Korean Society for Sexual Medicine and Andrology (KSSMA) Guideline on Erectile Dysfunction

In February 2011, the Korean Society for Sexual Medicine and Andrology (KSSMA) realized the necessity of developing a guideline on erectile dysfunction (ED) appropriate for the local context, and established a committee for the development of a guideline on ED. As many international guidelines based on objective evidence are available, the committee decided to adapt these guidelines for local needs instead of developing a new guideline. Considering the extensive research activities on ED in Korea, data with a high level of evidence among those reported by Korean researchers have been collected and included in the guideline development process. The latest KSSMA guideline on ED has been developed for urologists. The KSSMA hopes that this guideline will help urologists in clinical practice.

Relaxation Response of Rabbit Cavernous Smooth Muscle to Estrogen / 대한남성과학회지

PURPOSE: Estrogen relaxes vascular smooth muscle via genomic and non-genomic mechanisms. Most studies of the role of estrogen in the relaxation response have been conducted in females, and little information is available in males. This study investigated whether estrogen plays a role in relaxation of the rabbit cavernous smooth muscle. MATERIALS AND METHODS: Relaxation responses of rabbit cavernous smooth muscle to estrogen (30 nM, 300 nM, 3 micrometer, 30 micrometer) were observed in vitro. The responses of the muscle strips to estrogen after incubation with the transcription inhibitor dactinomycin (10 micrometer) or the nonspecific nitric oxide (NO) synthase inhibitor L-NAME (10 micrometer) also were evaluated. RESULTS: Estrogen caused dose-dependent relaxation of strips contracted by norepinephrine. The maximal response was seen about 10 minutes after treatment. Estrogen-induced relaxation was not prevented by dactinomycin or L-NAME, suggesting that the response was not mediated by gene transcription or NO. CONCLUSIONS: Estrogen may be involved in relaxation of rabbit cavernous smooth muscle via a non-genomic NO-independent mechanism.

Relaxation Response of the Rabbit Clitoral Corpus Cavernosal Smooth Muscle in Chronic Estrogen-Deficiency State / 대한비뇨기과학회지

PURPOSE: To investigate involvement of chronic estrogen deficiency in impairment of relaxation response of the clitoral cavernous smooth muscle. MATERIALS AND METHODS: New Zealand white female rabbits were randomly divided control (sham operation, n=6) and experimental groups; 1) bilateral oophorectomy (n=8), 2) oophorectomy with estradiol replacement (n=7), 3) oophorectomy with flutamide treatment (n=6). All the rabbits were sacrificed 12 weeks after the operations. Blood levels of estradiol and lipid fractions were measured just before the operations and sacrifice. Clitoral cavernous strips were obtained to observe relaxation responses to endothelium-dependent and -independent vasodilators, and electrical field stimulation (ESF). RESULTS: The uterus weight and serum estradiol level decreased significantly (p<0.01) in the oophorectomy group compared with the baseline data. The serum levels of total cholesterol, triglyceride, and low density lipoprotein increased significantly (p<0.01) in the oophorectomy group. The relaxations of the clitoral strips to acetylcholine were significantly attenuated in the oophorectomy group compared with those of the control and estrogen replacement groups. However, sodium nitroprusside- and nonadrenergic noncholinergic-induced relaxations were not significantly different among the 4 groups. No significant histologic changes were noted in the clitoral tissues of the oophorectomy group. CONCLUSIONS: Chronic estrogen deficiency in the rabbits may cause impairment of endothelium-dependent relaxation of clitoral corpus cavernosal smooth muscles. Further studies are needed to determine whether the hypoesterogenemia itself and/or secondary hypercholesterolemia due to the chronic estrogen deficiency may result in the impairment.

