufficient efficacy (31 patients, 42%), adverse events (21 patients, 28%), or symptom improvement (8 patients, 11%). Patients who continued tadalafil were significantly younger than those who withdrew it due to insufficient efficiency (71.4 ± 9.6 vs. 74.9 ± 9.1 years). CONCLUSIONS: Most patients withdrew tadalafil due to insufficient efficacy. Older patients are likely to withdraw the treatment because of insufficient efficacy, thus, tadalafil for male LUTS could be more effective for younger patients.

9.
Hinyokika Kiyo ; 66(2): 41-44, 2020 Feb.
Artigo em Japonês | MEDLINE | ID: mdl-32160731

RESUMO

Psoas muscle mass index (PMI) is related to sarcopenia. We examined whether PMI is associated with early complications after radical cystectomy. Seventy one male and 29 female patients who were 65 years old or older and who had undergone radical cystectomy at our hospital from April 2005 to March 2018 were retrospectively analyzed. Psoas muscle section area was measured manually on preoperative computed tomography (CT) scan and normalized by patient's height. Early postoperative complications of grade 3 or more occurred in 12 male (16.9%) and 5 female (17.2%) patients. PMI was lower in male patients who had early postoperative complications of grade 3 or more than in those without complications (5.61 vs 6.54 cm2 /m2, p=0. 08), although the difference was not statistically significant. There was suggested to be a relationship between early postoperative complications after radical cystectomy and preoperative PMI in elderly male patients.


Assuntos
Cistectomia , Sarcopenia , Idoso , Feminino , Humanos , Masculino , Complicações Pós-Operatórias , Músculos Psoas , Estudos Retrospectivos
10.
Int J Urol ; 27(4): 276-288, 2020 Apr.
Artigo em Inglês | MEDLINE | ID: mdl-32077161

RESUMO

The present article is an abridged English translation of the Japanese clinical guidelines for the diagnosis and treatment of lower urinary tract dysfunction in patients with spinal cord injury updated as of July 2019. The patients are adult spinal cord injured patients with lower urinary tract dysfunction; special consideration of pediatric and elderly populations is presented separately. The target audience is healthcare providers who are engaged in the medical care of patients with spinal cord injury. The mandatory assessment includes medical history, physical examination, frequency-volume chart, urinalysis, blood chemistry, transabdominal ultrasonography, measurement of post-void residual urine, uroflowmetry and video-urodynamic study. Optional assessments include questionnaires on the quality of life, renal scintigraphy and cystourethroscopy. The presence or absence of risk factors for renal damage and symptomatic urinary tract infection affects urinary management, as well as pharmacological treatments. Further treatment is recommended if the maximum conservative treatment fails to improve or prevent renal damage and symptomatic urinary tract infection. In addition, management of urinary incontinence should be considered individually in patients with risk factors for urinary incontinence and decreased quality of life.

