Search

The present article is an abridged English translation of the Japanese Clinical Guidelines for Female Lower Urinary Tract Symptoms (second edition), published in September 2019. These guidelines consist of a total of 212 pages and are unique worldwide in that they cover female lower urinary tract symptoms other than urinary incontinence. They contain two algorithms for "primary treatment" and "specialized treatment," respectively. These guidelines, consisting of six chapters, address a total of 26 clinical questions including: (i) treatment algorithms; (ii) what are female lower urinary tract symptoms?; (iii) epidemiology and quality of life; (iv) pathology and illness; (v) diagnosis; and (vi) treatment. When the patient's symptoms mainly involve voiding and post-micturition symptoms, specialized treatment should be considered. In the event of voiding symptoms concurrent with storage symptoms, residual urine should be measured; if the residual urine volume is <100 mL, then diagnosis and treatment for storage symptoms is prioritized, and if the volume is ≥100 mL, then specialized treatment should be considered. When storage symptoms are the primary condition, then the patient is subject to the primary treatment algorithm. Specialized treatment for refractory overactive bladder includes botulinum toxin injection and sacral nerve stimulation. For stress urinary incontinence, surgical treatment is indicated, such as urethral slings. The two causes of voiding symptoms and post-micturition symptoms are lower urinary tract obstruction and detrusor underactivity (underactive bladder). Mechanical lower urinary tract obstruction, such as pelvic organ prolapse, is expected to improve with surgery., (© 2021 The Japanese Urological Association.)

Background: Benign prostatic hyperplasia (BPH) is a common urologic disease in older men. Prostatic inflammation research has focused on the magnitude of inflammation; its location has received little attention. We investigated whether the anatomic location of prostatic inflammation is related to the severity of lower urinary tract symptoms (LUTS), measured subjectively and objectively., Methods: We retrospectively analyzed hematoxylin+eosin-stained tissue specimens from 179 BPH patients who underwent transurethral resection of the prostate (TURP) or holmium laser enucleation of the prostate (HoLEP). Chronic prostatic inflammation was assessed by the grade (lymphocyte density), extent (lymphocyte distribution), and location of inflammation. Each inflammation-finding type was evaluated in relation to these clinical parameters: age, prostate volume, prostate-specific antigen (PSA) value, body mass index (BMI), the frequency of acute urinary retention (AUR) episodes, the international prostatic symptom score (IPSS), and urodynamic study results., Results: The magnitude and extent of inflammation were not associated with any clinical parameters. We classified the BPH patients into stromal (n = 72) versus non-stromal (n = 105) groups based on their inflammation's dominant location. The stromal group's prostatic volume was significantly larger than the non-stromal group's (63.8 vs 53.8 mL; P = 0.032). AUR episodes were more significantly frequent in the stromal group (36.1% vs 11.4%; P = 0.006). Between-group differences in storage parameters (ie, maximum cystometric capacity) in the urodynamic study were not significantly different. Voiding parameters differed significantly between the stromal and non-stromal groups: maximum detrusor pressure (maxPdet) (116.8 vs 94.5 cmH 2 O, P = 0.014), Pdet at the maximum flow rate (Qmax) (95.8 vs 75.4 cmH 2 O, P = 0.014), and the bladder outlet obstruction index (BOOI) (78.5 vs 56.3, P = 0.014). The stromal group's Qmax was significantly lower than the non-stromal group's (7.3 vs 9.8 mL/s, P = 0.004)., Conclusions: The location of inflammation in the prostate might be an important factor affecting the severity of LUTS, especially voiding dysfunction., (© 2018 Wiley Periodicals, Inc.)