Effects of Various Tricyclic Antidepressants on Contractile Response of the Rat Vas Deferens to Electrical Stimulation of Hypogastric Nerve / 대한비뇨기과학회지

PURPOSE: To compare the inhibitory effects of various tricyclic antidepressants (TCAs) on contractile response of the rat vas deferens to electrical stimulation of hypogastric nerve. MATERIALS AND METHODS: A total of forty Spraque Dawley rats (weight 300-350gm) were divided into 8 groups (n=5 in each): doxepine, amitriptyline, trimipramine, desipramine, imipramine, clomipramine, protriptyline, and prazosin treated groups. Before (baseline pressure) and 20 minutes after intravenous injection of each agent (0.1-, 1-, 10-, and 20-fold of therapeutic doses for human in each agent), the hypogastric nerves, iden tified under operative microscope, were electrically stimulated with rectangular pulses of 0.5 mseconds duration, 10 Hz, and 10 V for 10 seconds. Dose of drug administered was gradually increased in order of 0.1- to 20-fold dose. RESULTS: All drugs tested in this study caused dose-dependent inhibition of the rat intravasal pressure induced by the electrical stimulation of hypogastric nerve. Inhibitory potency of each drug was doxepine (88.5% and 96.5% at 10- and 20-fold dose)> OR = amitriptyline (76.8% and 91.8%)>clomipramine (66.7% and 74.4%)> OR =imipramine (48.2% and 67.0%)=prazosin (45.6% and 63.5%)=trimipramine (52.7% and 65.4%)> OR =desi pramine (45.3% and 49.0%)> protriptyline (18.9% and 19.9%). CONCLUSIONS: Inhibitory effects of TCAs on contractile response of the rat vas deferens to electrical stimulation of hypogastric nerve would increase in proportion to their potency of alpha1-adrenoceptor blocking actions.

Priapism Lasting for Over 24 hours Induced by Intracavernous Vasoactive Agents / 대한남성과학회지

PURPOSE: Retrospective study was done to evaluate the causes of priapism lasting for over 24 hours induced by intracavernous vasoactive agents. MATERIALS AND METHODS: Thirteen patients of priapism lasting for 24-60 hours, induced by intracavernous vasoactive drugs, were retrospectively evaluated using medical records or by telephone interviews. Injected vasoactive drugs, providers of the drugs, purpose of the injection, reasons leaving the priapism untreated so long, treatment modalities of the priapism, and change of potency after the treatment were evaluated. RESULTS: Only 2 patients (15.4%) were self-injected to treat erectile dysfunction by doctor's prescription. The others, who received the drugs without doctor's prescription, had injections to enhance their potency (46.1%, n=6) or to treat premature ejaculation (15.4%, n=2). The drugs injected were papaverine (23.1%, n=3), papaverine and phentolamine (23.1%, n=3) or prostaglandin E1(7.7%, n=1), but unknown in 6 (46.1%). The reasons of leaving the priapism untreated were mostly due to lack of no knowledge about the priapism (53.8%, n=7). Aspiration and irrigation with alpha-agonist of corpus cavernosum were applied to all patients. Four patients who did not respond to the treatment underwent shunt operations. All the patients complained of weakened potency after the priapism. CONCLUSIONS: Priapism lasting for over 24 hours induced by intracavernous vasoactive drugs were mostly due to abuse or misuse of the drugs and resulted in weakened potency. To avoid this disaster, the drugs should be given to patients by doctor's prescription with full explanation about the side effects of the drug.

Effects of Serotonergic Drugs on Intraluminal Pressure of Vas Deferens Induced by Electrical Stimulation of Rat Hypogastric Nerve / 대한남성과학회지