11.
BJU Int ; 125(5): 709-717, 2020 05.
Artigo em Inglês | MEDLINE | ID: mdl-31991511

RESUMO

OBJECTIVE: To evaluate the efficacy of a novel and selective ß3-adrenoreceptor agonist vibegron on urgency urinary incontinence (UUI) in patients with overactive bladder (OAB). PATIENTS AND METHODS: A post hoc analysis was performed in patients with UUI (>0 episodes/day) who were assigned to receive vibegron or placebo in a vibegron phase 3 study. Patients were subclassified into mild/moderate (>0 to <3 UUI episodes/day) or severe UUI (≥3 UUI episodes/day) subgroup. Changes from baseline in number of UUI episodes/day, in number of urgency episodes/day, and in voided volume/micturition were compared between the groups. The percentage of patients who became UUI-free ('diary-dry' rate) and the response rate (percentage of patients with scores 1 [feeling much better] or 2 [feeling better] assessed by the Patient Global Impression scale [PGI]) were evaluated. RESULTS: Changes in numbers of UUI episodes at week 12 in the vibegron 50 mg, vibegron 100 mg and placebo groups, respectively, were -1.35, -1.47 and -1.08 in all patients, -1.04, -1.13 and -0.89 in the mild/moderate UUI subgroup, and -2.95, -3.28 and -2.10 in the severe UUI subgroup. The changes were significant in the vibegron 50 and 100 mg groups vs placebo regardless of symptom severity. Change in number of urgency episodes/day was significant in the vibegron 100 mg group vs placebo in all patients and in both severity subgroups. In the vibegron 50 mg group, a significant change vs placebo was observed in all patients and in the mild/moderate UUI subgroup. Change in voided volume/micturition was significantly greater in the vibegron 50 and 100 mg groups vs placebo in all patients, as well as in the both severity subgroups. Diary-dry rates in the vibegron 50 and 100 mg groups were significantly greater vs placebo in all patients and in the mild/moderate UUI subgroup. In the severe UUI subgroup, however, a significant difference was observed only in the vibegron 50 mg group. Response rates assessed by the PGI were significantly higher in the vibegron groups vs placebo in all patients and in the both severity subgroups. Vibegron administration, OAB duration ≤37 months, mean number of micturitions/day at baseline <12.0 and mean number of UUI episodes/day at baseline <3.0 were identified as factors significantly associated with normalization of UUI. CONCLUSIONS: Vibegron, a novel ß3-adrenoreceptor agonist, significantly reduced the number of UUI episodes/day and significantly increased the voided volume/micturition in patients with OAB including those with severe UUI, with the response rate exceeding 50%. These results suggest that vibegron can be an effective therapeutic option for OAB patients with UUI.


Assuntos
Pirimidinonas/uso terapêutico , Pirrolidinas/uso terapêutico , Bexiga Urinária Hiperativa/tratamento farmacológico , Incontinência Urinária/tratamento farmacológico , Micção/efeitos dos fármacos , Agonistas de Receptores Adrenérgicos beta 3/uso terapêutico , Método Duplo-Cego , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Índice de Gravidade de Doença , Resultado do Tratamento , Bexiga Urinária Hiperativa/complicações , Bexiga Urinária Hiperativa/fisiopatologia , Incontinência Urinária/etiologia , Incontinência Urinária/fisiopatologia
12.
Eur Urol Focus ; 6(4): 729-737, 2020 07 15.
Artigo em Inglês | MEDLINE | ID: mdl-31718957

RESUMO

BACKGROUND: Men with lower urinary tract symptoms (LUTS) treated with α-blockers (eg, tamsulosin) may experience overactive bladder (OAB) symptoms and receive add-on antimuscarinics. Mirabegron (a ß3-adrenoreceptor agonist) is an alternative add-on therapy. OBJECTIVE: To evaluate the efficacy of mirabegron versus placebo in men with OAB symptoms receiving tamsulosin for LUTS. DESIGN, SETTING, AND PARTICIPANTS: Japanese and Korean men with OAB treated with tamsulosin for LUTS (January 2016-July 2017). INTERVENTION: Single-blind, 4-wk screening: tamsulosin plus placebo orally once daily; double-blind, 12-wk treatment: patients randomized (n=568) to mirabegron 50mg or placebo, as add-on to tamsulosin. OUTCOME MEASUREMENTS AND STATISTICAL ANALYSIS: Primary endpoint: baseline to end of treatment (EoT) change in the mean number of micturitions/24h, based on a 3-d voiding diary. Secondary endpoints: change in other diary variables and patient-reported outcomes from baseline to EoT. The primary endpoint was analyzed by analysis of covariance, including treatment group and region as fixed factors and baseline as a covariate. RESULTS AND LIMITATIONS: Mirabegron add-on therapy was superior to placebo in improving the primary endpoint (adjusted mean difference [95% confidence interval] vs placebo -0.52 [-0.82 to -0.21]) and secondary endpoints, including mean volume voided/micturition (12.08 [6.33-17.84]), OAB symptom score (-0.65 [-1.04 to -0.26]), International Prostate Symptom Score total (-1.19 [-1.94 to -0.44]), storage (-0.78 [-1.13 to -0.43]), quality of life scores (-0.29 [-0.51 to -0.07]), OAB symptom bother (-4.52 [-6.91 to -2.13]), and total health-related quality of life (2.79 [1.13 to 4.44]). Differences, compared with placebo, in urgency, urgency urinary incontinence, and nocturia were not statistically significant. Mirabegron was well tolerated, with no major safety concerns. Limitations included a lack of antimuscarinic comparison. CONCLUSIONS: The mirabegron add-on therapy to tamsulosin for 12 wk in men with LUTS and OAB symptoms demonstrated superior efficacy to placebo and was well tolerated. PATIENT SUMMARY: We looked at the efficacy and safety of mirabegron compared with placebo in men being treated with tamsulosin but who still had overactive bladder symptoms. Mirabegron improved overactive bladder symptoms and patient-reported outcomes compared with placebo, and was well tolerated.

