PURPOSE:

Vascular Targeted Photodynamic (VTP) therapy with TOOKAD®Soluble is in phase III clinical trials through an interstitial transperineal approach for focal therapy of prostate cancer. Herein we investigated the safety and efficacy of the endourethral route in the context of Benign Prostatic Hyperplasia (BPH) in the dog model.

MATERIALS AND METHODS:

An optical laser fiber was positioned in the prostatic urethra of 34 dogs, including 4 controls, and connected to a 753nm diode laser at a fluence of 200mW/cm delivering 200-300J. TOOKAD®Soluble (5-15mg/Kg) was infused i.v. in two modes: continuous, starting 5-15min prior and during illumination or a bolus 5-10min before. Prostate ultrasound, cystourethrography, urodynamics and histopathology were performed. Follow-up ranged from 1-week to 1-year.

RESULTS:

Endourethral TOOKAD®Soluble-VTP was uneventful in all but one dog experiencing urinary retention but reached the 1-week enpoint. All prostates except controls presented hemorrhagic lesions. They consisted of two levels of concentric alterations: peri-urethral necrosis with destruction of the endothelial layer and adjacent inflammation/atrophy with normal blood vessels. Prostatic urethral width increased as early as 6 weeks post-treatment while prostatic volume decreased, reaching 25% by 18-26 weeks. A parallel decrease in urethral pressures was demonstrated at 6 weeks and lasted up to 1 year.

CONCLUSIONS:

We confirmed the vascular effect of endourethral TOOKAD®Soluble-VTP and showed for the first time that resulting peri-urethral necrosis lead to a significant and sustained widening of the prostatic urethra, accompanied by long-term improvement of urodynamic parameters. These findings support future clinical applications of this minimally invasive approach for BPH treatment.

To investigate the prevalence of benign prostatic hyperplasia (BPH) in Pingliang City of Gansu Province.We performed a cross-sectional randomized study of 836 men aged > or = 40 years from 26 communities of Pingliang, obtained their IPSS, measured the prostate volume by transabdominal ultrasonography, recorded the maximum flow (Qmax) by uroflowmetry, and processed the data by one-way analysis of variance.Totally 820 subjects meeting the study criteria were included in the investigation. The men ranged in age from 40 to 83 years, averaging 61.5 years. The mean IPSS, prostate volume and Qmax were 9.3 +/- 7.8, (29.2 +/- 18.6) ml and (15.3 +/- 7.2) ml/s, respectively, all correlated with age. The prevalence of moderate-severe lower urinary tract symptoms (LUTS) was 46.8% (384/820). The prostate volume was > 20 ml in 63.5% (521/820), and Qmax <15 ml/s in 48.5% (398/805) of the subjects. The incidence rate of BPH, defined as IPSS >7, Qmax <15 ml/s and prostate volume > 20 ml, was 23.5% (193/820).Among the men aged > or = 40 years in Pingliang, LUTS and prostate volume were correlated positively, while Qmax negatively with age, and the prevalence of BPH was 23.5%.

To explore the expressions of SIgA and alphal-AR in benign prostatic hyperplasia (BPH) complicated by chronic prostatitis (CP) and their implications.According to the preoperative findings of expressed prostatic secretion (EPS), transrectal prostate ultrasonography, prostate-specific antigen (PSA), international prostate symptom score (IPSS), clinical symptoms, chronic pelvic pain syndrome (CPPS) and postoperative histopathology, 62 cases of BPH pathologically confirmed after transurethal plasmakinetic resection of the prostate (PKRP) were divided into a BPH group (n = 32) and a BPH + CP group (n = 30). The expressions of SIgA and alpha1-AR in the prostate tissue were determined by immunohistochemistry and PT-PCR.Of the 62 cases, 30 were found to be BPH + CP, and the other 32 to be BPH. The expressions of SIgA and alpha1-AR were significantly higher in the BPH + CP than in the BPH group (0.380 8 +/- 0.144 3 vs 0.295 4 +/- 0.008 4 and 0.440 5 +/- 0.104 1 vs 0.383 2 +/- 0.013 6, P < 0.05).The upregulated expressions of SIgA and alpha1-AR expression in BPH complicated by CP suggest a certain association between CP and BPH, and that inflammation may be a pathogenic factor of BPH and correlate with its pathological development.