PURPOSE: To compare the effects of various serotonergic drugs on the inhibition of intraluminal pressure rise in the rat vas deferens induced by electrical stimulation of the hypogastric nerve. MATERIAL AND METHODS: Twenty-five Sprague Dawley rats (250-300 gm) were randomly divided into five groups of five animals each, which received intravenous injection of normal saline, clomipramine, sertraline, paroxetine, or fluoxetine. Before (baseline pressure) and 30 minutes after intravenous injection of four different doses (0.1 to 20 the therapeutic dose) of each agent, the hypogastric nerve, identified using microsurgical technique, was electrically stimulated, and the intraluminal pressure of the vas deferens was measured (central effect group). To evaluate the peripheral effects of clomipramine and sertraline, intraluminal vasal pressure was also measured after transection of all proximal sympathetic nerves projecting to the hypogastric nerve and the commissural branches between the right and left major and accessory pelvic ganglia. The adrenal veins were ligated bilaterally. RESULTS: Repeated stimulation of the hypogastric nerves, anesthesia of long duration (3hours), and repeated intravenous injection of normal saline did not result in significant changes in the intraluminal pressure of the vas deferens in a dose-dependent manner (p<0.05). The extent of inhibition by 20-fold therapeutic doses of clomipramine, sertraline, paroxetine, and fluoxetin were 74.4 1.8%, 34.1 8.3%, 24.8 7.8%, and 8.1 3.5%, respectively. At doses 10- and 20-fold the therapeutic dose, clomipramine had the strongest inhibitory effect, followed by sertraline and paroxetin, then fluoxetine (p<0.05). Definite inhibition was noted in all rats receiving clomipramine at 10- and 20-fold the therapeutic dose; the degree of inhibition was 80% in the sertraline-, 60% in the paroxetine-, and 20% in the fluoxetin-treated group. The inhibitory effect of sertraline on the elevation of the intraluminal vasal pressure in the peripheral-effect group was significantly (p<0.01) less than that in the central-effect group. However, there was no difference in the inhibitory effect of clomipramine in the two groups. CONCLUSIONS: Clomipramine was the most potent inhibitor of the elevation of the intraluminal pressure of the rat vas after electrical stimulation of the hypogastric nerve. The greater effect might be attributable to an additional peripheral effect of this drug on the vas deferens.

Could Serum Level of Prostate-specific Antigen after High Energy Transurethral Microwave Thermotherapy for Benign Prostatic Hyperplasia Predict and Represent Efficacy of the Treatment? / 대한비뇨기과학회지

PURPOSE: To investigate serum level of prostate-specific antigen(PSA) after high energy transurethral microwave thermotherapy(HE-TUMT) for benign prostatic hyperplasia(BPH) could predict and represent efficacy of the treatment. MATERIALS AND METHODS: In patients with BPH who underwent HE-TUMT using Prostatron with Prostasoft 2.5(EDAP-Technomed, France), serum levels of PSA at 7 days(n=37), 3 months(n=40), and 6 months(n=26) after the treatment were compared with Madsen and international prostate symptom score(MSS and IPSS), maximal and average uroflow rate(MFR and AFR), and postvoiding residual urine(PVR) of 6 months after the treatment. RESULTS: The subjective(MSS and IPSS) and objective(PFR, AFR, and PVR) parameters were significantly(p<0.05) improved at 6 months after the treatment. The postoperative serum level of PSA showed a 643.2% increase(0.5-2870%) at 7 days(more than 500% increase in 18 men and less than 500% in 19), a 34.9% increase(79% decrease?303% increase) at 3 months, and a 8.5% decrease(74.7% decrease?53.7% increase). There was no significant difference in the both subjective and objective parameters at 6 months between the two groups; more and less than 500% increase on the 7th day, and among the three groups; more than 20% decrease(n=14), less than 20% decrease or increase(n=13), and more than 20% increase(n=13). However, improvement of MFR and AFR was significantly(p<0.05) higher at 6 months in 20% decrease group(n=9) compared with that of the remainder(n=17) although symptom scores and PVR not significantly different. CONCLUSIONS: Serum level of PSA at 7 days and 3 months after HE-TUMT could not predict efficacy of the treatment at 6 months. However, the extent of decrease in PSA level may represent relieved bladder outlet obstruction resulting from reduction of prostate volume.

