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Opening Lecture

OL-1

The current status and the future prospect of men's health in japan

S. Horie

Department of Urology, Teikyo University School of Medicine, Japan

Statistics show that men are more likely than women to suffer an early death. A persistent longevity gap has existed in almost every country.

Men die of just about every one of the leading causes of death at younger ages than women, from cancers, coronary heart disease to diabetes, and suicide.

We, as men's health advocates, need to focus public attention on the health disparity between the sexes. We should encourage men to have the literacy to assess their health status, seek preventive care and make changes in habits, if necessary. Indeed, in Chiba prefecture, local health-care office is now taking action to promote men's health awareness.

Recently, the role of testosterone for men's health has been reappraised. Several lines of evidence have shown that the level of testosterone might function as a surrogate marker as an index for the susceptibility of those illness. Indeed men with higher testosterone level are likely to enjoy the longevity.

In this lecture, I will review the current status and the future prospect of men's health in Japan. Furthermore, the utility of salivary testosterone to evaluate men's health in a large cohort will be discussed.

OL-2

The aging male in asia

H.M. Tan

Faculty of Medicine, University of Malaya, Malaysia

The aging male population in Asia will increase by at least 3 folds within the next 40 years. Like our Western counterpart, the Asian baby boomers are a unique cohort and have gone through many imprints in their life. With a marked decline in fertility and rapidly aging population, Asian countries are imminently heading for many upheavals in the demographic and economic scenarios. The gloomy future is exacerbated or compounded by an unprecedented global economic crisis. There is definitely an urgent call for concerted strategies to help steer the future of mankind out of the many potential catastrophes which are implanted along the many uncharted paths.

One of the major decision makers as well as stake holders on the wellbeing of the aging Asian males are the medical and health professionals. If we could equilibrate the health and life expectancies of Asian males and females, as well as equilibrate health and life expectancies of the male population between the various countries and regions in Asia, we would have solved many important socio-demographic and socioeconomic problems in Asia. The challenge is for the healthcare professions to come up with effective measures to improve and maintain health (physical, mental, and psychological), minimizing risk factors by taking a life course approach in fostering healthy lifestyle and habits, and implementing personalized preventive medical care to a receptive male population. Men's health promotion will call for use of effective communication tools and measures to coerce men to seek physicians' consultations, emphasizing on both life threatening diseases and quality of life issues.

Promotions of men's health in Asia should also take into consideration of the diverse socio-cultural and socioeconomic factors, identifying and profiling the various categories of men to understand their psychobehavioral attitudes and health seeking behaviors. Developing an attractive man's healthcare services will also need to address many vital health issues, and concerns to men like sexual, cosmetic, and masculinity attributes.

Asian philosophy of a successful aging man should be incorporated into any men's health consultations. These time tested wisdom and experience on the importance of psychological wellbeing and disposition, dietary care and advice, and the great benefits of Asian traditional exercise could be emphasized and promoted. New medical knowledge on factors important to achieve exceptional longevity of men and how to reap the fruits of high quality of life in Centenarians are most encouraging.

Part of the solutions to overcome the many daunting challenges faced by many graying Asian countries is by sharing resources. Sharing of manpower and workforce may mitigate many imminent demographic problems like shortage of workers and inequality of intellectual resources. Sharing of knowledge on diseases (including pandemics), and research findings on Asian diets and traditional exercises will help to improve the healthcare of Asian communities. Outsourcing of health and support may help to improve the quality of life of the rapidly increasing population of retirees in Asia.

The future health of the Asian males may lie in improving the environmental health in Asia. Indifferent or uncaring attitudes toward environmental health akin to negligence of health throughout a man's life course will eventually bring about catastrophic repercussion to both Man and Nature.

In conclusion, the future of aging Asian men is rigged with many obstacles. However, with the pooling of resources and implementing evidence-based healthcare as well as environmental care, the outlook of the graying Asian population can be greatly mitigated and brightened.

Satellite Symposium (ED & LUTS)

SA-1

Gene therapy with superenzyme for ED after radical prostatectomy

R. Wang

University of Texas Medical School at Houston; MD Anderson Cancer Center, Houston, USA

Erectile dysfunction (ED) after radical prostatectomy (RP) is an almost unavoidable condition. ED and erectile function recovery rates are widely disparate. RP induced neuropraxia causes lack of erection, which leads to poor oxygenation of the corporal bodies, eventually progressing to cavernosal fibrosis, and ultimately causing a venous leak seen clinically as venogenic ED. There is a strong need for novel methods targeting these pathogenesis pathways of ED after RP. SuperEnzyme is a new recombined protein with cyclooxygenase 2 and prostacyclin synthase (PGIS) activities that converts arachidonic acid (AA) directly to PGI₂. PGI₂ is one of the main vasodilators and a vascular protector. Gene therapy with SuperEnzyme may produce high levels of PGI₂; it may also reverse neuropraxia induced hypoxia and preserve penile function. Our laboratory recently used adenovirus to successfully transfect the SuperEnzyme into rat penes in the bilateral cavernous nerve crush (BCNC) model. It showed an increase in PGI₂ production, and an increase in ICP/MAP ratios under cavernous nerve stimulation. Penile tissue immunohistochemistry (IHC) revealed BCNC dramatically increased HIF_1α expression and SuperEnzyme therapy significantly reversed it. Terminal uridine deoxynucleotidyl transferase dUTP nick end labeling (TUNEL) assay showed SuperEnzyme therapy reversed BCNC-induced penile tissue apoptosis. Masson's trichrome revealed SuperEnzyme therapy partially prevented BCNC induced collagen sediment and disorganization, whereas IHC indicated SuperEnzyme therapy preserved the expression of eNOS and α-smooth muscle actin, and inhibited the expression of TGF-β₁. Our data indicates that SuperEnzyme therapy may preserve the veno-occlusive structure through antihypoxic and antiapoptotic mechanism, which may be the rationale for SuperEnzyme gene therapy in preserving penile erection after RP. Further research will transfect the SuperEnzyme construct into the endothelial-like fat cells (ELFCs), and inject the SuperEnzyme engineered ELFCs directly into the rat penis. The success of this research will prepare the way for the SuperEnzyme therapy in human clinical trials.

SA-2

Erectile dysfunction and lower urinary tract symptoms

L.J. Gooren

VU Medical Center, Amsterdam, The Netherlands

There is an association between erectile dysfunction (ED) and lower urinary tract symptoms (LUTS). What could be the pathophysiological link between ED and LUTS? (1) Nitric oxide (NO) acts as a nonadrenergic noncholinergic neurotransmitter, not only in genital structures but also in the urinary tract, and exerts smooth muscle relaxing effects. NO is a mediator of erection but also of dilatation of the bladder neck and urethra. Phosphodiesterases (PDE) play important roles in this process by modulating the levels of cyclic nucleotides and their duration of action, and they appear in the urinary bladder. PDE5 is an inhibitor of nitric oxide/cGMP signaling. PDE5 expression and activity in the human bladder, regulates smooth muscle tone of the bladder. PDE5 inhibitors appeared to block PDE5 activity, and therefore, may be a possible therapeutic option for bladder dysfunction by ameliorating irritative LUTS. (2) Androgens might, similar to erectile tissue in the penis, maintain the functionality of the urinary tract in adult life. Androgen receptors are present in the epithelial cells of the urethra and the bladder, and maintain the reflex activity in the pelvic part of the autonomic nervous system. Testosterone impacts on postsynaptic non-genomic receptors which are suppressing detrusor activity. Declining testosterone production with aging mighty contribute to the discomfort elderly men experience with micturition. Restoring testosterone to normal levels improves LUTS. (3) The relationship between the metabolic syndrome and LUTS may be based on the fact that the metabolic syndrome is associated with an overactivity of autonomic nervous system, which may play a key role in increasing the severity of LUTS above an intrinsic basal intensity that is determined by the genitourinary anatomical/pathophysiological characteristics of other ailments leading to LUTS. The insight into the relationship between ED and LUTS is growing and both PDE5-inhibitors and testosterone may be helpful.

SA-3

Second line therapy for Men with erectile dysfunction

C.M. Earle

Keogh Institute for Medical Research, Australia

Better methods of treatment for Erectile Dysfunction (ED) are being developed all the time. The cause of the ED will determine the treatment option used. Sometimes several options can be incorporated into the treatment plan. This presentation will describe the history of ED and the history of the current second line therapies and how they are implemented today.

Up until the early 1980s there were only 3 main treatment options available penile prosthesis surgery, sexual counseling, and vascular surgery.

In 2009, now, depending on the etiology of their ED, most patients prefer to trial one or all three types of PDE5 inhibitors, unless there are contraindications to do so. Sexual counseling may also be useful. Failing this, second line therapies are considered. A trial of Medicated Urethral System of Erection (MUSE) or a Vacuum Erection Device (VED) may be worthwhile before embarking on an Intracavernosal Injections (ICI) programme. In practice, some 75% of ED patients respond to these types of therapies.

By far the most common second line therapy practiced worldwide is ICI. Three groups of drugs are currently used for ICI worldwide: papaverine, alpha-adrenoceptor blocking agents such as phentolamine or moxisylyte; and prostaglandin E1 (PGE1). They have all proved to be effective in the treatment of ED.

VEDs provide an alternative to the more common treatment modes of ICI therapy or oral therapy with PDE5 inhibitors. There is wide patient acceptance for trialing this type of therapy for ED as it is noninvasive and can be easily offered by the physician in their office.

MUSE was originally established as an alternative to ICI as it avoided the use of a penile injection. Instead, it delivered the PGE1 medication via transurethral application.

Despite the obvious effectiveness of PDE5 inhibitors there is still room for effective and appropriate use of second line therapies such as MUSE, VED's, and ICI in the treatment of ED. The ICI, VED, and MUSE procedures and their safety profile will also be discussed in detail.

SA-4

Lower urinary tract symptoms (LUTS) and erectile dysfunction (ED) – is metabolic syndrome the link?

H.M. Tan

Faculty of Medicine, University of Malaya, Malaysia

LUTS is an independent risk factors for ED in aging male even after controlling for age and comorbiditiesCitation1. Conversely, is ED an independent risk factors for LUTS? LUTS secondary to BHI may be part of metabolic syndrome which is a known risk factor for EDCitation2. The common pathways for both LUTS and ED may be because of increased sympathetic activity.

Many studies including our 2006 Subang Men's Health Study revealed a close association between metabolic syndrome and ED. The individual parameters of metabolic syndrome have also been reported to be related to EDCitation3. Lately, there is increasing evidence showing BPH may be part of cardiometabolic disease processCitation4.

The relationship between LUTS and ED may be explained by the following pathophysiological mechanism viz. (i) the nitric oxide synthase (NOS)/NO theory, (ii) the autonomic hyperactivity and metabolic syndrome hypothesis, (iii) the Rho-kinase activation/endothelin pathway, and (iv) pelvic atherosclerosis.

Like many other reported studies, our recently concluded Subang Aging Male (SAM) Study, revealed a strong association between LUTS (IPSS score) and ED (IIEF-5 score). Men who reported moderate to severe LUTS had 2.402 higher chance of having moderate to severe ED (O.R 2.402 CI: 1.685–3.423, p < 0.001). For men who had severe LUTS, the odds ratio for moderate to severe ED was 3.423 (CI: 1.688–6.940, p < 0.001).

In the SAM study, men with LUTS were more likely to have metabolic syndrome (based on IDF, Asian criteria), with an O.R of 2.03 (CI: 1.225–3.371, p = 0.005). Further evaluation showed that men with moderate to severe LUTS were more likely to self-report hypertension (O.R 1.447 CI:1.092–1918, p = 0.001), self-report dyslipidaemia (OR 1.489, CI: 1.135–1.954, p = 0.004), and more likely to have fasting blood sugar ≥7.0 mmol/L (O.R 1.333 CI: 0.970–1.831, p = 0.075).

Men with severe LUTS or suffered acute retention of urine have been known to suffer higher morbidity, or even mortality. Our SAM study clearly revealed that men with complaint of severe LUTS have higher self-reported hypertension (O.R 2.069, CI: 1.261–3.394, p = 0.003), self-reported diabetes mellitus (O.R 2.108, CI: 1.217–3.651, p = 0.007), and self-reported coronary heart disease (O.R 2.444, CI: 13.47–4.435, p = 0.002).

In conclusion, the SAM data confirmed that the close association between LUTS and ED may be linked by the common cardiometabolic factors which result in the common pathophysiological pathways.

SA-5

The prospect of ED and LUTS in the elderly

K. Marumo

Department of Urology, Tokyo Dental College, Ichikawa General Hospital, Japan

Current reports of ED incidence, pathophysiology, and treatment have shown a possible link between LUTS and ED. ED and LUTS increase with age with an overall prevalence of greater than 40 to 50% in men of 50 years or older. The etiology of ED indicates that a number of factors contribute to the disorder. The effects of age and concomitant chronic illnesses such as diabetes, vascular disease, hepatic failure, chronic renal failure, and neurologic disease are well documented. A questionnaire from the International Index of Erectile Function (IIEF) was given to 2311 men aged 23 to 79 years along with a survey of health status. There was a significant correlation between age and the scores for erectile function, orgasmic function, sexual desire, and intercourse satisfaction.

The current standard of care in men with bothersome LUTS caused by BPH is treatment with an alpha 1-adrenergic blocker. Although they are effective, these drugs can produce side effects, including dizziness, hypotension, or sexual dysfunction. PDE5 inhibitors are gaining increased attention for LUTS. Although the exact mechanism of efficacy by which PDE5 inhibitors may improve LUTS is not perfectly known, some possible mechanisms are currently under investigation. One mechanism focuses on the accumulation of intracellular prostatic and bladder smooth muscle cyclic GMP following PDE5 inhibition, which may reduce tension in the smooth muscle of the prostatic stroma and capsule.

Although recent studies produced fundamental data concerning the epidemiology of ED and LUTS, the interactive effects of ED and LUTS in different countries and its prevalence because of individual risk factors are still uncertain. Further research and analysis of individual risk factors is required. Asian andrologists, armed with our extensive experience with these agents and needs of patient population, make ourselves possible to design more effective future strategies for the treatment of ED and LUTS.

Lecture 1 (Aging male and prostate)

L-1-1

The prostate as an ejaculation device in healthy male and benign prostatic hyperplasia in the aging male

A. Nagai

Department of Urology, Kawasaki Medical School, Japan

Lower urinary tract symptoms (LUTS) are a major health problem among the aging male. LUTS are usually considered synonymous with benign prostatic hyperplasia (BPH). The prostate acts as an ejaculation device, however, it is adversely affected by BPH in the aging male.

To confirm the prostate ejaculation function, we observed human ejaculation using color Doppler ultrasonography in healthy men. With manual penile stimulation, blood flow in the prostate and prostatic venous plexus increased. After constriction of the bladder neck the ejaculatory stream spurted from the seminal vesicles to the bulbous urethra. We also observed human ejaculation in healthy males after intake of silodosin (alpha1-blocker) to clinically investigate the mechanism of ejaculatory dysfunction attributable to alpha1-blocker. The bladder neck was clearly open and did not completely close during the ejaculation. The flow of seminal fluid into the bladder was observed. This shows that alpha1-blocker is effective in relaxing the smooth muscle of the prostate and opening the bladder neck of BPH patients.

Recent study suggests that an age-related impairment of blood supply to the prostate plays a key role in the development of BPH. To prevent BPH, it is important to avoid atherosclerosis. From our study we can surmise that ejaculation is beneficial for the aging male because of the good blood flow in the prostate observed during the ejaculation phase.

Moreover, it is important to alleviate the urinary symptoms derived from BPH/LUTS for the aging male. We assessed the efficacy and safety of propiverine hydrochloride (antimuscarinics) and naftopidil (alpha1-blocker), both in patients with male LUTS suggestive of BPH and in patients with concomitant overactive bladder (OAB), in a prospective randomized study. The combination therapy showed effectiveness for male LUTS with OAB.

Urologists should keep the prostate healthy to combat male aging.

L-1-2

Aging men: coping with life transition

W.Y. Low

Health Research Development Unit, Faculty of Medicine, University of Malaya, Malaysia

As adults approach their senior years, they are expected to face many challenges in their golden years. One has to cope with life transitions, be it physical changes in oneself, economic or social changes such as children leaving home (the empty nest syndrome), childlessness, widowhood, being a grandparent, or relocation. One also has to cope with the psychological and the emotional baggage that comes with it. Retirement is one of those changes that one has to cope with. Retirement is a major psycho-social life transition. It has a positive or a negative impact on one's quality of life. Some may look forward to it, whereas others may struggle with retirement. In our community-based study on 381 aging male, above 50 years of age, in Klang Valley, the study found that Malaysian retired men have significantly higher chronic illnesses such as heart problem, joint pain, and prostate problem compared with working men. The quality of life measure using the SF-12 showed a difference between the groups in physical and social function and in overall physical composite score, but no difference in mental health. This lecture further looks at the various stages of retirement and examines factors that causes problem in retirement. Patterns of coping and strategies for a successful and health aging will be examined. In summary, one has to think positively and realistically look at these transitions and learn to cope with aging in order to establish a more fulfilling life in the golden years.

Lecture 2 (Hormone effect on bone & brain)

L-2-1

Fracture prevention and hormone

S. Ogawa

Department of Geriatric Medicine, Graduate School of Medicine, The University of Tokyo, Japan

Aging process involves an increase in the incidence of osteoporotic fracture, and morbidity and mortality after osteoporotic fractures appear to be more serious compared with nonfracture group in elderly. Osteoporosis and falls are known to be major risk factors for fractures, and systemic management as well as risk assessment of these factors are important to lower the incidence of fractures. In practice, physical activity and exercise help to maintain mobility, physical functioning, bone mineral property, and muscle strength which may lead to prevention of osteoporosis, sarcopenia, and fractures.

Recent findings suggest that sex hormones are crucial for skeletal development and maintenance of bone mineral properties, mainly mediated by androgen receptor and estrogen receptor, respectively. It is also suggested that sex hormones improve body composition, cognitive function which may lead to risk reduction of falls. In this seminar, relationship between osteoporosis, sarcopenia, and hormone status will be focused, and strategies for fracture prevention including pharmacological interventions by hormones will be also introduced.

L-2-2

The effect of testosterone on L-arginine- and apomorphine-induced penile erection through activation of paraventricular nucleus of hypothalamus in the rat

K.K. Chen^1,2

¹Division of Urology, Department of Surgery, Taipei Veterans General Hospital, Taiwan;²Department of Urology, School of Medicine and Shu-Tien Urological Research Center, National Yang-Ming University, Taipei, Taiwan

Purpose. Testosterone may activate nitric oxide (NO) synthase in the brain of animals with intact gonads. Our previous study revealed involvement of L-arginine/NO pathway and dopaminergic neurotransmission at the paraventricular nucleus of hypothalamus (PVN) in regulation of penile erection in the rat. In addition, castration may diminish or eliminate the dopamine receptors in the PVN. Therefore, the aim of this study is to investigate the effect of testosterone on L-arginine- and apomorphine-induced penile erection through activation of PVN in the rat.

Materials and methods. Male adult Sprague-Dawley rats were used. A 26-gauge needle was inserted into the corpus cavernosum to measure the intracavernous pressure (ICP). Six groups of study were arranged: (1) stereotaxical application of L-arginine 500 nmol/500 nl into PVN; (2) administration of L-arginine 500 nmol into PVN 6 weeks after bilateral orchiectomy in a young rat; (3) testosterone replacement with subcutaneous implantation of a silicon tube (filled with 85 mg testosterone) after bilateral orchiectomy in a young rat, then delivery of L-arginine 500 nmol into PVN 8 weeks later; (4) sham operation, then delivery of L-arginine 500 nmol into PVN 6 weeks later; (5) injection of saline 500 nl into PVN as a control; and (6) intracavernous injection of L-arginine 250 nmol. For the apomorphine experiments, the amount of apomorphine administration to PVN was 0.1 nmol/100 nl. The testosterone replacement was executed by intramuscular injection of testosterone propionate 1 mg, twice a week for 2 weeks. The other experimental procedures were similar to the L-arginine study.

Results. There was a significant increase of ICP from resting 11.3 ± 3.4 mmHg to a peak at 65.5 ± 11.9 mmHg with a duration of 24.7 ± 5.6 min upon administration of L-arginine into PVN. However, there was no significant change of ICP upon administration of L-arginine into PVN in the rats 6 weeks after bilateral orchiectomy. After testosterone replacement, administration of L-arginine 500 nmol into PVN elicited a significant increase of ICP to peaked at 59.2 ± 13.7 mm Hg. In the rats underwent sham operation, administration of L-arginine into PVN induced a significant increase of ICP to peaked at 61.7 ± 9.4 mmHg. Application of saline 500 nl into PVN or intracavernous administration of L-arginine 250 nmol was ineffective to elicit a significant change of ICP. Serum testosterone was in the castration Level 2 weeks after bilateral orchiectomy, and returned to near-normal Level 1 month after testosterone replacement. There was a significant increase of ICP to 50.7 ± 5.3 mmHg after administration of apomorphine into PVN. After castration, the ICP failed to increase after application of apomorphine into PVN. The ICP was significantly increased again after testosterone replacement.

Conclusions. The results of this study demonstrate that testosterone deprivation by bilateral orchiectomy may eliminate the L-arginine- or apomorphine-induced penile erection through PVN in the rat. After testosterone replacement, the L-arginine- or apomorphine-induced penile erection may recover. These observations suggest that testosterone may have a pivotal effect on L-arginine- or apomorphine-induced penile erection through PVN in the rat.

Lecture 3 (Nocturia & sleep disturbance)

L-3-1

Nocturia and sleep disturbance

K. Ratana-Olarn

Department of Surgery, Faculty of Medicine, Ramathibodi Hospital, Mahidol University, Bangkok, Thailand

Nocturia is a prevalent condition. However, it is usually ignored by the patients and also by the physicians. In men, it is commonly considered that nocturia is an irritative symptom of benign postatic hyperplasia (BPH) and overactive bladder syndrome (OAB) but nocturia is usually unresponsive to various BPH + OAB treatments. Nocturia is in fact a multifactorial disorder and is a bothersome condition which causes negative effects on quality of life and multiple consequences especially the sleep disturbance. Poor sleep is associated not only with day time sleepiness but also with deficits in daily functioning. It also compromises the general health with an increased risk of cardiovascular disease, diabetes, and impaired immune response. Though every patient with nocturia does not need treatment but those who are awakened by nocturia and suffer from sleep disturbance are candidates for evaluation and require proper management.

L-3-2

Nocturia and sleep disturbance

Y. Sugita^1,2,3

¹Health Care Center, Osaka University, Japan; ²Department of Psychiatric Health Medicine, Division of Preventive and Environmental Medicine, Osaka University Graduate School of Medicine; ³Sleep Medical Center, Osaka University Hospital

In the last years, the interest in the relationship between urologic symptoms and sleep disturbances has been markedly increasing. Patients with Obstructive sleep apnea syndrome (OSAS), prevalence of which is estimated at 1–5% of adult men, suffer from sleep fragmentation, nocturia, excessive daytime sleepiness, and decreased psychomotor function. Medical treatment with nocturnal nasal continuous positive airway pressure reverses these symptoms. The pathophysiology of airflow obstruction in OSAS, such as repetitive respiratory efforts, arousals (sleep fragmentation), and hypoxia, is related with nocturia and may be related with daytime urinary symptoms.

Nocturia, waking at night to void, is a common syndrome. It is associated with a profound decrease in QOL, and causes a various range of sleep disturbances and adversely affects daytime functioning. Nocturia has been defined by the International Continence Society as “the complaint that the individual has to wake up at night one or more times to void”. Defining nocturia as two or more urination episodes per night, the prevalence is 10% in the general population. Urination at least twice at night has induced sleep disruption and daytime fatigue. The sleep disruption related with nocturia has been reported to be associated with a twofold increase in the risk of falls during the 24-h day in the elderly. Nocturia-induced abnormal sleep might also be a significant health risk in the general population.

We have tried to investigate the relationship between the score of the International Prostate Symptom score (IPSS) for lower urinary tract symptoms including nocturia and several sleep parameters, including total sleep time, sleep efficiency, sleep latency and REM latency, arousal index, and apnea-hypopnea index through polysomnography among the patients with sleep problems. In this talk, I would like to discuss the potential mechanism of nocturia and overactive bladder symptoms related to sleep disturbances, particularly in regard to the pathophysiology of OSAS.

Lecture 4 (Testosterone & prostate)

L-4-1

Androgen and prostate cancer in aging male and race

R. Dahiya¹, H. Enokida², M. Nakagawa², A. Okuyama³

¹San Francisco Veterans Affairs Medical Center and University of California, San Francisco, USA; ²Kagoshima University, Kagoshima, Japan; ³Osaka University Graduate School of Medicine, Osaka, Japan

Androgen and aging play an important role in the etiology of prostate cancer. The incidence and mortality of prostate cancer (PC) among African American males in the highest in the world. The incidence of PC among Asians is significantly lower than African Americans and Caucasians. There is no report to explain the racial disparities in the incidence of prostate cancer. We conducted this study to investigate the molecular basis for racial disparities in prostate cancer using a series of molecular biomarkers. We hypothesize that inactivation of GSTP1 genes through CpG methylation plays a role in the pathogenesis of PC, and its ability to serve as a diagnostic marker that differs among ethnic groups. GSTP1 promoter hypermethylation and its correlation with clinico-pathological findings were evaluated in 291 PC (Asian = 170; African-American = 44; Caucasian = 77) and 172 benign prostate hypertrophy samples (BPH) (Asian = 96; African-American = 38; Caucasian = 38) using methylation-specific PCR. In PC cells, 5-aza-dC treatment increased expression of GSTP1 mRNA transcripts. The methylation of all CpG sites was found in 191 of 291 PC (65.6%), but only in 34 of 139 BPH (24.5%). The GSTP1 hypermethylation was significantly higher in PC when compared with BPH in each ethnic group. Logistic regression analysis (PC vs. BPH) showed that African-Americans had a higher hazard ratio (HR) compared with Caucasians and Asian. χ² analysis showed correlation of GSTP1 hypermethylation with pathological findings (pT categories and higher Gleason sum) in Asian PC but not in African-Americans and Caucasian PC. Our results suggest that GSTP1 hypermethylation is a sensitive biomarker in African-Americans when compared with that in Caucasians or Asian, and that it strongly influences tumor progression in Asian PC. Ours is the first study investigating GSTP1 methylation differences in PC among African-American, Caucasian, and Asian. We will also discuss the novel biomarkers for prostate cancer detection and progression in aging males.

L-4-2

Testosterone, androgen receptor, and prostate cancer

T. Ichikawa, M. Yano, K. Kawamura, N. Kamiya, T. Imamoto, H. Suzuki

Department of Urology, Graduate School of Medicine, Chiba University, Japan

Recent studies have shown complicated relationships between serum testosterone (T) levels and pathogenesis of prostate cancer (PCa). According to both in vitro and in vivo studies, androgens stimulate PCa, whereas there is an upper limit of the growth rate even with a higher androgen level. This suggests that T is like water for a thirsty tumor but not like food for a hungry tumor. Prospective studies have also shown a low frequency of PCa in association with T replacement therapy. Several studies have shown that low T seems to be associated with advanced stage of PCa at presentation, positive surgical margins, and worse overall survival. We have also shown a significant postoperative rise in T level, particularly in patients with a preoperatively low T level. These suggest that PCa cells in these patients might produce some substances that suppress T level.

Most PCas are androgen-dependent and essentially respond to androgen ablation therapy. However, these tumors eventually become androgen-independent and grow despite androgen ablation. Because the androgen receptor (AR) sequence was determined, numerous studies have shown that AR plays a critical role in the development of androgen-refractory PCa. A recent study has shown that T levels within metastases from anorchid men were significantly higher than levels within primary PCas from untreated eugonadal men. Those androgen levels of the metastases were at concentrations capable of activating AR target genes.

In future, measurement of both serum T and T in prostatic tissue might be required to further investigate associations between T levels and the prognosis for PCa.

Lecture 5 (Metabolic syndrome & LUTS)

L-5-1

Metabolic syndrome and lower urinary tract symptoms

S.C. Kim

Department of Urology, College of Medicine Chung-Ang University, Seoul, Republic of Korea

The pathogenesis of lower urinary tract symptoms (LUTS) in men is complex and multi-factorial. Several studies have suggested a relationship between LUTS and metabolic syndrome (MS), and it is accepted that men with MS are more likely to develop severe LUTS. In a recent study, it was hypothesized that MS is associated with overactivity of the sympathetic nervous system, and that insulin resistance, a key element of MS might be responsible. Overactivity of the sympathetic nervous system is supposedly not responsible for the development of LUTS, but rather is believed to play a key role in increasing LUTS severity above an intrinsic basal intensity.

Another recent study provided evidence that the inflammatory infiltrates, which are frequently found in and around nodules of BPH, elevate serum CRP concentration, a nonspecific marker of inflammation. Furthermore, the presence of MS might mediate intraprostatic inflammation because of its association with an elevated serum CRP concentration, which would link MS to symptomatic BPH. In addition, it has been suggested that NO may play a major role in the dilatation of the bladder neck and urethra during the micturition reflex, whereas insulin resistance causes reduction in NO production.

Recently, testosterone deficiency has attracted attention because it is a possible risk factor of MS. There was an inverse correlation between testosterone level and serum level of glucose, triglycerides, BMI, and fasting insulin resistance index, whereas a significant positive association was found between testosterone and the quantitative insulin sensitivity check index and HDL cholesterol level in serum, which suggests that testosterone may protect against the development of MS. Preliminary evidence indicates that there was a significant negative relationship between testosterone and IPSS, and men with LUTS benefit from testosterone treatment, which suggests that testosterone deficiency provides a pathophysiologic basis for the connection between LUTS and MS.