13.
Am J Physiol Renal Physiol ; 317(5): F1305-F1310, 2019 11 01.
Artigo em Inglês | MEDLINE | ID: mdl-31566429

RESUMO

We investigated the involvement of brain-derived neurotrophic factor (BDNF) in bladder and urethral dysfunction using spinal cord-injured mice. We evaluated bladder and urethral function of female mice with 4-wk spinal cord injury (SCI) by filling cystometry and electromyography (EMG) of the external urethral sphincter (EUS) under a conscious condition. Anti-BDNF antibodies (10 µg·kg-1·h-1) were administered in some mice for 1 wk before the evaluation. Bladder and spinal (L6-S1) BDNF protein levels were examined by ELISA. Transcript levels of transient receptor potential channels or acid-sensing ion channels (Asic) in L6-S1 dorsal root ganglia were evaluated by RT-PCR. Voided volume and voiding efficiency were significantly increased without any changes in nonvoiding contractions, and the duration of reduced EMG activity during the voiding phase was significantly prolonged in anti-BDNF antibody-treated SCI mice. Compared with spinal cord-intact mice, SCI mice showed increased concentrations of bladder and spinal BDNF. Anti-BDNF antibody treatment decreased bladder and spinal BDNF protein concentrations of SCI mice. Asic2 and Asic3 transcripts were significantly increased after SCI but decreased after anti-BDNF antibody administration. These results indicate that upregulated expression of bladder and spinal BDNF is involved in the emergence of inefficient voiding in SCI mice. Thus, BDNF-targeting treatment could be an effective modality for the treatment of voiding problems, including inefficient voiding and detrusor sphincter dyssynergia after SCI.


Assuntos
Anticorpos , Fator Neurotrófico Derivado do Encéfalo/antagonistas & inibidores , Traumatismos da Medula Espinal/complicações , Transtornos Urinários/etiologia , Canais Iônicos Sensíveis a Ácido/genética , Canais Iônicos Sensíveis a Ácido/metabolismo , Animais , Fator Neurotrófico Derivado do Encéfalo/imunologia , Fator Neurotrófico Derivado do Encéfalo/metabolismo , Feminino , Regulação da Expressão Gênica/imunologia , Camundongos , DNA Polimerase Dirigida por RNA , Reação em Cadeia da Polimerase em Tempo Real , Medula Espinal/metabolismo , Regulação para Cima , Bexiga Urinária/metabolismo
14.
Int J Urol ; 26(11): 1071-1075, 2019 11.
Artigo em Inglês | MEDLINE | ID: mdl-31512277