Incidence of Vascular Risk Factors in Patients with Erectile Dysfunction Aged Over 40 Years: Comparison with Normal Men of Corresponding Age / 대한남성과학회지

PURPOSE: The incidences of four main vascular risk factors (VRFs) - diabetes mellitus (DM), smoking, hyperlipidemia (HLP), and obesity were investigated in men aged over 40 years with or without erectile dysfunction. PATIENTS AND METHODS: There were 943 patients with erectile dysfunction (mean age 55.0 years; range 40-73 years) and 242 normal men (mean age 50.6; range 40-71 years). Blood levels of various lipid fractions (triglycerides, total cholesterol, low-density lipoprotein, high-density lipoprotein), body weight, and height were measured in all subjects. Abnormal VRFs were defined as follows: hypertension = >160 mmHg (systolic pressure) or 95 mmHg (diastoic pressure), hyperlipidemia = at least one abnormal fraction (triglycerides > 160 mg/dl, total cholesterol >250 mg/dl, LDL >150 mg/dl), and obesity = >120% of ideal body weight. The presence or absence of DM, hypertension, smoking, and erectile dysfunction was determined by a self-reported subject questionnaire and history. RESULTS: The incidence of abnormal LDL was significantly (p<0.05) higher in patients than the control men. The incidences of HLP, DM, and hypertension were significantly (all p<0.05) higher in the patients 40 to 59 years of age than in the control men of corresponding ages, but differences in the incidences of smoking and obesity were not statistically significant. Abnormal VRFs were significantly (all p<0.01) more common in patients aged 40 to 59 years than in the control men of the same ages. In men over 60 years of age, there were no differences between the patients and control subjects in number of VRFs or the incidences of HLP, DM, and hypertension. CONCLUSIONS: Especially in men 40 to 59 years of age, DM, HLP, and hypertension were significantly correlated with erectile dysfunction. The aging process, rather than such specific risk factors, might be a main cause of erectile dysfunction in men aged over 60 years.

Comparison of relaxation responses of cavernous and trigonal smooth muscles from rabbits by alpha1-adrenoceptor antagonists; prazosin, terazosin, doxazosin, and tamsulosin

Alpha1a-adrenergic receptor (AR) primarily mediates the contraction of the prostatic and cavernous smooth muscles. Among clinically available alpha1-AR antagonists for the medical management of benign prostatic hyperplasia (BPH), tamsulosin has a modest selectivity for alpha1A- and alpha1D- over alpha1B-ARs. To compare the effects of various alpha1-AR antagonists on relaxation responses of cavernous and trigonal smooth muscles, isometric tension studies with relatively selective (tamsulosin) and non-selective (prazosin, doxazosin, and terazosin) alpha1A-AR antagonists, were conducted in the cavernous and trigonal muscle strips of rabbits (n=10 each). Tamsulosin had the strongest inhibitory effect on contraction of trigonal smooth muscle among the various alpha1-AR antagonists, and the inhibitory activities of prazosin, doxazosin, and terazosin were not statistically different. All alpha1-AR antagonists caused concentration-dependent relaxation of the cavernous muscle strips. Tamsulosin was shown to have greater potency than prazosin (more than 100-fold), doxazosin (more than 1000-fold), and terazosin (more than 1000-fold), in relaxation of cavernous smooth muscle. In conclusion, tamsulosin might be the most effective drug among the four commonly used alpha1-AR antagonists for the medical management of BPH. Tamsulosin might be a potential substitute for phentolamine in combination with vasoactive agents as an intracavernous injection therapy for patients with erectile dysfunction.

