Urodynamic analysis in 245 patients with benign prostatic hypertrophy

To study the mechanism of voiding disorder and promote thediagnosic accuracy of bladder outlet obstruction (BOO), a full setof urodynamic examination were employed with self-made semi-supine bed and Manneu Danec Urodynamic device in 245 patients.The results showed definite BOO in 161 cases, doubtful BOO in 50cases, detrusor muscle dysfunction in 65 cases, depressed bladdercompliance in 70 cases, urethral sphincter dyssynergia in 114 cas-es , and unstable bladder in 59 cases. There is a close relationshipbetween the functional urethral length and the prostatic urethrallength as determined by B ultrasound. It suggests that both the dy-namic and mechanical factors are attributed to voiding disorder inpatients with BPH. The urodynamic examination plays an importantrole in the diagnosis of BOO. (Chin J Androl 2000; 4: 234 - 236)     

Clinical significance of α1-adrenoceptor selectivity in the management of benign prostatic hyperplasia

Alpha₁-adrenoceptor antagonists have beenshown to provide effective relief from symptomsof benign prostatic hyperplasia (BPH) withattendant improvements in quality of life.Although the _1A-adrenoceptorsubtype predominates over other subtypes of₁ adrenoceptors in the prostategland, there is no evidence that a subselective-adrenoceptor antagonist provides aclinical advantage over a selective₁-adrenoceptor antagonist in thetreatment of patients with BPH. Thepharmacokinetic profiles of_1A-adrenoceptorantagonists and their documented penetration ofthe blood-brain barrier (CNS adverse effects)preclude a clinical benefit of subselective-adrenoceptor blockers over selective₁ blockers.     

Pharmacoeconomic evaluation of combination therapy with dutasteride and α1 blocker for treatment of benign prostatic hyperplasia in Japan

The cost-effectiveness of combination therapy with an α1 blocker and dutasteride in benign prostatic hyperplasia (BPH) was analyzed in comparison with α1 blocker monotherapy. A Markov model with seven health states related to BPH was constructed with 4-year and 10-year time horizons and from the entire payers perspective. The transition probabilities among different health states input into the model were mainly derived from CombAT Study data, while cost parameters were estimated from a clinical database including DPC claims. Effectiveness was defined as quality adjusted life year (QALY). The cost-effectiveness of combination therapy was assessed by the incremental cost-effectiveness ratio (ICER) threshold (6 to 7 million Japanese yen (JPY)/QALY gained). For a base-case analysis, combination therapy produced an incremental effectiveness versus monotherapy of 0.050 and 0.097 QALYs at 4 years and 10 years, respectively, while the concomitant incremental costs were estimated to be 257,172 and 579,908 JPY, respectively. The ICERs for combination therapy versus monotherapy calculated at 4 years and 10 years were 5,119,007 and 5,974,495 JPY/QALY gained, respectively, both below the acceptable ICER threshold. Sensitivity analyses revealed that the ICER tended to decrease with greater BPH severity. These findings suggest that combination therapy with an α1 blocker and dutasteride would be more cost-effective in BPH than α1 blocker monotherapy and more efficient in moderate-to-severe BPH.     

Transurethral microwave thermotherapy: an alternative to medical management in patients with benign prostatic hyperplasia?

Transurethral microwave thermotherapy (TUMT) is being increasingly considered as an alternative to medical management with alpha-blockers or finasteride in patients with lower urinary tract symptoms (LUTS) of benign prostate hyperplasia (BPH). Enduring clinical benefits have been demonstrated after a single 1-hour microwave treatment session under topical anesthesia, and the associated morbidity is low. Optimal results are obtained with the delivery of high thermal doses and accurate targeting of microwave energy. Extensive evidence from randomized clinical trials supports the safety and efficacy of both microwave treatment and medical management, but randomized trial data have only recently become available directly comparing these two approaches to BPH treatment. These data indicate that greater long-term improvements in symptoms, peak urinary flow rates, and quality of life are attained with microwave treatment than with alpha-blockade. Furthermore, the actuarial rate of treatment failure is markedly lower in patients undergoing microwave v alpha-blocker treatment. However, the onset of action of alpha-blocker treatment is more rapid. The principal limitations of alpha-blockade are side effects and lack of efficacy leading to treatment failure in some patients. The maximal effects of finasteride are modest and require a period of months to be manifested, although the side effect profile and tolerability of this agent are favorable. Neoadjuvant and adjuvant alpha-blocker therapy can accelerate symptom and flow rate improvement after TUMT. In contrast to medical management, microwave treatment is highly versatile, allowing patients over a broad range of baseline symptom severities and prostate sizes to be treated with a high probability of success.     