RESUMO

OBJECTIVES: To examine the long-term outcomes of transurethral resection of the prostate. METHODS: We retrospectively collected the data of patients who had undergone transurethral resection of the prostate before December 2010. Patients had been evaluated by urodynamics and the International Prostate Symptom Score preoperatively, and they were re-evaluated by using the International Prostate Symptom Score at the minimum 7 years after transurethral resection of the prostate. Patients who received any treatments to improve voiding symptoms were defined as having a relapse of voiding dysfunction. The Schäfer nomogram was used to assess the degree of obstruction and detrusor contractility. We assessed the change in International Prostate Symptom Score over time depending on obstruction (Schäfer grade 3-6) versus no obstruction (Schäfer grade 0-2), and normal detrusor contractility (strong and normal) versus detrusor underactivity (weak and very weak). Relapse rates of voiding dysfunction were determined using the Kaplan-Meier method. RESULTS: A total of 39 patients were included. The mean age at transurethral resection of the prostate was 69.8 years, and the mean observation period after transurethral resection of the prostate was 114 months. During the observation period, eight patients (21%) were categorized as relapse of voiding dysfunction and the mean time to relapse was 4.2 years. Patients categorized as no obstruction or detrusor underactivity had a higher recurrence rate of voiding dysfunction with a statistical significance between those with versus without obstruction. Except for patients with relapse of voiding dysfunction, improvement of the International Prostate Symptom Score was maintained over a period of 10 years after transurethral resection of the prostate. CONCLUSIONS: Favorable long-term symptomatic outcome after transurethral resection of the prostate is likely in patients with urodynamic obstruction. Patients without urodynamic obstruction are likely to have a relapse of voiding symptoms and require additional treatments in the long term.


Assuntos
Sintomas do Trato Urinário Inferior/epidemiologia , Complicações Pós-Operatórias/epidemiologia , Ressecção Transuretral da Próstata/reabilitação , Idoso , Idoso de 80 Anos ou mais , Humanos , Japão/epidemiologia , Sintomas do Trato Urinário Inferior/etiologia , Masculino , Pessoa de Meia-Idade , Complicações Pós-Operatórias/etiologia , Estudos Retrospectivos , Ressecção Transuretral da Próstata/efeitos adversos , Urodinâmica
15.
Hinyokika Kiyo ; 65(7): 305-308, 2019 Jul.
Artigo em Japonês | MEDLINE | ID: mdl-31501397

RESUMO

The patient was a 66-year-old man who had undergone ileocystoplasty and right nephrectomy at the age of 21 for the treatment of urinarytract tuberculosis. He had been receiving hemodialysis from the age of 58. Regular computed tomography (CT) examination at the age of 63 revealed a bladder mass, but the transurethral biopsyof the bladder mass did not reveal malignant findings. At the age of 66, his urine cytology indicated a suspicion of malignancy, and bladder tumor was detected by cystoscopy. The patient was referred to our hospital and we performed transurethral resection of the bladder tumor. Pathological diagnosis was papillaryadenocarcinoma. Because left lower ureteral cancer was also suspected byCT scan, we performed left nephroureterectomy and radical cystectomy. Pathological examination revealed adenocarcinoma of the reconstructed bladder. The patient remains free of disease for 1 year and 11 months after the operation. Forty-five cases of bladder cancer after enterocystoplasty have been reported in Japan. There are no guidelines for follow-up protocols after enterocystoplasty. A long-term follow-up is mandatory because of the possibilityof development of bladder malignancylong after the enterocystoplasty.


Assuntos
Adenocarcinoma , Neoplasias da Bexiga Urinária , Adenocarcinoma/diagnóstico , Adenocarcinoma/cirurgia , Idoso , Cistectomia , Humanos , Japão , Masculino , Fatores de Tempo , Neoplasias da Bexiga Urinária/diagnóstico , Neoplasias da Bexiga Urinária/cirurgia
16.
Int J Urol ; 26(3): 342-352, 2019 03.
Artigo em Inglês | MEDLINE | ID: mdl-30548692