Objectives: To determine whether early changes in International Prostate Symptom Score predict final improvement in the quality of life and treatment satisfaction of patients with lower urinary tract symptoms from benign prostatic hyperplasia receiving tadalafil., Methods: This post-hoc analysis of three randomized-controlled trials of tadalafil for lower urinary tract symptoms from benign prostatic hyperplasia used subpopulations based on treatment status (tadalafil, placebo) and region (Japan, Asia). Logistic regression, principal component analysis and hierarchical clustering analysis were applied to individual International Prostate Symptom Score and Patient Global Impression of Improvement response scores., Results: From logistic regression, most individual International Prostate Symptom Score items predicted either International Prostate Symptom Score remitter or responder status; only International Prostate Symptom Score Quality of Life predicted Patient Global Impression of Improvement responder status in tadalafil-treated patients. Among tadalafil-treated patients, principal component analysis showewd that improvement of International Prostate Symptom Score items 2, 4, 7 and International Prostate Symptom Score Quality of Life at early visits were associated with Patient Global Impression of Improvement (final visit), whereas International Prostate Symptom Score items 1, 3, 5 and 6 at early visits were associated with total International Prostate Symptom Score at the final visit. No clear predictive items for Patient Global Impression of Improvement and total International Prostate Symptom Score existed for placebo-treated patients. Hierarchical clustering analysis showed that the closest association was between International Prostate Symptom Score Quality of Life and International Prostate Symptom Score item 7 in placebo- and tadalafil-treated patients, which supports the principal component analysis results., Conclusions: Early changes of storage and voiding symptoms by tadalafil might lead to treatment satisfaction and overall International Prostate Symptom Score improvement, respectively. This finding could help physicians predict tadalafil treatment outcomes for patients with lower urinary tract symptoms from benign prostatic hyperplasia., (© 2017 The Japanese Urological Association.)

The present article is the abbreviated English translation of the Japanese guidelines for male lower urinary tract symptoms and benign prostatic hyperplasia updated as of the end of 2016. The target patients are men aged >50 years complaining of lower urinary tract symptoms, with or without benign prostatic hyperplasia, and the target readers are non-urological general physicians and urologists. Mandatory assessment for general physicians is medical history, physical examination, urinalysis and measurement of serum prostate-specific antigen. Additional mandatory assessment for urologists is symptoms and quality of life assessment by questionnaires, uroflowmetry, residual urine measurement, and prostate ultrasonography. Nocturia requires special attention, as it can result from nocturnal polyuria and/or sleep disturbance rather than lower urinary tract disorders. Functional lower urinary tract disorders with or without benign prostatic hyperplasia are primarily managed by conservative therapy and medications, such as α 1 -blockers and phosphodiesterase-type 5 inhibitors. Use of other medications or combination pharmacotherapy is to be reserved for urologists. 5α-Reductase inhibitors and anticholinergics or β3 agonists are indicated for men with enlarged prostates and overactive bladder symptoms, respectively. Surgical intervention for bladder outlet obstruction is considered for persistent symptoms or benign prostatic hyperplasia-related comorbidities. Surgical modalities should be optimized by the patient's characteristics, performance of equipment and the surgeon's experience., (© 2017 The Japanese Urological Association.)

Objectives: To evaluate the safety and efficacy of tadalafil plus α 1 -blocker combination therapy in Japanese patients with lower urinary tract symptoms suggestive of benign prostatic hyperplasia., Methods: The present multicenter, randomized, double-blind, placebo-controlled, two-period cross-over study compared the effects of tadalafil and a placebo added to ongoing α 1 -blocker therapy. A total of 171 Japanese patients were randomized., Results: Tadalafil combined with an α 1 -blocker did not decrease blood pressure in the orthostatic test. The only statistically significant differences in vital signs between the combination and monotherapy groups were diastolic blood pressure and pulse (P = 0.0194 and 0.0313, respectively). However, these changes were not considered clinically meaningful. Treatment-related adverse events occurred in 28.1% (47/167) and 24.2% (39/161) of patients in the combination therapy and α 1 -blocker monotherapy groups, respectively. Additionally, 56.7% (89/157) of patients preferred combination therapy to monotherapy, though this was not statistically significant (P = 0.0937). There was a statistically significant reduction in the International Prostate Symptom Score voiding subscore in the combination therapy group (P = 0.0442)., Conclusions: Concurrent treatment with tadalafil and an α 1 -blocker seems to be safe and well tolerated in Japanese patients with lower urinary tract symptoms suggestive of benign prostatic hyperplasia. Adding tadalafil to baseline α 1 -blocker therapy does not translate in adverse effects on the blood pressure. Patients tend to prefer combination therapy over monotherapy, and there seems to be a clinical benefit when using combination therapy., (© 2017 The Japanese Urological Association.)