L-5-2

Lower urinary tract dysfunction in aging male

Y. Homma

Department of Urology, Graduate School of Medicine, The University of Tokyo, Japan

The prevalence of lower urinary tract symptoms (LUTS) increases with advancing age, along with worsening severity and widening of the range of symptoms. This age-related increase in prevalence partly results from the increasing frequency of diseases of the lower urinary tract in aging men, such as bladder cancer or stones. Most LUTS in aging men, however, are attributable to functional abnormality. Recently, we have published a clinical guideline for male LUTS, which is targeted primarily to nonurologists caring for fit men aged more than 50. The guideline details pathophysiology of lower urinary tract dysfunction in aging men, dividing it into pathology of prostate-lower urinary tract organs, abnormality of neurological system, and other conditions (over-drinking, for example). It has been presumed that dysfunction in aging men is most commonly caused by benign prostatic hyperplasia (BPH). However, LUTS in aging male sometimes cannot be explained only by BPH or other obvious diseases; in other words, nothing but age-related dysfunction can explain LUTS in these instances. Specifically, the dysfunctions are exemplified by tissue degeneration, upregulated sympathetic nervous tone, or decreased nitric oxide production and Rho kinase activity. These are accelerated by genetic and acquired factors, the latter including ischemia (insufficient microcirculation) and oxidative stress. In this context, lower urinary tract dysfunction in aging men can be a phenotype of habitual diseases or collectively metabolic syndrome. Erectile dysfunction often coexists with LUTS and severity of these two dysfunctions correlate well with each other. Clinically, the guideline recommends core lower urinary tract symptom score (CLSS) questionnaire and prostate specific antigen test for the initial evaluation. CLSS addresses 10 important symptoms (daytime frequency, nocturia, urgency, urgency incontinence, stress incontinence, slow urinary stream, straining, incomplete emptying, bladder pain, and urethral pain), providing an overall assessment of relevant symptoms without significant omissions. It should be particularly useful for aging male visiting clinics for the first time.

Luncheon Seminar 1 (Prostate cancer)

LS-1-1

Prostate cancer and erectile dysfunction

I.D. Sharlip

Clinical Professor of Urology, University of California at San Francisco, California, USA

Prostate cancer occurs predominantly in men over 50 years of age, an age at which the incidence of erectile dysfunction (ED) begins to accelerate. Early stage prostate cancer does not cause ED. However, the treatment of all stages of prostate cancer often causes ED. The incidence of ED following radical prostatectomy has been reported to range from 30 to 80%. This large range of results is because of variations in the method of preoperative assessment of erectile function, whether the cavernous nerves are spared intraoperatively, age of the patient population, definition of ED, use of PDE5 inihibitors, method of postoperative evaluation and timing of postoperative evaluation. A realistic estimate of post-prostatectomy ED without the aid of PDE5 inhibitors at 1 year after radical prostatectomy is at least 50%. Some patients with ED will recover erectile function after 1 year, especially with the addition of PDE5 inhibitor therapy. There has been strong interest in penile rehabilitation programs which are intended to reduce the severity of ED in post-prostatectomy patients. These programs rely on a variety of different techniques to improve cavernous oxygenation. These techniques include regular or daily use of PDE5 inhibitors, intracavernous injection of vasoactive agents, intraurethral Alprostadil and vacuum therapy. The results of penile rehabilitation programs are controversial and at this time unproven. However, most experts in sexual medicine believe that penile rehabilitation programs are useful and at least partially effective. Radiation therapy for prostate cancer is also associated with ED. The incidence of ED with external beam radiation therapy and with prostatic brachytherapy is also difficult to determine precisely but the predominance of evidence suggests that ED after radiation therapy does not occur as frequently in the early post-treatment phase as it does after radical prostatectomy. However, by about 5 years after radiation treatment, the prevalence of ED is equal to the prevelance of ED after surgery. If androgen deprivation therapy is used as neoadvuvant therapy with radiation treatment, the incidence of ED is even higher. For men whose ED after treatment of prostate cancer is refractory to PDE5 inhibitors, intracavernous injections, intraurethral therapy, vacuum therapy and/or implantation of a penile prosthesis can be used. One of more of these techniques will be successful in restoring adequate erectile function in about 90% of men.

LS-1-2

Assessment of sexual function and bother following treatment intervention for localized prostate cancer

Y. Kakehi

Department of Urology, Kagawa University Faculty of Medicine, Japan

Erectile dysfunction is one of the most concerning toxicities for patients in the treatment of prostate cancer. Generally, impairment of sexual function following radical prostatectomy (RP) has been reported to be more serious than that following external beam irradiation (EBRT) and seed implantation (BRTx). Recent data as to long-term follow-up, however, have revealed that deterioration of sexual function following EBRT and BRTx also frequently occurred with time and negatively influences patients' quality of life (QOL). On the other, androgen deprivation therapy (ADT) has been carried out in various clinical setting for the treatment of localized prostate cancer but its negative impact on both physical and mental health QOL had not been adequately highlighted. Evaluating QOL outcomes following prostate cancer treatment therefore is important because toxicity profile and its association with patients' QOL with time seem to be different between treatment options although every treatment modality can achieve similar survival outcomes. In this symposium, results of QOL assessment in patients with localized prostate cancer treated with RP, EBRT, BRTx, and ADT is presented. In particular, the impact of sexual function deterioration on patients' physical and mental health QOL will be discussed. In order to overcome erectile dysfunction after RP, cavernous reconstruction (nerve-grafting) has been performed in our institution. Assessment of health-related QOL including sexual function and bother was assessed with the Expanded Prostate Cancer Composite for the patients who underwent nerve-grafting RP. The results indicate that nerve-grafting surgery provides better sexual function recovery than RP without nerve spare/grafting procedure. Sexual bother, however, was more serious in nerve-sparing/nerve-grafting patients than in patients who underwent RP without nerve spare/grafting. Excessive expectation as to the recovery of sexual function may be one of major cause of the bother feeling. These results indicate that counseling and psychological support with regard to the change in sexual function after treatment are particularly important for sexually active prostate cancer patients.

Luncheon Seminar 2 (New concept in sexual medicine – STD & ED–)

LS-2-1

Topics of male urethritis, including drug-resistant Neisseria gonorrhoeae and newly recognized pathogens causing non-gonococcal urethritis

T. Deguchi

Department of Urology, Gifu University School of Medicine, Japan

Urethritis, one of the most common urinary and genital tract infections in men, is classified as gonococcal or non-gonococcal depending on the presence or absence of Neisseria gonorrhoeae. In this seminar, I will focus on drug-resistant N. gonorrhoeae and newly recognized pathogens causing non-gonococcal urethritis in male urethritis.

In Japan, there has been an increase in clinical strains of N. gonorrhoeae with decreased susceptibility to fluoroquinolones since the late 1990s. In 1999, fluoroquinolones were excluded from recommendations and guidelines for treatment of gonococcal infections. As alternatives to fluoroquinolones, oral cephalosporins were commonly used. Since 2001, however, a decrease in susceptibility of clinical strains to them has also been observed. The emergence and spread of such strains forced exclusion of cefixime from the 2006 recommendations and guidelines. No longer are there oral regimens for treatment of gonorrhea in Japan. However, resistance to spectinomycin and ceftriaxone is rare. Strains with decreased susceptibility to cefixime are still sensitive to ceftriaxone. Ceftriaxone is also effective against gonococcal pharyngeal infection. In Japan, therefore, ceftriaxone is the only agent recommended as the first-choice treatment for gonococcal infections.

Chlamydia trachomatis is a cause of acute non-gonococcal urethritis. In the 1990s, detection of Mycoplasma genitalium by polymerase chain reaction assay became possible, and the results of many studies have suggested that M. genitalium causes non-gonococcal urethritis. Our studies, which specifically identified Ureaplasma parvum (biovar 1) and U. urealyticum (biovar 2) in cases of non-gonococcal urethritis, suggested that U. urealyticum (biovar 2) is significantly associated with non-gonococcal urethritis. However, clinical data on such non-gonococcal urethritis are still limited. For non-gonococcal urethritis, including mycoplasma- or ureaplasma-positive disease, new diagnostic methods and a new treatment algorithm are needed.

LS-2-2

Penile rehabilitation – new thoughts for a new sex therapy

H.S. Chiang

Asian Pacific Society of Sexual Medicine, Taiwan

Recent literature evidence suggests early postoperative penile rehabilitation after radical prostatectomy can prevent cavernosal hypoxia fibrosis and penile atrophy. Serial reviews also show the penile rehabilitation can definitely decrease the incidence of permanent erectile dysfunction. According to the above theories, we start our protocol of penile rehabilitation for patients after radical prostatectomy since this year. On the basis of our experience, we found the following thoughts might be more beneficial for the couples to have penile rehabilitation:

Preoperative counseling should be more comprehensive: including psychosocial concerns of their sexuality; questionnaire for the quality of life; the detail of sex therapy thereafter etc.
The regimen of penile rehabilitation should be more flexible. We provide different program of regular intracavernosal injection or/and oral intake of phosphodiesterase type 5 inhibitors (PDE-5) for the couples. The programs could also be switched during the treatment. It became more acceptable for the couples.
The penile rehabilitation should be taught and followed up by a special personnel. It would be even better performed by a clinical psychologist in combination with sex therapy. Our preliminary result felt that early penile rehabilitation with sex therapy can remain the couple's sexually active and easily achieve sexual satisfaction for them.

It is a new goal of penile rehabilitation for restoring a more complete sexual function. The concept of a “new sex therapy” may be promoted in other medical fields such as for any other major surgeries, for critical medical diseases and even for the aging couples whom lose of sexual function for a long period.

Luncheon Seminar 3 (Chemotherapy for the elderly bladder cancer)

LS-3-1

Chemotherapy for elderly patients with bladder cancer

N. Nonomura

Department of Urology, Osaka University Graduate School of Medicine, Japan

It is well known that the life span of the Japanese people is the longest in the world. As the life span is getting longer, we have more chances to see urological cancres such as urothelial cancer and prostate cancer in elderly patients. In this seminar, I summarize the results of chemotherapy for urothelial cancer in elderly patients. At first, I reviewed 17 patients older than 70 years who underwent systemic chemotherapy against urothelial cancer. Thirteen patients received M-VAC (methotrexate, vinblastine, adriamycin and cisplatin), and 4 patients treated with GC (gemcitabine and cisplatin) or GN (gemcitabine and nedaplatin) were reviewed retrospectively. M-VAC was applied as first line regimen, while GC or GN was applied as second line. Though GC or GN was applied to patients as second line regimen, dose reduction was not necessary because adverse effects are not so severe compared to M-VAC. For elderly patients, GC or GN seemed to be safer than M-VAC. In general, the efficacy of GN is equal to that of GC therapy. Because nedaplatin does not need hydration and it does not deteriorate renal function as cisplatin does, we use nedaplatin for patients with impaired renal function. GC or GN therapy seems to be a relevant and tolerable chemotherapy for elderly patients with advanced or recurrent urothelial cancer.

LS-3-2

The consideration of systemic chemotherapy for elderly patients with bladder cancer

S.W. Lee

Department of Urology, Samsung Medical Center, Sungkyunkwan University School of Medicine, Republic of Korea

The elderly means usually men over 65 years of age, but chronologic age cannot be used to predict the degree of comorbidity and of functional deterioration of the single individual. Aging involves changes in different domains, including health, function, cognition, motional, and social status. These changes, that are highly individualized, influence the treatment of cancer in several ways: limited life-expectancy, decreased tolerance to treatment, inability to obtain treatment because of a number of social barriers. Therefore, multidisciplinary assessments, referred to as comprehensive geriatric assessment, the instrumental activities of daily living, and the activities of daily living have been developed and proven useful in preventing death and disability in a number of settings, including hospitalized older individuals and individuals with a number of chronic diseases.

The question as to whether chemotherapy for the treatment of a tumor in the elderly is appropriate or not, and if so what doses are required, depends in particular on the potentially increased toxicity of the drug in the old patient. In fact, the elderly has few differences from the young in absorption and bioavailability of drugs although oral absorption, metabolic rate in G-I tracts, and 1st pass effect are reported to decrease a little in the elderly compared with the young. However, impairment of renal function and reduction of stem cells within bone marrow, and possible comorbidity of the elderly tend to make the side effects of chemotherapy aggravate. Therefore clinician should consider that whether the elderly patients have comorbidity, what kinds of medications they take, and the exact evaluation of renal, cardiopulmonary, and cognitive function.

Bladder cancer is primarily a disease of the elderly, with 80% of cases occurring in the 50- to 79-year-olds, with a peak in the 7th decade. Approximately 50% of all diagnosed patients with muscle-invasive disease develop metastases within 2 years of the initial diagnosis. Median survival of untreated patients with metastatic disease is 3–6 months.

Bladder urothelial cancer is chemo-sensitive. Therefore, systemic chemotherapy such as methotrexate/vinblastine/doxorubicin/cisplatin, gemcitabin/cisplatin, and recently carboplatin or oxaliplatin is an effective management modality for advanced bladder cancer. Systemic chemotherapy are associated with substantial toxicities, including grade 3–4 neutropenia, infective complications, and significant mucositis. Nausea and vomiting, renal, cardiac, and neurological toxicities have been observed as well. These side effects are especially problematic in elderly patients, who usually have significant comorbidity. In addition, chemotherapy has a negative effect on gonad, inducing gonadal dysfunction, and impaired infertility.

In this lecture, I will review detailed pharmacological difference and effects on gonadal function of systemic chemotherapy and suggest several points to be considered when systemic chemotherapy is applied to elderly patients with bladder cancer.

Symposium 1 [Podium for selected paper](ED)

SY-1-1

Withdrawn

SY-1-2

Increased prevalence of erectile dysfunction (ED): results of the second epidemiological study on sexual activity and prevalence of ED in Thai males

S. Permpongkosol¹, A. Kongkanand², K. Ratana-Olarn¹, A. Tantiwong³, K. Tantiwongse⁴

¹Division of Urology, Department of Surgery, Faculty of Medicine, Ramathibodi Hospital, Mahidol University, Bangkok, Thailand; ²Division of Urology, Department of Surgery, Bumrungrad Hospital, Bangkok; ³Department of Surgery, Faculty of Medicine, Siriraj Hospital, Mahidol University, Bangkok; ⁴Division of Urology, Department of Surgery, Chulalongkorn University Hospital, Bangkok, Thailand

Objective. The aim of this study is to investigate changes in sexual activity and the prevalence of erectile dysfunction (ED) in Thai males. In addition, the treatment-seeking behavior of Thai patients suffering from ED is also investigated.

Materials and methods. In a cross sectional study using a standardized questionnaire with a multistage stratified random sampling, 2269 men aged 40–70 were interviewed. The questionnaire was designed to investigate the effects of socioeconomic factors, medical conditions and unhealthy lifestyles on the development of ED. Furthermore, the questionnaire was designed to characterize the treatment-seeking behavior of Thai patients suffering from ED.

Results.Compared with the first report dated the year 2000, the prevalence of ED has increased from 37.5% to 42.18%. In terms of socioeconomic factors, the highest prevalence of ED was observed among unemployed men (78.51%). Prostatism and/or prostatitis [Odd ratios (OR) = 2.02] and long histories of smoking (more than 30 years, OR = 2.36) were identified as statistically significant risk factors for ED, with p-values of <0.001. It is important to notice that 38.78% of the ED patients wanted to discuss their problem with spouses or partners. Three quarters of the ED patients (74.54%) preferred oral medication as therapy.

Conclusions. The epidemiology of ED in Thailand is changing. An increased prevalence of ED does require further epidemiological studies on a regular basis in order to better understand the etiology of ED and look for measures (such as education) to counter the disease.

SY-1-3

Health-related quality of life in patients with localized prostate cancer received high-dose-rate brachytherapy: a time-course analysis

Y. Jo, A. Nagai

Department of Urology, Kawasaki Medical School, Japan

Purpose/Objectives. The purpose of this study is to make a time-course analysis of HRQoL in patients with localized prostate cancer receiving High-dose-rate brachytherapy (HDR-BT) employing general and disease-specific measures.

Materials and methods. Examination of HRQoL has been performed since 1 May 2004. The 36-item Short-Form Health Survey version 2.0 (SF-36v2) and the University of California Los Angeles Prostate Cancer Index (UCLA-PCI) were adopted. Patients were required to complete these two questionnaires before (baseline), and 1, 6, 12, and 24 months after treatment and patients who completed them at all points were eligible for this study. The average scores of both the SF-36 and the UCLA-PCI were calculated at every point to make clear the time-course change.

Results. The total number of patients was 229. The average scores in all aspects of the SF-36 at 24 months were better than those at the baseline. For the UCLA-PCI, the average scores for urination (UF and UB) and bowel movement (BF and BB) showed similar transition to the SF-36, but those for sexuality (SF and SB) showed a significant declination.

Conclusion. HRQoL associated with HDR-BT seemed to be favorable, but the effects on sexual function and sexual bother were not so favorable. Therefore, more attention should be paid to sexuality to achieve a better patient HRQoL.

SY-1-4

Relationships among urinary, bowel, sexual, and hormonal functions in the elderly: examinations of baseline data from the expanded prostate cancer index composite (EPIC) study of localized prostate cancer patients cohort

Y. Sakai, H. Masuda, N. Numao, Y. Okada, F. Koga, Y. Fujii, S. Kawakami, K. Kihara

Tokyo Medical and Dental University, Japan

Objectives. There are few reports focused on the bowel function in the elderly men. This study investigated the factors contributing to bowel function by using EPIC score in the localized prostate cancer patients cohort.

Materials and methods. 97 patients with hormone-naive localized prostate carcinoma were included. Average age was 67 (range, 50–88) and average prostate specific antigen level was 8.0 (range, 2.8–23) ng/ml. EPIC questionnaire was administered. Urinary, bowel, sexual, and hormonal functions were scored, respectively. High score means good QOL and the perfect score is 100. The relationships among age, urinary, bowel, sexual, and hormonal functions were analyzed using the pearson correlation coefficient (γ) and multivariate analysis.

Results. Average scores of urinary, bowel, sexual, and hormonal functions were 94 (range, 58–100), 92 (range, 54–100), 26 (range, 0–72), and 89 (range, 55–100), respectively. The correlation coefficients (γ) of bowel function with age, urinary, sexual, and hormonal functions were 0.163, 0.282 (p = 0.0042), −0.0038, and 0.3918 (p = 0.0005). Also, multivariate analysis demonstrated that urinary and hormonal functions are independent predictor of bowel function (p < 0.05).

Discussions. Urinary and bowel functions have a close relationship to each other. Bowel and hormonal functions also seemed to show intimate connections because bowel functions and hormonal subscore (vitality and body weight) are closely related.

SY-1-5

Erectile dysfunction in patients with chronic renal failure

K. Kuratsukuri, T. Naganuma, T. Tanaka, T. Nakatani

Department of Urology, Graduate School of Medicine, Osaka City University, Japan

Erectile dysfunction (ED) is very common in patients with chronic renal failure. There are a lot of hemodialysis patients in Japan, when correcting it by the population. Particularly, in recent years the trend has been towards ailing aging and rapid increase in patients with diabetic neuropathy. On the other hand, quality of life in hemodialysis patients has been associated with treatment outcomes. The incidence of ED is about 50–80% of male hemodialysis patients by Japanese literatures. High frequency of ED is admitted compared with the same age, healthy man.

According to the latest US reporting, about 80% of the male HD patient is ED. It is suggested that especially the aging and diabetes mellitus are a risk factor. Moreover, our data shows that 94% of male hemodialysis patients are ED and the level of the International Index of Erectile Function 5 (IIEF5) score is equal to standard ED patient. The cause of ED is complicated in chronic renal failure and hemodialysis patients. Angiopathy and low testosterone are intertwined and ED is caused. To complications, such as renal anemia and secondary hyperparathyroidism were improved by progress of a cure and new drug, the treatment of ED is a little, though the frequency of ED are a lot in male hemodialysis patients.

Fifty-three male hemodialysis patients were asked to complete the IIEF5 and LOH questionnaire, and also to assay their hormone level. In this presentation, I will present and discuss (1) cause of ED in chronic renal failure and hemodialysis patients, (2) investigation of sexual dysfunction in male hemodialysis patients, (3) late-onset hypogonadism (LOH) syndrome in male hemodialysis patients – correlation with clinical parameters and serum testosterone level –, and (4) treatments of ED and its problems in male hemodialysis patients.

Symposium 2 [Podium for selected paper] (Metabolic syndrome)

SY-2-1

Association between lower urinary tract symptoms, erectile dysfunction, and endothelial function in men

Y. Miwa, N. Oyama, H. Akino, O. Yokoyama

Department of Urology, University of Fukui, Japan

Introduction and objective. In recent studies, lower urinary tract symptoms (LUTS) and erectile dysfunction (ED) have been shown to be strongly associated with metabolic syndrome. Under metabolic syndrome, increased oxidative stress impairs endothelial function. Peripheral endothelial dysfunction is quantified by the determination of flow-mediated vasodilation (FMD). The aim of this study was to investigate a possible association between the severity of LUTS, ED, and endothelial function in men.

Methods. A total of 48 volunteers were recruited. An International Prostate Symptom Score (IPSS) and an International Index of Erectile Function (IIEF) were determined, and their sera were evaluated for levels of lipids and nitric oxide metabolites. The FMD% was evaluated by measuring the percent of the increase in diameter of the brachial artery by ultrasonographic imaging after a 5-min occlusion of the flow. The association between the IPSS or IIEF evaluations and the values of FMD%, serum lipids, or nitric oxide metabolites was determined.

Results. The mean age of the study participants was 41.7 years (range, 24 to 76 years). The total IPSS and voiding symptoms were significantly associated with FMD% and age. The total IIEF and IIEF erectile function domain scores were significantly associated with FMD% and age. No association was seen between the IPSS or IIEF evaluations and the serum lipids or nitric oxide metabolites levels. On multivariate linear regression analysis, FMD% and age were significantly associated with IIEF erectile function domain scores.

Conclusions. In our pilot study, univariate analysis showed that the severity of LUTS and ED is associated with FMD% of the brachial artery in men. However, the dominant predictor of LUTS was age on multivariate analysis. Although further investigation will be necessary, our results have shown that endothelial dysfunction may play a role in the pathogenesis of LUTS and ED.

SY-2-2

Effect of dehydroepiandrosterone sulfate on cardiovascular risk factors

Y. Kim, Y. Kim, S. Lee, J. Lee, D. Jeong

Department of Family Medicine, Pusan National University Hospital, Republic of Korea

Purpose.Cardiovascular disease is the number one cause of mortality and morbidity in worldwide. High blood pressure, high blood cholesterol, diabetes, and obesity are well-known risk factors of cardiovascular disease. Dehydroepiandrosterone Sulfate (DHEA-S) is a multifunctional steroid and several studies suggested that DHEA-S correlated with a lower risk of death or cardiovascular disease. It remains controversies. So, we conducted this study to investigate the relationship between DHEA-S and cardiovascular risk factors.

Methods. 621 men who underwent annual health check-ups at Pusan National University Hospital in Busan, Korea, between 2001 and 2002 were enrolled in this cross-sectional study. Anthropometric measurements and blood pressure were examined by a single trained nurse. And plasma lipid profile and DHEA-S were analyzed. Statistical analysis obtained by SPSS.

Results. Mean DHEA-S of subjects was 210.6 μg/dl and DHEA-S concentration decreased according to age. There is significant association between DHEA-S and body mass index (BMI) after controlling age. Also, waist circumference and weight were significantly associated with DHEA-S. Diastolic blood pressure and systolic blood pressure were significantly associated with DHEA-S. By logistic regression analysis, increased HDL-cholesterol was related to higher DHEA-S after adjustment for age and BMI (P < 0.05).

Conclusions. This study suggests that the plasma DHEA-S concentration can impact on HDL-cholesterol, which has a protective effect for cardiovascular disease. Further prospective studies about the clinical significance of DHEA-S in cardiovascular disease are needed.

SY-2-3

The relation between androgens and insulin resistance in Japanese men with metabolic syndrome

H. Ueshiba, S. Nakano, G. Yoshino

Division of Diabetes, Metabolism and Endocrinology, Toho University School of Medicine, Japan

Low testosterone levels in men have been found to predict insulin resistance. Studies in healthy men have shown an inverse relationship between total testosterone levels and insulin concentrations. Insulin resistance is an essential component of the metabolic syndrome. Dehydroepiandrosterone (DHEA) and DHEA-Sulfate (DHEA-S), adrenal androgens, have been shown to have antiatherogenic, antiobesity, antidiabetic, antiosteoporotic, and antitumorogenic actions. It has been reported that there is a negative correlation between DHEA or DHEA-S levels and insulin levels or homeostasis model assessment (HOMA-R) as an index of insulin resistance.

We examined the relation between androgens and insulin resistance in 52 Japanese men with metabolic syndrome (age: 56.8 ± 9.5 years, BMI: 27.0 ± 3.5, waist: 90.6 ± 5.2 cm; Mean ± SD). Fasting plasma glucose (FPG), fasting serum insulin (F-IRI), HOMA-R, HbA1c, total cholesterol (TCHO), triglyceride (TG), HDL-cholesterol (HDL-C), free testosterone, DHEA, and DHEA-S were measured. We investigated the relation between free testosterone, DHEA, and DHEA-S and each parameter.

Results were the following: waist 90.6 ± 5.2 cm, FPG 124 ± 12 mg/dl, F-IRI 15 ± 10 μU/ml, HOMA-R 4.3 ± 1.9, HbA1c 6.7 ± 0.5%, TCHO 241 ± 32 mg/dl, TG 172 ± 43 mg/dl, HDL-C 43 ± 12 mg/dl, free testosterone 9.6 ± 4.5 pg/ml, DHEA 3.5 ± 1.5 ng/ml, DHEA-S 75 ± 24 μg/dl. Free testosterone levels correlated negatively with HOMA-R index (r = −0.393, p < 0.01) and waist (r = −0.269, p < 0.05). There was no correlation between DHEA or DHEA-S and each parameter.

In conclusion, it is suggested that free testosterone level is associated with insulin resistance in Japanese men with metabolic syndrome.

SY-2-4

Aging induces glucose intolerance in renal transplant recipients

J. Uchida, K. Kitamoto, Y. Machida, T. Iguchi, T. Naganuma, K. Kuratsukuri, T. Nakatani

Department of Urology, Osaka City Graduate School of Medicine, Japan

Introduction. Glucose intolerance is one of the criteria of metabolic syndrome. Insulin resistance and insulin secretion play a major role of glucose intolerance. New onset diabetes mellitus (NODAT) is well-recognized and serious complication of renal transplantation. Previous reports have shown one of the risk factors in NODAT were the age levels of recipients at the time of transplant. The older recipients may have abnormal glucose metabolism without prior diagnosis of diabetes. This study was designed to evaluate the relationship of patients' age and glucose intolerance in renal transplant recipients.

Patients and methods. A total of 110 renal transplant recipients without prior evidence of diabetes were enrolled in this study. Patients were divided into two groups by age at the time of transplant: Group A (age 55 years and over, n = 17) and Group B (under age 55, n = 93). The frequency of glucose intolerance, insulin secretion and insulin resistance were evaluated after 75g-OGTT and compared between the two groups. Categories of glucose tolerance were defined according to World Health Organization criteria.

Results. Glucose intolerance (impaired glucose tolerance; IGT, impaired fasting glucose; IFG, diabetes mellitus; DM) was detected in 11 patients (64.7%) of the Group A, whereas 18 patients (20.4%) had glucose intolerance in the Group B. The homeostasis model assessment of beta cell (HOMA-beta) and insulinogenic index was lower in the group A than the Group B. Liner regression analysis showed that the increase of body mass index (BMI) in renal transplant recipients significantly correlated with HOMA-R.

Conclusion. The frequency of glucose intolerance was significantly higher and insulin secretion was lower in older renal transplant recipients than in younger recipients. We revealed that insulin secretion was impaired by aging, and that the increase of BMI induced insulin resistance in renal transplant recipients.

SY-2-5

The change of contractility and relaxation on the corpus cavernosum of hyperlipidemia rabbit in vitro

J.H. Liu, K. Rao, R.B. Chen, H.P. Zhang, T. Wang, S.G. Wang, W.M. Yang, Z.Q. Ye

Department of Urology, Tongji Hospital, Tongji Medical College of Huazhong University of Science and Technology, China

Objective. To investigate the mechanisms of erectile dysfunction induced by hyperlipidemia through researching the change of contractility and relaxation on the corpus cavernosum of hypercholesterolemic rabbit in vitro.

Materials and methods.New Zealand white rabbits were randomly divided into control and experiment groups. The control group (n = 20) received a regular diet for 8 weeks, whereas the experimental group (n = 20) were fed a 1% cholesterol diet for 8 weeks. We conducted isometric tension studies with phenylephrine, endothelium-dependent vasodilators (acetylcholine), endothelium-independent vasodilators (sodium nitroprusside), and rho kinase inhibitor (Fasudil) on isolated strips of corpus cavernosum.

Results. The weight (2.42 ± 0.24 kg vs. 1.95 ± 0.14 kg) and total serum cholesterol (24.21 ± 0.84 mmol/l vs. 3.22 ± 0.15 mmol/l) were significantly improved (P < 0.01) in experimental group, compared with the experimental group which were not fed. The total serum cholesterol (24.21 ± 0.84 mmol/l vs. 3.39 ± 0.28 mmol/l) was significantly improved (P < 0.01) in experimental group, compared with the control group. The contractility responses to phenylephrine in experiment group in doses (0.5, 1, 5, 10, 50, 100 μmol) were 4.79% ± 2.00%, 8.84% ± 2.95%, 12.81% ± 3.77%, 14.63% ± 5.38%, 25.01% ± 6.14%, and 34.69% ± 8.53%. The contractility responses to phenylephrine in control group were 1.00% ± 0.13%, 2.60% ± 0.72%, 4.28% ± 1.27%, 5.91% ± 2.09%, 6.49% ± 4.02%, and 5.64% ± 11.87%. The contractility responses to phenylephrine were significantly improved (P < 0.01) in experimental group in these doses, compared with the control group. The relaxation responses to acetylcholine in experimental group in doses (1, 10, and 100 μmol) were 36.28% ± 4.71%, 48.81% ± 4.36%, and 56.27% ± 11.93%. The relaxation responses in control group were 48.04% ± 4.78%, 69.12% ± 5.27%, and 78.23% ± 5.30%. There were significantly reduced (P < 0.01) in experimental group in these doses, compared with the control group. No differences were found among the two groups in the relaxation response to sodium nitroprusside. The relaxation responses to fasudil in experimental group in doses (0.5, 1.25, 5, and 12.5 μmol) were 1.56% ± 0.43%, 5.03% ± 1.02%, 8.28% ± 1.35%, and 16.77% ± 3.57%. The relaxation responses in control group were 4.69% ± 1.23%, 10.39% ± 2.05%, 15.08% ± 3.04%, and 25.22% ± 3.72%. There were significantly reduced (P < 0.01) in experimental group in these doses, compared with the control group.