RESUMO

OBJECTIVES: To evaluate the long-term safety (primary objective) and efficacy (secondary objective) of antimuscarinic add-on therapy in patients receiving mirabegron. METHODS: During a 2-week screening period, patients (aged ≥20 years, mirabegron treatment for ≥6 weeks, residual overactive bladder symptoms) received mirabegron 50 mg once daily. These patients were subsequently randomized to 52 weeks' treatment with mirabegron 50 mg/day plus an antimuscarinic (solifenacin 5 mg, propiverine 20 mg, imidafenacin 0.2 mg, or tolterodine 4 mg) with the potential to double the antimuscarinic dose (except for tolterodine) at week 8. Safety assessments included treatment-emergent adverse events, vital signs, 12-lead electrocardiograms, post-void residual volume, and laboratory evaluations. Efficacy was assessed using changes from baseline in overactive bladder symptom score total score; overactive bladder questionnaire short form score; micturitions, urgency episodes, urinary incontinence episodes, and urgency urinary incontinence episodes/24 h; mean volume voided per micturition; and number of night-time micturitions. RESULTS: Overall, 80.2% of patients (88.1% women, mean age 65 years) experienced at least one treatment-emergent adverse event, with similar rates for all treatments. The adverse events most commonly reported were dry mouth, nasopharyngitis, and constipation. No marked change was observed in systolic or diastolic blood pressure for any treatment, although pulse rate increased slightly in the mirabegron and propiverine, and mirabegron and tolterodine groups. For all treatments, significant improvements were observed in all efficacy parameters, including overactive bladder symptom score total and questionnaire short form scores. CONCLUSIONS: Antimuscarinic add-on therapy is well tolerated and effective after initial treatment with mirabegron in patients with overactive bladder symptoms.


Assuntos
Acetanilidas/efeitos adversos , Agonistas de Receptores Adrenérgicos beta 3/efeitos adversos , Antagonistas Muscarínicos/efeitos adversos , Tiazóis/efeitos adversos , Bexiga Urinária Hiperativa/tratamento farmacológico , Incontinência Urinária/tratamento farmacológico , Acetanilidas/administração & dosagem , Agonistas de Receptores Adrenérgicos beta 3/administração & dosagem , Adulto , Idoso , Idoso de 80 Anos ou mais , Benzilatos/administração & dosagem , Benzilatos/efeitos adversos , Pressão Sanguínea/efeitos dos fármacos , Constipação Intestinal/induzido quimicamente , Constipação Intestinal/epidemiologia , Método Duplo-Cego , Quimioterapia Combinada/efeitos adversos , Quimioterapia Combinada/métodos , Feminino , Humanos , Imidazóis/administração & dosagem , Imidazóis/efeitos adversos , Japão , Masculino , Pessoa de Meia-Idade , Antagonistas Muscarínicos/administração & dosagem , Nasofaringite/induzido quimicamente , Nasofaringite/epidemiologia , Índice de Gravidade de Doença , Succinato de Solifenacina/administração & dosagem , Succinato de Solifenacina/efeitos adversos , Tiazóis/administração & dosagem , Fatores de Tempo , Tartarato de Tolterodina/administração & dosagem , Tartarato de Tolterodina/efeitos adversos , Resultado do Tratamento , Bexiga Urinária Hiperativa/complicações , Bexiga Urinária Hiperativa/diagnóstico , Incontinência Urinária/diagnóstico , Incontinência Urinária/etiologia , Xerostomia/induzido quimicamente , Xerostomia/epidemiologia
17.
Neurourol Urodyn ; 38(2): 545-552, 2019 02.
Artigo em Inglês | MEDLINE | ID: mdl-30576004

RESUMO

AIMS: The International Consultation on Incontinence has published an update of the recommendations for the diagnosis and management of urine incontinence (ICI2016). This manuscript summarizes the consultations committee-recommendations with regard to urodynamic assessment. METHODS: Expert consensus on the basis of structured evidence assessment has been the basis of the consultations publication and has been summarized by the committee for this manuscript. RESULTS: Patients that are not satisfied with their initial management on the basis of their reported signs and symptoms of urinary incontinence, as well as all patients with neurological abnormalities that are potentially relevant for the function of the lower urinary tract, may very likely profit from objective diagnosis and staging and grading of their dysfunction, with urodynamic testing, regardless their age, vulnerability and/or comorbidities. The principles and technical innovations as well as the principal recommendations for the utilization of (invasive) urodynamic assessment for women, men, children, and vulnerable elderly, with or without neurogenic lower urinary tract dysfunction with urinary incontinence are provided in this abbreviated ICI recommendations-document. CONCLUSIONS: The ICI2016 committee on urodynamics presents an executive summary of the most important reasons and recommendations for the use of urodynamic investigations for patients with urinary incontinence.