Differential expression of transforming growth factor-β1 and β3 as well as C-FOS mRNA in normal human prostate,benign prostatic hyperplasia and prostatic cancer

Summary The discrepancy between the incidence of latent prostate cancer and that of clinically overt carcinoma suggests that there can be different courses in the biological progression of prostate cancer. As this cancer is detected increasingly at an infraclinical stage, markers are needed to indicate which lesions will progress and lead to the patient's death. To investigate the possibility that specific growth factors and/or proto-oncogenes are expressed differentially, we measured mRNA levels of transforming growth factors 1 (TGF-1), TGF-2 and TGF-3 and of the c-fos and c-jun oncogenes by Northern blotting in normal prostate, benign prostatic hyperplasia (BPH) and prostate cancer. Our data demonstrate that expression of TGF-1 increased, whereas that of TGF-3 fell to an almost undetectable level in carcinoma. Expression of c-fos followed the TGF-1 pattern, whereas no difference could be seen in c-jun expression in cancer as compared with BPH and normal prostate. The differential expression of TGF-1, TGF-3 and c-fos could possibly be used to improve the characterisation of prostate cancer. Long-term follow-up of patients may indicate whether mRNA levels of these growth factors and oncogenes correlate clinically and whether they can be used as markers for progression in human prostate cancer.     

Combined tadalafil and α-blocker therapy for benign prostatic hyperplasia in patients with erectile dysfunction: a multicenter, prospective study

This prospective study evaluated the safety of tadalafil 5 mg taken once a day in terms of hypotensive side effects and whether it improves lower urinary tract symptoms (LUTS) and restores sexual function in patients with erectile dysfunction who are receiving concomitant α-blocker (AB) therapy for benign prostatic hyperplasia (BPH). A total of 158 LUTS/BPH patients receiving AB therapy for ≥3 months were given tadalafil 5 mg once a day. Before treatment with tadalafil (V1), and 4 weeks (V2) and 12 weeks (V3) after starting tadalafil, blood pressure, heart rate, International Prostate Symptom Score (IPSS), maximal urine flow rate (Qmax), postvoiding residual urine volume, and International Index of Erectile Function (IIEF-5) score were measured. Of the 158 LUTS/BPH patients, a total of 119 completed the trial. Blood pressure (systolic and diastolic) and heart rate did not change. IPSS and IIEF-5 scores improved significantly, but Qmax and postvoiding residual urine volume did not; however, in the 39 men with a low baseline Qmax (≤10 mL/s), Qmax rose significantly from 7.97 ± 1.44 mL/s (baseline) to 8.91 ± 1.60 mL/s (V3; P = .012). The remaining patients (baseline Qmax >10 mL/s) did not change. At V2 and V3, adverse side effects were observed in 10 men (7.30%) and 6 men (5.04%), respectively. Facial flushing was the most common adverse side effect (6 men at V2 and 4 men at V3), followed by headache (2 men each at V2 and V3) and dizziness (2 men at V2). Two patients dropped out of the study because of adverse side effects. In conclusion, tadalafil 5 mg once a day in combination with AB appeared to have few adverse effects on hypotensive events and can improve LUTS and restore sexual function.     

Can the intraprostatic concentration of epidermal growth factor influence the variance of serum prostate specific antigen levels in patients with benign prostatic hyperplasia?

PURPOSE: Except for prostate volume, little is known about the factors influencing serum prostate specific antigen (PSA) levels. Considering that dihydrotestosterone and epidermal growth factor are regulators of the proliferation and differentiation in the epithelial component of human prostate tissue and that PSA is produced only by the epithelial cells of the gland, studies were performed on patients with a histological diagnosis of benign prostatic hyperplasia (BPH) to establish whether a significant association exists between the intraprostatic concentration of dihydrotestosterone or epidermal growth factor and serum PSA levels. MATERIALS AND METHODS: A total of 20 patients with BPH who had not been previously treated were part of a larger study on the correlation among PSA, prostate volume and age, and were evaluated according to the algorithm in the guidelines of the international consultation on BPH. All men underwent open suprapubic prostatectomy to enucleate the entire adenoma and in each case sections were made in the periurethral, subcapsular and intermediate zones of the BPH tissue. Dihydrotestosterone and epidermal growth factor concentrations were evaluated by radioimmunoassay in the periurethral zone and in total BPH tissue. RESULTS: In these 20 patients with BPH serum PSA levels were significantly associated with epidermal growth factor but not with dihydrotestosterone concentrations in total BPH tissue (r = 0.7762, p = 0.00002836 and r = 0.3923, p = 0.0956307, respectively). A stronger association was found between PSA levels and the periurethral concentration of epidermal growth factor and dihydrotestosterone (r = 0.8117, p = 0.000005 and r = 0.5656, p = 0.0098326, respectively). On the contrary, epidermal growth factor and dihydrotestosterone were not significantly associated with prostate volume (p = 0.957415 and p = 0.531439, respectively). CONCLUSIONS: To our knowledge this study is the first report in the literature to demonstrate an association between serum PSA, and dihydrotestosterone and epidermal growth factor levels, particularly in the periurethral zone of human BPH tissue. These data suggest the importance of epidermal growth factor and dihydrotestosterone in influencing serum PSA levels.     