Efficacy and Safety of Androderm(TM) in Partially Androgen-deficient Aging Men with Erectile Dysfunction / 대한남성과학회지

PURPOSES: To evaluate the effect of Androderm(TM) on sexual function and its safety in partially androgen-deficient aging men with erectile dysfunction. MATERIALS AND METHODS: Two Androderm patches, designed to deliver 5mg of testosterone per day, were applied daily for 4 months to the back, abdomen, upper arm, or thigh of 21 patients (mean age 52.4+/-6.76 years; range 41-63 years) with partial androgen deficiency and erectile dysfunction, The degree of symptom using the Watts (sexual arousal, desire, orgasm, and satisfaction) and Davidson (number and quality of penile erections) questionnaires, Blood levels of total and bioavailable testosterone, estradiol, luteinizing hormone, follicle-stimulating hormone, and sex hormone-binding globulin were measured monthly. The safety variables examined were lipid profiles, liver and kidney function tests, prostate specific antigen, hematologic values, body mass index, and local skin reaction. RESULTS: Blood concentrations of total and bioavailable testosterone and estradiol were significantly (p<0.05) increased, but all were within the normal range during androgen replacement with Androderm. One third of the patients reported improvement in the quality of their erections. there were no significant differences in Watts sexual function scores, number of spontaneous and morning erections, or the quality of erections compared with baseline data. No changes in blood lipid profiles, measures of liver and kidney function, PSA, hematologic values, or body mass index were noted. However, 22% of the patients dropped out of the trial because of severe skin irritation symptoms. CONCLUSION: Androderm was partially effective in improving the quality of erection in partially androgen-deficient aging men and is physiologic and safe.

Efficacy and Safety of Androderm(TM) in Partially Androgen-deficient Aging Men with Erectile Dysfunction / 대한남성과학회지

PURPOSES: To evaluate the effect of Androderm(TM) on sexual function and its safety in partially androgen-deficient aging men with erectile dysfunction. MATERIALS AND METHODS: Two Androderm patches, designed to deliver 5mg of testosterone per day, were applied daily for 4 months to the back, abdomen, upper arm, or thigh of 21 patients (mean age 52.4+/-6.76 years; range 41-63 years) with partial androgen deficiency and erectile dysfunction, The degree of symptom using the Watts (sexual arousal, desire, orgasm, and satisfaction) and Davidson (number and quality of penile erections) questionnaires, Blood levels of total and bioavailable testosterone, estradiol, luteinizing hormone, follicle-stimulating hormone, and sex hormone-binding globulin were measured monthly. The safety variables examined were lipid profiles, liver and kidney function tests, prostate specific antigen, hematologic values, body mass index, and local skin reaction. RESULTS: Blood concentrations of total and bioavailable testosterone and estradiol were significantly (p<0.05) increased, but all were within the normal range during androgen replacement with Androderm. One third of the patients reported improvement in the quality of their erections. there were no significant differences in Watts sexual function scores, number of spontaneous and morning erections, or the quality of erections compared with baseline data. No changes in blood lipid profiles, measures of liver and kidney function, PSA, hematologic values, or body mass index were noted. However, 22% of the patients dropped out of the trial because of severe skin irritation symptoms. CONCLUSION: Androderm was partially effective in improving the quality of erection in partially androgen-deficient aging men and is physiologic and safe.

Efficacy of Oral Pharmacotherapy according to Results of Biothesiometry, BCRL and DNSEP in Patients with Premature Ejaculation / 대한비뇨기과학회지

