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.     

Are clinical characteristics of familial benign prostatic hyperplasia different than in sporadic cases?

OBJECTIVE: Familial benign prostatic hyperplasia (BPH) is a recently popularized entity with yet uncertain clinical and pathological features. In the present study we investigated whether there was any difference between clinical characteristics of familial and sporadic BPH in a series of 148 surgically treated BPH patients. MATERIALS AND METHODS: A retrospective analysis was performed in 148 patients subjected to transvesical or transurethral prostatectomy to determine the clinical features of familial BPH. Patients were categorised as having familial BPH when 3 or more (including the patient) first-degree family members gave a history of BPH. Accordingly 23 cases who fit this criterion were accepted as having familial BPH and the rest of the cases were taken as the control group. The two groups were compared with respect to age, International Prostate Symptom Score (IPSS), quality of life score, prostate specific antigen (PSA), maximum urinary flow rate and the weight of the surgical prostate specimen. RESULTS: The mean age, IPSS, quality of life score, total PSA, maximum urinary flow rate and the weight of the surgical prostate specimen were found as 65.13 +/- 5.51 years, 23.13 +/- 4.82, 4.78 +/- 0.95, 6.0 +/- 4.1 ng/ml, 6.9 +/- 2.7 ml/s and 62.96 +/- 38.76 g, respectively, in the familial BPH group whereas the same parameters were measured as 68.13 +/- 7.68 years, 24.74 +/- 3.73, 4.52 +/- 0.85, 5.93 +/- 4.75 ng/ml, 4.6 +/- 1.71 ml/s and 70.87 +/- 53.21 g, respectively. No significant difference was present between familial and sporadic BPH cases in any of the studied parameters. CONCLUSION: The clinical features of familial BPH did not differ significantly from those of sporadic BPH.     

Does the prostatic vascular system contribute to the development of benign prostatic hyperplasia?

Benign prostatic hyperplasia (BPH) is a disease condition characterized by abnormal prostate growth in conjunction with distinct lower urinary tract symptoms. This paper considers the extent to which the prostatic vascular system contributes to normal prostate growth control as well as whether abnormal blood flow patterns in the aging prostate gland might lead to hypoxia-stimulated prostate growth. This relationship is posited from accumulated research that suggests the prostatic vascular system is a primary androgen action target and other research demonstrating the diverse effects of hypoxia in eliciting cell death or cell growth responses. This hypothesis is further supported by the coincidental clinical finding that the presence of cardiovascular disease conditions are among the general risk factors for the development of BPH, and that cardiovascular-active drugs can be used for the treatment of BPH symptoms. This hypothesis has major implications for our understanding of the etiology of BPH, as well as for the development of new and better treatments for this extremely common condition.     

Evaluation for Madigan＇s prostatectomy in patients with benign prostatic hyperplasia

Aim: To comparatively evaluate the efficacy and post-operative complications of the Madigan‘s prostatectomy (MPC) and suprapubic prostatectomy (SPPC). Methods: A total of 43 patients with benign prostatic hyperplasia were divided into two groups: 21 underwent MPC and 22, SPPC. In all the patients, the international prostate symptom score (IPSS) and urinary pressure-flow studies were assessed before and 6 months after operation. The International Continence Society (ICS) nomogram, Abrams-Gfiffiths (AG) number and linear passive urethral resistance relation analysis (L-PURR) were used to diagnose and grade bladder outlet obstruction (BOO). The IPSS and the urodynamic parameters before and after operation, as well as the advantages and post-operative complications were recorded and compared. Results: Patients of both the MPC and SPPC groups had a significant improvement in IPSS and urodynamic parameters. Obstruction was relieved in 81.0% of MPC and 86.4% of SPPC patients. MPC has the advantages of the absence of postoperative hematuria and post-catheter stricture, a shorter period of hospitalization, and lower incidence of retrograde ejaculation and erectile dysfunction. Conclusion: Both MPC and SPPC can effectively relieve BOO. MPC has certain advantages and a lower incidence of complications as compared with SPPC.     

Could inflammation be a key component in the progression of benign prostatic hyperplasia?