A systematic review and meta-analysis on the use of phosphodiesterase 5 inhibitors alone or in combination with α-blockers for lower urinary tract symptoms due to benign prostatic hyperplasia

Context

Several randomized controlled trials (RCTs) on phosphodiesterase type 5 inhibitors (PDE5-Is) have showed significant improvements in both lower urinary tract symptoms (LUTS) and erectile dysfunction (ED) in men affected by one or both conditions, without a significant increase in adverse events. However, the results are inconsistent.

Objective

Perform a systematic review and meta-analysis of available prospective and cross-sectional studies on the use of PDE5-Is alone or in combination with α1-adrenergic blockers in patients with LUTS/benign prostatic hyperplasia (BPH).

Evidence acquisition

A systematic search was performed using the Medline, Embase, and Cochrane Library databases through September 2011 including the combination of the following terms: LUTS, BPH, PDE5-Is, sildenafil, tadalafil, vardenafil, udenafil, α-blockers, and α1-adrenergic blocker. The meta-analysis was conducted according to the guidelines for observational studies in epidemiology.

Evidence synthesis

Of 107 retrieved articles, 12 were included in the present meta-analysis: 7 on PDE5-Is versus placebo, with 3214 men, and 5 on the combination of PDE5-Is with α1-adrenergic blockers versus α1-adrenergic blockers alone, with 216 men. Median follow-up of all RCTs was 12 wk.Combining the results of those trials, the use of PDE5-Is alone was associated with a significant improvement of the International Index of Erectile Function (IIEF) score (+5.5; p < 0.0001) and International Prostate Symptom Score (IPSS) (−2.8; p < 0.0001) but not the maximum flow rate (Q_max) (−0.00; p = not significant) at the end of the study as compared with placebo. The association of PDE5-Is and α1-adrenergic blockers improved the IIEF score (+3.6; p < 0.0001), IPSS score (−1.8; p = 0.05), and Q_max (+1.5; p < 0.0001) at the end of the study as compared with α-blockers alone.

Conclusions

The meta-analysis of the available cross-sectional data suggests that PDE5-Is can significantly improve LUTS and erectile function in men with BPH. PDE5-Is seem to be a promising treatment option for patients with LUTS secondary to BPH with or without ED.     

β3-Adrenoceptor agonist mirabegron is effective for overactive bladder that is unresponsive to antimuscarinic treatment or is related to benign prostatic hyperplasia in men

Purpose

To investigate the safety and efficacy of mirabegron for patients with overactive bladder (OAB) that is unresponsive to antimuscarinic agents or is related to benign prostatic hyperplasia (BPH).

Methods

Fifty-two newly diagnosed OAB patients (M group) and 45 patients with OAB that was unresponsive to antimuscarinics (S group) received mirabegron 50 mg once daily and were evaluated by OAB symptom score (OABSS), IPSS-QOL index, and IPSS at the time of baseline, 4 and 8 weeks. Newly diagnosed OAB patients treated with antimuscarinic agents were compared as controls.

Results

Mirabegron was effective for 85.2 % in M group. Significant improvements were seen in each domain of OABSS, and there was no significant difference with antimuscarinic therapy. Mirabegron was efficacious for 61.6 % of S group, and significant decreases of OABSS and IPSS-QOL index were observed. Significant improvements were also seen in voiding symptoms in men. Post-void residual urine volumes before and after treatment were 32.1 and 34.8 ml, and 26.2 and 31.3 ml in M and S group, respectively, and there was no significant difference. The incidence of adverse events was 8.4 %, although none were serious, and the patients recovered spontaneously after mirabegron was discontinued.

Conclusion

The present study suggests mirabegron is as effective as antimuscarinics for OAB. It improves OAB symptoms in patients with OAB for which antimuscarinic agents are insufficient. This study revealed that mirabegron improves not only OAB symptoms related to BPH, but also voiding symptoms in men. Low and mild incidences of side effects support the safe utility of mirabegron.     

Effects of insulin resistance on left ventricular hypertrophy in patients with CKD stage 1–3

Background

Left ventricular hypertrophy (LVH) existed in patients with early stage chronic kidney disease (CKD). But whether insulin resistance (IR) exists in these patients and has some definite relationship with LVH, is unknown.