Historically, transurethral resection of the prostate has been the gold standard for the treatment of benign prostatic hyperplasia (BPH). Laser technology has been used to treat BPH for > 15 years. Over the past decade, it has gained wide acceptance by experienced urologists. This review provides an evidence-based update on laser surgery for BPH with a focus on photoselective laser vaporization and holmium laser enucleation of the prostate surgeries and assesses the safety, efficacy, and durability of these techniques.

The etiological factors associated with prostate cancer (CaP) have not been completely understood as yet. Genetic predisposition and inflammation is fast emerging as risk factors for CaP is a key player in the innate immune response and plays role in immune- surveillance and inflammation. The present study was conducted to evaluate TLR-4 gene polymorphism in patients with CaP.DNA was isolated from blood samples of 198 patients with CaP, 200 cases of Benign Prostatic Hyperplasia (BPH) and 119 controls. TLR-4 gene polymorphisms Asp299Gly and Thr399Ile were determined by Restriction Fragment Length Polymorphism (RFLP) technique using Nco1 and Hinf 1 restriction enzymes. All statistical calculations were performed using SPSS for windows, version 13 (SPSS Inc., Chicago, Illinois, USA).A significantly high proportion of patients with CaP had AG genotype (16.6%) as compared to control (4.2%) [OR-4.4, 95% CI (1.57-13.26), P =0.0013] with respect to Asp299Gly single nucleotide polymorphism (SNP). AA genotype showed a protective effect towards CaP development [OR-0.39, 95% CI (0.18-0.83), P=0.007). A trend was observed towards development of BPH with respect to AG genotype (P=0.06). Thr399Ile SNP was not significantly different among the population groups studied.This finding highlights the genetic predispositions to CaP with respect to TLR-4 gene. Individuals with Asp299Gly polymorphism having AG genotype appear to have four fold higher risk for development of Prostate cancer.

BACKGROUND:

Prostate cancer (CaP) in India is the 10th most common malignancy affecting men. CaP incidence in India is low, but rising like other countries. The reasons for this racial disparity are uncertain. The foremost reasons that may underlie regional/ethnic differences are genetic polymorphisms, altered hormonal status, socioeconomic status, and obesity. This study aimed at investigating the role of adipocytokines in stimulating the promotion and progression of CaP.

METHODS:

A cross-sectional study on histopathologically proven prostate cancer (N=95) and benign prostatic hyperplasia (N=95) patients was undertaken. CaP patients were classified into high-grade (N=62) and low-grade (N=33), and high stage (N=31) and low stage (N=64) groups. The level of body mass index (BMI), waste to hip ratio (WHR), interleukin-6 (IL-6), leptin, and adiponectin were compared between BPH and CaP groups and between grades and stages of prostate cancer.

RESULTS:

The level of BMI was significantly (p<0.001) higher in CaP patients (26.58±4.76) in comparison to BPH (22.15±2.90). Similarly, WHR was significantly (p<0.0001) higher in the CaP patients (1.08±0.37) in comparison to BPH (0.86±0.15). Leptin (BPH: 25.60, CaP: 56.00) and II-6 levels (BPH: 9.90, CaP: 32.30) were significantly higher, but adiponectin was significantly lower in CaP patients as compared to BPH. High grade CaP patients had significantly higher BMI and WHR in comparison to low grade, and WHR was also higher in high stage CaP. Leptin and IL-6 level were higher in high stage and high grade, but adiponectin was low in high stage and high grade groups in comparison to low stage and low grade groups.

CONCLUSIONS:

Higher BMI and WHR correlate with prostate cancer independently, suggesting obesity to be a promoter of poor prostate health. Leptin and IL-6 appear to have stimulating effect on prostate cancer cells inducing the promotion and progression of CaP, but adiponectin appears to be protective against prostate cancer.

Introduction: Benign prostatic hyperplasia (BPH) is a common medical problem in nearly 80% of geriatric male population severely affecting the quality of life. Several strategies has been suggested in the past for the management of BPH, but only α-blockers and 5α-reductase inhibitors are in clinical use. This review aims to give deep insight into advances in the design and discovery of newer chemical entities as 'druggable' molecule for the management of BPH. Areas covered: In this review, the authors cover various classes of drugs that have shown their potential for management of BPH. These drugs include α-adrenergic antagonists, 5α-reductase inhibitors, phytochemical agents, phosphodiesterase inhibitor, luteinizing hormone releasing hormone antagonists and muscarinic receptor antagonists. Literature searches were carried out using Google Scholar, SciFinder and PubMed. Expert opinion: The exact etiology of BPH is unknown; however, several mechanisms may be involved in the progression of the disease. Beside surgery and watchful waiting, medical therapies to treat BPH include α-adrenergic antagonist and 5α-reductase inhibitors. Phytotherapeutic agents are also used in some countries. Various other chemical classes of drugs are proposed for the treatment of the disease, but none of them have reached the clinic. Many classes of drugs are currently undergoing clinical trials such as phosphodiesterase inhibitors, luteinizing hormone releasing hormone antagonists and muscarinic receptor antagonists. The current need is to develop a potent, efficacious and highly selective drug for the treatment of BPH.