PURPOSE OF REVIEW: This review covers recent developments in the role of chronic inflammation in the pathogenesis and progression of benign prostatic hyperplasia (BPH). RECENT FINDINGS: A paper on the subanalysis of the Medical Therapy of Prostate Symptoms study highlighted the role of chronic inflammation in the progression of BPH as determined by the pathological tissue obtained in the 4.5-year study. It shows patients with inflammation had significantly larger prostates, higher serum prostate specific antigen and a greater risk of urinary retention. This follows several other in-situ studies which demonstrated that elevated expression of pro-inflammatory cytokines in BPH. IL-6, IL-8 and IL-17 may perpetuate chronic immune response in BPH and induce fibromuscular growth by an autocrine or paracrine loop or via induction of COX-2 expression. Immune reaction may be activated via Toll-like receptor signalling and mediated by macrophages and T cells. Conversely, anti-inflammatory factors such as macrophage inhibitory cytokine-1 decreased in symptomatic BPH tissues. Animal models provided evidence for the presence of unique T-cell subsets which may suppress autoimmunity in healthy Sprague-Dawley rats resistant to chronic nonbacterial prostatitis. SUMMARY: The pathogenesis of BPH is still unresolved, although chronic inflammation may play a significant role in disease progression. Further research is required to determine the putative (auto)antigen, the influence of infiltrating inflammatory cells on the stromal/epithelial cell crosstalk and a new classification of BPH quantifying local and systemic inflammatory/immune reactions in relation to clinical relevance. New treatments for BPH investigating these specific inflammatory pathways may arise as we learn more about the way they work.     

Dihydrotestosterone and the concept of 5α-reductase inhibition in human benign prostatic hyperplasia

The development of human benign prostatic hyperplasia (BPH) clearly requires a combination of testicular androgens and the ageing process. Although the role of androgens as the causative factor for human benign prostatic hyperplasia is debated, they undoubtedly play, at least, a permissive role. The principal prostatic androgen is dihydrotestosterone. Although not elevated in human benign prostatic hyperplasia, dihydrotestosterone levels in the prostate remain at a normal level with ageing, despite a decrease in the plasma testosterone. Dihydrotestosterone (DHT) is generated by a reduction in testosterone. Two isoenzymes of 5alpha-reductase have been discovered. Type 1 is present in most tissues in the body where 5alpha-reductase is expressed, and is the dominant form in sebaceous glands. Type 2 5alpha-reductase is the dominant isoenzyme in genital tissues, including the prostate. Finasteride is a 5alpha-reductase inhibitor that has been used to treat BPH and male-pattern baldness. At doses used clinically, its major effect is to suppress type 2 5alpha-reductase, because it has a much lower affinity for the type 1 isoenzyme. Finasteride suppresses DHT by about 70% in serum and by as much as 85%-90% in the prostate. The remaining DHT in the prostate is likely to be the result of type 1 5alpha-reductase. The suppression of both 5alpha-reductase isoenzymes with GI198745 results in greater and more consistent containment of serum dihydrotestosterone than that observed with a selective inhibitor of type 2 5alpha-reductase. Physiological and clinical studies comparing dual 5alpha-reductase inhibitors, such as GI198745, with selective type 2, such as finasteride, will be needed to determine the clinical relevance of type 1 5alpha-reductase within the prostate. There have been two large, international multicentre, phase III trials published documenting the safety and efficacy of finasteride in treating human benign prostatic hyperplasia. Combining these two studies, randomised, controlled data are available for 12 months. Non-controlled extension of these data from a subset of patients, who elected to continue on the drug for 3, 4 and 5 years, are also available. Long-term medical therapy with finasteride can reduce clinically significant endpoints, such as acute urinary retention or surgery. According to the meta-analysis of six randomised, clinical trials with finasteride, finasteride is most effective in men with large prostates. A more effective dual inhibitor of type 1 and 2 human 5alpha-reductase may lower circulating dihydrotestosterone to a greater extent than finasteride and show advantages in treating human benign prostatic hyperplasia and other disease states that depend on dihydrotestosterone. A clinical evaluation of potent dual 5alpha-reductase inhibitors may help to define the relative roles of human type 1 and 2 5alpha-reductase in the pathophysiology of benign prostatic hyperplasia and other androgen-dependent diseases.     

Lower urinary tract symptoms,benign prostatic hyperplasia/benign prostatic enlargement and erectile dysfunction: Are these conditions related to vascular dysfunction?

Although the pathogenesis of lower urinary tract symptoms, benign prostatic hyperplasia/benign prostatic enlargement and erectile dysfunction is poorly understood and thought to be multifactorial, it has been traditionally recognized that these conditions increase with age. There is increasing evidence that there is an association between cardiovascular disease and lower urinary tract symptoms as well as benign prostatic hyperplasia/benign prostatic enlargement and erectile dysfunction in elderly patients. Age might activate systemic vascular risk factors, resulting in disturbed blood flow. Hypertension, diabetes, hyperlipidemia and atherosclerosis are also linked to the etiology of lower urinary tract symptoms, benign prostatic hyperplasia/benign prostatic enlargement and erectile dysfunction. In the present review, we discuss the relationship between decreased pelvic blood flow and lower urinary tract symptoms, benign prostatic hyperplasia/benign prostatic enlargement and erectile dysfunction. Furthermore, we suggest possible common mechanisms underlining these urological conditions.     

