Special Lectures (SL)

• SL1  |  SL2  |  SL3  |  SL4  |  SL5  |  SL6 

Lunch Seminars

• Session 1 - Molecular mechanisms of Erectile dysfunction in aging and diabetes
• Session 2 - The evolving management of erectile dysfunction
• Session 3 - Premature Ejaculation

The microvascular architecture of the human corpus cavernosum penis was studied by scanning electron microscopy of vascular corrosion casts. The corpus cavernosum was supplied by the penile deep artery. It gave off branches to become either arteries distributed within the corpus cavernosum or those directly supplying the dorpus spongiosum urethrae. The former arteries further divided into small arteries which fell into two categories: 1) arteries breaking up into capillaries, and 2) arteries draining directly into the cavernous sinuses. The capillaries were collected into venular networks just beneath the tunica albuginea (the subalbugineal venular plexus), while the cavernous sinuses were collected into vunules at the periphery of the corpus cavernosum. These postcavemous venules also received venules from the subalbugineal venular plexus, and left the corpus cavernosum. Thus, two cieculatory routes are evident within the corpus cavernosum. These findings suggested that the penile erectile cycle is controlled by hemodynamic changes between these two routes within the corpus cavernosum.

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Special lecture  2  (SL2)
"A novel computerized image study of penile histology in impotent men"
Yung Ming Lin
Department of Urology, National Cheng Kung University of Medical College, Tainan, Taiwan, ROC
Chairperson : Johnny Shin Nan Lin (Taiwan, ROC)

Introduction

The standard test for determining the component of intra-corporal structure is still inconclusive and is not yet widely used. Recently, we design an automated image analysis system to objectively quantitate the components of corpus cavernosum. This system can capture image and drive the slide automatically and the calculation time for each specimen is short. Automated computer morphometric system The system consists of 3 subsystem: image acquisition and section-position subsystem, sample-training subsystem and processing subsystem. At beginning, a trained image is selected to include 3 regions (smooth muscle cell, collagen fiber cell and background) that are manually acquired to train the parameters of canonical transform. Images stored by the RGB (red, green, and blue) color model are acquired at 108X magnification. Then the processing subsystem drives the positioning subsystem to acquire image from the cavernous section for analysis.

Observer variation

The inter-observer variances for the automated and manual methods were both estimated to be zero, whereas the estimated intra-observer variance for the manual methods were 35.6 times of that for the automated method (10.793 vs. 0.303). The percentage of intra-observer variance with respect to total variance was 6.5% for the manual method and was 0.3% for the automated method. So the variation contributed by observer's instability to the total variation was much higher for the manual method. Cavernous collagen fiber contents in impotent men Thirty-three impotent men and 2 normal potent men (control) underwent corpus cavernous biopsies, and the specimens were analyzed. Significant differences were found between normal potent and arteriogenic groups(48.2 ± 1.4% vs 73.2 ± 4.4%), and between normal potent and idiopathic groups(48.2 ± 1.4% ,vs 77.4 ± 4.2%) (p<0.05, respectively). Patients with age more than 60 y/o have a higher collagen fiber content (70.4 ± 3.7%) compared to those with age less than 50 y/o (58.6 ± 5.2%).

Conclusions

The present automated image analysis system is believed to be a reliable, accurate quantitative measurement tool for the studies of penile tissue.

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Pelvic nerve raised from parasympathetic preganglionic nucleus at sacral spinal cord and made synapse at pelvic ganglia. Pelvic ganglia located near prostate and/or neck of the urinary bladder. Penile nerve contained post-ganglionic fibers from pelvic ganglia and stimulation of the nerve caused penile election in man and animals.

Stimulation of penile nerve increased cavernous pressure (CV) and CV sustained during stimulation of the nerve. Threshold intensity was 2V and maximized at 6V. Threshold frequency was 2Hz and maximized 1 OHz. Stimulation of hypogastric nerve (HGN), lumbar sympathetic nerve, or lumbo-sacral sympathetic chain (LSSC) did not elicit increasing CV pressure. Stimulation of LSSC but not HGN inhibited pelvic nerve evoked CV-pressure increase. Since adrenergic inhibition was present at the pelvic ganglia, sympathetic modulation of penile nerve evoked CVpressure might be occurred at the ganglia.

Cells in the pelvic ganglia that received excitatory input from pelvic nerve, In normal, spontaneous firing was not observed. After denervetion of pelvic nerve chronically (4 weeks), spontaneous firing occurred in the ganglia. The activities occurred every 2 - 5 sec. The activities were blocked with tetrodotoxin or hexamethonium. Immunohistochemical demonstration indicated that the number of VIP containing neurons increased. Spontaneous neuronal activities at pelvic ganglia could be important for maintaining penile function after loss of pelvic nerve efferent pathways.