Conclusions. It is concluded that the improvement of cavernous smooth muscle contractility and the impairment of cavernous smooth muscle relaxation in response to endothelium-mediated stimuli were the mechanisms of erectile dysfunction induced by hyperlipidemia.

Symposium 3 [Podium for selected paper] (Testosterone)

SY-3-1

Testosterone and prostate cancer: from myth to scientific understanding a review of the current knowledge

F. Saad

Bayer Schering Pharma, Scientific Affairs Men's Healthcare, Berlin, Germany

A belief passed on from one generation of doctors to the next, is that testosterone (T) plays a significant role in the development of prostate cancer (PCa)Citation1. This belief stems from the facts that the prostate for its development and growth is exquisitely androgen-dependent and that androgen ablation, either by surgical or chemical castration, is a treatment mode for PCa. There are now compelling insights to change that view and to recognize that testosterone is rather an innocent bystander than a culprit in the development of PCa:

The vast majority of PCa develops at an age when T levels are declining.
There are good reasons to hypothesize a saturation model of the prostate for effects of T. Exogenous T does not raise intra-prostatic concentrations of T or DHT. Hypogonadal men receiving T treatment show an increase of prostate volume and prostate specific antigen (PSA) reaching within 1 year. (Much) higher doses of T do not affect prostate volume nor PSA.
Neither levels of endogenous T or resulting from T administration have been associated with higher rates of PCa.
Surprisingly, low serum T is associated with greater PCa risk, and more malignant features (Gleason scores) of PCa, and poorer PSA failure-free survival.

Although there are as yet no large-scale, prospective, long-term controlled studies of T therapy to provide a definitive assessment of the risk, it is now regarded as a responsible practice to treat elderly men with proven hypogonadism with T. The aging population at risk for T deficiency overlaps with the population at risk for PCa. Therefore, it is strongly recommended that men undergoing T therapy undergo regular monitoring for ProCa, as outlined in recent guidelinesCitation2.

SY-3-2

The impact of testosterone replacement on the morphological change of abdominal fat cell in an aging male rat

S. Hisasue¹, K. Kobayashi¹, K. Hashimoto¹, R. Kato², T. Tanaka¹, N. Masumori¹, T. Tsukamoto¹

¹Department of Urology, Sapporo Medical University, Japan; ²Department of Urology, Muroran General Hospital, Muroran, Japan

Purpose. Testosterone replacement clinically improves metabolic syndrome parameters in testosterone deficiency syndrome patients, although histological change of fat cell in this population is still unclear. The goal of our study was to clarify the morphological change in subcutaneous and abdominal fat cell after testosterone replacement in aging male rats.

Materials and methods. We investigated Sprague-Dawley rats aged 20 to 22 months. We divided the rats into two groups; aging male rats group (n = 5) and aging male rats with testosterone replacement (n = 5). We injected testosterone enanthate 25 mg intraperitoneally every 2 weeks for 6 weeks. We sacrificed the animals at 6 weeks (three injections of testosterone) and harvested abdominal and subcutaneous adipose tissue. We analyzed the area of fat cells with Image-J software (NIH).

Results. The median testosterone level before study was 0.87 ng/ml (range, 0.61–1.78). Baseline body weight of aging male group was 937.5 ± 45.5 g, and that of testosterone replacement group was 862.5 ± 31.5 g (p = NS). The body weight change at 2, 4, and 6 weeks after testosterone replacement was 800.0 ± 35.4, 767.5 ± 46.3, and 780 ± 40.4 g, respectively (p = NS). Median subcutaneous fat cell size was 4.85 × 10³ (0.85–12.53 × 10³) μm² in the aging group, and 4.93 × 10³ (6.42–19.7 × 10³) μm² in the testosterone group, respectively (p = NS). On the contrary, median abdominal fat cell size was significantly smaller in testosterone replacement group; 4.93 × 10³μm² (0.51–14.88 × 10³) than in aging group; 6.08 × 10³μm² (0.77–19.97 × 10³) (p < 0.001, Mann–Whitney U test).

Conclusions. This study suggested that testosterone replacement could decrease the size of abdominal fat cell which might be responsible for the metabolic syndrome in aging male rats.

SY-3-3

Effect of testosterone supplementation on cognitive function in older men with cognitive impairment

S. Fukai¹, M. Akishita¹, S. Yamada², S. Ogawa¹, H. Nishiya², T. Hama², K. Toba³, Y. Ouchi¹

¹Department of Geriatric Medicine, Graduate School of Medicine, The University of Tokyo, Japan; ²Kikyogahara Hospital, Nagano, Japan; ³Department of Geriatric Medicine, Kyorin University School of Medicine, Tokyo

Context. We have reported that endogenous testosterone levels are associated with physical and psychological functions including cognition in frail older men.

Objectve. We conducted a pilot study to investigate the effect of oral testosterone supplementation on cognitive function in older men with mild to moderate cognitive decline.

Methods. Eleven men with cognitive impairment, aged 71–91 years (mean ± SD age = 81 ± 6 years), were assigned to receive oral Testosterone Undecanoate 40 mg/day for 6 months. The control group (n = 13) matched for age (81 ± 13 years) and cognitive function was followed without hormone replacement. Comprehensive geriatric assessment was performed including cognitive function by Hasegawa Dementia Scale-Revised (HDS-R) and Mini-Mental State Examination (MMSE), basic activity of daily living (ADL) by Barthel Index and ADL-related vitality by Vitality Index at baseline and at 3 and 6 months. Plasma hormone levels including total-, free-, and bioavailable testosterone, DHEA-sulfate and estradiol were also followed up.

Results. After 6 months, subjects who received testosterone showed a significant increase in HDS-R and MMSE scores compared with baseline (17.6 ± 5.9 to 20.6 ± 7.3 and 20.2 ± 5.9 to 22.6 ± 6.5, respectively; p < 0.05 by paired t-test), whereas both scores remained unchanged in the control group (p < 0.05 by unpaired t-test). No significant changes were observed in basic ADL and vitality in both groups. PSA and liver function were not affected, and no other adverse side effects were observed.

Conclusions. Our preliminary study showed that testosterone supplementation during 6 months improved cognitive function. Randomized controlled studies are needed to confirm our results.

SY-3-4

Impact of salivary testosterone level on the vitality, QOL, and living functioning in the elderly

S. Horie¹, Y. Kimura¹, H. Masuda², Y. Murata²

¹Department of Urology, Teikyo University School of Medicine, Japan; ²Program of Gerontological Research, Organization for Interdisciplinary Research, The University of Tokyo

Purpose. To evaluate the impact of salivary testosterone level on the physical activity, QOL, and living functioning in the elderly in order to prevent/improve their disable or bed-bound conditions and to allow them to live physically and socially independent lives.

Subjects and methods. Community dwelling males and females aged 50 years or more, residing in Miyakojima, Okinawa, participated in filling out the vitality index (VI) questionnaire, QOL (WHO/QOL26), and a questionnaire for functioning in the elderly (QFE) as well as the survey for the diet, smoking, and exercise. Their salivary testosterone levels were measured by ELISA.

Results. Salivary testosterone levels correlated significantly with VI, QOL, and QFE in males over 65 years old. Men who received higher education or living with spouses had significantly lower testosterone levels. In female, testosterone levels significantly correlated with QOL. A structural equation model indicated that salivary testosterone levels had significant impact on the psychological subscales such as prevention of depression in QFE, mood and wellness in VI, and domains of psychology social relationship, and satisfaction in QOL.

Conclusions. Testosterone levels correlates significantly with the vitality and QOL of elderly male. Testosterone levels had significant impact on the psychological subscales. Those data indicated that testosterone levels would play a major role for the fulfillment of healthy longevity.

SY-3-5

Association of serum testosterone with recurrence of nonmuscle-invasive bladder cancer

T. Kumamoto, S. Muto, H. Ide, S. Horie

Department of Urology, School of Medicine, Teikyo University, Japan

Purpose. We evaluated the possible involvement of serum Testosterone in the recurrence of Nonmuscle-invasive bladder cancer after TUR-Bt.

Method. Serum level of Testosterone was measured prospectively in patients scheduled for TUR-Bt for Nonmuscle-invasive bladder cancer between April 2003 and January 2009.

Results. The study included 168 patients with a median follow-up of 36.5 months (range, 3 to 259). Progression- and recurrence-free 10-year survival rates were 98.7% and 66.7%, respectively. On univariate analysis, serum Testosterone level was found to be significant predictors (p = 0.0465) of local recurrence. According to a three-tier system reflecting the EORTC recurrence risk tables, we defined low-, intermediate-, and high-risk groups. Although not significant, the serum testosterone levels in high-risk group (439.3 pg/ml) are lower than that in low-risk-group (512.6 pg/ml).

Conclusions. Low-serum testosterone levels before TUR-Bt in patients with nonmuscle-invasive bladder nicer are associated with poor outcome. Further larger scale studies are needed to confirm these results.

Symposium 4 [Podium for selected paper] (Prostate cancer)

SY-4-1

The efficacy and limitation of bisphosphonate in treatment of osteoporosis caused by androgen deprivation therapy for prostate cancer

K. Marumo¹, K. Hata², J. Hagiuda¹, M. Matsumoto¹, Y. Hanawa¹

¹Department of Urology, Tokyo Dental College, Ichikawa General Hospital, Japan; ²Department of Urology, Jikei University

Objectives. Androgen deprivation therapy (ADT) is the mainstay of treatment for men with systemic disease and is utilized as primary therapy or in combination with other therapies for localized disease. We explored ADT-related bone loss in prostate cancer and efficacy of oral resedronate.

Patients and methods. A hundred and forty-nine patients with prostate cancer receiving continuous ADT were studied. Bone mineral density (BMD) at femoral neck was determined by dual X-ray absorptiometry (DXA) every 6 months after entry to the study. When patients were diagnosed based on YAM% (young adult male) as having osteoporotic BMD, oral risedronate was given at a daily dose of 2.5 mg.

Results. At initial measurements of BMD, ages of the patients ranged from 65 to 91 years, duration of ADT ranged 0–148 months, and 27 patients had osteopenia and 31 patients had osteoporosis, but there was no significant correlation between BMD and ages of the patients (r = −0.209, n = 149, p = 0.105). On the other hand, patients had lower BMD when they had ADT of longer duration (r = −0.163, n = 148, p = 0.048). In 33 patients, who were not treated by risedronate, BMD decreased from 0.756 to 0.698 g/cm² in 6 months of initial measurements of BMD (p < 0.001). On the other hand, in 38 patients, who were treated for osteoporosis by risedronate, BMD decreased from 0.695 to 0.633 g/cm² in 6 months, however, it was statistically not significant (p = 0.415).

Conclusions. This study showed that ADT for prostate cancer decrease BMD with the duration of therapy. Oral resedronate prevented loss of bone mineral density, however, efficacy was limited. In order to prevent or treat osteoporosis, concomitant administration of calcium or vitamin D as well as lifestyle interventions are recommended.

SY-4-2

Transforming growth factor-beta regulates neuroendocrine like transdifferentiation of human prostate cancer

T. Inamoto, N. Ibuki, K. Koyama, K. Komura, Y. Fujisue, Y. Kotake, T. Ubai, H. Azuma, Y. Katsuoka

Department of Urology, Osaka Medical College, Osaka, Japan

Purpose. Neuroendocrine population of prostate cancer correlates with the androgen-independent growth and dismal prognosis with unknown mechanism. We tried to examine the specific role of multifunctional growth factor, TGF-beta in its' process.

Materials and methods. We established an androgen-independent subclone (NECaP) with neuroendocrine-like terminal transdifferentiation from androgen-dependent LNCaP by culturing it in androgen-deprived environment, which resembles androgen ablation therapy in clinical settings. Gene expression of TGF-beta-1, -2, -3 in LNCaP and NECaP was evaluated by realtime semiquantitive RT-PCR. Specific role of endogenous TGF-beta system in LNCaP and NECaP was determined by introduction of neutralizing antibody of TGF-beta, and siRNA against TGF-beta Type 2 receptor. TGF-beta downstream signaling in LNCaP and NECaP was assessed by Western blot analysis, 2- (2-Methoxy-4-nitrophenyl)- 3-(4-nitrophenyl)- 5-(2,4-disulfophenyl)- 2H-tetrazolium assay, along with Luciferase assay.

Results. LNCaP cultured in androgen depleted medium for over 4 weeks demonstrated neuroendocrine like features including morphological changes and expression of neuron-specific enolase (NSE). LNCaP cultured in the presence of androgen, neutralizing antibody of TGF-beta, or siRNA against TGF-beta Type 2 receptor did not show the morphological changes, nor NSE expression. NECaP demonstrated neuronal morphology and NSE in the presence of androgen, or siRNA against TGF-beta Type 2 receptor. LNCaP was growth-inhibited by the addition of exogenous TGF-beta, with the Luciferase activity being upregulated, and was found to enhance the activation of Smad2/3. In contrast, NECaP was growth-inhibited albeit to a lesser extent than LNCaP.

Conclusions. Androgen independence of human prostate cancer may partly explained by TGF-beta dependent neuroendocrine transdifferentiation.

SY-4-3

IPSS irritative subscore is an independent negative predictor of prostate cancer detection

H. Masuda, S. Kawakami, Y. Fujii, F. Koga, Y. Sakai, N. Numao, M. Sakura, S. Yano, Y. Okada, K. Kihara

Department of Urology, Tokyo Medical and Dental University, Japan

Objective. To examine whether lower urinary tract symptoms (LUTS) adds any significant information to the prediction of positive prostate biopsy in referred men with moderately elevated prostate-specific antigen (PSA).

Methods. A total of 595 consecutive Japanese men with PSA less than 50 ng/ml who underwent prostate biopsy under transrectal ultrasound (TRUS) were included in the study cohort. Age, digital rectal examination (DRE), PSA, the International Prostate Symptoms Score (IPSS) subscores (obstructive and irritative), and prostate volume were evaluated in regard to their association with prostate cancer.

Results. The mean PSA level and patient age were 9.3 ng/ml and 67.0 years, respectively. 17.5% of men had abnormal DRE. The mean obstructive and irritative subscores were 6.4 points and 5.3 points, respectively. The positive biopsy rate was 40.5%. Multivariate analysis demonstrated that age, DRE, and PSA were independent positive predictor and that IPSS irritative subscore and prostate volume were independent negative predictor for detecting prostate cancer. IPSS obstructive subscore was statistically significant negative predictor in univariate analysis but was not left in multivariate analysis.

Conclusions. IPSS score, especially in irritative subscore, may be an important variable to consider when counseling patients before biopsy and when designing patient algorithms for prostate biopsy.

SY-4-4

The prevalence of hot flushes in Japanese older men: a comparison between those receiving endocrine therapy for prostate cancer and the general population

M. Kajiwara¹, M. Oki², H. Moriyama², K. Mita¹, J. Teishima¹, K. Mutaguchi³, A. Matsubara¹

¹Department of Urology, Graduate School of Hiroshima University, Japan; ²Department of Urology, JA Onomichi General Hospital; ³Department of Urology, Nakatsu Daiichi Hospital

Objective. Hot flushes (HF) are a bothersome adverse reaction that occur frequently in patients receiving endocrine therapy for prostate cancer (PC) in western countries. However, recent studies of Japanese PC patients undergoing endocrine therapy suggest that the prevalence of HF is lower than expected, and that in fact HF is not a marked symptom. The purpose of this study was to clarify the prevalence of HF and its impact on HRQOL in Japanese patients undergoing endocrine therapy, and to compare them with those in a general population of older men.

Patients and methods.A total of 182 older men who consulted our outpatient department with a chief compliant of lower urinary tract symptoms (noncastrated group, age 68.5 years) and a total of 113 patients receiving endocrine therapy for PC (castrated group, age 73.7 years) were enrolled into the study between 2004 and 2009. The prevalence of HF and their impact on QOL were investigated using a HF questionnaire and assessed quantitatively using the formula: number of HF attacks/week × severity (hot flush score), plus a QOL questionnaire.

Results. The prevalence of HF in the castrated and noncastrated groups was 31.9% and 12.6%, respectively (p < 0.005). The QOL survey demonstrated that HF had a significant impact in 69.4% and 21.7% of these patients, respectively.

Conclusions. Although the number of patients was small, and the questionnaire used to evaluate the prevalence and impact of HF on QOL was not validated, our study confirmed that the prevalence of HF in Japanese PC patients receiving endocrine therapy is only about 30%. On the other hand, the prevalence of HF is more than 10% even in the general population of older Japanese men, having a significant impact on QOL in more than one fifth of those affected.

SY-4-5

Involvement of the estrogen receptor-beta in genistein-induced expression of p21waf1/cip1 in PC-3 prostate cancer cells

T. Tanaka, K. Matsumura, K. Kuratsukuri, T. Nakatani

Department of Uroloy, Osaka City University Graduate School of Medicine, Japan

Background. Dietary genistein, a phytoestrogen derived from soybean, has been suggested as a chemopreventive agent for prostate cancer. Genistein has been reported to exert its anticancer effects via a variety of functional pathways, but the upstream signaling of molecules regulated by genistein remains unclear. In this study, we investigated whether ER-beta was involved in genistein-induced expression of cell cycle inhibitors in PC-3 prostate cancer cells.

Materials and methods. Cell proliferation of PC-3 exposed to genistein was measured by WST-1 proliferation assay. The expression of p21, p27, and ER-beta in PC-3 cells was assessed by quantitative real-time reverse transcription-PCR. ER-beta silencing was performed using a small interfering RNA (siRNA). The transcriotional activity of p21 promoter was determined by the luciferase reporter assay.

Symposium 5 [Podium for selected paper] (HRT)

SY-5-1

52-week treatment with diet and exercise + transdermal testosterone reverses the metabolic syndrome and improves glycemic control in hypogonadal men with newly diagnosed Type 2 diabetes

F. Saad^1,2, A. Heufelder³, M.C. Bunck⁴, L.J. Gooren⁴

¹Bayer Schering Pharma, Scientific Affairs Men's Healthcare, Germany; ²Gulf Medical University, Ajman, UAE; ³Private Practice of Internal Medicine and Diabetology, Munich, Germany; ⁴VU Medical Center, Department of Endocrinology, Amsterdam, The Netherlands

Objectives. Men with the metabolic syndrome (MetS) and Type 2 diabetes (T2D) often have low testosterone levels. Elevating low testosterone levels may improve features of the MetS and glycemic control.

Subjects and methods. In a single blind, 52-week randomized clinical trial, the effects of supervised diet and exercise (D&E) with or without transdermal testosterone administration on components of the MetS in hypogonadal men with the MetS and newly diagnosed T2D were assessed. 32 hypogonadal men (total testosterone <12.0 nmol/l) with the MetS as defined by the Adult Treatment Panel-III and the International Diabetes Federation, and newly diagnosed T2D received supervised D&E but 16 in combination with testosterone gel 50 mg once daily (n = 16). No glucose lowering agents were administered prior to or during the study period. Outcome measures were components of the MetS as defined by the ATPIII and IDF.

Results. Serum testosterone, HbA1c, fasting plasma glucose, HDL-cholesterol, and triglyceride concentrations, and the waist circumference improved in both treatment groups after 52-weeks of treatment. Addition of testosterone significantly further improved these measures compared with D&E alone. All D&E+T patients reached the HbA1c goal of <7.0%, 87.5% reached an HbA1c <6.5%. On the basis of ATPIII, 81.3% of the patients randomized to D&E+T no longer matched the criteria of the MetS, whereas only 31.3% of the D&E alone patients no longer fulfilled the MetS definition. Additionally, testosterone treatment improved insulin sensitivity, adiponectin, and high-sensitivity C-reactive protein.

Conclusions. Addition of testosterone to supervised D&E results in greater therapeutic improvements of glycaemic control and reverses the MetS after 52-weeks of treatment in hypogonadal patients with the MetS and newly diagnosed T2D.

Keywords:Male hypogonadism, insulin resistance, HbA1c, lipids

SY-5-2

Beneficial effects of 2 years of administration of parenteral testosterone undecanoate on the metabolic syndrome and on non-alcoholic liver steatosis and C-reactive protein

F. Saad¹, A. Haider², L.J. Gooren³, P. Padungtod⁴

¹Bayer Schering Pharma, Scientific Affairs Men's Healthcare, Berlin, Germany; ²Private Urology Practice, Bremerhaven, Germany; ³VUMC, Department of Endocrinology, Amsterdam, The Netherlands; ⁴Faculty of Veterinary Medicine, University of Chiang Mai, Chiang Mai, Thailand

Background. In elderly men often an association between a decline of testosterone and features of the metabolic syndrome are found. This study tested the effects of normalization of testosterone.

Materials and methods. 122 hypogonadal men (18–83 years, mean 59.6 ± 8.0 years), with testosterone levels between 0.14 and 4.51 ng/ml (N > 4.90 ng/ml) were treated with parenteral testosterone undecanoate for 2 year as the sole intervention.

Results. Plasma testosterone rose from 3.3 ± 1.9 ng/ml to 4.1 ± 1.5 ng/ml (P < 0.01) at 3 months, then stabilized at 6.8 ± 1.3 ng/ml after the first 6 months. There was a remarkable progressive linear decline of body weight, BMI, and waist circumference over the full study period. Plasma cholesterol decreased significantly over the first 12 months, then stabilized. Plasma glucose, triglyceride, LDL-cholesterol and C-reactive protein decreased significantly and HDL-cholesterol increased significantly over the 24 month study period in a nonlinear fashion. There was a significant decrease of levels of aspartate aminotransferase (AST) and alanine aminotransferase (ALT) over the first 12 and 9 months, then values leveled off. Changes in variables were largely correlated with changes in testosterone levels. At baseline 47/122 met the criteria of the metabolic syndrome as defined by the National Cholesterol Education Program (2001); after 2 years of testosterone treatment this number had declined to 11/122.

Conclusions. With testosterone treatment over 2 years, the most significant improvement of the metabolic syndrome was noted over the first 12 months but over the following 12 months further improvement was observed.

SY-5-3

Health related quality of life in Japanese late onset hypogonadism patients administered androgen replacement therapy in past years

H. Taniguchi, G. Kawa, H. Kinoshita, T. Matsuda

Kansai Medical University, Japan

Introduction and objectives. The duration of androgen replacement therapy (ART) is controversial. Therefore, we examined the effects of ART on comprehensive health-related QOL (SF-36) scores in late onset hypogonadism (LOH) patients who received ART for six months.

Methods. We obtained answers to the SF-36 questionnaires from 15 men aged 37 to 74 years (mean 58.1) who had undergone ART (250 mg of testosterone enanthate injected intra-muscularly once per 3 weeks) for six months between September 2002 and June 2007. We mailed the questionnaires, and the patients completed them at home and returned them in postage prepaid envelopes. The duration from the last injection was 42.4 to 67.5 months (mean 60.4 months). The mean serum total testosterone level before ART was 2.85 +/− 0.67 ng/ml, ranging from 1.1 to 3.9 ng/ml. We evaluated changes in the SF-36 scores measured prior to treatment, during treatment and after treatment.

Results. We mailed 82 questionnaires and received 33 back. We analyzed 15 patients who answered their questionnaires completely before the ART, during the ART and at this time. The prior to ART subcategory scores on the SF-36 were all lower than those for the age-matched healthy Japanese men. Nevertheless, several scores were significantly improved after beginning ART and were maintained, although it took a long time after ART, especially the scores for physical functioning, role-emotional, social functioning, mental health, vitality and general health subscales. No significant differences were noted between during treatment and the after ART patients in any subcategory score.

Conclusions. ART for LOH patients is effective in curing their symptoms, and also improves the HR-QOL. The effects of ART manifest during the early treatment period, and are maintained after stopping the treatment. We believe it is not necessary to continue ART, especially for Japanese LOH patients, from the viewpoint of improving the HR-QOL.

SY-5-4

Long acting intramuscular testosterone undecanoate for the treatment of 135 late-onset hypogonadisms

S. Permpongkosol, R. Talubsri, K. Ratana-Olarn

Division of Urology, Department of Surgery, Faculty of Medicine, Ramathibodi Hospital, Mahidol University, Bangkok, Thailand

Objective. To investigate the effects of long-acting testosterone undecanoate (TU) (1000 mg) in late-onset hypogonadism in Thai men.

Methods. In this study, 135 men with documented late-onset hypogonadism were investigated. The mean age and body mass index of patients were 60.16 (SD 9.15) years and 25.89 (SD 3.51) kg/m², respectively. Patients received TU 1000 mg on Day 1, Day 42, and thereafter every 12 weeks. The mean duration of treatment was 60 weeks (range, 6–138 weeks). During the follow-up the patients were physically examined and serum levels of total- and free-testosterone were measured. In addition, TU therapy effects were assessed by using the Aging Males' Symptoms rating scale (AMS) questionnaire, International Prostate Symptom Score (IPSS) questionnaire, the International Index of Erectile Function (IIEF-5 and -15), and satisfaction scores.

Results. During the 30-week follow-up, the mean total- and free-testosterone serum levels increased from 289.12 (SD 103.29), and 6.40 (SD 2.50) ng/dl to 558.88 SD 231.69, and 13.24 SD 6.40 ng/dl, respectively. In 93% of patients, the testosterone serum level reached the normal limit (300 ng/dl). PSA and haematocrit levels increased in 44% and 47% of patients, respectively. The mean changes were 0.296 (SD 0.216) ng/ml and 2.99 (SD 0.27) %, respectively. Side effects were weight gain in 10% of patients, headache and dizziness in 2%, larger or painful breasts in 4%, pruritus in 2%, and acne in 3%. The analysis of the questionnaires showed treatment satisfaction in 89% of patients, although the AMS and IIEF-5 scores did not show significant improvements after three TU injections.

Conclusions. We have observed promising effects of the treatment with TU in late-onset hypogonadism in Thai men. Further studies with longer follow-up are warranted to optimize the administration schedule and to explore the long term effects of TU in these patients.

SY-5-5

The efficacy of testosterone replacement therapy in men with late-onset hypogonadism

K. Yamaguchi, M. Ando, K. Chiba, M. Fujisawa

Division of Urology, Department of Organs Therapeutics, Faculty of Medicine, Kobe University Graduate School of Medicine, Kobe, Japan

Introduction and objectives. LOH is defined as subnormal serum testosterone (T) levels in connection with physical, psychic, and sexual symptoms, generally related to male hypogonadism. We report clinical assessments of efficacy and side effects of T replacement therapy (TRT) in men with LOH.

Methods. This study included 56 patients who were diagnosed with LOH and treated with TRT at least as long as 6 months at our institution. All of them were administered T enanthate 250 mg intra muscularly per 3 or 4 weeks. Before and 6 months after the initiation of TRT, AMS scale, and ADAM questionnaires were examined. Fasting blood samples were analyzed for sex hormones, total cholesterol (TC), HDL, and LDL cholesterol, triglycerides (TG). To evaluate the adverse effect of the therapy, liver function (AST, ALT, and gamma-GTP), erythropoiesis (RBC and Hb), and PSA were also analyzed.

Results. Psychological and physical symptoms scores measured by the AMS scale and the ADAM questionnaire had showed significant improvement on total (53.1–44.5; p < 0.05) and psychological (15.5–10.7; p < 0.001) symptoms score measured by the AMS scale and the ADAM questionnaire score (8.3–6.8; p < 0.05). There were no significant differences in somatic and sexual symptoms score measured by AMS scale after the therapy. There were also no significant differences in all parameters for lipid analysis including the levels of TC, HDL and LDL cholesterol, and TG. With regard to the adverse effects of the therapy, AST, ALT, gamma-GTP, RBC, Hb, and PSA did not significantly change after the therapy.

Conclusions.LOH syndrome is primarily based on various vague, subjective symptoms in healthy aging men. Regardless of retrospective and short time-course study, we have revealed that TRT for men with LOH caused favorable changes in psychological conditions. We consider TRT is effective and may be recommended for treatment of the men.

Symposium 6 [Podium for selected paper] (Life style)

SY-6-1

Effects of health promotion elderly program on prevent dementia disease

S. Wongkasant, O. Pankong

Boromarajonani College of Nursing, Praputhabat, Saraburi, Thailand

The purpose of this experimental study was to investigate the effect of prevented Dementia program in a sample of 60 elderly with Hypertension or Diabetes Mellitus. Thirty elderly were in a study group and another 30 elderly were in a control group. The study groups participated in the program once a week for four consecutive weeks. Data were collected using the health promotion behavior and perceived benefit in elderly questionnaire. Data were analyzed using mean, Standard deviation, and t-test.

The findings could be summarized as follow:

The study group reported significant increased scores of participation and perceiving benefit of the program (p < .05).
The study group significantly reported the higher score of the program than the control group (p < .05).
The study group significantly reported the higher score of health behavior than the control group (p < .01).

SY-6-2

Current status of palliative care in a cancer base hospital in Japan

N. Meguro, H. Kiyohara

Department of Urology and Palliative Care Team of Toyonaka Munincipal Hospital, Japan

Objective. Although 90% of Japanese cancer patients die in hospitals, many would prefer to die at home. The Cancer Treatment Basic Law is a major national project on cancer treatment, which is characterized by an emphasis on palliative care, which had not attracted much attention previously. This study was designed to investigate the trend in deaths at home and current status of palliative care at the regional level in Osaka prefecture.