Background: Chronic prostatic inflammation is implicated in the pathogenesis of benign prostatic hyperplasia (BPH)-associated lower urinary tract symptoms (LUTS). Previous studies evaluated the degree of chronic prostatic inflammation based on histological scores, which may contain subjective factors. We previously demonstrated that the number of high endothelial venule (HEV)-like vessels correlates positively with the magnitude of inflammation in chronic inflammatory gastrointestinal diseases. Here, we evaluated the degree of BPH-associated chronic prostate inflammation based on appearance of HEV-like vessels and determined whether the extent of inflammation correlated with LUTS severity, as evaluated by a urodynamic study., Methods: Eighty-six BPH tissue specimens derived from patients who had undergone urodynamic analysis were immunostained for CD34 and MECA-79 to determine HEV-like vessel number. Triple immunohistochemistry for either CD3 and CD20 or CD4 and CD8, together with MECA-79, was conducted to identify lymphocyte subsets associated with HEV-like vessels. We also determined whether the magnitude of chronic prostatic inflammation, as assessed by HEV-like vessel number, correlated with the degree of LUTS., Results: HEV-like vessels were induced in lymphoid aggregates seen frequently in BPH. The number of HEV-like vessels positively correlated not only with the magnitude of chronic prostatic inflammation but also with the degree of LUTS, particularly with symptoms associated with voiding function, which was measured objectively in a pressure flow study., Conclusions: Chronic prostate inflammation may promote BPH and resulting voiding dysfunction. Assessment of the number of HEV-like vessels could be a surrogate for identifying the degree of chronic prostatic inflammation. Prostate 77:794-802, 2017. © 2017 Wiley Periodicals, Inc., (© 2017 Wiley Periodicals, Inc.)

The "Japanese Clinical Guideline for Female Lower Urinary Tract Symptoms," published in Japan in November 2013, contains two algorithms (a primary and a specialized treatment algorithm) that are novel worldwide as they cover female lower urinary tract symptoms other than urinary incontinence. For primary treatment, necessary types of evaluation include querying the patient regarding symptoms and medical history, examining physical findings, and performing urinalysis. The types of evaluations that should be performed for select cases include evaluation with symptom/quality of life (QOL) questionnaires, urination records, residual urine measurement, urine cytology, urine culture, serum creatinine measurement, and ultrasonography. If the main symptoms are voiding/post-voiding, specialized treatment should be considered because multiple conditions may be involved. When storage difficulties are the main symptoms, the patient should be assessed using the primary algorithm. When conditions such as overactive bladder or stress incontinence are diagnosed and treatment is administered, but sufficient improvement is not achieved, the specialized algorithm should be considered. In case of specialized treatment, physiological re-evaluation, urinary tract/pelvic imaging evaluation, and urodynamic testing are conducted for conditions such as refractory overactive bladder and stress incontinence. There are two causes of voiding/post-voiding symptoms: lower urinary tract obstruction and detrusor underactivity. Lower urinary tract obstruction caused by pelvic organ prolapse may be improved by surgery., (© 2015 Wiley Publishing Asia Pty Ltd.)