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1. The limited efficacy of treatment methods for erectile dysfunction Treatment options for Erectile dysfunction(ED) are numerous and diverse. However, none of these is gold standard, In other words, most treatments methods have their own advantages and shortcomings. Vacuum constriction device can be considered as primary treatment option without the need of further testing. However, patients may complain of mostly the lack of spontaneity, pain, coldness, numbness, petechiae of the penis, and difficulty in ejaculation. The use of intracavemous injection of vasoactive drugs has become an widely accepted method of treating erectile dysfunction. Self-injection therapy dose, however, have some major shortcomings and these include the occurrence of fibrotic complication and patient's needle-phobia. In the patients not responding to intracavernosal injection of vasoactive agents, Transurethral alprostadil has been reported to produce an erection sufficient for intercourse in some patients. However, drawbacks include high cost, incomplete response, and negative influence of psychological inhibition of the response. Most preferred route of adrru'nistration for ED medication is oral. Yohimbin and trazodone are two drugs that have been commonly used as first-line oral therapy. These two drugs, however, have the disadvantage of poor efficacy. Androgens has effects on the lirru'ted impotent patients with marked hypogonadism, and modest stimulatory effect on sexual interest of the eugonadal man. Contrary to these drugs, the efficacy of sildenafil has been reported to range from 50 to 80% rate of improvement in sexual function in patients of various etiologies. Sildenafil can apparently be the the drug of choice.

2. The request of patients with ED for improving general health with enhancement of potency Most treatment methods for ED enable patient to get erection itself not improving general health. Physicians frequently encounter patients who want to be stronger and healthier, and consequently to get potency improved . Non surgical treatment methods can be divided into 2 categories. One induces erection by acting locally in the penis and the other improves the erectile capacity by promoting general health status. Sildenafil can only induce erection. Drugs for treating ED should prevent aging process and enhance general health condition. Testosterone could be used for these purposes; improving general health with enhancement of potency.

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Innervation of the sympathetic pathway from the spinal cord to the seminal tract and reconstruction of the pathway after injury were investigated. Methods) Responses of the vas deferens, bladder neck and prostate to electrical stimulation of the peripheral sympathetic nerve were examined in dogs and rats whose nerves were intact, transacted or reattached.

Results:

1. Stimulation of the 2nd-5th lumbar splanchnic nerve elicited responses of the vas deferens, bladder neck and prostate, while that of the intermesenteric nerve elicited no significant responses.

2. After transaction of the contralateral or ipsilateral hypogastric nerve, stimulation of each lumbar splanchnic nerve elicited responses of the seminal tract bilaterally, indicating existence of multiple cross-innervation mechanism.

3. After transaction of the hypogastric nerve, compensatory mechanisms such as reorganization of synaptic connection in the pelvic plexus or enhancement of the remaining sympathetic pathways can be generated.

4. Stimulation of the major splanchnic nerve caused catecholamine-secretion from the adrenal medulla which induced ejaculatory responses as well as systemic reactions observed during ejaculation.

5. After partial transaction of the hypogastric nerve bilaterally, responses of the seminal tract to stimulation of a lumbar splanchnic nerve were recovered spontaneously.

6. After hypogastric nerve-hypogastric nerve reattachment bilaterally, responses of the seminal tract to stimulation of alumbar splanchnic nerve were recovered and cross-innervation mechanism described was preserved.

7. The hypogastric nerve graft restored the ejaculatory function. Conclusions) The sympathetic nerve pathways controlling ejaculation involves elaborate protective mechanisms against various injuries and can be reconstructed surgically.

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The spectrum of ejaculatory dysfunction extends from premature ejaculation (P.E.), through retarded ejaculation (R.E.) to a complete inability to ejaculate, anejaculation, and includes retrograde ejaculation. Ejaculatory dysfunction is the most common male sexual disorders and premature ejaculation (P.E), the most common presentation of ejaculatory dysfunction. Convincing data from controlled clinical studies to support sustainable long term efficacy of psychosexual counseling in the management of P.E. is lacking. The pharmacological treatment of P.E. is now receiving increased attention from both physicians with an interest in sexual medicine and from the pharmaceutical industry. Recent advances in both the understanding of the pathogenesis and the treatment of erectile dysfunction (E.D.), have prompted many men with E.D. to seek treatment. Many men seek, as part of their sexual rehabilitation, improvement in other domains of sexual function particularly ejaculatory control. The pharmacological modulation of ejaculatory threshold represents a novel and refreshing approach to the treatment of P.E. and a radical departure from the psychosexual model of treatment, previously regarded as the corner stone of treatment. It appears to fill a treatment "hiatus" produced by both the limitations and non-acceptance of psychosexual counseling by some sufferers and by the lack of convincing longitudinal clinical efficacy data. Pharmacological treatment offers patients a high likelihood of achieving improved ejaculatory control within a few days of initiating treating, consequential improvements in sexual desire and other sexual domains and a favourable adverse effect profile. It fails to directly address causal psychological or relationship factors and data on the efficacy of combined psychosexual counseling and pharmacological treatment, and the maintenance of improved ejaculatory control after drug withdrawal is either lacking or scarce. This presentation reviews both recent and past milestone advances in ejaculatory physiology, the pathogenesis of P.E. and its pharmacological treatment.