Patients and methods. The following two items were investigated: (1) deaths from cancer in Osaka prefecture from 1995 to 2003 were summarized to determine the number of deaths at home by year, cancer type, and region; and (2) local medical institutions (hospitals, clinics, and visiting care stations) were asked about regional cooperation in palliative care.

Results. (1) Only 5.7% of cancer patients died at home in Osaka prefecture. The most common cancer type associated with death at home was prostate cancer. The number of deaths at home was negatively correlated with population density and positively correlated with the number of persons per household, number of employed persons per household, number of persons involved in primary industry per population, and home floor area. (2) The most commonly reported issues of palliative home care at the regional level included the maintenance of the 24-hour care system and actions to cope with sudden changes in patients' conditions. About 15% of medical institutions provided palliative home care on a 24-hour basis.

Discussion. The requirements for the home care of cancer patients include selection by cancer type, adequate space in the home, and support from family members and medical staff. Prefectural pivotal hospitals for cancer treatment are required to provide special medical attention during palliative care and accept patients who experience sudden changes in their condition.

SY-6-3

Primary care doctors' views of men's health screening in Malaysia: a preliminary analysis of a qualitative study

S. Tong¹, W.Y. Low², S. Bahari Ismail³, S. Willcock¹

¹University of Sydney, Australia; ²University of Malaya, Malaysia; ³University of Science Malaysia, Malaysia

Background. Men's health screening is an important part of health promotion and prevention to improve the health status of men. Primary care settings provide an optimal position to implement men's health screening. We aimed to explore the opinion of primary care doctors (PCDs) relating to current attitudes to men's health screening.

Methods. We used a qualitative approach to explore the opinions of primary care doctors in 10 in-depth interviews and eight focus group discussions. Purposeful sampling of GPs was done to ensure maximum variation in the PCD sample. Semistructured open ended questions were used in the interview. Interviews were recorded and transcribed verbatim for analysis. Open coding with thematic analysis was used to identify key issues raised in the interview.

Results. 48 PCDs from private and public settings were interviewed. Three main themes emerged in the preliminary analysis of some of the depth-interviews. (1) There was no clear understanding of the concept of men's health among PCDs. (2) There was dissatisfaction with the present state of men's health screening, with men's health screening perceived as fragmented and neglected. (3) There were many obstacles in practicing men's health screening, including lack of skills and knowledge among PCDs, competing interest during consultations, poor societal awareness, unstructured health screening systems, and negative perceptions of men's health seeking behavior. The main reason for offering men's health screening was a direct request from men.

Conclusion. The concept of men's health was new to PCDs. The decision to practice men's health screening faced many challenges. Effective implementation of men's health screening may involve more than just imparting knowledge and skills to PCDs. It should simultaneously address other obstacles.

SY-6-4

Withdrawn

SY-6-5

Social and health characteristics of urban men in empty nest

V.K.M. Lee¹, W.Y. Low², E.M. Khoo², H.M. Tan^2,3

¹International Medical University, Malaysia; ²University of Malaya; ³Sime Darby Medical Centre

Introduction. Men suffer most when their children leave home, when they realized they are running short of time playing an active role in fatherhood. This article described the prevalence of aging men in the empty nest phase, and its social and health correlates.

Methods. This was a population survey in an urban community. Five hundred men aged 50 years and above were randomly selected with 351 agreed (response rate 70.2%). Sociodemographic information, lifestyle indicators, and medical conditions were collected via a structured face-to-face interview. The 12-Item Short-Form Health Survey (SF-12) and Geratric Depression Scale (GDS-15) were completed. Empty nest was defined as man who has at least one child, and none of his children was currently staying with him.

Results. The prevalence of men with empty nest (EN) was 14.8%. They were significantly older than men without empty nest (no-EN) (mean age 61.9 ± 6.9 vs. 57.5 ± 6.9, p < 0.001). There were no significant differences in their marital status, economic and general health, but there was significant difference in relationship problem with family members (p = 0.04). The composite scores of SF-12 in EN in both physical (33.2 ± 6.3) and mental domain (34.9 ± 5.0) were lower than the reference norm scores of the US population. However, there was no significant difference in the specific domains between EN and no-EN, except for social function, where EN had a significantly lower score. Men with EN received significantly more social support from their children. There was no significant difference in depression scores and home care preferences in later years.

Conclusion. The prevalence of men with empty nest phase was relatively low in this urban community and their quality of life was not significantly different from aging men who live with their children, possibly because of good social support.

Symposium 7 [Podium for selected paper] (BPH)

SY-7-1

Testosterone replacement therapy relieves lower urinary tract symptoms (LUTS) in late onset hypogonadism (LOH) patients

T. Amano, T. Imao, K. Takemae

Department of Urology, Nagano Red Cross Hospital, Nagano, Japan

Introduction and objective. Late onset hypogonadism (LOH) patients suffer from various symptoms, including physical, psychological, and sexual disturbance. The objects of this study are to clarify lower urinary tract symptoms (LUTS) situations in LOH patients, and evaluate the efficacy of testosterone replace therapy (TRT) for LUTS besides LOH.

Methods. The score of international index of erectile function (IIEF 5), international prostate symptom score (IPSS) and aging male symptom (AMS) scale were obtained LOH patients in our out patient clinic. These three scores were compared before and after TRT using 6 mg/day of testosterone ointment (Glowmin) for 3 months in 40 LOH patients.

Results. The 3 parameters of IIEF 5, IPSS, and AMS relieved significantly after 3 months TRT (p = 0.0002, 0.0041, <0.0001, respectively; simple regression). In addition, voiding disturbance have been improved much better than storage disturbance (p = 0.0096 vs. 0.0414) in LOH patients treated by TRT. Thus, TRT is considered to be effective to improve ED, LUTS (especially voiding disturbance) and LOH symptoms of LOH patients.

Conclusions. Our previous report revealed that TRT using testosterone ointment (Glowmin) appeared to be suitable for improvement of LOH symptoms, including psychological, physical, and sexual disturbance. According to the results of this study, the efficacy of TRT for LOH patients was observed not only for LOH symptoms, but also for LUTS.

SY-7-2

Withdrawn

SY-7-3

Correlation among lower urinary tract symptoms, bothersomeness, and QOL in patients with benign prostatic hyperplasia and associated fluctuations with tamsulosin administration

S. Hagikura, Y. Matsukawa, M. Gotoh

Department of Urology, Nagoya University Graduate School of Medicine, Japan

Objective. In providing medical care for patients with benign prostatic hyperplasia (BPH), bother and QOL assessment of patients with lower urinary tract symptoms (LUTS) have recently been suggested as important, in addition to LUTS assessment itself. This study estimated correlations among LUTS, bothersomeness, and QOL and fluctuations in these factors following α1-blocker administration.

Methods. Untreated BPH patients with international prostate symptom scores (IPSS) of eight and over, and with IPSS-QOL scores of two and over, were administered tamsulosin at 0.2 mg/day for 4 weeks. We subsequently estimated IPSS, bothersomeness score for each IPSS item according to a face scale of 5 points, BPH impact index (BII), and IPSS-QOL score before and after 4 weeks of administration. We also analyzed LUTS that might strongly influence QOL using a path analysis model.

Results. Analyzable data were obtained from 198 of the 257 patients enrolled. In IPSS, LUTS evaluation yielded the highest score for slow stream, followed by increased daytime frequency and nocturia. LUTS with the highest bothersomeness score was for slow stream, followed by nocturia. For slow stream, both IPSS and bother scores were highest. We observed dissociations between IPSS and bothersomeness scores in both increased daytime frequency and nocturia. Following tamsulosin administration, IPSS total and individual scores, bother total and individual symptom scores, BII total and individual index scores, and IPSS-QOL score demonstrated significant improvements. Via path analysis, BII items strongly influencing QOL comprised physical discomfort, and bothersomeness. Furthermore, LUTS that strongly influenced QOL comprised feelings of incomplete emptying, urgency, and slow stream.

Conclusions. Tamsulosin administration improved patient QOL by possible mechanisms via improvement in subjective symptoms and bothersomeness. The important symptoms of LUTS that strongly influenced QOL comprised feeling of incomplete emptying, urgency, and slow stream.

SY-7-4

Effect of selective estrogen receptor modulators on cell proliferation and estrogen receptor activities in normal human prostate stromal and epithelial cells: role of estrogen receptors in pathogenesis of BPH

H. Kawashima, H. Nomura, T. Tanaka, S. Tamada, T. Nakatani

Department of Urology, Osaka City University Graduate School of Medicine, Japan

Background. Although estrogens are involved in the pathogenesis of benign prostatic hyperplasia, an issue has not been solved whether the estrogen receptors (ERs) in normal prostate cells are actually activated by ligands causing changes in cell proliferation.

Materials and methods. We added E2 or selective estrogen receptor modulators (SERMs) to the culture of normal human prostatic stromal and epithelial cells, and measured the estrogen receptor (ER) activities by luciferase assays and assessed cell growth by WST-1 assay. The cells were also transfected with ERα- or ERβ-interfering RNA, and the cell proliferation was assessed.

Results. SERMs such as toremifene, raloxifene, and tamoxifen suppressed the proliferation of prostate epithelial and stromal cells whereas anti-androgens did not: the result emphasizes the importance of estrogenic signaling in normal prostate. In prostate stromal cells, the activities of ERs were enhanced by adding E2, and reduced remarkably by adding toremifene. In stromal cells, the proliferation was significantly reduced by transfecting cells with siRNA for ERβ in the medium without E2.

Conclusions. Endogenous estrogen receptors were functional in normal human prostate cells, and the estrogen receptor-mediated pathway plays a central role in the growth of normal prostate epithelial and stromal cells.

SY-7-5

Investigation of chronic kidney disease in benign prostatic hyperplasia

T. Yamasaki, T. Naganuma, Y. Takemoto, T. Nakatani

Osaka City University Medical School, Japan

Background. Despite the high prevalence of BPH and CKD in elderly males, there is limited knowledge on the association between these 2 conditions. Present study is performed to ascertain the prevalence of CKD and co-morbid conditions in BPH patients.

Methods. We performed cross-sectional study in BPH patients to investigate the prevalence of CKD and associated factors. The study population consisted of 170 patients, who were diagnosed as BPH, and had performed medical treatment with Alpha-1 Adrenergic blockers and agreed to enroll in this study from April 2008 to March 2009 in Osaka City University Hospital. We determined the prevalence of CKD and co-morbid conditions in our BPH patients. Using logistic regression analysis, significant risk factors of CKD were explored among the parameters including, age, presence of diabetes mellitus (DM), presence of dyslipidemia, presence of CVD and presence of residual urine. Moreover, we investigate the relationship between eGFR and post-void residual urine volume.

Results. In this study, the overall prevalence of CKD was 43.5% (74/170). Among the 170 BPH patients,49 (28.8%) in Stage 3 and 5 (2.9%) in Stage 4. The prevalence of subjects with eGFR less than 60 ml/min/1.73 m² is 31.7%. Multivariate analysis demonstrated that age, DM and post-void residual urine were significantly independent risk factors. The group with the lowest residual urine volume (Group A/RU < 15 ml) had a significantly higher eGFR than those in the other two quartiles (Group B/15 < RU < 50 ml and Group C/50 < RU). The eGFR correlated with the residual urine volume (r = −0.339, p = 0.0001).

Conclusions. In BPH patients, the prevalence of CKD stage 3 and 4, 5 is about 30%. Multivariate analysis revealed advanced age, DM and post-void residual urine volume are risk factors for CKD in BPH patients.

Poster Session

P-1

Perceived health and other subjectively evaluated physical/mental health of relatively healthy inhabitants aged 85 or over in Japan

T. Kawada¹, S. Suzuki², T. Tsukioka³, S. Iesaki³

¹Department of Hygiene and Public Health, Nippon Medical School, Japan; ²International Eco-health Study Group; ³Gunma Medical Association

Background. Perceived health and self-rated physical/mental health of relatively healthy oldest male inhabitants of Japan was studied to identify its change by aging.

Objective. The health status of the aged was evaluated to know the change of their health status including perceived health as expressed on a comprehensive rating scale.

Methods. A health questionnaire including the Total Health Index (THI) was applied to 205 inhabitants of central Japan, aged 85 years or older. THI is a symptom check list composed of 130 questions. Twelve scale scores were calculated. Response rate was 100%. A question “How is your health?” with five ordinal response options was used to assess perceived health.

Results. The percentages of poor perceived health stratified by three age groups (85–89, 90–94, 95–98) were 7.0% (10/142), 3.6% (2/56), and 0% (0/6), respectively (Cochran-Armitage test, not significant). The mean values of each THI scale score stratified by three age groups did not show significant difference. For example, the mean (standard deviation) of “physical symptoms” stratified by three age groups were 28.5 (6.4), 28.3 (6.5), and 26.2 (5.5), respectively. The mean (standard deviation) of “depressive state” stratified by three age groups were 13.1 (3.6), 13.3 (3.2), and 13.3 (2.3), respectively. Health practice index, scored by sum total of desirable lifestyle using smoking, drinking, sleep, exercise, breakfast, and snack also showed no significant difference by aging [4.68 (0.89), 4.81 (0.81), and 4.83 (0.41)]. There was no trend in the mean value of each THI scale score and HPI by aging (Jonckheere-Terpstra test, not significant).

Conclusions. Old male inhabitants aged 85 or over showed smaller percent of poor perceived health. Each symptoms and mental health status did not become worse by aging. “Healthy inhabitant effect” might contribute to this result. Follow-up study is recommended to know the change of health status.

P-2

Effects of a community-based health promotion program on health promoting behavior and satisfaction with the participation of older persons

O. Pankong, S. Wongkasant

Boromarajonani College of Nursing, Praputhabat, Saraburi, Thailand

The purpose of this study was to investigate the effect of community participatory approach on the health promotion behavior of older persons and satisfaction participatory. Participants were health personals, nurses, older persons, caregivers of Dementia, Health volunteers, and local researchers in a Donput community, Saraburi province Thailand. Participatory action research method, including community meeting for brain storming Problem solving. Project planning and evaluation, was used to obtain data. Data were collected using the health promotion behavior of elderly questionnaire, the satisfaction participatory questionnaire, and participatory observation before and after the experiment. Data were analyzed by using descriptive statistics and t-test.

The major results revealed that:

The older persons group showed significant increased scores of health promotion behavior after the experiment (p < .01).
Other group showed significant increased satisfaction participatory score after the experiment (p < .05) Qualitative data revealed that community concerned and supported the program. In sum, the findings showed that this program was successful.

P-3

Does a stimulating lifestyle postpone the onset of dementia?

S. Paillard-Borg^1,2, L. Fratiglioni^1,2, H.X. Wang^1,2, B. Winblad¹

¹Karolinska Institute, Aging Research Center (NVS), Sweden; ²Stockholm Gerontology Research Center

Objective. To test the hypothesis that an active lifestyle delays dementia onset.

Methods. In the Kungsholmen Project, Stockholm, Sweden, 436 participants were diagnosed as incident cases of clinically definite dementia over 9-year follow-up according to the DSM-III-R criteria. After excluding 224 incident cases at the first 3-year follow-up, 212 (167 women and 45 men) incident cases were left for the analysis. An active lifestyle was measured by the mental, social, and physical component scores estimated in a previous study. The following analyses were used: (1) Linear regression to examine the association between the lifestyle factors and age at dementia onset; (2) General linear models to estimate the mean age at dementia onset in relation to the activity level; and (3) Kaplan-Meier survival curves to visualize the difference between the different activity levels.

Results. Dementia developed at significantly later age in individuals who had a higher level of participation in activities with high physical, mental or social component. When the three components were integrated into an index, we found that the broader the spectrum of participation (higher levels in at least two of the components) the later the age at dementia onset (Beta = 0.62; p < 0.01). The same tendency was seen for men (Beta = 0.62; p < 0.3) but did not reach statistical significance.

Conclusions. The findings suggest that participation in a broad spectrum of activities is beneficial in postponing age at dementia onset.

P-4

Bupropion sustained-release therapy for cigarette smoking cessation

K. Moon¹, Y. Kim², S. Lee²

¹Orthopedic Medicine, Pusan National University Hospital, Pusan, Republic of Korea; ²Family Medicine, Pusan National University Hospital

Background. Smoking is one of the most common forms of drug use. Smoking effect on cardiovascular risk and have carcinogenic effects. Therefore, the effective counseling and medication treatments to patients who use tobacco are most important factor for disease prevention. In this study, we investigated the effect of bupropion sustained-release (bupropion SR) for the treatment of smoking.

Methods. 33 male cigarette smokers who have not convulsion, brain damage, bulimia nervosa and anorexia nervosa, included into this cross-sectional study. We assessed stage of change based on the transtheoretical model of Prochaska. Subjects who considered quitting smoking were included. Subjects were asked about the average number of cigarettes smoked per day and total years of smoking. All subjects received bupropion SR titrated to 150 mg by mouth twice daily for 4 weeks along with behavioral therapy. Self-reported smoking abstinence was recorded.

Results. Mean age of subjects was 49.8 years. Mean number of cigarettes smoked per day was 27.0 cigarettes/day. Twenty-four subjects (72.7%) stopped smoking at 1 month. There are no significant difference in age and daily number of cigarettes between smoking -abstinent subjects and nonabstinent subjects (p > 0.05). There are no serious adverse effects associated with bupropion SR.

Conclusions. Monotherapy with bupropion SR may be effective treatment for smoking abstinence.

P-5

Effects of virtual reality-based exercise program on the physical performance, muscle strength and balance in older men

C.H. Song

Department of Physical Therapy, Sahmyook University, Republic of Korea

Physical inactivity is common among older men due to age related changes that are decreasing muscle strength, balance, and physical performance. Virtual reality (VR) training has been used successfully to rehabilitate functional balance and mobility in elderly subjects. This study was aimed at determining the effect of virtual reality-based exercise program on the physical performance, muscle strength and balance in older men. Twenty-six older men (age = 68.40 ± 4.02 years) performed an exercise program twice a week during 8 weeks, at the rehabilitation unit. VR-based exercise program is compromised of VR program and treadmill training. VR program was performed by playstation eyetoy play that provided visual and auditory feedbacks as well as movements of upper and lower extremities for 30 min. Treadmill training was instructed subjects to continue walking for as long as they felt comfort for 30 min. Outcome Measures included Timed up and go test (TUG), 6-min walk test, Functional reach test, sway during quiet stance in eye open and eye closed condition, and manual muscle strength testing of the knee and ankle. The measures of physical performance, muscle strength, balance were recorded before and after exercise. Physical performance was improved significantly after the completion of the VR-based exercise program (p < 0.05). Muscle strength showed a significant increase in knee extension and flexion, and ankle plantar flexion (p < 0.05). Postural sway for balance during quiet stance was decreased significantly (p < 0.05). VR-based exercise program was showed the improvement on the physical performance, muscle strength, and balance in older men. This exercise program is both effective and interesting for this age group of men.

P-6

Is masculinity trait associated with better psychological wellbeing? Results from the Subang aging male (SAM) study

S.F. Tong¹, W.Y. Low², H.M. Tan^2,3, E.M. Khoo², B.C. Lee¹, V.K.M. Lee⁴, C.J. Ng²

¹University Kebangsaan Malaysia, Malaysia; ²University of Malaya; ³Sime Darby Medical Centre; ⁴International Medical University Malaysia

Background. Masculinity traits have been implicated for negative health seeking behavior and poor health among men. We explored whether this assumption applies to psychological wellbeing of community urban men in Malaysia.

Methods. We conducted a community-based cross sectional study in 2008. Participants from the original cohort of 1046 men in the year 2006 men's health survey and local community in Subang were invited to participate. The participants completed a series of questionnaires with assistance: demographic characteristics, Depression Anxiety Stress Scale (DASS), and Personality Attributes Questionnaire (PAQ). A higher DASS score signifies poorer psychological wellbeing. Significant anxiety, depression and stress were defined as moderate to very severe categories in each of the subscale in DASS. The gender-role of men was classified into masculine, feminine, androgyny, and undifferentiated based on PAQ scores.

Results. 1007 men completed the survey, consisting of 52.5% Chinese men, 22.9% Malay, and 21.8% Indian. Mean age was 56.6 ± 8.3 years. The median monthly income was RM4500 (US$1300) and 62.1% were employed. The prevalence of significant anxiety (21.2%) was higher than depression (11%) and stress (6%). 24.9% of men were masculine, 5.8% feminine, 20.9% androgyny, and 47.7% undifferentiated in their gender-role orientation. Higher masculinity scores were negatively correlated with depression (r = −0.25, p < 0.001), anxiety (r = −0.18, p < 0.001) and stress score (r = −0.20, p < 0.001). Masculine and androgyny gender-role were associated with lower depression (F = 22.2, df = 3, p < 0.001), anxiety (F = 11.4, df = 3, p < 0.001) and stress (F = 14.1, df = 3, p < 0.001) subscale score of DASS.

Conclusions. High masculinity score may act as a protective buffer to psychological wellbeing.

P-7

Olanzapine increase the severity of seizures in elderly mice

T. Çelik, E. Akdag, K. Ulusoy, E. Macit

Department of Pharmacology, Gülhane Medical Schools, Ankara, Turkey

The present study was designed to investigate the effects of olanzapine, an antipsychotic agent which is often used in psychotic disorders in Alzheimer Disease, on pentylenetetrazole (PTZ)- and maximal electroconvulsive shock (MES)-induced seizures in elderly and adult mice. 30 minutes after Olanzapine 1 mg/kg or saline was administered to mice 24 months (elderly) and 6 months (adult) of age, PTZ (80 mg/kg) was injected intraperitoneally. Immediately afterward, times of onset of the first myoclonic jerk (FMJ), generalized clonic seizures (GCS), and tonic extension (TE) were recorded. In the MES groups, we used the MES protocol to induce convulsions characterized by tonic hindlimb extension. Similarly, 30 min after olanzapine (1 mg/kg) or saline administration, an electroshock was evoked by ear-clip electrodes to induce convulsion. Olanzapine (1 mg/kg) had no significant effect on the time of onset of FMJ, GCS, or TE induced by PTZ. In the MES induced groups elderly mice had longer duration of GCS then the adult ones and this prolongation is reduced by olanzapine (1 mg/kg). The duration of TE is not different between elderly and adult mice, but olanzapine in elderly mice significantly prolonged the duration of TE than the adult mice. Our results suggest that elderly mice are more susceptible to seizures and antipsychotic olanzapine changes the severity and duration of seizures in elderly mice.

P-8

A randomized crossover trial of amoxapine and vitamin B12 in the treatment of retrograde ejaculation

K. Nagao, T. Tai, H. Kobayashi, F. Yamabe, N. Tanaka, K. Nakajima, H. Hara, K. Miura, N. Ishii

Department of Urology, Toho University School of Medicine, Japan

Introduction. Imipramine and pseudoephedrine are commonly used to treat retrograde ejaculation (RE) however, the overall success rate for these drugs is no greater than 50%, and adverse effects are frequent. In the treatment of depression, amoxapine results in far fewer adverse effects than imipramine.

Patients.Patient age ranged from 28 to 54 years (mean, 40.8) and the duration of RE ranged from 1 month to 25 years (mean, 4.5). The cause of RE was diabetes mellitus in 15 patients, rectal carcinoma in 6 patients, depression in 1 patient, and unknown in 3 patients. Fourteen men were unmarried; 11 were married.

Methods. A diagnosis of RE was based on the presence of spermatozoa in postmasturbatory urine. We conducted a randomized crossover trial of amoxapine and vitamin B12 in the treatment of RE. The patients medical record numbers were used for randomization. The 13 patients with an even number took amoxapine 50 mg daily before bed for 1 month after a washout period of 1 week, the medication was changed to vitamin B12 500 μg thrice daily after meals for 1 month. The 12 patients with an odd numbered medical record were placed on the reverse regimen. The primary endpoint was ejaculation of white fluid (semen), as reported by patients, more than once during a 1 month treatment period.

Results.The success rate for amoxapine was 84% (21 of 25 patients), whereas the success rate for vitamin B12 was 16% (4 of 25 patients). Amoxapine was significantly (P < 0.0001) more effective than vitamin B12 in the treatment of RE. The only observed side effect of amoxapine treatment was sleepiness, which was reported in 4% (1 case) of participants; no side effects were noted with vitamin B12 treatment. Spontaneous pregnancy occurred in the partner of one participant.

Conclusions. Our findings indicate that amoxapine is more effective than vitamin B12 in the treatment of RE.

P-9

Treatment of ED with tadalafil in elder BPH patients

V. Kamarauskas

Clinic of Urology and Andrology, Lithuania

Although around 70% of men aged 65–75 years are suffering from BPH and have complete ED. Some men assume that ED is a natural part of aging process.

The aim of this study was to compare the efficacy of tadalafil in BPH patients before open prostatectomy and after surgical treatment.

Material and methods. 74 patients with BPH suffering from ED were treated with tadalafil once a week 20 mg, 38 patients before surgical treatment and 36 patients after open prostatectomy.

Results of examination were made after 5 month of treatment for each patient. All patients before and after treatment were examined by penal doplerografy and tested by IIEF -5 version Vascular insufficiency was obtained in 21 (76.31%) in first group and 28 (77.77%) in the second group. IIEF-5 score show several ED-16 (42.1%), moderate ED-14 (36.87%), mild ED-8 (21.1%) in first group and severe ED-(50%), moderate ED-12 (31.58%), mild ED-7 (18.42%) in second group. After treatment vascular insufficiency in first group was 16 (42.1%) and 19 (52.77%) in second group respectively. IIEF-5 score show several ED-12 (31.5%), moderate ED-10 (26.32%), mild ED-16 (42.18%) in first group and 11 (30.56%), 8 (22.22%), 17 (47.22%) in second group. Assessment of men partners before treatment in first group was excellent – 7 (18.43%), good – 9 (23.68%), pure – 22 (57.89%), in the second group 6 (16.66%), 8 (22.22%), 22 (61.12%), respectively. After treatment results show excellent – 14 (36.84%) good – 14 (36.84%), and poor – 10 (26.32%) in first group and excellent – 17 (47.22%), good – 10 (27.78%), and poor – 9 (25.0%) in second group.

Conclusions. Tadalafil treatment significantly helps in BPH patients after open prostatectomy Tadalafil treatment markedly improve the quality of life for patients partners.

P-10

Clinical characteristics of patients who underwent penile augmentation procedure in Korea

S.K. Byon, S.Y. Jang, W.H. Lee, J.H. Moon

LJ Genitourinary Surgery Institute, Seoul, Republic of Korea

Object. This study was conducted to evaluate the clinical characteristics of Korean patients who penile augmentation procedure was performed on.

Materials and methods. From June 2006 to September 2007, 230 penile augmentation procedures were performed. We examined the clinical characteristics (age, married status, penile length and girth, circumcision) of the patients.

Result. The mean age was 39.5 year (range, 21–62) and the number of married patients and circumcised was 156 (67.8%), 154 (66.9%), respectively. The mean preoperative flaccid circumference was 8.2 cm (range, 5.8–10.5) and flaccid length 6.0 cm (range, 3.0–10.8). After penile augmentation, the mean circumference and length was 10.4 cm (range, 8.2–12.4), 7.3 cm (range, 5.1–10.6), respectively.

Conclusion. The flaccid penile circumference and length of Korean adults who had the penile augmentation procedure, was 8.2 and 6.0 cm, respectively. The most common was in men, in the age range of their 30's and 40's and married men. Compared with average Korean circumference and length (8.3, 7.4), It is common for men who were in the lesser than normal range.

P-11

Comparison of penile augmentation procedure using Lyoplant® and SureDerm™ implant

S.K. Byon, S.Y. Jang, W.H. Lee, J.H. Moon

LJ Genitourinary Surgery Institute, Seoul, Republic of Korea

Object. Because auto graft dermal fat grafts for penile augmentation require a donor site and, therefore, incision and scar, there are various ways of enlarging the penis to reduce any disadvantages. So we compared the results of two materials widely used in Korea instead of auto graft during the penile augmentation procedure [Lyoplant® (bovine collagen derivative) and SureDerm™ (acellular allodermal graft)].

Materials and methods.From June 2006 to September 2007, 230 penile augmentation procedures were performed using Lyoplant® (117, Group I) and SureDerm™ (113, Group II). We compared the age, preoperative and postoperative flaccid circumference and length and the complications between the two groups.

Result. The two groups did not show any significant differences for their mean age (Group I: 39.6 ± 7.31 year, Group II: 39.5 ± 7.5 year), preoperative circumference and length (Group I: 8.61 ± 0.82 cm, 6.32 ± 1.48 cm, respectively, Group II: 7.90 ± 0.85 cm, 5.80 ± 0.86 cm, respectively) and the postoperative circumference and length (Group I: 10.75 ± 0.70 cm, 8.04 ± 1.02 cm, respectively, Group II: 10.20 ± 1.43 cm, 7.50 ± 1.08 cm, respectively). There were only minor and temporary complications in both groups (temporary swelling of the penis four in Group I, six in Group II, delayed wound healing two in Group I, three in Group II).

Conclusion. Our results suggest that the penile augmentation procedure using Lyoplant® and SureDerm™ can be performed safely and effectively instead of using auto graft.

P-12

Dapoxetine in treatment of premature ejaculation: a systematic review

Q. Dong, Q. Wei, Y. Mao, Y.B. Wang

West China Hospital of Sichuan University, China

Objectives. To assess the effectiveness and safety of dapoxetine in the treatment of premature ejaculation.

Methods. The Cochrane Library, MEDLINE, EMBASE and CNKI, CBM, VIP between January 1979 and March 2009 were searched. Both English and Chinese studies were included in the review if they were RCTs (randomized controlled trails) involving men with PE who were treated with dapoxetine.