Are neuroendocrine cells responsible for the development of benign prostatic hyperplasia?

OBJECTIVES: To examine the possible relationship between the distribution of neuroendocrine (NE) cells and the development of benign prostatic hyperplasia (BPH) in the human prostate, we performed an NE cells-distribution analysis and made morphological observations of acinous structures in different-aged prostates.METHODS: Forty-three human prostates obtained from surgical and autopsy cases aged from 2 months to 86 years were examined immunohistochemically using Chromogranin A and analyzed with special reference to the development of BPH.RESULTS: NE cells were distributed predominantly in the verumontanum and main prostatic ducts and were fewer in number in the terminal acini. As BPH development progressed, the NE cells were greatly diminished in number or completely lost from most adenoma nodules.CONCLUSIONS: The NE cells of the prostate may be distributed and transported from the periurethral region near the verumontanum to the terminal acini during the development of the acinar structures. The distribution pattern is relatively consistent among prostates of all ages. However, NE cells do not appear in acquired tissue within BPH nodules as the nodules develop. Thus, the distribution of NE cells does not seem to be related to the development of BPH.     

The efficacy and safety of 2-μm continuous laser in the treatment of high-risk patients with benign prostatic hyperplasia

Two-micrometer laser resection of prostate-tangerine technique dissects whole prostatic lobes off the surgical capsular, similar to peeling a tangerine. The present study aimed to evaluate the safety and efficacy of 2-μm continuous laser vaporization in the treatment of high-risk patients with benign prostatic hyperplasia (BPH) during the 24-month follow-up. The study included 248 patients with moderate to severe lower urinary tract symptoms who underwent 2-μm continuous laser vaporization of the prostate. All patients were accompanied with different degree comorbidities and 94 patients were taking oral anticoagulants. BPH was successfully treated with 2-μm continuous laser vaporization in all patients. Mean pre-operative prostate volume was 76?±?25.3 ml and mean operative time was 49.8?±?16.5 min. There were no major complications intra-operatively or postoperatively, and no blood transfusions were needed. About 20 patients (8.1%) needed bladder irrigation postoperatively. Average catheterization time was 2.0?±?1.8 days (range 1–5 days). Four patients required reoperation due to enlarged prostates from residual adenoma. At 3-, 6-, 12-, and 24-month follow-ups, maximum urinary flow rates (Qmax) increased from 6.9?±?1.7 to 19.1?±?4.2, 19.5?±?4.6, 19.4?±?4.6, and 19.5?±?4.1 ml/s, respectively. Mean International Prostate Symptom Scores (IPSS) decreased from 27.6?±?5.1 (pre-operation) to 9.2?±?2.6, 7.12?±?1.42, 6.18?±?1.32, and 6.25?±?1.30 at 3-, 6-, 12-, and 24-month post-operation, respectively. Two-micrometer continuous laser vaporization is a safe and effective surgical endoscopic technique associated with low complication rate in BPH patients at high risk and those on anticoagulation therapy who have severe LUTS caused by BPH.     

Does intraprostatic inflammation have a role in the pathogenesis and progression of benign prostatic hyperplasia?

OBJECTIVE: To compare the incidence of acute and/or chronic intraprostatic inflammation (ACI) in men undergoing transurethral resection of the prostate (TURP) for urinary retention and lower urinary tract symptoms (LUTS), as recently a role was suggested for ACI in the pathogenesis and progression of BPH, and urinary retention is considered an endpoint in the natural history of this condition. PATIENTS AND METHODS: Details of TURPs done between January 2003 and December 2005 at one institution were obtained from the operating theatre database. Patients were divided by indication (retention/LUTS). Clinical data and histology reports were then reviewed and bivariate and logistic regression used to compare the pathological features between these groups. RESULTS: Of 406 patients, 374 had evaluable data; 70% of men with urinary retention had ACI, vs 45% of those with LUTS (P < 0.001). On logistic regression, the pathological factors associated with TURP for acute retention compared to that for LUTS were ACI, old age, and resection weight to a lesser degree. CONCLUSION: Inflammation appears to be important in the pathogenesis and progression of BPH. In this study, the risk of urinary retention due to BPH was significantly greater in men with ACI than in those without, and the association of TURP for retention with ACI was stronger than that with prostate weight. This finding might offer new avenues for the medical treatment of men with LUTS due to BPH.     