Assuntos
Técnicas de Diagnóstico Urológico , Bexiga Urinária/fisiopatologia , Incontinência Urinária/diagnóstico , Urodinâmica/fisiologia , Adulto , Criança , Consenso , Feminino , Humanos , Masculino , Encaminhamento e Consulta , Incontinência Urinária/fisiopatologia
18.
Int J Urol ; 26(3): 369-375, 2019 03.
Artigo em Inglês | MEDLINE | ID: mdl-30557916

RESUMO

OBJECTIVES: To investigate the efficacy of vibegron on nocturia in patients with overactive bladder. METHODS: Among the Japanese overactive bladder patients enrolled in the placebo-controlled, multicenter, randomized, double-blind phase 3 study of vibegron, a total of 669 patients with nocturia (≥1 nocturnal void) were included. Changes from baseline in micturition parameters were compared for vibegron treatment (50 and 100 mg/day) versus placebo. Correlations of hours of undisturbed sleep with the frequency of nocturnal voiding and the volume of the first nocturnal voiding were examined. Demographics and baseline characteristics contributing to reduction in the frequency of nocturnal voiding were also analyzed. RESULTS: At week 12, the frequency of nocturnal voiding was reduced from baseline by 0.74 and 0.78, respectively, for the vibegron 50 and 100 mg groups; the reductions were significant when compared with the placebo group (P < 0.05 and P < 0.001, respectively). The mean volume of nocturnal voids and the volume of the first nocturnal voiding were significantly greater in the vibegron groups than in the placebo group. The vibegron groups showed significant correlations of hours of undisturbed sleep with the changes in the frequency of nocturnal voiding and in the volume of the first nocturnal voiding. Vibegron treatment, no previous treatment with anticholinergics, ≥12 voids per day and hours of undisturbed sleep <180 min significantly contributed to a reduction in the frequency of nocturnal voiding. CONCLUSIONS: Vibegron is a useful therapeutic option for improving nocturia in patients with overactive bladder.


Assuntos
Agonistas de Receptores Adrenérgicos beta 3/administração & dosagem , Noctúria/tratamento farmacológico , Pirimidinonas/administração & dosagem , Pirrolidinas/administração & dosagem , Bexiga Urinária Hiperativa/tratamento farmacológico , Agonistas de Receptores Adrenérgicos beta 3/efeitos adversos , Idoso , Relação Dose-Resposta a Droga , Método Duplo-Cego , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Noctúria/diagnóstico , Noctúria/etiologia , Placebos/administração & dosagem , Placebos/efeitos adversos , Pirimidinonas/efeitos adversos , Pirrolidinas/efeitos adversos , Qualidade de Vida , Resultado do Tratamento , Bexiga Urinária Hiperativa/complicações
19.
Biomed Res ; 39(4): 197-214, 2018.
Artigo em Inglês | MEDLINE | ID: mdl-30101840

RESUMO

Despite their pharmacologically opposite actions, long-acting depot formulations of both GnRH agonists and antagonists have been clinically applied for treatment of androgen-sensitive prostate cancer. Sustained treatment with GnRH analogues commonly suppresses both the synthesis and release of gonadotropins, leading to depletion of testicular testosterone. To clarify the underlying differences in the effects of GnRH agonists and antagonists on spermatogenesis, we compared histological changes in the seminiferous epithelium after administration of depot formulations of GnRH agonist leuprorelin and antagonist degarelix to male rats. Testicular weight had markedly declined by 28 days after administration of both GnRH analogues, although the testicular weight was decreased more promptly by leuprorelin compared with degarelix. Shortly after administration, massive exfoliation of premature spermatids and anomalous multinucleated giant cells was observed in seminiferous tubules of leuprorelin-treated rats, probably via the initial hyperstimulatory effects on the hypothalamic-pituitary-testicular axis, whereas no discernible changes were found in those of degarelix-treated rats. Long term treatment with both types of GnRH analogues similarly induced a marked reduction in the height of the epithelium and deformation of apical cytoplasm in Sertoli cells, resulting in premature detachment of spermatids from the epithelium. Lipid droplets had accumulated progressively in Sertoli cells, especially in those of degarelix-treated rats. These findings clearly demonstrate the differences in the effects of GnRH agonists and antagonists on the spermatogenic process. This study suggests that an appropriate choice of GnRH analogues is necessary to minimize their adverse effects on spermatogenesis when reproductive functions should be preserved in patients.