Results. 5 RCTs involving 4951 patients were included in the Meta analysis. 3 articles are A grade and two are B grade according to the quality evaluation of methodology. Intravaginal Ejaculatory Latency Time (IELT), Patient-reported Global Impression of change (PGI), Satisfaction with sexual intercourse (SSI), Perceived control over ejaculation (PCOE), Personal distress related to ejaculation (PDRE) were used to assess. Meta analysis based on included studies showed that: after treated with dapoxetine for 9–24 weeks, (1) the difference of the IELT between treatment and control groups was statistically significant, [Z = 15.84 (p < 0.001), WMD (95%CI) is 1.38 (1.21, 1.55)]; (2) the difference of the PGIs of development in PE between 2 groups was statistically significant, [Z = 7.91 (p < 0.001), OR (95%CI) is 3.56 (2.60, 4.88)]; (3) the difference of the patients' satisfaction rate between 2 groups was statistically significant, [Z = 4.31 (p < 0.001), OR (95%CI) is 3.85 (2.08, 7.10)]; the difference of the SSI between 2 groups was statistically significant, [Z = 15.92 (p < 0.001), WMD (95%CI) is 0.55 (0.48, 0.62)]; (4) the difference of the PCOE between groups was statistically significant, [Z = 9.32 (p < 0.001), OR (95%CI) is 2.87 (2.30, 3.58)]; (5) the difference of the patients' changement of personal distress related to ejaculation between groups was statistically significant, [Z = 7.66 (p < 0.001), OR (95%CI) is 2.02 (1.69, 2.42)].

Conclusions.Dapoxetine would improve the symptoms of PE, prolong IELT, and well tolerated over 9–24 weeks in patients and significantly improved all patient PROs and the PGIs of PE.

Keywords:Dapoxetine, PE (premature ejaculation), SSRI (selective serotonin reuptake inhibitor), Meta analysis

P-13

Intracavernous transplantation of bone marrow-derived mesenchymal stem cells (MSCs) improves erectile function of diabetic rats through paracrine and consequent trigger of endogenous repair mechanism

Y. Dai¹, X. Qiu¹, X. Han²

¹Department of Urology, Nanjing Drum Tower Hospital, China; ²Nanjing University School of Medicine

Aim. This study aims to demonstrate that if there exists other mechanism to improve erectile function in diabetic rats being transplanted with MSCs.

Methods.Syngenic Sprague-Dawley rat MSCs were separated, ex vivo expanded and identified. Diabetes was induced by streptozocin (STZ) intraperitoneal injection in SD rats. Eight weeks after STZ, Passage 3 MSCs labeled with CM-Dil were transplanted into the penis of diabetic rats. Erectile function was assessed by cavernosal nerve electrostimulation respectively at the phases of 1, 2 and 3 weeks after transplantation. Numbers of MSCs, SMA positive smooth muscle cells, vWF positive endothelial cell and CD34 positive stem cell were determined by histological analysis. RT-PCR was used to determine the expression of many growth factors, including VEGF, IGF-1, bFGF, HGF, TGF-beta, and PDGF, in the corpus cavernosum of transplanted rats. The apoptotic cells in the corpus cavernosum were determined using Tunnel staining.

Results. Intracavernous administration of MSCs improved erection of diabetic rats at the phases of 2 and 3 weeks after transplantation. The increased erectile function was associated with up regulation of VEGF, IGF-1, bFGF, and TGF-beta in corpus cavernosum. MSCs could survive in the corpus cavernosum for at least 3 weeks. There were no statistical differences between erectile function at the phases of 2 and 3 weeks in diabetic rats transplanted. Tunnel staining shows that apoptosis in corpus cavernosum of transplanted rats is significantly suppressed compared with diabetic controls. Immnuohistochemistry analysis revealed that SMA positive smooth muscle cells and vWF positive endothelial cells significantly increased in transplanted rats. Also, the number of CD34 positive cells increased in corpus cavernosum of these rats.

Conclusion. Intracavernous transplantation of MSCs can improve erectile function of diabetic rats. The therapeutic effects of MSCs result in secretion of many growth factors by MSCs and consequent trigger of endogenous repair mechanism.

P-14

Successful treatment of posttraumatic high-flow priapism with superselective arterial embolization: 2 cases report

X. Junping

Department of Urology and Andrology, The First Affiliated Hospital, Xi'an Jiaotong University, School of Medicine, China

Objective. High-flow priapism resulting from uncontrolled arterial inflow into the cavernosum describes a persistent erection lasting more than 4 h that is not induced by sexual stimulation. Here, we report our experience with superselective transcatheter embolization in the treatment of high-flow priapism.

Methods. Between 2007 and 2009, 2 men presented with posttraumatic high-flow priapism, the diagnosis was based on colour Doppler ultrasound, cavernous blood gas analysis with arterial blood saturation levels, failed medical or surgical therapy and superselective pudendal arteriography. The superselective transcatheter embolization was performed with Gelfoam and was unilateral in one case, bilateral in the other cases.

Results. Detumescence occurred in a few hours in two cases. Transient erectile dysfunction was observed in both cases, 1 year later, the patient's erectile function was completely restored, and there had been no recurrence of the priapism.

Conclusions. Superselective arterial embolization could be an alternative treatment for posttraumatic high-flow priapism and erectile function could be recovered weeks later.

P-15

The effect of cigarette smoke on erectile tissue in rats

T. Wu

Urology Department of Renmin Hospital of Wuhan University, China

Aim. To investigate the effect of cigarette smoke on erectile tissues and evaluate the effects of GSH.

Method. Twenty-four male SD rats were divided randomly into three groups (n = 8, each): Group A were used as control. Group B were exposed to cigarette smoke and Group C were exposed to cigarette smoke and received daily intramuscular injection of GSH. 60 days later, the rats were sacrificed and excised erectile tissues. The cell apoptosis was detected by TUNEL method, and using streptavidin-biotin peroxidase (S-P) method to detect the expression of Bcl-2 and Bax.

Results. There were no statistical difference in three groups (P > 0.05) for Bcl-2 expression and highly statistical difference in three groups (P < 0.01) for Bax expression by Non-parameter Test. Apoptosis Index (AI) had highly statistical difference in three groups (P < 0.01) by One-Way ANOVA. The correlation coefficient in AI and Bcl-2 expression was −0.444 (P < 0.05) by Pearson analyse and that in AI and Bax expression was 0.738 (P < 0.01).

Conclusions. Cigarette smoke induced highly apoptosis in rats erectile tissue, leading to erectile dysfunction (ED).

Keywords:Cigarette smoke, erectile tissue, erectile dysfunction, apoptosis, Bcl-2/Bax

P-16

One-stage direct vision internal urethrotomy and penile prosthesis implantation for severe erectile dysfunction with urethra stricture

W.D. Song¹, Y.G. Wu², Y.M. Yuan¹, J. Peng¹, Z.C. Zhang¹, B. Gao¹, X.Y. He¹, Z.C. Xin¹

¹Andrology Center, Peking University First Hospital, China; ²Department of Urology, Chinese PLA General Hospital

Objective. The safety and efficacy of one stage direct vision internal urethrotomy and penile prosthesis implantation (DVIU/PPI) in severe erectile dysfunction (SED) patients combined with urethra stricture were investigated.

Patients and methods. Among 108 cases of SED treated with PPI from June 2002 to May 2007, five patients with urethra stricture caused by pelvic fracture and urethra injuries were underwent DVIU/PPI (AMS700CXM) according to patient's requirements with informed consent. Patients aged 20–35 years old and had been treated by urethrourethral anastomy previously. The erectile function and the urinary function were evaluated by assessing the International index of erectile function (IIEF5), the quality of life index (QOL), the maximum urinary flow rate (Qmax) and the urethrography pre- and post-operation. The duration of following up were 18–30 months.

Results. Patients were confirmed as vasculogenic ED in 2 cases and vasculogenic combined with nurogenic ED in 3 cases, and the mean length of urethral stricture was 10.00 ± 3.97 mm. All of 5 patients were successfully treated by one-stage DVIU/PPI under spinal anesthesia, and satisfied with their sexual activity and urinary function postoperation. The mean scores of IIEF5, Qmax, QOL, and the diameter of the urethra stricture postoperation were 24.4 ± 0.55, 19.54 ± 4.80 ml/s, 1.80 ± 0.84, and 7.16 ± 0.43 mm respectively, which were significantly improved compared with those previous the surgery (P < 0.05). No severe complications were noted in all of five patients.

Conclusions. One-stage DVIU/PPI was an effective and safe procedure for treating patients suffered SED combined with urethra stricture.

Keywords:Erectile dysfunction, urethra stricture, urethrotomy, penile prosthesis

P-17

Study on relation of erectile dysfunction and symptomatic benign prostate hyperplasia

J.H. Deng¹, L.P. Yang², J.B. Hu², Z.Q. Ye¹

¹Tongji Hospital, Tongji Medical College, Hua Zhong University of Science and Technology, China; ²Department of Urology, The First Municipal People's Hospital, China

Objective. To Study on relation of erectile dysfunction and symptomatic benign prostate hyperplasia.

Methods. The enrolled patients with symptomatic benign prostate hyperplasia were evaluated using of International Index Erectile Function. According the value and diagnosis criteria of IIEF-5, the patients were divided into four groups: Erectile Function normal group, slight abnormal group, moderately abnormal group, and sever abnormal group. To research the inner correlation between ED and BPH, the value of IPSS, Qmax and volume of prostate were comparison among four groups with analysis of variance (F test).

Results. The total eighty patients with symptomatic benign prostate hyperplasia were enrolled, age range form 52–91 years with average 71.4 years. According the value and diagnosis criteria of IIEF-5, there are six patients in Function normal group, 20 patients in slight abnormal group, 22 moderately abnormal group, and 32 patients in sever abnormal group, respectively. The morbidity of ED is 93%. The value (x ± s) of IPSS among four groups are 16.67 ± 4.04, 21.6 ± 7.89, 21 ± 7.06, 23.06 ± 6.56, of Qmax are 12.34 ± 2.28, 8.91 ± 7.67, 5.4 ± 4.39, 8.93 ± 4.49, of volume of prostate are 34.71 ± 10.48, 76.61 ± 29.41, 91.93 ± 41.35, 69 ± 34.83, respectively. The significant variance was discovered in IPSS among four groups.

Conclusions. There are high incidence rate of ED in the patient with symptomatic benign prostate hyperplasia concomitantly; furthermore, there are some extent correlation between the sever degree of ED and the sever degree of low urethral symptoms.

Keywords:Erectile dysfunction, benign prostate hyperplasia, correlation

P-18

MSCs modified with AKT1 and/or VEGF gene can promote erectile function

J.H. Liu, G.Y. Song, R.B. Chen, T. Wang, S.G. Wang, Z.Q. Ye

Department of Urology, Tongji Hospital, Tongji Medical College of Huazhong University of Science and Technology, China

Objective. To evaluate whether mesenchymal stem cells (MSCs) can be induced to differentiate directly in rat penis, we hypothesize that cell-based replacement therapy with MSCs can enhance endothelial function and promote the regeneration of penile smooth muscle, which will possibly improve erectile responses.

Materials and methods. MSCs from bone marrow of one month rats were isolated and ex vivo expanded, these were then subjected to immunocytochemistry for specific markers of stem cells, to improve survival rate and differentiation directly in vivo of MSCs, MSCs were modified with akt1 and/or VEGF gene, for in vivo experiments, MSCs that were labeled genetically by an expression construct for green/red fluorescent protein. The aged rats with erectile dysfunction (ED) were divided five groups, were intracavernosally injected respectively with PBS, MSCs, akt1 modified MSCs, VEGF modified MSCs, akt1 and VEGF modified MSCs. In 7, 14, and 21 days after injection, the differentiation and localization of MSCs were observed by fluorescence microscope. The total and ser phosphorylated in 1179 site of amino acid sequence eNOS expressing level was tested by Western blot analysis. The peak and total ICP of rats that underwent cavernosal nerve stimulation were measured to assess erectile function.

Results.There were no inflammatory cells in rat corpora cavernosa observed under microscope; MSCs modified with akt1 and/or VEGF gene were able to differentiate in rat penis evaluated by immunofluorescence and immunohistochemistry observation; after injection, in the group with the respective use of MSCs modified with akt1 or VEGF gene, not only were the expressing level of both the total eNOS and phosphorylated eNOS increased but also the total and peak of ICP were increased in aged rat penis by compared with PBS treated group, this change was more significant in the group with MSCs modified with akt1 and VEGF gene.

Conclusions.According to our experiment results, akt1 could increase the survival rate of MSCs; VEGF might induce directly differentiation, localization, and improve endothelial function in penis. Moreover, the application of MSCs modified with akt1 and VEGF gene could improve erectile function more significantly than simply use of MSCs, MSCs modified with akt1 or VEGF gene. Our results suggest that the use of MSCs modified with akt1 and VEGF gene might be an effective and safe method for the treatment of ED.

P-19

Diagnosis and treatments of ED according its different degrees Combining CDFI

X.J. Xuan¹, P. Sun², J.B. Teng³, H. Mei⁴

¹Division of Urology, The Sun Yat-sen Memorial Hospital Affiliated to Sun Yat-sen University, China; ²Division of Urology, Shandong Provincial Hospital, Jinan, China; ³Shandong Provincial Medical Imaging Institute, Ji’ nan, China; ⁴Division of Urology, The First Affiliated Hospital, Sun Yat-sen University, Guangzhou, China

Objective. To investigate a reasonable pattern of goal diagnosis and therapy for male erectile dysfunction.

Materials and methods. 198 male patients suffered with erectile dysfunction were divided into 4 groups by their penial stiffness based on Schramek penial stiffness degree after colour Doppler flowimaging (CDFI) and intracavernosa vasoactive agent injection (ICI) with papaverine 60 mg and prostaglandian E₁ 10 μg. The therapeutic methods such as antibiotics to ED patients with prostititis, sexual behavior therapy, sildenafil, vacuum constriction device (VCD), vena fistula repairing operation, prosthesis implantation, and enhanced external counterpulsation (EECP) were recommended to patients according to their different penial stiffiness degree and their different inclinations. All data were analyzed with SPSS 12.0® for Windows statistical software. Measurement data were show by [xbar] ± SD. T-test, χ²-test, F-test and Duncan's new multiple range method were performed. P < 0.05 was regarded as statistically significant.

Results. 143 cases were enrolled in the V degree group, 23 in the IV degree group, 18 in the III degree group and 14 in the II degree group after ICI. Before ICI, there was no significant difference in the cavernosa artery peak systolic velocities (PSV), end diastolic velocities (EDV), resistant indexes (RI), the dorsal artery PSV, EDV, RI and the deep dorsal vein velocity (V) (P > 0.05). After ICI, the cavernosa artery PSV, EDV, and RI were significant different (P < 0.05), whereas other indexes were not significant different (P > 0.05). We treated the patients according to their inclination and the different methods which they selected. The selective goal oriented therapy increased the satisfactory rate to 91.41%.

Conclusions. This oriented therapeutic method increases the clinic satisfactory rate of ED greatly and is also a reasonable pattern of goal diagnosis and therapy for male erectile dysfunction. Enhanced external counterpulsition (EECP) is a new, and effective method to treat diabetes mellitus erectile dysfunction, but it need further research.

P-20

Effects of renewal SS-cream on the bulbocavernosus reflex (BCR) in rabbits

L. Tian, Y.G. Wu, Z. Jin, Y.C. Zhu, X.C. Qin, Y.Q. Gong, Z.C. Xin

Andrology Center of Peking University First Hospital, Peking University, Institute of Urology Peking University, China

Objective. To investigate the efficacy of Renewal SS-cream on premature ejaculation as demonstrated by the bulbocavernosus reflex (BCR) in rabbits.

Methods. Sixty male New Zealand white rabbits (weights: 2.5–3.0 kg) were divided into 3 groups randomly. Either Renewal or original SS-cream or placebo (provided by CJ Co. LTD) was topically applied to the glans penis of rabbits in a double-blind manner. The bulbocavernosus reflex (BCR) was elicited by electrical stimulation of the glans penis. The latency of BCR (BCRLT) and the amplitude of BCR (BCRAP) were recorded on an electrophysiograph (Poseidomn, Shanghai, China) before and at 10, 30, and 60 min after application of the test agents. Representative tracings of BCRLT and BCRAP were recorded and analyzed.

Results. The mean BCRLT values were significantly prolonged in post-application groups of SS-cream and Renewal SS-cream, compared with those in pre-application and placebo groups (p < 0.05). There was no significant difference (p > 0.05) in efficacies between SS-cream and Renewal SS-cream groups. The mean BCRAP showed decreasing tendencies following application of SS-cream and Renewal SS-cream; however, they were not significantly different (p > 0.05). Both of original SS-cream and Renewal SS-cream prolong the BCRLT after their application to the glans penis in rabbits.

Conclusions. The results indicate that they have local desensitizing effects on the sensory receptors of the dorsal nerve of the glans penis and may help control the ejaculatory reflex in patients with premature ejaculation.

Keywords:Renewal SS-cream, premature ejaculation, BCR, rabbit

P-21

Erectile function after superselective arterial embolization with microcoils in patients with high-flow priapism

B.X. Liu, Z.C. Xin, Y. Yuan, J. Peng, J. Zhang, B. Gao, Z.C. Zhang, Y.H. Zou

Andrology Center, Peking University First Hospital, China; Institute of Urology, Peking University, Beijing, China

Objective. To observe the erectile function after superselective cavernous artery embolization with microcoils in high-flow priapism patients.

Methods. Eight cases with high-flow priapism were diagnosis by intracavernosal gas analysis, color duplex sonograph and selective pudendal arteriography with the presence of arteriocavernous fistula. Superselective cavernous artery embolization with microcoils were performed in all patients with successful detumescence. The 5-item International Index of Erectile Function (IIEF-5) and the Sexual Life Quality Questionnaire (SLQQ)-Quality of Life (QoL) domain were used to access the erectile function before the onset of priapism, 6 months and 18 months after embolization.

Results. The IIEF-5 score after 6 months and 18 months embolization were 19.57 ± 5.35 and 19.14 ± 5.24, respectively, with no significant difference compared with the IIEF-5 score before the onset of priapism (19.86 ± 4.84) (P > 0.05). The SLQQ-QOL score after 6 months and 18 months embolization were 34.14 ± 7.73 and 32.43 ± 8.66 with no significant difference compared with before the onset of priapism (P > 0.05).

Conclusions. Superselective cavernous artery embolization with microcoils in patients with high-flow priapism is a safe and effective method without significantly influencing erectile function in younger potential patients.

Keywords:High-flow priapism, microcoil, arterial embolization, erectile function

P-22

The effect of cigarette smoke on erectile tissue and protective effects of Γ-GSH

X.B. Liu, T.P. Wu, O.Y. Hai, X.S. Zhan, N. Qian

Department of Urology, Renmin Hospital of HuBei Province, WuHan University, China

Aim. Cigarette smoke has an adverse effect on erectile tissues through many kinds of ways, but the knowledge of its mechanism and therapy is still limited. To investigate the effect of cigarette smoke on erectile tissues apoptosis and evaluate the effects of γ-GSH.

Main outcome measures. Expression of Bcl-2/Bax and Apoptosis Index were determined.

Method. Twenty-four male SD rats (8 weeks old) were divided randomly into three groups (n = 8, each): Group A were used as control. Group B were exposed to cigarette smoke and Group C were exposed to cigarette smoke and received daily intramuscular injection of γ-GSH. 60 days later, the rats were sacrificed and excised epididymis tissues. The cell apoptosis was detected by TUNEL method, and using streptavidin-biotin peroxidase (S-P) method to detect the expression of Bcl-2 and Bax.

Results. There were no statistical difference in three groups (P > 0.05) for Bcl-2 expression and highly statistical difference in three groups (P < 0.01) for Bax expression by Non-parameter Test. Apoptosis Index (AI) had highly statistical difference in three groups (P < 0.01) by One-Way ANOVA. The correlation coefficient in AI and Bcl-2 expression was -0.444 (P < 0.05) by Pearson analyze and that in AI and Bax expression was 0.738 (P < 0.01).

Conclusions. Cigarette smoke induced highly apoptosis in rats erectile tissue, which broke down the balance of smooth muscle and connective tissue, leading to erectile dysfunction (ED). And decreases in the synthesis of eNOS because of the deduction of the vascular endothelial cells may lead to ED. γ-GSH can improve the degree of apoptosis, providing an alternative route in erectile disfunction treatment.

Keywords:Cigarette smoke, erectile tissue, erectile dysfunction, apoptosis, Bcl-2/Bax, γ-GSH

P-23

Effects of Icariside II on intracavernosal pressure and systematic arterial blood pressure of rat

J. Zhang, T. Liu, W.R. Li, W.S. Cui, X.C. Qin, Y.Q. Gong, Z.C. Xin

Andrology Center, Peking University First Hospital, Peking University, China

Objective. Icariside II was isolate from natural herbal medicine and to realize the effect of Icariside II on erectile function, the effect of Icariside II on erectile function (ICP) and the influence on mean arterial pressure (MAP) and its mechanism were investigated in in vivo study.

Methods. Adult male Wistar rats (n = 145) used for in vivo study. The rat corpora cavernosa (CC) and left carotid artery was isolated unilaterally, a 26G needle catheter was inserted into the left CC to monitor the intracavernou pressure (ICP) and give drug administration. Another catheter was placed into the carotid artery to monitor MAP. Rat cavernous nerve (CN) was identified for electro stimulation. Different concentrations of Icariside II was administrated intracavernosally, and the ICP and MAP were recorded during electric stimulation on CN. Icariin, Sildenafil, and Papaverine were used as positive controls. The effects of soluble guanylate cyclase inhibitor H-Citation1,Citation2,Citation4 oxadiazole [4,3,-a] quinoxalin-1-one (ODQ), nitric oxide syntheses (NOS) inhibitor Nω-nitro-L-arginine (LNNA) and nitric oxide formation inhibitor methylene blue (MB) on Icariside II (10⁻⁴ mol/L) induced ICP changes were also investigated.

Results. Icariside, Icariin, Sildenafil, and Papaverine increased the ICP in a dose-depended manner (P < 0.01), and Icariside, Icariin, and Sildenafil did not influence the MAP (P > 0.05). However, Papaverine at the concentration of 10⁻⁶ mol/L significantly reduced MAP (P < 0.05). EC50 of Icariside II, Icariin, Sildenafil, and Papaverine on ICP/MAP were 1.69 μmol/L, 4.12 μmol/L, 0.381 μmol/L, and 10.8 μmol/L, respectively. LNNA, ODQ, and MB significantly inhibited ICP induced by Icariside II (P < 0.01).

Conclusions. These results suggested that Icariside II could enhancing erectile function without influence on MAP by specific activation NO-cGMP signal pathway on CC.

P-24

Empirical study on treating ED with Zhenxiong granula

W. Gao, C. Yu

Andriatrics, HuBei Provincial Hospital of Traditional Chinese Medicine, China

Objective. Zhenxiong granula is epurated and elaborated with naturally occurring drugs including Epimedium Herb, Dodder Seed, Barbary Wolfberry Fruit, and so on by scientific methods, which is a effective prescription developed by author according to the theory of integrated traditional and western medicine to treat ED. The purpose of this investigation is to investigate the mechanism of action on treating ED with Zhenxiong granula.

Methods. (1) Erection experiment. 30 SD rats (male) were divided into 3 groups random, normal control, castration control group, and castration with Zhenxiong granula group, the change of eclipse period of erection were observed. (2) Renal deficiency experiment. 30 SD rats (male) were divided into 3 groups random, normal control, castration control group, and castration with Zhenxiong granula group, the change of organ index number of accessory sex gland were observed. (3) 20 SD rats (males) were divided into two groups random, the influence on eclipse period of Pounce-Catch, eclipse period of ejaculation by Zhenxiong granula were observed. (4) 20 SD rats were selected random to accept toxicity test.

Results. (1) Compared with the normal control, there is significant difference (P < 0.01=) on the eclipse period of erection and organ index number of accessory sex gland in the castration control group; (2) Eclipse period of erection in castration with Zhenxiong granula group is shorter than that in castration control group (P < 0.01=); (3) The eclipse period of Pounce-Catch, eclipse period of ejaculation in Zhenxiong granula group is shorter than that in normal control (P < 0.01=).

Conclusions. Zhenxiong granula possess effects including shortening eclipse period of erection of rats, increasing organ index number of accessory sex gland, shortening eclipse period of Pounce-Catch and eclipse period of ejaculation, which hint that Zhenxiong granula have drug action increasing the sexual function of rats. His mechanism of action needs further study.

P-25

Role of testosterone in different practice guidelines for erectile dysfunction

C.C. Lu

Division of Urology, Department of Surgery, Chi Mei Medical Center, Liouying, Chinese Taipei

Objectives. To assess the role of testosterone in different clinical practice guidelines (CPGs) for erectile dysfunction (ED).

Materials and methods. The printed and online materials in CPGs for ED of British Society for Sexual Medicine (BSSM), Japanese Society for Sexual Medicine (JSSM), and Singapore Urological Association (SUA) were reviewed.

Results. The latest English versions of CPGs for ED of JSSM, BSSM, and SUA were available in 2008, 2008, and 2006, respectively. Most were based on guidelines from European Association of Urology. In SUA, guidelines were separated into two parts, Andropause and ED. The major panel in developing guidelines was urologists in SUA. In JSSM and BSSM, panel was more diversified with internal medicine, psychiatry, sex therapy and nursing. In laboratory investigation, serum free testosterone was recommended in JSSM, the reference values for free testosterone were considered as low, borderline and normal with <8.5 pg/ml, 8.5 to 11.8 pg/ml and >11.8 pg/ml, respectively. The Japanese reference range for total testosterone was 2.01–7.50 ng/ml. Although in BSSM morning total testosterone checking was recommended, bio-available/calculated free testosterone was preferred. Normal testosterone reference values were 11 nmol/l, 346 ng/dl in BSSM, and SUA, respectively. Although no clear relationship was established between testosterone replacement therapy (TRT) and prostate cancer, it was contraindicated for patients with history of prostate cancer in JSSM, BSSM, and SUA. When testosterones were normal, no indications for TRT to improve ED in JSSM, BSSM. Topical (gel, cream), injection type and oral preparations were recommended in the guidelines. Only in BSSM, TRT was clearly recommended for non-responders to phosphodiesterase Type 5 inhibitors in the ED treatment algorithm.

Conclusions. In this limited review, a variety of differences are noted in different guidelines. Different regions may use different values as normal testosterone. TRT is not considered in patients with prostate cancer with ED.

P-26

Intermittent docetaxel therapy with estramustine: the optimal option for hormone refractory prostate cancer in high age and high risk cases

N. Soga, H. Kise, K. Arima, Y. Sugimura

Division of Nephro-Urologic Surgery and Andrology, Mie University Graduate School of Medicine, Japan

Background. Since prostate cancer often occur in elderly age cases, the chemotherapy must be performed under focusing on the quality of life and reducing side effect, without sacrificing survival. We evaluated the efficacy and toxicity of intermittent docetaxel (DCT) with estramustine (EM) for hormone refractory prostate cancer (HRPC).

Methods. Fifteen patients were enrolled. They received injected DCT (70 mg/m² body surface) on Day 1 in association with oral EM 560 mg/day (Days 1–5). Treatments were repeated every three weeks. Serum prostate specific antigen (PSA) levels were categorized based on the first three courses. Cases exhibiting either a response or stable disease (SD) could have a holiday (intermittent). The holiday continued until the PSA level elevation from nadir base line level three times. All patients were evaluated for toxicity and quality of life (QOL). Survival curves were established using Kaplan-Meier graphs.

Results. The median courses of DCT/EM therapy was 5 courses (range = 3–12 courses). The response rate of the first cycle was 53%: 3 cases with complete response (CR), 5 cases with partial response (PR), 4 cases with SD, and 3 cases with disease progression. Eight cases could enter into the re-entry second cycle. No case showed a CR, two cases exhibited PR, 4 cases were SD, and the overall response rate was 25%. For survival ratios, one-year and two-year estimates were 93% and 26.1%, respectively. Grade 3–4 anemia was observed in 2 (13.3%), neutropenia in 11 (73.3%) and thrombocytopenia in 2 (13.3%). The QOL scales showed good QOL after 6 months, with improvements for nausea and vomiting.

Conclusion. Intermittent DCT/EM therapy was well tolerated, additional promise was shown by maintaining a good quality of life, by taking a holiday from treatment with a high QOL in HRPC. Especially, this schedule may be an optimal choice for elderly and high-risk cases.

P-27

Combined inhibitory effects of isoflavones and curcumin on prostate cancer cells

H. Ide, K. Nishio, S. Isotani, S. Muto, S. Horie

Teikyo University School of Medicine, Japan

Introduction. Sustained chronic inflammation in the prostate promotes prostate carcinogenesis. However, in the efforts of screening prostate cancer, considerable numbers of people were left with high value of prostate specific antigen (PSA) once cancer was not detected by repeated prostate biopsies. Since elevated level of PSA per se reflects the presence of inflammation, intervention to improve the PSA value might have a beneficial effect for the prevention of the development of prostate cancer. Isoflavones and curcumin have anti-inflammatory and antioxidant properties. We examined the biological effects of soy isoflavones and curcumin on LNCaP, a prostate cancer cell line.

Materials and methods. The growth effects of isoflavones and curcumin were examined in LNCaP cells. We also examined the effects of isoflavones and curcumin on the expression of PSA and androgen receptor, and modulation of DNA damage response proteins including ATM (ataxia-telangiectasia-mutated kinase), H2AX (histone H2AX variant), Chk2 (checkpoint kinase2) and p53.

Results. The growth of LNCaP cells was completely inhibited, when both the curcumin and DHT were added to the medium. Combined treatment of isoflavones and curcumin synergistically suppressed the expression of PSA, androgen receptor, and induced the phosphorylation of DNA damage response genes such as ATM, H2AX Chk2, and p53.

Conclusions. Our results may indicate that isoflavone and curcumin can modulate serum PSA level and presumably suppress the prostate carcinogenesis through the suppression of the androgen receptor expression and activation of DNA damage signaling pathways.