Simultaneous quantification of oestrogens and androgens in the serum of patients with benign prostatic hyperplasia by liquid chromatography–Tandem mass spectrometry

Benign prostate hyperplasia (BPH) is a common disease in elderly men. It has been found that the occurrence of BPH was closely related to dysregulated steroid hormones. Here, a rapid, sensitive, accurate and specific method for the quantitative profiling of five androgens in man serum was developed and validated by the use of liquid chromatography–tandem mass spectrometry (LC-MS/MS). Using this method, dehydroepiandrosterone (DHEA), androstenedione (A4), testosterone (T), androsterone (A), dihydrotestosterone (DHT), oestrone (E1) and oestradiol (E2) were quantified in serum from man with and without BPH. BPH patients were characterised by the decreases in DHEA, A4 and T as well as increases in DHT, E2 and E1 in serum. Meanwhile, DHEA and DHT in serum were screened as sensitive biomarkers of BPH patients. This study will provide a new perspective of dysregulated steroid hormones for the diagnosis and prevention of BPH.     

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.     

Study on the prevalence of benlgn prostatic hyperplasia and prostatic cancer in China

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Expression of β-tubulin isotypes in urothelial carcinoma of the bladder

Purpose

Our study aims to investigate the expressions of β-tubulin isotypes and their significances in urothelial carcinoma of the bladder (UCB) as altered expression of a specific β-tubulin isotype is associated with chemoresistance and poor prognosis in other malignancies.

Materials and methods

Expression of β-tubulin isotypes was retrospectively examined in 342 UCB samples obtained from 1995 to 2010 by immunohistochemistry.

Results

TUBB1 (307/342, 89.8 %) was most frequently overexpressed in the cytoplasm of UCB cases, followed by TUBB4 (101/342, 29.5 %), TUBB2 (85/342, 24.9 %), and TUBB3 (60/342, 17.5 %). TUBB1 overexpression was associated with older age (p = 0.032), high WHO grade (p = 0.001), and advanced TNM stage (p = 0.006). High levels of TUBB2 expression were associated with high WHO grade (p < 0.001), advanced TNM stage (p < 0.001), and non-papillary growth pattern (p = 0.007). TUBB3 overexpression was related to high WHO grade (p = 0.029). In univariate and multivariate survival analyses, TUBB1 overexpression was associated with poor recurrence-free survival (RFS) rates of all cases (hazard ratio 1.98, p = 0.031) and of the patients with transurethral and/or partial resection (hazard ratio 2.12, p = 0.031). TUBB2 overexpression was correlated with a short RFS of the patients with T2–T4 stages (hazard ratio 3.48, p = 0.007). TUBB3 overexpression was related to a poor RFS of the patients undergoing radical cystectomy (hazard ratio 5.90, p = 0.002).

Conclusions

High TUBB1, TUBB2, and TUBB3 expressions are associated with unfavorable clinicopathologic factors and are independent prognostic factors for recurrence-free survival of UCB.     

The impact of minimally invasive surgeries for the treatment of symptomatic benign prostatic hyperplasia on male sexual function： a systematic review

A systematic review of randomized controlled trials and cohort studies was conducted to evaluate data for the effects of minimally invasive procedures for treatment of symptomatic benign prostatic hyperplasia （BPH） on male sexual function. The studies searched were trials that enrolled men with symptomatic BPH who were treated with laser surgeries, transurethral microwave therapy （TUMT）, transurethral needle ablation of the prostate （TUNA）, transurethral ethanol ablation of the prostate （TEAP） and high-intensity frequency ultrasound （HIFU）, in comparison with traditional transurethral resection of the prostate （TURP） or sham operations. A total of 72 studies were identified, of which 33 met the inclusion criteria. Of the 33 studies, 21 were concerned with laser surgeries, six with TUMT, four with TUNA and two with TEAP containing information regarding male sexual function. No study is available regarding the effect of HIFU for BPH on male sexual function. Our analysis shows that minimally invasive surgeries for BPH have comparable effects to those of TURP on male erectile function. Collectively, less than 15.4% or 15.2% of patients will have either decrease or increase, respectively, of erectile function after laser procedures, TUMT and TUNA. As observed with TURP, a high incidence of ejaculatory dysfunction （EjD） is common after treatment of BPH with holmium, potassium-titanyl-phosphate and thulium laser therapies （〉 33.6%）. TUMT, TUNA and neodymium：yttrium aluminum garnet visual laser ablation or interstitial laser coagulation for BPH has less incidence of EjD, but these procedures are considered less effective for BPH treatment when compared with TURP.     

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.