Many patients with benign prostatic hyperplasia (BPH) have not only voiding symptoms but also storage symptoms. Despite the many types of treatment that have been developed for BPH, storage symptoms persist. We conducted an assessment of the efficacy of transurethral resection of the prostate (TURP) and the change in the International Prostate Symptoms Score (IPSS) storage sub-score after the procedure according to prostate size in patients with BPH.Men aged 50 years or older who had BPH were enrolled in this study. 186 patients were divided into two groups according to prostate size measuring using transrectal ultrasonography: In group 1, prostate size was less than 30 ml (51 patients), and in group 2, prostate size was greater than 30 ml (135 patients). All of the patients underwent TURP. We examined whether the degree of change in the IPSS, voiding symptoms, storage symptoms, and quality of life (QoL) differed before and after TURP and according to prostate size.After three months of TURP, the subjects in both groups showed significant improvement in the IPSS, voiding symptoms, storage symptoms, QoL, and maximum flow rate (p<0.05). The scores for the IPSS, voiding symptoms, storage symptoms, and QoL of group 1 and 2 after three months of TURP were 16.36, 14.25 (p=0.233), 8.21, 8.24 (p=0.980), 8.11, 5.16 (p=0.014), 2.89, and 2.10 (p=0.030), respectively.TURP is an effective treatment for patients with BPH, regardless of prostate size. However, while the improvement in the storage symptoms of patients with a prostate size of less than 30 ml was not significant, it was in patients with a prostate size greater than 30 ml.

To evaluate the actual impact of testosterone replacement therapy (TRT) on patients with lower urinary tract symptom (LUTS), without benign prostate hyperplasia (BPH) medication.Two hundreds forty-six patients underwent TRT using intramuscular injection of 3 months bases injection of testosterone 100 mg undecanoate over a year. Among them, 17 patients had moderate LUTS with a maximal flow rate of at least 10 ml/s but did not take any BPH-specific medication during TRT. The changes in prostate specific antigen (PSA), International Prostate Symptom Score (IPSS), and uroflowmetery were measured before and after TRT.After TRT, PSA remained unchanged after a year of treatment (p=0.078). Compared with their counterparts (n=229), the patients without BPH medication had similar baseline prostate characteristics in all variables, including prostate volume, IPSS, maximal flow rate, voiding volume, and PSA, except the median amount of residual urine, which was higher in the patients without BPH medication (21 ml vs. 10 ml). In the no-BPH medication group, the total IPSS score was decreased significantly (p=0.028), both in storage symptoms (questionnaire 2, 4, 7) and voiding symptoms (questionnaire 1, 3, 5, 6), while the maximal flow rate and residual urine amount remained unchanged after a year of TRT. During the median follow up of 15.1 months, no patients experienced urinary retention, BPH-related surgery, or admission for urinary tract infection.Over a year of TRT for the no-BPH medication patients with moderate LUTS and maintained a relatively high maximal flow rate and improved both storage and voiding symptoms, without the clinical progression of BPH or rising PSA.

Androgen-related diseases impair the well-being of many aging men. Unfortunately, the medications used to treat these diseases have many side effects. Therefore, there is a significant need for the development of novel drugs to treat androgen-related diseases. In this study, we investigated the effects of Monascus cursory extraction (M-CE) on androgen-related diseases, including androgenetic alopecia (AGA), benign prostatic hyperplasia (BPH) and prostate cancer. We found that M-CE suppressed baldness in male B6CBAF1/j mice. Furthermore, M-CE decreased PSA levels, indicating a protective effect of M-CE on testosterone-induced hyperplasia. M-CE also significantly decreased tumor volume and tumor incidence in an N-methyl-N-nitrosourea (MNU)/testosterone-induced rat prostate cancer model and markedly decreased dihydrotestosterone (DHT) but not testosterone. Additionally, PCNA expression was decreased in the prostate of rats treated with M-CE. These results suggest that M-CE could be a new potential therapeutic candidate for the treatment of androgen-related diseases.