P-28

Quality of life evaluation in patients undergoing cavernous nerve graft reconstruction during radical prostatectomy

M. Yamashita, Y. Matsuoka, H. Arai, T. Yano, H. Hirama, H. Tsunemori, H. Uetsuki, M. Inui, M. Sugimoto, Y. Kakehi

Faculty of Medicine, Department of Urology, Kagawa University, Japan

Introduction. Nerve-grafting technique after resection of neuro-vascular bundles (NVB) during radical prostatectomy is one of the promising resolutions for dilemma between cancer control and functional preservation. The objective of this study is to evaluate the effect of nerve-grafting procedure on health related quality of life (HRQOL) in localized prostate cancer patients assessed with the Japanese version of Extended Prostate Cancer Index Composite (EPIC) and Medical Outcomes Study 8 Items Short Form Health Survey (SF-8).

Materials and methods. A total of 95 patients followed for a minimum of 12 months after surgery with median follow-up of 48 months were enrolled in this study. In those, 24 patients underwent unilateral nerve-sparing with contralateral nerve-grafting or bilateral nerve-grafting and 64 patients underwent prostatectomy without nerve-sparing procedure. HRQOL assessed with EPIC and SF-8 was analyzed horizontally.

Results. Patients in nerve-grafting group who recovered potency demonstrated higher sexual function scores compared with those without nerve-sparing procedure. However, sexual bother scores in nerve-grafting group who recovered potency were lower than those without nerve-sparing procedure throughout the observation periods. The physical health summary scores in nerve-grafting patients were higher than those without nerve-sparing procedure throughout the follow-up period.

Conclusions. Positive effects were observed on sexual function and physical health in nerve-grafting patients as compared with bilateral resection patients. Nevertheless, negative impact was observed on sexual bother in nerve-grafting patients. It should be noted that patients who opted potency preserving operation expected considerable recovery of sexual function.

P-29

Pathological characteristics and manganese superoxide dismutase genetic polymorphism of prostate cancer in men 70 years or older: an autopsy study

T. Iguchi^1,2, C.Y. Wang², N.B. Delongchamps^2,3, G. De La Roza⁴, Y. Nitta¹, H. Naganuma¹, K. Kuratsukuri^1,2, T. Tanaka¹, J. Uchida¹, H. Kawashima¹, G.P. Haas², T. Nakatani¹

¹Department of Urology, Osaka City University Medical School, Osaka, Japan; ²Department of Urology, SUNY Upstate Medical University, Syracuse, NY, USA; ³Department of Urology, University of Paris, Paris, France; ⁴Department of Pathology, SUNY Upstate Medical University, Syracuse, NY, USA

Introduction and objective. Recent guidelines recommend that men over 75 years old should not be screened for prostate cancer (PCa). However, increased life expectancy and the availability of less invasive treatment methods have led to an interest in the characterization of PCa in elderly men. It has been suggested that PCa in elderly men may have lesser biological aggressiveness and lower clinical significance than PCa in younger men. Our research group has a long tradition of investigating the prevalence of PCa through autopsy studies, and the current study is part of a larger effort by an international consortium.

Methods. We studied the difference in the pathological characteristics and manganese superoxide dismutase (MnSOD) genetic polymorphism of PCa in autopsied glands from men over 70 and compared our findings to men under 70. All men deceased of causes unrelated to PCa, and their prostates were processed whole-mounted at 5-mm intervals. Cancers were defined as clinically “significant” or “insignificant” based on established histological characteristics. Genomic DNA was extracted from the prostate tissue and MnSOD genotypeing was performed using PCR restriction fragment length polymorphism analysis.

Results.About 211 prostates were evaluated, 74 of which were from men over 70. There were 33 PCa identified in this group (45%) versus 26/137 (19%) in men under 70 (p < 0.01). Men over 70 had significantly larger cancers and had more clinically significant cancers (64%vs. 23%, p < 0.05). MnSOD AA genotype was associated with PCa risk in older group, but the association was not observed in younger group.

Conclusions. Men over the age of 70 are more likely to have larger, higher grade, and clinically significant PCa compared with younger men. MnSOD polymorphism is associated with PCa risk only in elderly men. Autopsy studies provide important information regarding the prevalence and genetic characteristics of PCa in desired age groups.

P-30

Serum adiponectin level in Japanese patients with prostate cancer

K. Mita, M. Ota, Y. Shigematsu, Y. Sekino, H. Masumoto, S. Inoue, S. Ohara, K. Kobayashi, M. Kajiwara, J. Teishima, A. Matsubara

Department of Urology, Graduate School of Medical Sciences, Hiroshima University, Japan

Objective. To assess the level of serum adiponectin in Japanese patients with prostate cancer.

Patients and methods. From 2006 to 2008, 194 patients underwent a prostate biopsy in the Department of Urology at Hiroshima University Hospital due to a suspicion of prostate cancer. These patients were divided into two groups based on the final pathological diagnosis: those with prostate cancer and those without prostate cancer. The patients with prostate cancer were further classified into two groups with Gleason scores of >8 (HGS) and <8 (LGS). Background factors including age, body mass index (BMI), prostate volume, testicular size, serum levels of prostate specific antigen (PSA), free testosterone (FT), and serum adiponectin were compared among the patient groups.

Results. Of the 194 patients, 89 were diagnosed with prostate cancer, and these patients had a higher age (P < 0.0001), higher PSA level (P = 0.0002), lower FT level (P = 0.0034), and smaller prostate volume (P = 0.0023) compared to those without prostate cancer. BMI, testicular size, and adiponectin level did not differ significantly between these groups of patients. Multiple logistic regression analysis showed that age, PSA, and prostate volume, but not FT, were significant predictive factors for prostate cancer. The level of PSA was significantly higher in the HGS subgroup of patients with prostate cancer compared with the LGS subgroup, but age, BMI, testicular size, prostate volume, FT, and adiponectin did not differ significantly between these subgroups.

Conclusions. In this study the level of serum adiponectin did not differ between Japanese patients with and without prostate cancer or between prostate cancer patients with high and low Gleason scores.

P-31

Declined urethral sphincter function related to aging contributes to urinary incontinence after radical prostatectomy

Y. Matsukawa, R. Hattori, M. Gotoh

Department of Urology, Nagoya University Graduate School of Medicine, Japan

Introduction. Urinary incontinence is one of the distressing complications after radical prostatectomy. Although the surgical technique should be an important factor related to the occurrence of postoperative urinary incontinence, it is important to investigate other contributing factors related to aging. In this study, we compared the urethral sphincter function of elderly patients with younger ones undergoing laparoscopic radical prostatectomy.

Methods. The records of pre- and postoperative urodynamic studies were retrospectively investigated in 195 patients who underwent laparoscopic radical prostatectomy between January 2001 and January 2007. The data on urethral pressure profile were analyzed by subdividing the patients into two groups: Group 1 comprised 73 men aged 70 years or older and Group 2 comprised 122 men younger than 70 years. We compared the incidence of postoperative incontinence and the urethral sphincter function between the two groups. The urethral sphincter function was assessed in terms of maximum urethral closing pressure (MUCP) and functional profile length (FPL), measured on urethral pressure profile before and 3 months after surgery.

Results. The continence rates of Group 1 at 3 and 12 months after surgery were 24.9% and 72.9%, respectively. Those of group 2 were 47.4%, and 91.8%, respectively. Continence rate in group 1 was significantly lower as compared with group 2. On urethral pressure profile, preoperative mean MUCP/ FPL was 54.6 cmH₂O/43.7 mm in group 1, and 66.0 cmH₂O/39.6 mm in group 2. Postoperative mean MUCP/FPL was 32.6 cmH₂O/21.3 mm in group 1, and 41.2 cmH₂O/23.8 mm in group 2. Mean MUCP and FPL were significantly declined after surgery in both group. Mean MUCP in group 1 was significantly lower than in group 2 both in pre- and postoperative examination.

Conclusions. The declined urethral function, in terms of reduced urethral sphincter tension, related with aging might be a contributing factor to postoperative urinary incontinence after radical prostatectomy.

P-32

Androgen receptor is a tumor suppressor and proliferator in prostate cancer

W. Changli, N. Yuanjie, H. Ruifa

Tianjin Institute of Urological Surgery, China

Targeting androgens/androgen receptor (AR) functions via androgen deprivation therapy (ADT) remains the standard treatment for prostate cancer. However, most tumors eventually recur in spite of ADT. Here we demonstrate that the prostate AR may function as a suppressor and a proliferator to suppress or promote prostate cancer metastasis. Results from orthotopically co-inoculated stromal WPMY1 cells with epithelial PC3 prostate cancer cells demonstrated that gain-of-function of AR in epithelial PC3 cells or knockdown of AR in stromal WPMY1 cells suppressed prostate cancer metastasis. Knockdown of the AR in epithelial CWR22rv1 prostate cancer cells also resulted in increased cell invasion in vitro and in vivo. Mice lacking the prostate epithelial AR have increased apoptosis in epithelial luminal cells and increased proliferation in epithelial basal cells. The consequences of these two contrasting results led to the expansion of CK5/CK8 positive intermediate cells and mice developed larger and more invasive metastatic tumors in lymph nodes and died earlier than wild-type littermates. Mechanistic dissection suggested that androgen/AR might directly or indirectly modulate metastasis-related genes and suppression of TGF1 signals results in the partial inhibition of AR-mediated metastasis. Collectively, our understanding of these opposing roles of prostatic AR may revolutionize the way we combat prostate cancer, and allow the development of new and better therapies, which target only the proliferative AR.

P-33

Clinical analysis of using the improved 8-core prostate biopsy protocol to diagnose prostatic carcinoma earlier

Q. Xie, J. Chu, W. Zhu, M. Cao, X. Yang, S. Chen, H. Zhang

Department of Urology, The Affliated ZhuHai Hospital of JiNan University, China

Objective. Review the contribution of improved 8-core prostate biopsy protocol in the prostatic carcinoma detection. To investigate the best prostate biopsy stategy.

Methods. 47 patients who were highly suspected as the prostatic carcinoma during December 2007∼ January 2009 were included in the study. TURS guided the improved 8-core prostate biopsy protocol was conducted in each patient. The prostatic carcinoma detection rate fore each biopsy core was calculated.

Results. The prostatic carcinoma were detected in 19 of 47 patients. Prostatic intraepithelial neoplasm was detected in 6 patients. Benign prostatic hyperplasia with chronic inflammation was detected in 5 patients. The last 17 patients were diagnosed as benign prostatic hyperplasia. The positive rate of the special core which was named as “ASHI” point was 53.57%. The cores at the apex, mid gland, lateral mid, and base yielded a high percentage of prostatic carcinoma.

Conclusions. The improved 8-core prostate biopsy protocol that combines cores at the base, mid gland, apex, lateral mid, and “ASHI” point should be the preferred strategy in early detection of prostatic carcinoma.

Keywords:Prostatic carcinoma, biopsy, ultrasonography

P-34

Measurement-specific bioavailable testosterone (BT) using concanavalin A precipitation

E. Koh, K. Yamamoto, F. Matsui, K. Sugimoto, H.S. Sin, Y. Maeda, M. Namiki

Department of Integrative Cancer Therapy and Urology, Kanazawa University Graduate School of Medical Science, Japan

Introduction. The decline of testosterone may be involved in late-onset hypogonadism (LOH) which is responsible for age-related changes, such as muscular weakness, decrease in bone mineral density, and depressed mood. Bioavailable testosterone (BT) is considered a better biological marker of androgen status than total testosterone (TT) and free testosterone (FT) in men. Much of testosterone binds to sex hormone binding globulin (SHBG). We developed a method to quantify BT as non-SHBG-bound testosterone using the specificity of concanavalin-A (ConA) for SHBG. On the other hand, the calculated method is a simple method used to measure BT. BT level can be calculated from the levels of TT, SHBG, and albumin. The formula for calculated BT (cBT) is available from the ISSAM homepage. Although a simple approach offers advantages for assessing these hormones, few have been verified the actual values. The aim of present study was to compare the value of cBT and assayed BT (aBT) in utilizing the diagnosis of LOH.

Methods. To assay non-SHBG testosterone (aBT) in serum, SHBG was precipitated with conA and then testosterone was measured using liquid chromatography-tendem mass spectrometry. To validate the non-SHBG-bound testosterone, gel filtration chromatography, and conA sepharose were used. Following this validation, the usefulness between aBT and cBT was evaluated.

Results. The mean age of 88 healthy male volunteers was 65.6 (SD: 9.0, range: 50–86, median: 67) years. There was a correlation between cBT and aBT (R² = 0.53) and the mean value ratio (cBT/aBT) was 2.48. Both cBT (R² = 0.122) and aBT (R² = 0.251) decreased with age. Variations in aBT were less marked than those for cBT, suggesting that aBT can be used to determine age-related reduced testosterone levels.

Conclusions. The aBT level is more useful than the cBT level in utilizing the diagnosis of LOH in middle aged and elderly persons.

P-35

The role of testosterone and impact of castration on bone mineral density in male rats

T. Hala¹, P. Zivny², H. Zivna³, F. Senk⁴, V. Palicka²

¹CCBR-SYNARC, Pardubice, Czech Republic; ²Osteocentre, Teaching Hospital Hradec Kralove, Czech Republic; ³Radio-isotope Laboratory, Teaching Hospital Hradec Kralove, Czech Republic; ⁴Osteocentre, Hospital Havlickuv Brod, Czech Republic

Introduction and hypothesis. Men with hypogonadism are at increased risk of osteoporosis. Osteoporotic fractures may be associated with loss of independence, premature mortality, and increased health care expeditures. Androgen deficiency may represent a key pathophysiological pathway in the osteoporosis developement. Surgical or chemical castration induces a complete decline of testosterone level. Skeletal effect of gonadectomy has not been clearly established.

Methods. Twenty male Wistar rats, housed in group-cages, were fed at rat chow and water ad libitum and maintained in a room with constant temperature on a 12-h light:12-h dark cycle. The animals were randomly assigned to one of three groups: (1) intact sham control (n = 8); (2) orchiectomy (n = 6), and (3) administration of GnRH (gonadotropine-releasing hormone) agonist leuprolerine (n = 6). Leuprolerine was administered subcutaneously at the baseline. The bone mineral density (BMD) was measured by densitometry with small animal software (Hologic) after 6 weeks from baseline. We evaluated lumbar spine (R1); femur (R2), and tail (R3).

Results (BMD in g/cm²):

Table

Download CSV Display Table

The intact R1, R2, and R3 values were significantly higher than R1, R2, and R3 values in orchiectomy group (p < 0.001; p < 0.01; p < 0.01) and GnRH agonist group (p < 0.001; p < 0.001; p < 0.01).

Discussion. Loss of testosterone increases the rate of bone remodeling with effect on osteoblastogenesis and osteoclastogenesis. These changes lead to the imbalance between resorption and formation by prolonging the lifespan of osteoclasts and shortening the lifespan of osteoblasts. The changes result in bone loss and subsequent development of osteoporosis.

Conclusions. We have demonstrated substantial effect of castration on both cancellous and cortical bone.

P-36

Age-related changes in plasma androgen levels and their association with cardiovascular risk factors in male Japanese office workers

S. Fukai¹, M. Akishita¹, Y. Kameyama¹, M. Miyao¹, K. Ishida², K. Toba³, Y. Ouchi¹

¹Department of Geriatric Medicine, Graduate School of Medicine, The University of Tokyo, Japan; ²Clinic, Asahi Mutual Life Insurance Company; ³Department of Geriatric Medicine, Kyorin University School of Medicine, Tokyo

Aim.We aimed to assess the age-related change in plasma androgen levels in healthy middle-aged men and whether any clinical parameters are associated with the hormonal change.

Methods. The study comprised male Japanese office-workers aged 40–64 years, who had undergone an annual health check-up in 2002 and 2007 (96 men and 76 men, respectively). Body mass index and blood pressure were measured, and serum concentration of lipids, glucose, and uric acid in addition to plasma total testosterone, free testosterone, and dehydroepiandrosterone sulfate (DHEA-S) levels were determined in the morning after an overnight fast. The five-year hormonal changes and their associations with clinical parameters were analyzed in 33 men who repeated the examination at both check-ups. The cross-sectional associations of hormonal levels with clinical parameters were also investigated.

Results. Age was negatively associated with free testosterone (r = −0.399, p < 0.001 in 2002; r = −0.458, p < 0.001 in 2007) and DHEA-S (r = −0.233, p = 0.02 in 2002; r = −0.336, p < 0.01 in 2007) but not with total testosterone, whereas the 5-year changes of free-testosterone and DHEA-S levels were not significant and showed no associations with major cardiovascular risk factors. Cross-sectionally, after adjustment for age, linear regression analysis showed associations only between free testosterone and blood hemoglobin (β = 0.263, p < 0.05 in 2002; β = 0.367, p < 0.01 in 2007) and between total testosterone and serum uric acid (β = (0.259, p < 0.05 in 2002; β = (0.245, p < 0.05 in 2007).

Conclusions. In Japanese middle-aged men, 5-year androgen decline is too subtle to detect, and endogenous androgen levels seem to have relatively weak association with cardiovascular risk profiles.

P-37

Oral testosterone use behavior among 254 symptomatic late-onset hypogonadal men

S. Permpongkosol, P. Preechawong, K. Ratana-Olarn

Faculty of Medicine, Ramathibodi Hospital, Mahidol University, Thailand

Objective. The objective of the study was to evaluate oral testosterone use behavior among symptomatic late-onset hypogonadal men.

Methods. From March 1999 to November 2008 (10-year period), a total of 254 men aged 37–82 years (mean 64.8 ± 7.1 years) documented LOH receiving an oral testosterone replacement therapy at a men health's clinic. An oral testosterone use behavior questionnaire was posted to all patients and the response rate was 169 (66.5%).

Results. The LOH symptoms more frequently reported were decrease morning erection (59.2%), erectile dysfunction (52.7%) and decrease of sexual desire (49.7), respectively. For most of the LOH, the main medical history was dyslipidemia (48.5%), hypertension (37.9%), and benign prostate hyperplasia (30.8%), respectively. A mean of total period of using oral testosterone was 2.7 +/− 2.2 years (0.1–10 years). At the end of the study, thirty-six% of patients were still on hormonal replacement therapy. One hundred three cases (60.1%) responded that the main reason for ceasing the treatment were being clinical improve (32%), lower urinary tract symptom (18%), and clinical unimproved (10%). However, a number of patients expressed fear of developing cancer or other long term complications. The percentage of patients will recommend oral testosterone supplements to friends who are LOH was 40% with undecided 30% and nonrecommend 22%.

Conclusions. This study found that practice guidelines regarding oral testosterone therapy in LOH was needed including the risks and benefits of the long-term use of hormonal therapy.

P-38

Late-onset hypogonadism (LOH) in 223 Thai men at a men health clinic

S. Permpongkosol, P. Prechawong

Faculty of Medicine, Ramathibodi Hospital, Mahidol University, Thailand

Objective. To evaluate the prevalence of and risk factors for LOH in Thai men at a men health clinic in Bangkok, Thailand.

Material and method. From January 2007 to April 2009, a health screening was conducted by a men health clinic in Ramathibodi Hospital, and 223 men participated in this health screening. All participants completed a health questionnaire, received a detailed physical examination, and blood samples. Serum total testosterone (TT) albumin, and sex hormone-binding globulin levels was also examined, and calculated free (cFT) and bioavalable (cBT) testosterone levels were obtained. Clinical symptoms of LOH were assessed using all questions on the Aging Males Symptoms scale (AMS), International Prostate Symptom Score (IPSS), and International Index of Erectile Function-5 (IIEF-5), and correlations between these scores and serum testosterone level.

Results. Two hundred twenty-three men with mean age 58.8 +/− 9.4 years were included in this study. Mean values of TT, cFT, and cBT were 498.3 (+/−210.9) ng/dl, 9.75 (+/−4.94), and 222.77 (+/−114.5) ng/dl, respectively. Mean AMS total, psychological, somatovegetative, and sexual symptom scores were 39.29, 15.7, and, 13.2 respectively. The prevalence of LOH was 17% based on the criterion of TT level <300 ng/dL, and 13.5% based on the criterion of both TT < 300 ng/dL and FT < 7 ng/dL. The majority of patients (45.74%) presented with hyperlipidemia. The percentages of the patients presented with erectile dysfunction, lower urinary symptom, and hypogonadism were 53.36%, 20.18%, and 17.1%, respectively. A wide variety of conditions were diagnosed, including hypertension, diabetic, osteopenia, and osteoporosis. According to the AMS questionnaire, the prevalence of symptomatic androgen deficiency was 87.27% and increased with age.

Conclusions. Further study and a multidisciplinary approach are needed to explore the formative evaluation of The Men's Health Clinic in Thailand.

P-39

Changes in various hormone levels before and after androgen replacement therapy for late-onset hypogonadism (LOH) syndrome

J. Soh, N. Kanemitsu, Y. Naya, A. Ochiai, Y. Naitoh, K. Yoneda, Y. Itoh, A. Kawauchi, T. Miki

Department of Urology, Graduate School of Medical Science, Kyoto Prefectural University of Medicine, Japan

Introduction and objective. Late-onset hypogonadism (LOH) syndrome is essentially defined as multiple organ dysfunction associated with androgen deficiency, but hormones other than androgen also decrease with age, which have been reported to induce a variety of clinical symptoms. We compared the changes in various hormone levels before and after androgen replacement therapy.

Materials and methods. The subjects were 72 andropause who received androgen replacement therapy a total of six times and for whom blood tests were performed before and after replacement therapy (before replacement and immediately before the sixth replacement). Mean age was 55.8 years (36 to 68 years). General blood tests, blood chemistry, LH, FSH, PRL, T, free T, GH, IGF-I, IGFBP-3, DHEA-S, and PSA were determined. The patients were classified into 3 groups according to the administration interval of the replacement dose of Enarmon Depot (125) 1A: 1A/2 weeks (22 patients), 2A/2 weeks (18 patients) and 2A/2 weeks (32 patients). Changes in hormone levels were compared between each group.

Results. Hematocrit levels significantly increased in all 3 groups. T levels and free T levels were comparable with pre-replacement levels in the 2-week interval replacement groups of 1A/2 weeks and 2A/2 weeks, whereas they tended to decrease in the 3-week interval replacement groups of 2A/3 weeks. However, LH and FSH levels tended to decrease postreplacement in all 3 groups. No significant changes were seen in GH, IGF-I, IGFBP-3, or PSA levels, but levels of DHEA-S significantly decreased post-replacement in all 3 groups.

Conclusions.In all 3 groups that received replacement therapy, DHEA-S levels decreased following androgen replacement therapy, which could decrease the patient's concentration and memory that are considered related to DHEA, and conversely increase fatigue and malaise. Our results suggest the possibility that decreased DHEA-S following androgen replacement therapy is a cause of the variability of therapeutic efficacy.

P-40

Testosterone replacement: do not forget younger men

S.H. Teoh¹, E.J. Teoh²

¹Prime Medical Group Singapore, Singapore; ²Hammersmith Hospital London

Introduction. There is widespread attention on testosterone replacement for men with late onset hypogonadism. Treating young men with hypogonadism has been taken for granted. 3 men below 45 years of age with primary hypogonadism are presented.

Methods. A, B, and C presented between 2001 and 2008. Their case history and treatment are reviewed.

Results. A and B had mumps in their teenage years. A, 34 years old, presented with his wife for subfertility. B, 41 years old, experienced weakness and loss of libido for 2 years. He has diabetes which is well controlled. C, 27 years old complained of difficulty in sustaining penile erection during intercourse. Chromosome study showed Klinefelter Syndrome. There was evidence of virilisation in all three but less in C. All had testicular volumes ∼3 ml. FSH was raised in all three. LH in C was 24.69 IU/l. Pretreatment Testosterone (nmol/L) for A, B, and C were 4.0, 3.5, and 7.0.

A, seen in 2001, was put on oral Testosterone Undecanoate and reported little effect. After his wife conceived and delivered with donor sperm, he defaulted follow-up. B and C were treated with Injection Testosterone Undecanoate (Nebido). Post-treatment Testosterone for B and C were 13.7 and 18.1 nmol/L. Both reported growth of facial hair, required shaving and sex normalized. C reported increased volume of ejaculate. Examination showed increased pigmentation of his genitals and scrotal skin increased in rugosity.

Conclusion. Hypogonadal men like these patients reported are often overlooked and effort must be made to diagnose and treat them because testosterone is important in men's health. It is reported that only 25% of patients with Klinefelter Syndrome are diagnosed. Men with insufficient testosterone in early life enter old age worse off than eugonadal men. Injection Testosterone Undecanoate is an effective treatment option for hypogonadism in younger men.

P-41

Validation of an Arabic ADAM questionnaire for androgen deficiency in Saudi men

M. Arafa¹, D. Rabah²

¹King Saudi University, Princess Aljohara Al Ibrahim Center for Cancer Research, Prostate Cancer Research Unit, Saudi Arabia; ²Departement of Urology, King Saud University, Princess Aljohara Al Ibrahim Center for Cancer Research

Background. It is well documented that testosterone levels decline with age and this decline is associated with symptoms which could be assessed denoting androgen deficiency. We investigated the validity of an Arabic version of the Saint Louis University ADAM questionnaire to screen for androgen deficiency in Saudi men.

Methods. It was a cross-sectional study of ambulatory community-based Saudi men recruited from Volunteers in Riyadh city aged 18–80 years. 730 men agreed to fill the Arabic ADAM questionnaire, they were invited to a morning blood sample for total testosterone and sex hormone binding globulin, those who agreed to complete the whole study were only 407 men. Low serum bioavailable testosterone (BT) levels (androgen deficiency) were defined as <10th percentile of serum BT levels in young healthy Saudi men (18–30 years). Results: Cronbach Alpha of 0.71 (n = 730) showed a good internal consistency of the Arabic ADAM questionnaire. Among participants, 18.2% and 77.6% had low serum BT levels and a positive ADAM questionnaire, respectively. The prevalence of positive ADAM and low serum BT is increasing with age. The Arabic ADAM questionnaire had a high sensitivity of 86.5%, a low specificity of 24.3%, and +PVs and −PVs of 20.3% and 89%, respectively.

Conclusions. The Arabic ADAM questionnaire has a very good sensitivity but very low specificity for screening of androgen deficiency in Saudi men, therefore biological confirmation is needed, specially, when clinical symptoms of androgen deficiency are present.

P-42

The lower urinary tract symptoms have also been implicated in the sleep disorder

S. Sugimoto, T. Matsui, K. Yamaguchi, H. Hirakata, N. Kawata, S. Takahashi

Department of Urology, Nihon University, Japan

The nocturnal frequency is the worst impact on the quality of life in LUTS. There are many causes of nocturnal frequency including nocturnal polyuria, reduction of nocturnal bladder capacity, SD and so on. However, we often wonder whether nocturnal frequency goes ahead of SD. To elucidate the therapeutic target for nocturnal frequency and SD we evaluated the correlation between LUTS and SD. From October 2007 to February 2007, consecutively 519 new patients were analyzed by some questionnaires and examinations. The LUTS was assessed by International Prostate Symptom Score (I-PSS), Overactive Bladder Symptom Score (OABSS), uroflowmetry and residual urine by ultrasound. The sleep disorder was assessed by Pittsburgh Sleep Quality Index (PSQI). Of total 519 mean age was 57.4 years old (range, 16–93), 314 (60.5%) were male and 205 (39.5%) were female. The sleep quality of old generation was lower than age matched healthy volunteers in Japan. Total I-PSS, OABSS and the nocturnal frequency correlated with PSQI (Spearman's r = 0.3025, p = 0.0001, r = 0.2301, p = 0.0014 and r = 0.2152, p < 0.0001, respectively). The patients of serious and mild score in I-PSS (20–35 and 8–19 points) were significantly higher PSQI than the patients of slight score (0–7 points) (p < 0.0001 and p < 0.0001, respectively). The patients with overactive bladder (OAB) were higher PSQI than non-OAB patients (p = 0.0013). The results of the present study have revealed that not only storage symptoms but voiding symptoms got worse sleep quality. When 3 to 2 times decreased in the number of nocturnal frequency, the sleep quality and efficiency were significantly improved (p < 0.05 and p < 0.001, respectively).

P-43

Combination of tamsulosin and solifenacin in patients with overactive bladder with male lower urinary tract symptom

Y. Naya¹, S. Ushijima², H. Boku³, H. Fujii¹, S. Morita¹, K. Abe¹, M. Inaba¹, T. Nakanouchi¹

¹Department of Urology, Kyoto First Red Cross Hospital, Japan; ²Department of Urology, Omihachiman Community Medical Center; ³Department of Urology, Matsusita Memorial Hospital

We evaluated the efficacy and safety of combination of tamsulosin 0.2 mg/day and solifenacin 5 mg/day in patients with male lower urinary tract symptoms (LUTS) with over active bladder (OAB). Between March 2007 and December 2007, 38 patients with male LUTS and OAB were medicated with tamsulosin 0.2 mg/day for 2 weeks or longer. In 18 patients with have residual OAB after treatment with tamusulosin 0.2 mg/day, solifenacin was added at 5 mg/day. We gave a self-completion questionnaire of International prostate symptoms score (I-PSS), QOL score, Overactive bladder symptoms score (OABSS) at 4, 10, 22, and 34 weeks after treatment of solifenacin 5 mg/day. The patients with postvoid residual urine (PVR) of >100 ml or prostate volume of >50 ml were excluded.

All of the 18 patients reported a symptomatic improvement after taking solifenacin for 4 weeks. I-PSS, Over Active Bladder Symptoms Score (OABSS) and QOL scores were statistically significantly improved from Week 4 of solifenacin therapy, and this efficacy continued up to Week 34. There was no subject who discontinued this therapy because of adverse reactions or increased residual urine volume. Three patients of the 18 patients discontinued solifenacin after taking 10 and 22 weeks at our hospital. One patient reported significantly symptomatic improvement, and then he stopped taking solifenacin and tamsulocin. One patient underwent TURP. One patient was medicated these drugs by his family doctor. Although anticholinergic agents should be used carefully for overactive bladder patients with male LUTS, this study result indicates efficacy and safety of the long-term combination therapy of tamsulosin and solifenacin with evaluation of prostate volume and residual urine volume.