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Session 1 - Molecular mechanisms of Erectile dysfunction in aging and diabetes

Rajvir Dahiya, Koichi Nakajima, and Tom F. Lue
University of California, San Francisco and VA Medical Center, San Francisco, CA, USA

The main purpose of this lecture is to discuss the molecular mechanisms of erectile dysfunction associated with aging and diabetes using an animal model. We tested the hypothesis that growth factors (TGF-a, TGF-bl, TGF-b2, TGMb3, IGF, NGF), nitric oxide synthase and adrenoreceptor alpha I gene and protein expression may play a role in etiology of erectile dysfunction associated with aging and diabetes. The results of these experiments suggest that; (1) TGF- bI gene expression was significantly increased in old rat penis as compared to young; (2) mRNA transcripts for NGF and TGF- b3 were significantly lower in old rat penis as compared to old rat; (3) TGF-a, TGF- b2 and IGF mRNA expression did not change in young and old rat penis; (4) there was a decrease in bNOS-containing neurons and adrenergic neurons in the pelvic ganglia of old rats as compared to young; (5) NOS MRNA expression was significantly decreased in old rat penis as compared to old rat. In diabetic rats, there was a significant decrease in NOS containing nerve fibers in the dorsal and intracavemosal nerves. RT-PCR showed down-regulation of NNOS and ER MRNA in diabetic rat penis as compared to normal. In our recent studies, we have examined the genetic instability associated with Peyronie's disease. In conclusion, alterations in gene and protein expression of growth factors and NOS are involved in aging and diabetes associated impotence.

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Session 2 - The evolving management of erectile dysfunction

Ronald W. Lewis, MD
Chief of Urology, Medical College of Georgia Section of Urology

A clearer understanding of the physiology of erection and the pathophysiology of erectile dysfunction, especially in the realm of molecular biology, has led to a therapy that is less invasive but more systemic. The ease of delivery to the patient has been enhanced but the possibility of side effects playing a greater role compared to agents delivered directly to the cavemosal tissues is strong. Dr. Jeremy Heaton has suggested five theoretical classifications of treatment for erectile dysfunction: central initiators, central conditioners, peripheral initiators, peripheral conditioners, and others to be utilized in the classification of accepted and new therapies. As newer, more complex therapies are developed, the use of precise diagnostic tools will reemerge. In the future, combination therapy may emerge with intervention directed at several different sites of activity in the erectile cycle. At present, there is only one effective oral agent so there is less of a need to precisely diagnose the cause of the dysfunction as opposed to an empiric therapeutic trial. This lecture will stress the implications of the current understanding of the molecular pathophysiology of erectile dysfunction with regard to therapy and the role of current and future therapies in the management of erectile dysfunction. The delivery methods, side effects and uniqueness of each treatment choice will be discussed in detail.

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Session 3 – Premature Ejaculation

Hyung Ki Choi

Premature ejaculation (PE) is the most common type of ejaculatory dysfunction and the prevalence of PE tends to range between 20-30% of the male subjects. Medical therapies recently published for the treatment of PE have included the use of intracavernous injection therapy, sympathetic alpha block's, topical anesthetics along with clomipramine, and the more recent selective serotonin reuptake inhibitors (SSRI's).

SS-cream is a topical agent from extracts of 9 natural products (Ginseng Redix Alba, Angelicae Gigantic Radix, Cistanchis Herba, Zanthoxylli Fructs, Torlidis Semen, Asiasari Radix, Caryophylli Flos, Cinnamoni Cortex and Bufonis Veneum) for treatment of PE. The each active individual compositions of SScream were detectable (TCL analysis). Animal studies with SS-cream showed no toxicity (8: LD 5.@9.3 gm, @: 8.87 gm). Mild skin irritation action was noted but no irritation reaction on occuli of rabbits. No local and systemic histologic changes after long term application of SS-cream on the glans penis of rabbits and rats. The concentrations of main active components of SS-cream in systemic blood after the application of SS-cream on the penis of rabbits were undetectable (HPLC analysis). In patients with PE, SS-cream increases penile vibration threshold, and prolongs ejaculatory latency. A comparison of the clinical efficacy of placebo and SS-cream judged by ejaculatory latency prolonged more than two minutes were 15. 1 % and 79.8% respectively, and for the improvement of sexual satisfaction grade higher than effective were 19.8% and 82.2% respectively.

One hundred and three (16.2%) out of 636 trials of SS-cream showed mild local burning sense and mild pain. No adverse effect on sexual function and partner and no systemic side effects were observed.

With these results, SS-cream is effective and safe in the treatment of PE with mild local side effects.

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