Methods

Homeostatic model method was used for detecting homeostasis model assessment of insulin resistance (HOMA-IR) in 336 subjects including 286 patients with early stage CKD and 50 control subjects, and HOMA-IR and other clinical data in all subjects were obtained based on standard methods. Then, the relationship between LVH, IR and other relevant clinical data were analyzed.

Results

IR and LVH existed in early stage CKD patients. The prevalence of LVH in patients with IR was significantly higher than those without, and patients with LVH had a higher prevalence of IR than those without. The patients with IR or LVH had lower levels of e-GFR, hemoglobin (Hb) and total cholesterol, while higher levels of blood urea nitrogen (BUN), serum creatinine (Scr), intact parathyroid hormone (iPTH), CRP and systolic blood pressure (SBP). HOMA-IR had positive correlations with left ventricular mass index (LVMI). HOMA-IR and LVMI had positive correlations with BUN, Scr, iPTH and CRP, but negative with e-GFR and Hb. Multiple linear stepwise regression analysis showed that e-GFR, FINS, Hb and SBP enter the regression equation. Binary unconditional logistic regression analysis indicated that the main risk factors for LVH were CKD and IR (P < 0.05, respectively).

Conclusion

Both IR and LVH existed in early stage CKD patients and were more severe with the development of CKD. IR had a significant correlation with LVH. Furthermore, decline of e-GFR, hypertension and anemia were also associated with both IR and LVH and may have some effects in the mechanism of IR on the development of LVH.     

The effect of α-blocker therapy on erectile functions in patients with lower urinary tract symptoms due to benign prostate hyperplasia

In this study we aimed to evaluate the impact of doxazosin treatment on erectile functions in patients with lower urinary tract symptoms （LUTS） and having erectile dysfunction （ED） at baseline. Fifty-three patients with LUTS （IPSS score 〉 7） whose maximum flow rate （Qmax） 〈 15 mL s-1 and PSA 〈 4 ng dL^-1 were enrolled in the study. Patients received doxazosin 4 nag once daily for 6 weeks. Subjective efficacy was assessed by IPSS, IPSS- Quality of Life （IPSS-QoL） for LUTS and efficacy was assessed by International Index of Erectile Function （IIEF） for erectile functions at baseline and sixth weeks. The objective efficacy was assessed by Q The patients were classified according to their self reported erectile status： group I had ED and group II did not have ED. At the endpoint, doxazosin significantly improved the total IPSS score （-7.7 ±6.1, P = 0.006）, IPSS-QoL score （-1.5 ± 1.5, P = 0.024） and Qmax （3.2 ± 4.6 mL s^-1, P = 0.002） over baseline. Mean decrease in IPSS and IPSS-QoL scores after the treatment period were 6.9 ＋ 6.4 （P 〈 0.001） and 0.95 4- 1.80 （P 〈 0.05） in group I, whereas 8.2 4- 5.8 （P 〈 0.001） and 1.9 4- 1.1 in group IX （P 〈 0.001）, respectively. Mean changes of Qmax values were 2.3 4- 3.3 mL s^-1 in group I （P 〈 0.05） and 3.7 4- 5.3 mL s-1 in group II （P 〈 0.001）. The improvement of IIEF-EF scores after the treatment period was only significant for group I. The efficacy of a-blocker therapy for LUTS was better by means of symptomatic relief for patients who did not have ED when compared with patients who had ED at baseline. However, slight improvement in erectile functions with a-blocker therapy was only seen in LUTS patients with ED.     

Localization of specific binding sites for125I-TGF-β1 to fenestrated endothelium in bone and anastomosing capillary networks in enamel organ suggests a role for TGF-β1 in angiogenesis

Previous studies have shown endothelial cells to be a major target for endocrine TGF-β in several soft tissues in the normal growing rat [26]. The potent effect of TGF-β1 on bone formation prompted us to analyze in detail the localization of specific binding sites for endocrine TGF-β in hard tissues. At 2.5 minutes after injection of¹²⁵I-TGF-β1, specific binding, as demonstrated by quantitative radioautography, was localized to fenestrated endothelium participating in angiogenesis in the vascular invasion region of the growth plate in bone as well as to anatomizing capillary networks in the maturation zone of the enamel organ. At 15 minutes after injection, the bound ligand was internalized into endocytic vesicles of endothelial cells. In bone, quantitation revealed significant differences in receptor density between endothelia undergoing proliferation vs those in a state of elongation and anastomosis with neighboring endothelial cells. In the rat incisor, specific binding of¹²⁵I-TGF-β1 to endothelium correlated with increased formation of anastomotic capillary networks. These studies identify differential specific binding sites of¹²⁵I-TGF-β1 in angiogenically active endothelium, providing an important link between TGF-β1, the endothelium, and hard tissue development.