P-44

An extract (THC-002) of Ba-Wei-Die-Huang-Wan reduces tachykinins and sensory receptors expressed in urethra of old spontaneously hypertensive male rats

T. Imamura, O. Ishizuka, Y. Kurizaki, T. Nakayama, K. Ishikawa, Y. Igawa, O. Nishizawa

Department of Urology, Shinshu University School of Medicine, Japan

Aims. Old men sometimes complain about the urine dribbling after the urination, and Chinese herbal mixture is one of the choices for the treatment. However, the mechanism is not clear. Recently, it was reported that the tachykinins, sensory receptors (TRPV1 and P2X3 receptors) plays an important roles of voiding disorders, such as overactive bladder (OAB) and interstitial cystitis. Spontaneously, hypertensive rats (SHRs) are interesting experimental animal model which have not only hypertension but also erectile dysfunction and OAB. To clarify the urine dribbling mechanism, we investigated if there was the change of the tachykinins, and TRPV1 and P2X3 receptors within urethra of old SHRs, and THC-002 (HARNCARE®), a galenical produced from Chinese herbal mixture Ba-Wei-Die-Huang-Wan, had the effects on these tachykinins and sensory receptors.

Methods. 10 and 40 weeks-old male SHRs were randomly separated into three groups, respectively. Two groups were given 20 ml physiological saline solution per kg-body weight orally daily for 1 week. An hour after the administration of saline, one of the groups received 20 mg THC-002 per kg body weight, and the other a similar volume of THC-002 free saline. The third group received no treatments. The urethras, which were contacting with prostate, were analyzed by real time RT-PCR (n = 6) for the expression of tachykinins, and TRPV1 and P2X3 receptors.

Results. In both of the 10- and 40-weeks SHRs, mRNA expression levels of tachykinins, and TRPV1 and P2X3 receptors were not altered by the administration of saline. THC-002-treated 10-weeks-SHRs were significantly decreased the expression level of substance P. The mRNA expression levels of neurokinin B, substance P, and TRPV1 receptors in 40-weeks-SHRs were significantly higher than that of 10-weeks-SHRs. THC-002 significantly decreased these tachykinins and receptors.

Conclusions. THC-002 partially inhibited neurokinin B, substance P, and TRPV1 receptors increased according to aging.

P-45

Expression of alpha-adrenoceptor subtypes mrnas as a predictor of the efficacy of subtype-selective alpha1-adrenoceptor antagonists in the management of benign prostatic hyperplasia

S. Sasaki¹, Y. Kojima¹, Y. Umemoto¹, S. Iwatsuki¹, Y. Hayashi¹, H. Shinoura², G. Tsujimoto³, K. Kohri¹

¹Department of Nephro-urology, Nagoya City University Graduate School of Medical Sciences, Japan; ²Department of Molecular Cell Pharmacology, National Center for Child Health and Development Research Institute; ³Department of Genomic Drug Discovery Science, Graduate School of Pharmaceutical Sciences Kyoto University Faculty of Pharmaceutical Sciences, Kyoto University

Purpose. We examined the correlation between the expression of alpha1-adrenoceptor subtype mRNA in the human prostate and the clinical efficacy of subtype selective alpha1-adrenoceptor antagonists. We discuss the possibility of individualization drug therapy in patients with benign prostatic hyperplasia.

Materials and methods. A total of 33 patients randomized to the tamsulosin group and 28 randomized to the naftopidil group were enrolled in this study. Each group of patients was administered 0.2 mg tamsulosin hydrochloride (higher affinity for alpha1A-adrenoceptor) or 50 mg naftopidil (higher affinity for alpha1D-adrenoceptor) daily for 12 weeks. Four prostate needle biopsy specimens were obtained from the transition zone to examine the expression of alpha1-adrenoceptor subtypes. Specimens were stored −80°C centigrade until used for Taqman® quantitative reverse transcription-polymerase chain reaction, which was performed after 12 weeks of treatment.

Results. Based on the results of quantitative reverse transcription-polymerase chain reaction the tamsulosin and naftopidil group were grouped into alpha1a-adrenoceptor dominant (22 and 12 patients) and alpha1d-adrenoceptor dominant (11 and 16, respectively) subgroups. The efficacy of tamsulosin hydrochloride and naftopidil differed depending on the dominant expression of the alpha1-adrenoceptor subtype in the prostate. Tamsulosin hydrochloride was more effective in patients with dominant expression of the alpha1a-adrenoceptor subtype, whereas naftopidil was more effective in those with dominant expression the alpha1d-adrenoceptor subtype.

Conclusions. The expression level of alpha1-adrenoceptor subtype mRNA in the prostate could be a predictor of the efficacy of subtype selective alpha1-adrenoceptor antagonists in patients with benign prostatic hyperplasia. This result implies that genetic differences are responsible for the diverse responses to these drugs.

P-46

Lower urinary tract symptoms (LUTS) is associated with cardiometabolic risk factors – results of the subang aging male (SAM) study

H.M. Tan^1,2, S.F. Tong⁴, V.K.M. Lee³, E.M. Khoo¹, B.C. Lee⁴, W.Y. Low¹, C.J. Ng¹, Z. Zulkifli⁴

¹University of Malaya, Malaysia; ²Sime Darby Medical Centre; ³International Medical University; ⁴National University of Malaysia Medical Centre

Introduction and objective. Risk factors for LUTS have been reported to include increased age, obesity and men with metabolic syndrome. This article examines the association of cardiometabolic risk factors with severity of LUTS.

Methodology. Participants from a 2006 randomized cohort of 1046 men living in Subang were invited to participate in this 2008 Subang Aging Male (SAM) Study. The participants completed a set of validated and structured questionnaires including socio-demographic parameters with the assistance of research assistants. Fasting serum biochemical assessments were conducted. Various severity of LUTS were based on the IPSS (No, Mild, Moderate, and Severe)

Results. 1007 men completed the study. Mean age of respondents was 56.6 ± 8.3 years. There was no difference in the mean age of men with and without LUTS. However, the prevalence of metabolic syndrome (IDF Asian Criteria) was significantly higher in men with LUTS compared with men without LUTS (38.2%vs. 23.3%, p = 0.005). Men with LUTS was twice more likely to have metabolic syndrome (CI: 1.23–3.37, p = 0.005) compared with those without LUTS. Men with moderate to severe LUTS were more likely to self-report hypertension (38.2%vs. 30.0%, p = 0.010) self-report dyslipidaemia (47.1%vs. 37.4%, p = 0.004), and have elevated FBS, ≥7.0 mmol/L (25.2%vs.20.1%, p = 0.07) compare with men with no or mild LUTS (p < 0.05). Further, men with severe LUTS compared with men with lower severity of LUTS were found to have higher prevalence of self-reported hypertension (48.5%vs. 31.3%, p < 0.003), self-reported diabetes mellitus (29.4%vs. 16.5%, p < 0.007), and self-reported coronary artery disease (23.5%vs. 11.2%, p < 0.002).

Conclusions. Men without LUTS appear to be healthier whereas with men with increasing severity of LUTS reported increasingly higher prevalence of cardiometabolic problems.

P-47

Overactive bladder and its association with chronic diseases

E.M. Khoo¹, H.M. Tan^1,2, B.C. Lee³, V.K.M. Lee⁴, S.F. Tong³, W.Y. Low¹, C.J. Ng¹

¹University of Malaya, Malaysia; ²Sime Darby Medical Centre; ³National University of Malaysia Medical Centre; ⁴International Medical University Malaysia

Background. Overactive bladder (OAB) is defined as urgency, with or without urge incontinence.

Objective. To determine the prevalence of OAB and to examine its association with chronic diseases.

Methods. We conducted a cross-sectional study on men aged ≤40 years living in the Klang Valley, Malaysia. A total of 540 out of 1007 men approached participated (response rate 53.6%). The participants completed a set of questionnaires with assistance that included semi-structured questionnaire for socio-demography, self-reported medical illness, and OAB questionnaire which has a 6-point Likert scale measurement of bothersome symptom ranging from (1) Not at all to (6) A very great deal. The operational definition of OAB is a report of “quite a bit” to “a very great deal” of symptom in either question 3, “A sudden urge to urinate with little or no warning” or question 7, “An uncontrollable urge to urinate”.

Results.The prevalence of OAB was 12.7% (68 men). Men with OAB was significantly older than those without (non-OAB) (60.3 vs. 57.9 years, t = 2.304, df = 535, p < 0.05). A significant association was found between OAB and self-reported LUTS (OAB 33.8%, non-OAB 11.1%, χ² = 25.55, df = 1, p < 0.001), depression (OAB 7.4%, non-OAB 2.1%, χ² = 5.96, df = 1, p = 0.015), hearing problem (OAB 19.1%, non-OAB 9.6%, χ² = 5.59, df = 1, p = 0.018), and hypertension (OAB 41.2%, non-OAB 29.0%, χ² = 4.15, df = 1, p < 0.05). No significant associations were found between OAB and self-reported falls and fracture in the past 1 year, diabetes mellitus, myocardial infarction, heart failure, hypercholesterolaemia, back pain, joint pain, renal failure, kidney stone, mobility, obesity, stroke, visual problem, anxiety, chronic obstructive pulmonary disease, and erectile dysfunction.

Conclusions. OAB is common in men aged 40 and above. Its association with hypertension and hearing problem could be attributed to age related factors. However, the association with depression could be attributed to social impact of the illness and needs confirmation.

P-48

Overactive bladder and its impact on erectile function and sexual desire

B.C. Lee¹, H.M. Tan^2,4, V.K.M. Lee³, E.M. Khoo⁴, S.F. Tong¹, W.Y. Low⁴, C.J. Ng⁴, Z. Zulkifli¹

¹University Kebangsaan Malaysia, Malaysia; ²Sime Darby Medical Centre; ³International Medical University Malaysia; ⁴University of Malaya

Background. Overactive bladder (OAB) is defined as urgency, with or without urge incontinence. There is a postulated association between OAB and erectile function (ED)/sexual function as alluded by previous studies.

Objective. To determine the prevalence of OAB and its association with erectile function and sexual desire.

Methods.Men aged ≥40 years living in the Klang Valley, Malaysia were studied. A total of 540 out of 1007 men approached participated (response rate 53.6%). OAB was defined as men with significant urinary urgency based on two questions in the OAB-q. Assessment on sexual well-being was based on International Index of Erectile Function (IIEF-5) and two questions on sexual desire (Q1: “Over the last one month, how often have you felt sexual desire?” and Q2: “Over the last 1 month, how would you rate your level of sexual desire?”).

Results. The prevalence of OAB was 12.7% (68 men). The prevalence of ED was 69.2% overall, with mild ED (41.3%), mild to moderate ED (20.5%), moderate ED (4.8%), and severe ED (2.8%), respectively. 140 (25.9%) men did not have sexual activity for the past 4 weeks. There were no significant difference in the IIEF-5 score between men with and without OAB. For Q1, sexual desire was almost never/never felt (8.0%), felt a few times (16.5%), sometimes (41.1%), most times (24.4%), and almost always/always (10.0%) and for Q2, the level of sexual desire was rated as very low/not at all (8.5%), low (11.5%), moderate (50.4%), high (23.5%), and very high (6.1%). There was no significant association between OAB and sexual desire based on the two questions.

Conclusions. OAB did not appear to have any significant association with ED and sexual desire in our cohort. This finding is not inconsistent with previous reports and the reasons are unclear.

P-49

Men with overactive bladder and their quality of life: a preliminary finding

W.Y. Low¹, H.M. Tan^1,2, S.F. Tong³, V.K.M. Lee⁴, E.M. Khoo¹

¹University of Malaya, Malaysia; ²Sime Darby Medical Centre; ³University Kebangsaan Malaysia; ⁴International Medical University Malaysia

Objective. Overactive bladder (OAB) affects one's quality of life. This article assessed prevalence of OAB in urban men and their quality of life.

Methods. This cross-sectional study involved 1007 men above 40 years, who were invited to participate and interviewed face to face in the Klang Valley, Malaysia. The initial 540 respondents with OAB responses were analyzed. OAB was assessed using the OAB-q, measured on a 6-point scale from (1) Not at all to (6) A very great deal. Two items were utilized: “A sudden urge to urinate with little or no warning” and “An uncontrollable urge to urinate”. Scores 1,2,3 = No OAB, score 4,5,6 = clinically relevant OAB. Health-related quality of life (SF-12) was assessed, where a higher score indicates better quality of life.

Results.Mean age was 58 years (SD = 8 years old). Prevalence of OAB was 12.7% (68 men). Men with OAB (mean = 60 years) were slighter older than men without OAB (mean = 58 years) (p < 0.05). Among those with OAB, 11.8% of them are in their 40s, 35.3% in their 50s, 39.7% in their 60s and 13.2% above 70 years old. OAB was not significantly associated with ethnicity, marital status, and educational levels, except for occupational status (p < 0.05). On the basis of the SF-12, the overall mean physical component score (PCS) and the mental component score (MCS) of the OAB population were 45.66 and 41.06, respectively, i.e., slightly lower than the average norm of 50 of the US general population. No significant differences in PCS, MCS, bodily pain, general health, vitality, social functioning, and mental health between men with and without OAB, except for physical functioning (p < 0.05), role functioning (physical) (p < 0.01) and role functioning (emotional) scores (p < 0.05), where men without OAB have significantly better quality of life.

Conclusions. OAB does affect certain aspects of men's quality of life.

P-50

The laparoscopic enucleation of hyperplastic prostate

Y. Niu, C. Wu, R. Han

Tianjin Institute of Urological Surgery, China

Objective. To discuss the feasibility of laparoscopic enucleation of hyperplastic prostate, which is larger than 100 g.

Methods. From June 2007 to June 2009, laparoscopic prostatectomy were performed on 15 BPH patients with BPH after relevant examinations, and analyze some indexes as operation time, blood loss, bladder irrigation time, drainage retropubic stay, duration of catheterization, preoperative and postoperative 3-month follow-up parameters of international prostate score symptoms (IPSS), quality of life questionnaries (QOL), and maximum flow rate (Qmax).

Results. All operations were successful. The mean operative time was 125 (range, 90–240) min, and the estimated blood loss was 110 (range, 50–240) ml. The irrigation was not necessary in five cases, and the seven left were irrigated 1 day each. The average catheter preserved time was 2 (range, 1–4) days, and the average hospital stay is 3 (range, 2–4) days. Incontinence did not happened in all cases. The international prostate score symptoms (IPSS), quality of life questionnaries (QOL), and maximum flow rate (Qmax) were all improved significantly 3 months after operation. Conclusions: Laparoscopic enucleation of large benign hyperplastic prostate is an alternative and feasible method of less trauma and faster postoperative recovery.

P-51

Effect and safety of Chinese herb composition Tufuling tablet on chronic prostatitis with Damp heat and blood stasis syndrome

Z. Gao, Z. Liu

Urology Department of Xiyuan, Hospital of China Academy of Chinese Medical Sciences, China

Objective. To study the effect and safety of Chinese Herb composition Tufuling table on chronic prostatitis with Damp heat and blood stasis syndrome.

Methods. The study adopts random and comparison clinic method. Patients that conform to the conditions can be selected. The patients in test group were treated with Tufuling tablet and those in control group with sanjin tablet. Record and compare the clinical symptoms. Hardness of Prostate through touching, results of routine examination of prostatic secretion of the two groups before and after treatment. Doctors give the patients medicine according to sequence of patients coming to hospital and arrange the patient to the group of cure or the group of comparison. The study needs 4 weeks. The patient must go back to hospital at the end of 2 and 4 weeks. Two groups have significantly improved symptoms after treatment, but no statistically significant difference in the primary outcome was seen for Tufuling tablet versus sanjin tablet. Traditional Chinese medicine symptoms scores, NIH CPSI total scores, expressed prostatic secretion leukocytes EPS WBC, EPS decreased in both groups, expressed prostatic secretions lipid laden, peak flow rate increased in both groups. It shows both groups have good functions on chronic prostatitis.

Conclusions. The results of this controlled study demonstrates Tufuling tablet improves significantly symptoms and quality of life (QOL) without severe side effects.

P-52

Circulating CD4⁺CD25^high regulatory T cells in men with chronic prostatitis/chronic pelvic pain syndrome

S.G. Wang, J. Bai, J.H. Liu, Z.Q. Ye, X. Yu, Q.L. Xi, D.L. Hu, S.Q. Su

Department of Urology, Tongji Hospital, Tongji Medical College of Huazhong University of Science and Technology, China

Objective. This study was carried out to identify the characters of circulating CD4⁺CD25^high regulatory T cells in chronic prostatitis/ chronic pelvic pain syndrome (CP/CPPS). We sought to discover the possible mechanism how CP/CPPS is induced by autoimmune factors.

Methods. A total of 69 men with CP/CPPS and 25 age-matched, asymptomatic controls underwent quantification of peripheral blood CD4⁺CD25^high regulatory T cells using flow cytometry, followed by the measurement of interleukin-6 (IL-6), IL-10, tumor necrosis factor-alpha (TNF-alpha), transforming growth factor-beta 1 (TGF-beta 1) in seminal plasma and serum, and forkhead box P3 (FOXP3) mRNA level in peripheral blood mononuclear cells, utilizing enzyme-linked immunosorbent assay and real-time quantitative reverse transcriptase-polymerase chain reaction, respectively.

Results. Levels of TNF-alpha, IL-6 and IL-10 in seminal plasma from CP/CPPS patients were higher than those in the controls. Furthermore, the IL-10 level was positively associated with the pain severity of CP/CPPS patients. Reduced FOXP3 and TGF-beta 1 expression level and elevated serum TNF-alpha level were also observed in CP/CPPS patients. However, there was normal frequency of CD4⁺CD25^high T cells in CP/CPPS patients. In addition, the IL-6 production had apparent positive correlations with the National Institutes of Health-Chronic Prostatitis Symptom Index (NIH-CPSI) total score of CP/CPPS patients both in serum and seminal plasma.

Conclusion. The results indicate that FOXP3 and serum cytokines, such as TNF-alpha and TGF-beta 1, might play important roles in course of CP/CPPS and possibly affect the suppressive function of CD4⁺CD25^high regulatory T cells. This influence may result in the pathogenesis of CP/CPPS, but its assessment requires further study.

Keywords: CD4⁺CD25^high regulatory T cells, cytokines, FOXP3, prostatitis

P-53

The application of physical therapy in the early-term treatment of prostatitis

X.D. Li, S.H. Fan, Z.M. Mo, Y.G. Yu

Department of Andrology, No. 181 Hospital of PLA, Gulin, China

Objective. To investigate physical therapy in the early-term treatment of prostatitis.

Methods. (1) 90 cases of patients with prostatitis of Types II and III were divided into two groups at random. Group A was treated with α-receptor inhibitor, antibiotics, anodyne, and antidepressive drugs according to the symptoms; whereas Group B was treated with drug therapy as A, compounding physical therapy. The specific means were taken on basis of symptoms, such as microwave therapy vio rectum or urethra for urination dysfunction, short-wave or biofeedback therapy for pains, and negative suction for sexual dysfunction. The treatment last for 2–3 weeks. (2) Observation index: NIH-CPSI grade, anxiety index grade, EPS routine examination.

Results. On the aspect of NIH-CPSI and anxiety index grade, the treatment of B was better than A, whereas there was no obvious difference between the two groups on EPS routine examination.

Discussions. (1) The basic rules of treatment for prostatitis is to be according to its symptoms, and the symptoms can be obviously improved by drugs together with physical therapy, and besides NIH-CPSI grade and anxiety index grade go down at a high rate. (2) Physical therapy can not improve the EPS routine examination, and sometimes may even result in leukocytosis, making prostatitis of types II and III developing into that of type VI. It is not sure whether the deoppilation of some glandular tubes makes inflammatory exudates discard or there is absolutely no improvement in local areas, which needs long term follow-up. Schedules of physical therapy should be strictly chosen for the unmarried and non-sterile people, avoiding high temperature to testes, stenosis of ejaculatory duct, and urethral injury.

P-54

The experience of infertility treatment for senior patients of the over-sixties

Y. Kobori¹, H. Okada¹, R. Sato¹, Y. Ashizawa¹, H. Yagi¹, S. So¹, G. Arai¹, K. Terai²

¹Department of Urology, Dokkyo Medical University Koshigaya Hospital, Japan; ²Department of Urology, Juntendo University Hospital

In Japan, the over-sixties patients who visit a male infertility clinic increase rapidly, as elongation of expected life span, during last 20 years the average age of first marriage shifted older and modern assisted reproductive technology (modern ART) was introduced for the treatment of male factor infertility. We investigated clinical course of 12 male infertile patients of over-sixties who visited our department between 2004 and 2008. The patients aged between 60 and 72 years old, and their spouses aged between 35 and 50 years old. The marital history of five patients was the first marriage, and seven patients married again. All patients of remarriage had children with their ex-wives. The sexual function of first visit assessed by the International Index of Erectile Function-5 (IIEF-5) scored from 4 to 20 points. Only one patient complained complete erectile dysfunction. We investigated seminograms, background, hormonal analyses. We also investigated the modern ART used to overcome sterility. Intrauterine insemination (IUI) was performed in two patients are resulted one pregnancy. Intracytoplasmic sperm injection (ICSI) was performed nine patients are resulted three pregnancy. Although testicular sperm extraction (TESE) was tried in one patient with sexual dysfunction, sperm was not retrieved. The number of aged (over sixty) male infertile patients may increase continually. As a consequence the number of offspring birth with modern ART will increase. Now is the time to start careful follow-up to children from genetic and epigenetic point of view.

P-55

Anti-FSH autoantibody caused the germ cell apoptosis in rat testis

B. Yao, H.R. Xu, L. Hou, C.Y. Wang, C. Jiang, Z. Huang

Institute of Clinical Laboratory Medicine, Nanjing JingLin Hospital, China

Objective. To investigate whether anti-FSH autoantibody involved in the process of idiopathic oligoasthenospermia.

Methods. The rats were immunized seven times with polypeptide-KLH every 2 weeks. The serum FSH, LH, and Inhibin B levels were measured by enzyme-linked immunosorbent assay (ELISA). The apoptotic germ cells were detected using the in situ end labeling method (TUNEL). We also determined the Bax mRNA level in model rat testis by Fluorescent Quantitative PCR.

Results. The serum FSH level in experimental group that immunized for 77 days and 91 days was significantly lower than control group (P < 0.05). However, after immunized for 105 days, the serum FSH in experimental group increased to normal level. Compared with control group, the serum Inhibin B level significantly declined (P < 0.05). The serum LH level had no difference between control and experimental group. After immunized for 77, 91, and 105 days, the intratesticular Bax mRNA level in experimental group was 2.15-fold, 3.77–fold, and 1.89-fold compared with that in control group, respectively. The result of TUNEL indicated that the apoptotic index of germ cells in experimental group was significantly higher than that in control group (p < 0.01).

Conclusion. The decreased serum FSH level caused by anti-FSH autoantibody could induced the apoptosis of germ cells via the apoptotic path way involved in Bax further influence the ability of spermatogenesis.

Keywords:Anti-FSH autoantibody, FSH, inhibin B, cell apoptosis

P-56

Effects of GnRH agonist on annexin 5 and 3β-HSD expression in rat leydig cell

B. Yao, H.R. Xu, L. Hou, C.Y. Wang, C. Jiang, Z. Huang

Institute of Clinical Laboratory Medicine, Nanjing JingLin Hospital, China

Objective. To investigate the effects of GnRH analogue on annexin 5 and 3β-HSD expression in rat Leydig cell.

Methods. Leydig cell was separated, purified and identified in vitro. Different concentrations of GnRH analogue were administrated on cultured Leydig cells for 24 h. The expression of annexin5 and 3β-HSD were analyzed by Western blotting.

Results. Treatment with the GnRH agonist 10⁻⁵ mol/l, comparing with that in control group, has a 69.2% (P < 0.01) significant increase in annexin5 and 25.2% (P < 0.05) in 3β-HSD expression. Treatment with GnRHa (10⁻⁶ and 10⁻⁷ mol/l, respectively), there was a 61.5% (P < 0.05) and 16.64% (P > 0.05) increase in annexin5 and 7.7% (P > 0.05) and 2.22% (P > 0.05) increase in 3β-HSD expression.

Conclusions. GnRH agonist can regulate the annexin5 and 3β-HSD expression in primary Leydig cell in dose dependent manner.

Keywords:GnRH agonist, primary Leydig cell culture, annexin5, 3β-HSD

P-57

The effect of cigarette smoke on epididymis apoptosis and apoptosis-related genes Bcl-2/Bax in rats

T. Wu

Urology Department of Renmin Hospital of Wuhan University, China

Aim. Through constructing the model of rats passive smoking, to investigate the effect of cigarette smoke on epididymis apoptosis and apoptosis-related genes Bcl-2/Bax in SD rats.

Method. Twenty-four male SD rats (8 weeks old) were divided randomly into three groups (n = 8, each): Group A were used as control. Group B were exposed to cigarette smoke, and Group C were exposed to cigarette smoke and received daily intramuscular injection of GSH. 60 days later, the rats were sacrificed and excised epididymis tissues. The cell apoptosis was detected by TUNEL method, and using streptavidin-biotin peroxidase (S-P) method to detect the expression of Bcl-2 and Bax protein.

Results. (1) The mean values of three group rats body weights and epididymis weights have no significant difference (P > 0.05). (2) The epididymis ducts of Group A and Group C are normal or amost normal. In Group B, the epididymis ducts are abnormal. (3) There are no statistical difference in three groups (P > 0.05) for Bcl-2 and highly statistical difference in three groups (P < 0.01) for Bax by Non-parameter Test. (4) Apoptosis Index (AI) have highly statistical difference in three groups (P < 0.01) by One-Way ANOVA. (5) The correlation coefficient in AI and Bcl-2 expression is -0.412 (P < 0.05) by Pearson analyse and it in AI and Bax expression is 0.829 (P < 0.01).

Conclusions. Cigarette smoke induce oxidative stress injury in rats epididymis tissue, leading to highly apoptosis. Antioxidation treatment can improve the degree of apoptosis, to provide an alternative route in male infertility treatment.

Keywords:Cigarette smoke, epididymis, apoptosis, Bcl-2/Bax, infertility

P-58

Expression of connexin 43 in the testis of human with azoospermia

Y. Mao, Q. Wei, Y.B. Wang, Q. Dong

Department of Urology, West China Medical School, West China Hospital, Sichuan University, China

Objective. To investigate the expression of connexin 43 (cx43) proteins in the testis of adult men both with normal spermatogenesis and associated with spermatogenic impairment and the role of the connexin 43 during spermatogenesis.

Method. Investigation was performed on the needle biopsy of 267 infertile patients (age: 19–41 years, mean: 29.6 years). There were no sperm in their semen with the examination of semen twice. The volume of their testis is larger than 12 ml and the level of hormones is normal. The testicular biopsy specimens were fixed by immersion in Bouin fixative in 10 h and embedded in paraffin using standard techniques. The doctor who came from pathology department assayed the sections with HE staining. They clarified these sections by Joshen scores. Finally, we chose 108 sections from all sections in the norm of more seminiferous tubules (10–15), less inflitration of inflammatory cells and less injury of the tissues. Immunohistochemistry of Cx43 was performed on the 108 sections, then, we detect the expression of Cx43 in these sections.

Result. (1) All patients were given bilateral needle biopsy. 23 patients were lost at extracting the testicular tissue, meanwhile, 46 patients only got their testicular tissue one side. That means we complete the needle biopsy 534 times, and the rate of failure is 17.23%. However the rate of failure of getting one patient's testicular tissue is 8.61%. (2) Stain these sections in HE method and grade them in Johsen’ way with the microscope. We find, from 1 to 10 scores, the proportions of the patients are 1.64%, 11.48%, 7.79%, 4.92%, 8.20%, 10.25%, 6.97%, 34.43%, 10.66%, and 3.69%. (3) Regardless of the Joshen scores, Cx43 immunoreactivity was generally present between Leydig cells, not between peritubular myoid cells and not between testicular vascular smooth muscle cells. Within the normal seminiferous epithelium Cx43 immunoreactivity was localized between adjacent Sertoli cells and between Sertoli cell and germ cells. Although testes with hypospermatogenesis and spermatogenic arrest at the level of round spermatids or spermatocytes revealed a staining pattern similar to that of normal adult testis, the seminiferous tubules showing spermatogenic arrest at the level of spermatogonia and Sertoli-cell-only syndrome were completely immunonegative. The differences between the pathlogical groups have the statistical significance.

Conclusion. The bilateral needle biopsy could reduce the failure of getting the testicular tissue. Cx43 in testes expresses widely between Sertoli cells, between Sertoli cell and germ cells and between Leydig cells, but does not exhibit between peritubular myoid cells and between testicular vascular smooth muscle cells. Cx43 is the basis of the initiation and maintenance of spermatogenesis.

Keyword: Infertility, testis, testis needle biopsy, connexin 43

P-59

Identification and functional analysis of spermatogenesis related genes in testis

Z.M. Cai, Y.T. Gui, A.F. Tang, P. Xiao, J.X. Ye, Z.D. Yu, Y.C. Zhou, S.L. Sun, Q.L. Liu, Q.X. Yan, B. Yan, Z.M. Jiang, X.X. Li, L.C. Ni

The Key Laboratory of Male Reproductive and Genetic of Guangdong Province, Peking University of Shenzhen Hospital, China

Objective. To screen genes involved in testis spermatogenesis and to investigate expression pattern and function of these genes in spermatogenesis.

Methods. The transcription profile of mouse testis was determined by comparing samples of mice at the different postnatal stage using Affymetrix Genechip mouse microarrys (430.2) and novel spermatogenesis-related genes in testis were screened. The expression pattern and function of these genes in spermatogenesis were identified by bioinformatics analysis, RT-PCR, immunohistochemistry, in situ hybridization (ISH) and western blot.