Purpose: To evaluate the efficacy and safety of imidafenacin (IM), a novel short half-life anticholinergic, as add-on therapy for male LUTS with nocturia and nocturnal polyuria., Materials and Methods: This multicenter, prospective, randomized, open-labelled study was conducted and involved men who had frequency, urgency, and nocturia despite receiving a stable dose of α1-blocker for ≥1 month. Subjects were randomised to control (α1-blocker alone), IM twice/day (α1-blocker +0.1 mg imidafenacin twice daily), or IM nightly (α1-blocker plus 0.1 mg imidafenacin nightly) group; the treatment period was 8 weeks. Primary endpoints included improvements in night-time frequency and Nocturia Quality of Life Questionnaire (N-QOL) scores. Secondary endpoints included changes from the baseline in frequency volume chart variables, and post-void residual volume., Results and Limitations: Compared with the controls, IM twice/day and IM nightly patients had a significantly lower night-time frequency (changes from baseline: 0.1 ± 0.8 in control, -0.6 ± 0.9 in IM twice/day, and -0.4 ± 1.0 in IM nightly, p = 0.5227, 0.0006 and 0.0143, respectively). The hours of undisturbed sleep and N-QOL score were significantly improved in IM twice/day group, though not IM nightly group. Nocturnal urine volume was significantly reduced in IM nightly group, although total urine volume remained unchanged., Conclusions: A short half-life anticholinergic is suggested to be safe and effective as an add-on therapy for residual nocturia in patients with male LUTS receiving α1-blocker treatment. Anticholinergic administration nightly could reduce the nocturnal urine volume.

Objectives: To gain further evidence on the efficacy, safety and tolerability of tadalafil 5 mg once-daily in Asian men with lower urinary tract symptoms suggestive of benign prostatic hyperplasia., Methods: Japanese and Korean men with lower urinary tract symptoms suggestive of benign prostatic hyperplasia were randomized to once-daily tadalafil 5 mg (n = 306) or placebo (n = 304) for 12 weeks., Results: A significantly greater improvement (P < 0.001) in total International Prostate Symptom Score for the change from baseline (week 0) to study end-point (week 12) was observed for tadalafil (-6.0) versus placebo (-4.5). Significantly greater improvements (P < 0.01) in total International Prostate Symptom Score for the change from baseline to weeks 4 and 8 were observed for tadalafil versus placebo. Significantly greater improvements (P < 0.05) in International Prostate Symptom Score voiding and storage subscores, and International Prostate Symptom Score Quality of Life Index were observed for the change from baseline to end-point for tadalafil versus placebo. Significantly greater improvements (P < 0.001) in urinary symptoms were observed for tadalafil versus placebo for both Patient and Clinician Global Impressions of Improvement. No new safety concerns were identified., Conclusions: These findings confirm the efficacy and safety profile of tadalafil 5 mg once-daily in Asian men with lower urinary tract symptoms suggestive of benign prostatic hyperplasia., (© 2014 The Japanese Urological Association.)

Objectives: To examine the efficacy and safety of tadalafil in Asian men with lower urinary tract symptoms suggestive of benign prostatic hyperplasia., Methods: Asian men with lower urinary tract symptoms suggestive of benign prostatic hyperplasia were randomized to once-daily placebo (n=154), tadalafil 2.5 mg (n=151), tadalafil 5.0 mg (n=155) or tamsulosin 0.2 mg (active control, n=152) for 12 weeks., Results: Total International Prostate Symptom Score least-squares mean changes from baseline to end-point significantly improved with tadalafil 2.5 mg (-4.8, P=0.003) and 5 mg (-4.7, P=0.004) versus placebo (-3.0). Significant improvement in the International Prostate Symptom Score versus placebo was observed earlier (week 2) for tadalafil 5.0 mg than for tadalafil 2.5 mg (week 8). Significant improvements (P<0.05) in both tadalafil groups versus placebo were observed for the International Prostate Symptom Score voiding subscore, International Prostate Symptom Score Quality of Life, and for Patient and Clinician Global Impressions of Improvement. Significant improvements versus placebo were observed in the International Prostate Symptom Score storage subscore for tadalafil 5.0 mg (-1.7, P=0.021), but not tadalafil 2.5 mg (-1.5, P=0.072). No significant improvements in benign prostatic hyperplasia Impact Index or improvements in peak urinary flow rates were observed with tadalafil 2.5 mg or 5.0 mg versus placebo. Tamsulosin treatment resulted in significant improvements versus placebo across all efficacy parameters, except for peak urinary flow rates. Safety results were consistent with the known tadalafil and tamsulosin safety profiles., Conclusions: Tadalafil once daily represents an effective and well tolerated medical treatment for Asian men presenting with lower urinary tract symptoms suggestive of benign prostatic hyperplasia., (© 2012 The Japanese Urological Association.)