Assuntos
Hormônio Liberador de Gonadotropina , Leuprolida , Oligopeptídeos , Epitélio Seminífero/metabolismo , Espermatogênese/efeitos dos fármacos , Animais , Hormônio Liberador de Gonadotropina/agonistas , Hormônio Liberador de Gonadotropina/antagonistas & inibidores , Leuprolida/efeitos adversos , Leuprolida/farmacocinética , Leuprolida/farmacologia , Masculino , Oligopeptídeos/efeitos adversos , Oligopeptídeos/farmacocinética , Oligopeptídeos/farmacologia , Ratos , Ratos Wistar , Epitélio Seminífero/patologia , Células de Sertoli/metabolismo , Células de Sertoli/patologia , Espermátides/metabolismo , Espermátides/patologia
20.
Int J Urol ; 25(7): 668-675, 2018 07.
Artigo em Inglês | MEDLINE | ID: mdl-29752752

RESUMO

OBJECTIVES: To evaluate the long-term safety and efficacy of vibegron 50 mg and 100 mg, a novel ß3 -adrenoreceptor agonist, in Japanese patients with overactive bladder. METHODS: This was a 1-year, multicenter, open-label, non-controlled study. After a 1-week observation phase, patients were treated with vibegron for 52 weeks. When the efficacy was insufficient after an 8-week treatment with 50 mg, the dose was increased to 100 mg and maintained for an additional 44 weeks. RESULTS: Among a total of 169 patients receiving one or more doses of vibegron, 118 (69.8%) received vibegron 50 mg for 52 weeks, and the dose was increased to 100 mg in 51 (30.2%) patients. The incidence of drug-related adverse events was 18.1% (21/116) in the vibegron 50 mg group and 11.8% (6/51) in the vibegron 100 mg group. Most frequent drug-related adverse events were dry mouth (3.0%), residual urine volume increased (3.0%), constipation (2.4%) and cystitis (1.8%). Statistically significant changes in overactive bladder symptom variables (daily means of micturitions, urgency episodes, urgency incontinence episodes, incontinence episodes and night-time frequency) from baseline were observed at week 4 and maintained until week 52. The condition of patients who did not respond well to vibegron 50 mg was much improved by increasing the dose to 100 mg. Vibegron improved the quality of life, and the proportion of patients' satisfaction after the treatment with vibegron was high. CONCLUSIONS: Long-term (52-week) treatment with vibegron is safe, well-tolerated and effective in patients with overactive bladder.


Assuntos
Agonistas de Receptores Adrenérgicos beta 3/administração & dosagem , Pirimidinonas/administração & dosagem , Pirrolidinas/administração & dosagem , Bexiga Urinária Hiperativa/tratamento farmacológico , Agonistas de Receptores Adrenérgicos beta 3/efeitos adversos , Idoso , Constipação Intestinal/induzido quimicamente , Constipação Intestinal/epidemiologia , Cistite/induzido quimicamente , Cistite/epidemiologia , Relação Dose-Resposta a Droga , Feminino , Humanos , Incidência , Japão , Masculino , Pessoa de Meia-Idade , Satisfação do Paciente , Estudos Prospectivos , Pirimidinonas/efeitos adversos , Pirrolidinas/efeitos adversos , Qualidade de Vida , Resultado do Tratamento , Xerostomia/induzido quimicamente , Xerostomia/epidemiologia
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