Results. In mining the microarray data, 2058 genes were found to be expressed in a gradually increased manner in the developmental stages of mice testis. Eight novel testis-specific genes were isolated in mice and human testis, which were named TSC21, TSC24, TSC29, TSC31, TSC77, TSC279, TSG23, TSBAG, and TSCP, respectively. These eight genes were exclusively expressed in mice testis and their gradually increased expression began in the mice testis of around Day 18. TSC21, T279, and TSG23 were mainly located in mouse testicular seminiferous spermatocytes and spermatids.

Conclusions. The expression of TSC21, T279, and TSG23 significantly decreased in testis from the busulfan-induced azoospermia mice, cryptorchidism, and azoospermaic patients. These results indicated that these genes might be involved in the process of testis spermatogenesis.

P-60

The molecular mechanism and experimental treatment of azoospermatism

Z.M. Cai, Y.T. Gui, A.F. Tang, J. Yu, X.S. Xiao, X. Guo, J. Qin, G.H. Cui, Y.C. Zhou, S.L. Sun, Q.L. Liu, Q.X. Yan, B. Yan, Z.M. Jiang, X.X. Li, J.X. Ye

The Key Laboratory of Male Reproductive and Genetic of Guangdong Province, Peking University of Shenzhen Hospital, China

Objective.To investigate the molecular mechanism of azoospermatism and to explore a possible method for the treatment.

Methods. The semen quality of adult male and the incidence of male infertility in Shenzhen city were retrospectively analyzed. Karyotypic studies on azoospermatism and character of Y chromosome microdeletion were analyzed. Genes involved in testis spermatogenesis were screened by microarray technique. Expression pattern of these genes in human and mouse testis, and their differential expression between normal male and the patients with azoospermatism were analyzed by cytogenetic and biochemical techniques. Roles of these new genes in testis spermatogenesis were analyzed by gene knock-out and RNAi techniques. Spermatocyte maturation in vitro, the committed differentiation of stem cells, and allogeneic grafts of testis were carried out to develop new methods for the treatment of spermatogenic arrest.

Results and conclusion. The results indicated that the semen quality of adult male in Shenzhen city was lower than the average level of the country, and the semen quality of andrology outpatient was lower than the level of some parts of the country. The karyotypic studies of 3300 male infertility patients showed that the incidence rate of chromosome abnormality was 6.6%, of which 22 cases were firstly reported in the world, and the incidence rate of Y chromosome microdeletion was 9.8%. By microarray technique, eight new testis-specific genes involved in spermatogenesis were identified, of which the expression of seven genes were not detected in azoospermatismic patients's testis. By in vitro culture systems, spermatocytes from mouse and rat testis were differentiated to elongating spermatids, human testicular round spermatids to elongating spermatids, and rat bone marrow derived mesenchymal progenitor cells to spermatogenic cells. After grafted under the skin of castrated nude mice, the graftes from neonatal mouse testis were grewn well and the spermatogenesis could be observed. Spermatozoa derived from neonatal mouse testes grafted into immunodeficient mice were injected into mouse oocyte by intracytoplasmic sperm injection, and the zygote could be developed into an embryo.

P-61

Functional expression of ropporin in human testis and ejaculated spermatozoa

J. Chen, Y. Wang, Y.Q. Lai, Y.T. Gui, Z.M. Cai

The Key Laboratory of Male Reproductive and Genetic of Guangdong Province, Peking University of Shenzhen Hospital, China

Objective. To detect the expression of ropporin in human testis and sperm, and to verify whether decreased expression of ropporin in ejaculated spermatozoa from asthenozoospermic patients is associated with impaired sperm motility.

Methods. Expression of ropporin protein in human testis and sperm was detected respectively by immunohistochemistry and indirect immunoflorescence. Human spermatozoa in ejaculated spermatozoa from normozoospermic and asthenozoospermic men were purified by percoll discontinuous density gradients to separate the seminal plasma and other round cells. RT-PCR, Western blot and indirect immunoflorescence were used to compare the expression of ropporin between two sperm samples.

Results. Ropporin was predominantly expressed in round spermatids in human testis and located in the principle piece and end piece of sperm flagella. The expression of ropporin was detected significantly lower in spermatozoa from asthenozoospermic patients than that from normozoospermic men both in mRNA and protein level.

Conclusion. These data indicated that ropporin might play an important role in human sperm motility and decreased expression of ropporin in ejaculated spermatozoa from asthenozoospermic patients is associated with impaired sperm motility.

P-62

Expression profile of primordial germ cells differentiation-associated genes in mouse embryonic stem cells induced with all-trans retinoic acid

X. Guo, Z.Y. Qi, J. Qin, Y.M. Zhang, G.H. Chui, Y.T. Gui, Z.M. Cai

The Key Laboratory of Male Reproductive and Genetic of Guangdong Province, Peking University of Shenzhen Hospital, China

Objective. To explore the mechanism of all-trans retinoic acid (atRA) which is a known inducer of PGCs differentiation in vitro.

Methods. To determine RARE (retinoic acid response elements) which located within the promoter of PGCs differentiation-associated genes according to online bioinformatics software to predict atRA response genes, Stra8 (Stimulated by Retinoic Acid Gene 8, Stra8) was positive control as identified the primary response gene of atRA. mESCs-derivd EBs were maintained in culture medium containing 1 μM, 2 μM, and 5 μM atRA for 16 h, 2 d and 5 d, respectively. Real-time PCR was carried to measure the relative mRNA abundance of genes.

Results. The patterns of expression of seven genes could be organized into four groups: rapidly reaching peak value in 16 h (Stra8), reaching peak value in 2 days (Scp3), initially low and then increased to reach peak value in 5 days (Blimp1, Mvh, Pgk2, Prm1), or relatively unchanged (Fragilis). The pattern of expression of Mvh /Scp3 conform to the features of atRA secondary/primary response gene, and consistent with bioinformatics prediction, respectively. Predicting the primary response gene of atRA including Blimp1, Pgk2 and Prm1 exhibited the trait of secondary response gene. The effect of 1 μM atRA and 5 μM atRA induced significantly than that group of 2 μM atRA. The expression variation of genes associated PGCs differentiation is achieved in short time (2–5 d) with treatment of atRA.

Conclusion. Our findings establish the preliminary conclusion in the differentiation of mESCs for PGCs that atRA-regulated genes are secondary response genes including Blimp-1, Mvh, Pgk2 and Prm1, which are associated with a specific differentiation pathway. However, Fragilis regulated PGCs differentiation may be independent of atRA. The optimal condition of mESCs-derived EBs differentiated into PGCs is treated with 1 μM atRA for 5 days.

P-63

The developmental expression of Tesmin in mice

A.F. Tang, Q.X. Yan, R.Y. Diao, Z. Yu, L. Sun, Y.T. Gui, J.X. Ye, Z.M. Cai

Guangdong Provincial Lab of Male Reproduction and Genetic, Peking University Shenzhen Hospital, Shenzhen, China

Objective. To identify the developmental expression of Tesmin in mice.

Materials and methods. Testes cDNA samples from Balb/c mice of different postnatal days (4, 9, 18, 35, 54 days, and 6 months) were performed with mouse whole genome 430 2.0 Array (Affymetrix) chip. The characteristics of the selected gene, Tesmin, were analyzed by RT-PCR assay.

Results.The Affymetrix chip probe of mouse Tesmin was graduated higher expression with developmental stages of mouse testis. The scaling hybridization signal intensities of the tested testis on d4, d9, d18, d35, d54, and 6 months of postnatal were 31.4 (Absent expression, A), 34 (A), 1292 (Present expression, P), 856.6 (P), 977.2 (P), and 830.7 (P), respectively. These results indicated that the expression of mouse Tesmin wasn't detected on Day 4, and Day 9, but was detected on 18, 35, 54 days, and 6 months of mouse testis in our Affymetrix chip analysis. By combination with the RT-PCR analysis of mouse Tesmin, we observed mouse Tesmin begins to express at the age of d 18 in mouse.

Conclusions. The Tesmin was expressed in an time-dependent manner in mouse testis, and the expression of Tesmin begins after Day 18 of postnatal testis in mice, indicated Tesmin plays an important role in mouse spermatogenesis.

Keywords:DNA microarray, tesmin, spermatogenesis

P-64

Expression analysis of a highly expressed gene in mice testis, TNP2

X.X. Li¹, Y.Q. Lai¹, J.X. Ye¹, A.F. Tang², Z.D. Yu², Y.T. Gui², Z.M. Cai²

¹Department of Urology, Shenzhen Hospital of Peking University, China; ²The Male Reproductive and Genetic Priority Laboratory in Guangdong Province, Shenzhen, China

Objective. To screen genes involved in spermatogenesis.

Methods. Testes cDNA samples from Balb/C mice of different postnatal days were hybridized with mouse whole genome Affymetrix chip to screen the testis-related genes. The characteristics of the selected genes were analyzed by various bioinformatics tools. RT-PCR was used here to identify the expression of the selected genes in mice testis.

Results. By analyzing on gene chip signals of mice testis aged 4, 9, 18, 35, 54 days and 6 months, a testis related gene, TNP2, with a differential expression in the developmental stages of testis was identified. The full length of mouse TNP2 cDNA was 724bp, which contained an open reading frame of 375 bp. RT-PCR analysis showed that mouse TNP2 gene highly expressed in the testis of 35-day mice.

Conclusion. TNP2 is a testis related gene. The expression of TNP2 corresponds to the appearance of spermatids of mice and indicates that TNP2 may have an important role in male mammalian spermatogenesis.

Keywords:Oligonucleotide array sequence analysis, TNP2 gene, spermatogenesis

P-65

The effect of cigarette smoke on epididymis apoptosis and apoptosis-related genes Bcl-2/Bax in Sprague-Dawley (SD) rats

X.B. Liu, T.P. Wu, H. Ouyang, X.S. Zhan, Q. Nong

Department of Urology, Renmin Hospital of HuBei Province, WuHan University, China

Aim. Through constructing the model of rats passive smoking, to investigate the effect of cigarette smoke on epididymis apoptosis and apoptosis-related genes Bcl-2/Bax in SD rats.

Results. (1) The mean values of three group rats body weights and epididymis weights have no significant difference (P > 0.05). (2) The epididymis ducts of Group A and Group C are normal or amost normal. In Group B, The epididymis ducts are abnormal. (3) There are no statistical difference in three groups (P > 0.05) for Bcl-2 and highly statistical difference in three groups (P < 0.01) for Bax by Non-parameter Test. (4) Apoptosis Index (AI) have highly statistical difference in three groups (P < 0.01) by One-Way ANOVA. (5) The correlation coefficient in AI and Bcl-2 expression is (0.412 (P < 0.05) by Pearson analyse and it in AI and Bax expression is 0.829 (P < 0.01).

Conclusion. Cigarette smoke induce oxidative stress injury in rats epididymis tissue, leading to highly apoptosis. Antioxidation treatment can improve the degree of apoptosis, to provide an alternative route in male infertility treatment.

Keywords:Cigarette smoke, epididymis, apoptosis, Bcl-2/Bax, infertility

P-66

Comparison of two approaches of varicocelectomy for treatment of varicocele

Q. Xie, M. Cao, Y.D. Zhang, X. Yang, C. Xu, J. Deng, Z.R. Zhang, J. Chu

Department of Urology, The Affiliated Zhuhai Hospital of JiNan University, China

Objective. To compare the merits and demerits of two approaches of ligation for the treatment of varicocele.

Methods. 144 man with unilateral varicocele were prospectively randomized to undergo open (Group 1, n = 76), transperitoneoscopic (Group 2, n = 68) Varicocelectomy. The effectiveness, complications, and technical aspects of the two approaches were compared and discussed.

Results. All operations were performed successfully. Significant difference was found between open and laparoscopic approaches in terms of duration of surgery, spermatic cord inside arteries dissociation rate, blood loss, and postoperative recovering time Laparoscopic approaches is better than open. Though opening group hospital expenses under laparoscopic groups, but if plus related expenses, both the total cost of form is not statistically significant (P > 0.05).

Conclusions. Transperitoneoscopic varicocelectomy are effective and safe for the treatment of varicocele, whereas is better for the patient.

Keywords:Varicocele, surgical treatment, laparoscopy

P-67

Identification of the human embryonal carcinoma of testis proteins by two-dimensional gel electrophoresis and mass spectrometry

X.M. Mao¹, F. Li¹, Y.G. Zhou², Q.Z. Zhou¹, T.Q. Li¹, W.B. Guo¹, X.W. Jing¹, J.M. Li³

¹Department of Urology, Nanfang Hospital, Southern Medical University, China; ²Department of Stomatology, Southern Medical University; ³Department of Pathology, Southern Medical University

Objective. To separate and identify the human embryonal carcinoma of testis proteomics using two-dimensional electrophoresis (2-DE) and mass spectrometry.

Methods. Immobilized pH gradient two-dimensional polyacrylamide gel electrophoresis was used to separate the total proteins of the samples. After silver staining, PDQuest 7.30 image analysis software was applied to analyze 2-DE images. Three of the proteins high-expressed in the gel of the human embryonal carcinoma of testis were identified by matrix assisted laser adsorption/ionization-time of flight-tandem mass spectrometry (MALDI-TOF-MS/MS).

Results. 2-DE can screen the differentiate proteins between the two groups, Three proteins high-expressed in the gel of the human embryonal carcinoma were successfully identified.

Conclusion. The proteins of the human embryonal carcinoma of testis can be well separated and analyzed using 2-DE and mass spectrometry. Proteomic analysis technique offers a new means for further study of the human embryonal carcinoma of testis.

Keywords:Two-dimensional electrophoresis (2-DE), mass spectrometry, proteome, the human embryonal carcinoma of testis

P-68

Biodegradable poly (lactic-co-glycolic acid) maxpol-T/S as novel scaffold for adipose derived stem cells and fibroblast growth in vitro

Z. Jin, Y.Q. Gong, X.C. Qin, J. Zhang, Y.C. Zhu, Z.C. Xin

Andrology Center, Peking University First Hospital, Peking University, China

Objective. To explore the ability of MaxPol-T/S, a novel biodegradable poly-lactic-co-glycolic acid (PLGA) scaffold, in providing a cell-matrix interaction interface for cell growth.

Methods. We generated GFP positive adipose derived stem cell (ADSCGFP+) and fibroblasts (FCGFP+) for investigating the cellular growth on this biomaterial. The MaxPol-T/S was produced through salt-leaching/particulate-leaching technology for tissue engineering, which provides a modified surface for the best cellular attachment sites and nutrient supply and waste exchange conditions. The morphological features of MaxPol-T/S were studied with a scanning electron microscope and the ADSCGFP+ and FCGFP+ were confirmed by auto-fluorescence microscopy and flow cytometry assay.

Results. Being seeded onto the MaxPol-T/S in vitro, the growth and morphology of ADSCGFP+ and FCGFP+ were further verified by auto-fluorescence microscopy and MMT test. The ADSCs and fibroblasts, expressed strong GFP signals in the cytoplasm and nucleus, adhered and proliferated on the surface of scaffold MaxPol-T/S. Both cell lines survived on the scaffold more than 21 days in vitro and formed three-dimensional colonies on the surface of the MaxPol-T.

Conclusion. MaxPol-T/S is a novel PLGA scaffold for ADSCGFP+ and FCGFP+ and implies a promising technique for tissue engineering.

Keywords:Adipose-derived stem cells, fibroblasts, GFP, PLGA mesh, cell adhesion, tissue engineering

P-69

Clinical study on the safety and efficacy of penolasty using tissue engineered surgery for small penis syndrome

Z.C. Xin¹, Z. Jin¹, Y.G. Wu², X.Y. He²

¹Andrology Center, Peking University First Hospital, Peking University, China; ²Department of Urology, PLA 301 Hospital, China

Objective. To evaluate clinical safety and efficacy of penolasty using tissue engineering surgery with PLGA scaffold (Maxpol T) for small penis syndrome, the clinical study was performed in two medical centers.

Materials and methods. Sixty-nine patients suffering from small penis syndrome with a mean age was 34.4 ± 9.34 years old participated this study according to study protocol. At first, testis dermal tissue sized 1 × 2 cm was detached and fibroblast cell was isolated and cultured until number reached to 1 × 10⁷ in 2–3 weeks. The cultured cells were seeded into the conical shaped PLGA scaffold under the negative pressure and incubated for 2–3 h before transplantation. Pretreated scaffold with cells was inserted under the Buck's fascia of the penis by circumcision, and then skin closured layer by layer. All patients were checked penis girth using sonography and evaluated patient satisfaction score using Visual Analogue Scale (VAS) pre- and post-surgery 1, 3, and 6 months. The safety profile include erectile function were evaluated also.

Results. In the results, the penile girth were increased significantly post-operation compared with pre operation (p < 0.001), the mean penile girth increased 3.3 ± 1.34 cm (ranged from 1.8 to 4.0 cm). The efficacy of penile girth increasing in post 1, 3, 6 months showed no significantly different (p > 0.05) and 65 cases (94.2%) were satisfied with penile girth increasing according to results of VAS assessment. Six cases (8.69%) showed prolonged local mild edema, among of them, three cases showed pinpoint erosion and were treated by conservated medication.

Conclusion. These results suggested that penolasty using tissue engineering surgery with PLGA scaffold (Maxpol T) for small penis syndrome is safe and effective. Further large scale clinical study is recommended.

Keywords:PLGA scaffold, fibroblast cell, penis enlargement

P-70

The effects of penile transplantation of skeletal muscles derived stem cells in the castrated rats

S.J. Kim, D.W. Sohn, H.J. Cho, S.H. Hong, J.Y. Lee, T.K. Hwang, S.W. Kim

The Department of Urology, The Catholic University of Korea, Republic of Korea

Introduction. After castrated, the smooth muscles are atrophied and erectile function is deceased. Muscle-derived stem cells (MDSC) can be prepared from skeletal muscle biopsies, more accessible for autologous transplants than bone marrow and as such do not pose the immunogenic risks of embryonic stem cells. We investigated the effect of intracavernosal transplantation of MDSCs on the erectile function in castrated rats.

Material and methods.Bilateral orchiectomy was done in the experimental groups and rectus muscles were obtained for the isolation of MDSCs. The MDSCs were isolated using a modified preplate technique. Three experimental groups were included: a control group (Group I, n = 6); a bilateral orchiectomy group with MDSC injections (1X106 cells in 20 ml) into the penile corpus cavernosums (Group II, n = 6); and a bilateral orchiectomy group with HBSS injections into the penis, and studied at 4 weeks (Group III, n = 6). To investigate the penile erection, the peak intracavernosal pressure (ICP) and mean arterial pressure (MAP) were measured with electrical stimulation of the pelvic nerves at 4 weeks. We analyzed the survival rate of MDSCs through PKH26 staining.

Results. ICP/MAP of Group III was significantly lower than that of Group I. ICP/MAP of Group II was improved over Group II. PKH-25 labeled MDSCs were detected in the corpus cavernosum of MDSCs transplanted group.

Conclusion. Penile MDSCs transplantation can facilitate recovery of corpus cavernosum and improve erectile function in the castracted rats. This study suggests that MDSCs might be viable therapeutic approaches for hypogonadism related sexual dysfunction.

P-71

The effect of balance training with transcutaneous electrical nerve stimulation (TENS) on balance abilities in older men

S.W. Lee

Department of Physical Therapy, Sahmyook University, Seoul, Republic of Korea

Age-related changes in the ability to adjust to alterations in sensory information contribute to impaired postural stability. Somatosensory input is known to be essential for postural control and TENS is a form of somatosensory input. The purpose of this study was to investigate the effect of balance training with TENS on balance abilities in older men. The subjects of this study were 42 older participants who were possible to perform the balance training. Participants were randomly assigned to a balance training with TENS group (n = 21) or a balance training with sham TENS group (n = 21). Balance training was executed for 8 weeks. TENS applied to the posterior aspects of lower leg before balance training. Stimulation was delivered by 4.5 cm² round electrodes, utilizing biphasic pulses, at 100 μs pulse duration and 100 Hz frequency. Sham TENS group was applied the same method as TENS group, but there was no stimulation. Outcome measures included a functional reach test (FRT), static postural sway velocity on the floor and foam by using forceplate, timed up and go test (TUG). The mean age of the study group was 81.33 ± 4.58 years. After the completion of the balance training, FRT and TUG are showed statistically significant improvements in both the TENS and sham TENS groups (p < 0.05). In the static postural sway velocity, both conditions showed a significant decrease in both groups (p < 0.05). The differences between the TENS and sham TENS groups were not significant, however, rates of improvement were greater in TENS group. In conclusion, the application of TENS to older men whose somatosensory were deteriorated was effective for improvement balance ability.

P-72

Joint effect of cigarette smoking, alcohol consumption and hOGG1 Ser326Cys and XPD Lys751Gln polymorphisms on urothelial cancer risk

Y.H. Wang^1,2, M.C. Liu¹, C.W. Wang¹, C.K. Hsu¹, H.Y. Chiou², S.D. Yeh^1,3

¹Department of Urology, Taipei Medical University Hospital, Taipei, Taiwan;²School of Public Health, Taipei Medical University, Taipei, Taiwan; ³Institute of Biomedical Sciences, Academia Sinica, Taipei, Taiwan

Objectives. To investigate the joint effect of cigarette smoking, alcohol consumption and hOGG1 Ser326Cys and XPD Lys751Gln polymorphisms on urothelial cancer (UC) risk.

Methods. This hospital-based case-control study included 460 UC cases and 540 cancer-free controls who had been frequency matched by age and gender between August 2006 and October 2008. hOGG1 Ser326Cys and XPD Lys751Gln polymorphisms were detected using polymerase chain reaction-restriction fragment length polymorphism. Chi-square test was performed to examine the association between polymorphisms of hOGG1 and XPD and clinicopathological characteristics. Unconditional multivariate logistic regression was used to estimate odds ratios (ORs) and 95% confidence intervals (CIs).

Results. We observed that cigarette smoking and alcohol consumption were significantly associated with UC risk. Subjects who carried both A/C or C/C genotype of XPD and C/G or G/G genotype of hOGG1 have a significantly increased UC risk of 1.8 (95% CI = 1.01–3.0). Individuals who have history of cigarette smoking and alcohol consumption carrying both of risk genotypes of XPD and hOGG1 have the significantly highest UC risk of 9.9 (95% CI = 4.5–21.8). In addition, UC cases who carried A/C or C/C genotype of XPD have a significantly higher prevalence of high grade tumors as compared to those carrying the A/A genotype.

Conclusion. A significant joint effect of cigarette smoking, alcohol consumption and hOGG1 Ser326Cys and XPD Lys751Gln polymorphisms on UC risk was observed in this study. In addition, the A/C or C/C genotype of XPD conferred a significantly higher prevalence of high grade tumors of UC.

P-73

Association between Expression and Polymorphism of Survivin and Urothelial Cancer Risk

C.C. Wu¹, Y.H. Wang^1,2, H.Y. Lin¹, M.C. Liu¹, C.W. Wang¹, C.K. Hsu¹, S.D. Yeh^1,3, H.S. Chiang^1,4

¹Department of Urology, Taipei Medical University Hospital, Taipei, Taiwan; ²School of Public Health, Taipei Medical University, Taipei, Taiwan; ³Institute of Biomedical Sciences, Academia Sinica, Taipei, Taiwan; ⁴School of Medicine, College of Medicine, Fu Jen Catholic University, Taipei, Taiwan

The purpose of this study is to investigate the association between expression and polymorphism of survivin and the risk of urothelial cancer (UC). A total of 190 UC cases and 210 cancer-free controls were recruited from the Chiayi Christian Hospital between August 2006 and May 2008. Fifty paraffin-embedded tumor tissues were also collected from 190 UC cases. Immunohistochemistry (IHC) was used to detect the expression of survivin in UC tumor tissues. A −31 C/G polymorphism in survivin gene promoter was determined using the PCR-RFLP method. A chi-square test was applied to examine the association between expression and polymorphism of survivin and clinicopathological characteristics. Unconditional multivariate logistic regression was used to estimate odds ratios (ORs) and 95% confidence intervals (CIs). We observed that the expression of survivin in UC tumor tissues is significantly associated with the −31 C/G polymorphism (X² = 6.47, P = 0.04) and pathologic grade (X² = 18.7, P = 0.001) but not clinical stage (X² = 2.32, P = 0.31). In addition, compared with subjects carrying the G/G genotype of survivin, there were significantly increased UC risks for individuals carrying the C/G genotype (OR = 2.8, 95% CI = 1.7–4.6) and those with the C/C genotype (OR = 4.0, 95% CI = 2.3–7.2). Subjects carrying the C/G or C/C genotype had a significantly increased UC risk of 3.2 (95% CI = 1.9–5.2) as compared to those with the G/G genotype. Among UC cases, study subjects carrying the C/C genotype had a significantly higher prevalence of having invasive (T2-T4) or higher-grade (G3) tumors as compared to those with the G/G genotype. These findings suggest that the expression and the −31 C/G polymorphism of survivin are not only significantly associated with pathological grade or clinical stage of tumors but also related to the development of urothelial cancer.

Keywords: Survivin, Urothelial cancer, Polymorphism, Immunohistochemistry

P-74

Diode laser vaporization of the prostate in patients with prostate enlargement -- preliminary results

M. Liu, C.K. Hsu, C.H. Liu, H.S. Chiang, S.D. Yeh

Department of Urology, School of Medicine, Taipei Medical University (Hospital)

Purpose. TURP is the gold standard surgical method in treating patients with benign prostate hypertrophy (BPH) in the last two decades. It is relatively safe in treating low risk patients but it causes some side effects in high risk patients such as myocardial infarction or water intoxication. To solve these problems, several kinds of laser invented for treating BPH more safely and quickly. FDA approved diode laser in treating BPH in 2005. It is a continuous side firing laser and power could be raised to 150W. It is absorbed by both hemoglobin and water. It could vaporize tissue without hemoglobin in it more efficiently. We design this experiment to see the safety and effectiveness of diode laser among Taiwanese.

Materials and Methods. Patients with LUTS symptoms and need prostatectomy was included in this trial. Pre-operative evaluation includes transrectal ultrasound, uroflow study, international prostate symptoms and scores and PSA. Exclusion criteria include prostate cancer patients, prostate size less than 30 cm³ and maximum uroflow rate over 15 ml/sec. After diode laser vaporization of the prostate surgery, we recheck transrectal ultrasound, uroflow study, international prostate symptoms and scores and PSA four weeks and twelve weeks later separately. We analyzed symptomatic improvement after surgery, operation time, and hospital stay to study the benefit in diode laser vaporization of the prostate in Taiwanese.

Results. There are more than 49 patients receiving this surgery in the past one year. The average operation time is one hour and 11 minutes. The average hospital stay is 2.7 days. Average age was 71.14 years old (55–92). Average IPSS preoperatively was 23.53 (17–30). Patients had a preoperative prostate volume averaging 54.61 cubic centimeters (30–123). Nine patients had re-growth of prostate tissue from a prior transurethral resection of the prostate. The average preoperative peak flow rate (Q max) was 5.14 mL/sec (0.0–12.0). Postoperative average Q max was 17.29 ml/sec (9.0–25.0) at one month follow up. No one needs blood transfusion during surgery and hospital stay. And no one encounter major complication either. Only one patient experienced sloughing tissue obstructed bladder outlet one month after surgery.

Conclusion.: Diode laser prostate vaporization surgery is a relative safe and effective surgery. Blood loss is few in every patient. We hope we can get more definite conclusion one year after surgery.

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Abstracts

Opening Lecture

Satellite Symposium (ED & LUTS)

Lecture 1 (Aging male and prostate)

Lecture 2 (Hormone effect on bone & brain)

Lecture 3 (Nocturia & sleep disturbance)

Lecture 4 (Testosterone & prostate)

Lecture 5 (Metabolic syndrome & LUTS)

Sponsored Symposium 1 (Sexual dysfunction & LOH)

Sponsored Symposium 2 (Topics of ED & LUTS in Asia)

Sponsored Symposium 3 (LOH)

Sponsored Symposium 4 (ED & metabolic syndrome)

Luncheon Seminar 1 (Prostate cancer)

Luncheon Seminar 2 (New concept in sexual medicine – STD & ED–)

Luncheon Seminar 3 (Chemotherapy for the elderly bladder cancer)

Symposium 1 [Podium for selected paper](ED)

Symposium 2 [Podium for selected paper] (Metabolic syndrome)

Symposium 3 [Podium for selected paper] (Testosterone)

Symposium 4 [Podium for selected paper] (Prostate cancer)

Symposium 5 [Podium for selected paper] (HRT)

Symposium 6 [Podium for selected paper] (Life style)

Symposium 7 [Podium for selected paper] (BPH)

Poster Session

References

Information for

Open access

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Help and information

Abstracts

Opening Lecture

Satellite Symposium (ED & LUTS)

Lecture 1 (Aging male and prostate)

Lecture 2 (Hormone effect on bone & brain)

Lecture 3 (Nocturia & sleep disturbance)

Lecture 4 (Testosterone & prostate)

Lecture 5 (Metabolic syndrome & LUTS)

Sponsored Symposium 1 (Sexual dysfunction & LOH)

Sponsored Symposium 2 (Topics of ED & LUTS in Asia)

Sponsored Symposium 3 (LOH)

Sponsored Symposium 4 (ED & metabolic syndrome)

Luncheon Seminar 1 (Prostate cancer)

Luncheon Seminar 2 (New concept in sexual medicine – STD & ED–)

Luncheon Seminar 3 (Chemotherapy for the elderly bladder cancer)

Symposium 1 [Podium for selected paper](ED)

Symposium 2 [Podium for selected paper] (Metabolic syndrome)

Symposium 3 [Podium for selected paper] (Testosterone)

Symposium 4 [Podium for selected paper] (Prostate cancer)

Symposium 5 [Podium for selected paper] (HRT)

Symposium 6 [Podium for selected paper] (Life style)

Symposium 7 [Podium for selected paper] (BPH)

Poster Session

References

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