Aims: The existence of Angiotensin-II (Ang-II) receptors in the bladder wall and the pronounced contractile effect of Ang-II on the human detrusor muscle have been well established. Studies have presented the role of Ang-II as a mediator in smooth muscle growth and collagen production in the bladder with outlet obstruction. We investigated the associations between male lower urinary tract symptoms (LUTS) and hypertension (HT), and examined whether the medications used for HT treatment, particularly Ang-II receptor blockers (ARBs) influence LUTS., Methods: Among 4,298 men with LUTS who were nominated to participate in a Japanese study using the International Prostate Symptom Score (IPSS) to gain information on the effects and the safety of silodosin, a total of 3,790 men for whom a baseline IPSS was available were sub-analyzed. We analyzed the influence of HT treatment on IPSSs., Results: HT was the most common comorbidity (1,122 men, 29.6%), and 769 men (20.3%) were receiving some kinds of medication for the treatment. We found that the IPSS was lower in patients being treated for HT with ARB than in hypertensive patients who were not receiving any medication (16.8 ± 6.8 vs. 18.3 ± 6.6, P < 0.01). The baseline I-PSS in patients treated for HT with angiotensin converting enzyme inhibitor (ACE-I), calcium channel blocker (CCB), and normotensive patients were 18.3, 19.6, and 18.1, respectively., Conclusion: The IPSS is lower in patients with HT treated with ARB. Other drugs for HT, including ACE-I and CCB, did not improve the IPSS., (Copyright © 2012 Wiley Periodicals, Inc.)

Objectives: To evaluate the impact of smoking and the benefit of smoking cessation on lower urinary tract function and prostatic inflammation in patients with benign prostatic hyperplasia. Methods: The medical records of 118 benign prostatic hyperplasia patients who underwent transurethral prostatic surgery between 2006 and 2016 were analyzed. Their smoking history was confirmed. The relationship between smoking and main clinical parameters, International Prostate Symptom Scores, uroflowmetry, pressure flow study, magnitude of prostatic inflammation and the level of serum C‐reactive protein was investigated. Furthermore, the relationships between smoking cessation and these clinical parameters were assessed. Results: The International Prostate Symptom Scores for straining among the non‐smokers were significantly lower than those of the smokers (1.71 vs 2.60, P = 0.029). In the pressure flow study, there were negative correlations between the duration of smoking and strong desire to void (correlation coefficient −0.314, P = 0.013), urgency (correlation coefficient −0.349, P = 0.008) and bladder volume at initial detrusor overactivity (correlation coefficient −0.417, P = 0.021). The duration of smoking cessation was negatively correlated with the magnitude of chronic prostatic inflammation (correlation coefficient −0.253, P = 0.027). In the pressure flow study, the duration of smoking cessation was positively correlated with urgency (correlation coefficient 0.286, P = 0.030) and maximum cystometric capacity (correlation coefficient 0.241, P = 0.050). Conclusions: Smoking could be a risk factor for the exacerbation of storage dysfunction in benign prostatic hyperplasia patients. Smoking cessation is effective in improving chronic prostatic inflammation and storage dysfunction. [ABSTRACT FROM AUTHOR]

Tadalafil, a phosphodiesterase type 5 (PDE5) inhibitor, is approved worldwide for the treatment of lower urinary tract symptoms secondary to benign prostatic hyperplasia (BPH-LUTS). The purpose of this narrative review is to summarize the clinical data on tadalafil 5 mg once-daily, primarily focusing on Asian men with BPH-LUTS, and to update the current understanding of the mechanism of action underlying PDE5 inhibition. Findings from studies have demonstrated that PDE5 is highly expressed in the lower urinary tract and supporting vasculature, and that PDE5 inhibition potentially decreases smooth muscle cell proliferation in the prostate, relaxes smooth muscle in the prostate, bladder neck and supporting vasculature, increases blood perfusion to the lower urinary tract, and modulates bladder afferent nerve activity. A total of 11 larger, 12-week, double-blind, randomized, placebo-controlled studies of tadalafil, including four Asian studies, have been conducted globally, enrolling >3000 men with BPH-LUTS. In addition, two long-term (42- and 52-week) studies enrolled 394 Japanese and 428 North American men, respectively, with BPH-LUTS. Overall, tadalafil 5 mg once-daily resulted in significant improvements in the change from baseline to endpoint in total International Prostate Symptom Scores (IPSS), IPSS storage and voiding subscores, and IPSS quality of life index compared with placebo. Tadalafil was well tolerated and had a favorable safety profile. These findings support tadalafil 5 mg once-daily for treating men, including Asian men, with BPH-LUTS. [ABSTRACT FROM AUTHOR]

Objectives Assess the efficacy and safety of tadalafil 5 mg once-daily in Asian men with lower urinary tract symptoms by pooling data from three clinical studies. Methods Data on 1199 Japanese, Korean, and Taiwanese men given tadalafil 5 mg ( n = 601) or placebo ( n = 598) were pooled from three double-blind, placebo-controlled, 12-week studies. Efficacy measures included International Prostate Symptom Score, and Patient and Clinician Global Impressions of Improvement. These measures were also assessed for patient subgroups (age categories, baseline disease severity and/or prostate volume, prior alpha-blocker treatment). Safety measures included adverse events, including those in selected body systems. Efficacy measure changes throughout treatment were assessed by mixed-effect model repeated-measures analysis; baseline to end-point changes for the total population and subgroups were evaluated by analysis of covariance. Results Tadalafil 5 mg led to significant improvement ( vs placebo) in all International Prostate Symptom Scores at all time-points (week 4 P ≤ 0.013 for all measures; week 8 P ≤ 0.005, week 12 P < 0.001). End-point results for both global impressions scales also favored tadalafil (both P < 0.001 vs placebo). Tadalafil efficacy was similar between patient subgroups of varied disease severity (interaction P = 0.097), prior alpha-blocker use ( P = 0.580), and prostate volume ( P = 0.921). The drug was slightly less effective in older men (interaction P = 0.042). No unexpected adverse events were reported, and no meaningful adverse effects were observed in visual, auditory, or cardiovascular systems. Conclusions Tadalafil 5 mg once-daily for 12 weeks is efficacious and safe in Asian men with lower urinary tract symptoms. Tadalafil is also effective in men of different ages, disease severity, prior alpha-blocker exposure, and prostate volumes. [ABSTRACT FROM AUTHOR]

This article is a shortened version of the clinical guideline for lower urinary tract symptoms (LUTS), which has been developed in Japan for symptomatic men aged 50 years and over irrespective of presumed diagnoses. The guideline was formed on the PubMed database between 1995 and 2007 and other relevant sources. The causes of male LUTS are diverse and attributable to diseases/dysfunctions of the lower urinary tract, prostate, nervous system, and other organ systems, with benign prostatic hyperplasia, bladder dysfunction, polyuria, and their combination being most common. The mandatory assessment should comprise medical history, physical examination, urinalysis, and measurement of serum prostate-specific antigen. Symptom and quality of life questionnaires, bladder diary, residual urine measurement, urine cytology, urine culture, measurement of serum creatinine, and urinary tract ultrasonography would be optional tests. The Core Lower Urinary Tract Symptom Score Questionnaire may be useful in quickly capturing important symptoms. Severe symptoms, pain symptoms, and other clinical problems would indicate urological referral. One should be careful not to overlook underlying diseases such as infection or malignancy. The treatment should be initiated with conservative therapy and/or medicine such as α1-blockers. Treatment with anticholinergic agents should be reserved only for urologists, considering the risk of urinary retention. The present guideline should help urologists and especially non-urologists treat men with LUTS. [ABSTRACT FROM AUTHOR]