PURPOSE: To determine whether biothesiometry, bulbocavernous reflex latency(BCRL), and dorsal nerve somatosensory evoked potential(DNSEP) test could predict efficacy of tricyclic antidepressant(TCA) or selective serotonin reuptake inhibitor(SSRI) to prolong the ejaculatory latency in premature ejaculation. MATERIALS AND METHODS: A total of 33 patients with pramature ejaculation(mean age: 44 years) completed the entire study, Patients took each of clomipramine(50mg), sertraline(1 00mg), and fluoxetine(40mg) consecutively during a 4-week period per each agent. We obtained increased intravaginal ejaculatory latency by the most effective drug among 3 drugs. We analyzed correlations of the increased intravaginal ejaculatory latency with vibration threshold of penile shaft and glans, BCRL, and latency and amplitude of DNSEP. RESULTS: According to Pearson's correlation analysis, there was no correlation of intravaginal ejaculatory latency with vibration threshold of penile shaft and glans, BCRL, and latency and amplitude of DNSEP(all p> 0.05). There was no difference in intravaginal ejaculatory latency between the groups of high and low vibration threshold, long and short BCRL, long and short latency of DNSEP, and large and small amplitude at cerebral cortex on DNSEP test(all p> 0.05). CONCLUSIONS: It seems that biothesiometry, BCRL, and DNSEP test can not predict the efficacy of tricyclic antidepressant or selective serotonin reuptake inhibitor to prolong the ejaculatory latency in premature ejaculation.

Extensive Penile Necorsis Following Implantation of Malleable Penile Prosthesis: Two Cases / 대한남성과학회지

Penile necrosis is a rare, serious complication of penile prosthesis implantation. Severas factors, including systemic disease, compressive dressing, hematoma, edema, indwelling urethral catheter, and local infection may contribute to the complication. We report two cases of penile necrosis caused by hematoma and compressive dressings applied to control the bleeding.

Intracavernosal Self-Injection Therapy for the Patients with Erectile Dysfunction: Comparison of Erectile Response and Complications between Bimix and Trimix Solution / 대한비뇨기과학회지

PURPOSE: To compare the efficacy of Bimix solution (27.3 mg/ml papaverine and 0.9 mg/ml phentolamine) versus Trimix solution (18.8 mg/ml papaverine, 0.6 mg/ml phentolamine and 6.3ug/ml prostaglandin El) in terms of erectile response and complications. MATERIALS AND METHODS: We comparatively analyzed the erectile response and the incidence of pain, prolonged erection (>4 hours), and corporal fibrosis of either medication in the 155 impotent patients who used Bimix solution for intracavernous pharmacotherapy (mean duration: 15 months) and thereafter used Trimix solution (mean 12 months). RESULTS: Erectile response to Trimix solution was significantly better than Bimix solution (p<0.01). The mean dose of Bimix solution was higher than Trimix solution (0.43 ml. vs. 0.34 ml, p<0.05). The severe pain enough for impediment to ntercourse occurred in 6.5% of the Trimix group, while no patient of the Bimix group experienced (p<0.01). The corporal fibrosis was noted in 8.4% of the Trimix group and 16.1% of the Bimix group. However, there was no significant difference between the two groups (p=0.08). The incidence of prolonged erection was significantly lower (p<0.05) in the Trimix group (2.6%) than in the Bimix group (12.3%). A total of 139 patients (89.7%) finally selected Trimix solution. CONCLUSIONS: The Trimix solution was more effective and safer than Bimix solution for the treatment of erectile dysfunction.

Evaluation of Argyrophilic Nucleolar Organizer Regions in Renal Cell Carcinoma / 대한비뇨기과학회지

Nucleolar organizer regions(NORs) are intranucleolar segments of DNA coding for ribosomal RNA and contribute to the regulation of cellular protein synthesis. Since NOR-associated proteins are argyrophilic, silver staining method has been used for demonstration of NORs. The numbers of argyrophilic NORs(AgNORs) have been shown to be correlated with DNA ploidy and have prognostic value in diverse human neoplasms. However, the prognostic value of AgNORs in renal cell carcinoma(RCC) remain ill defined. We herein investigated the prognostic value of AgNORs in 39 patients with RCC. There was no significant relationship between mean number of AgNORs (m AgNORs) per nucleus and Robson stage and Fuhrman nunlear grade. However, there was significant relationship between the percentage of tumor cells with more than five AgNORs per nucleus (p AgNORs) and Robson stage and nuclear grade (p<0.05). There was significant difference in survival rate between patients with RCC in whom AgNORs were two or less and in whom AgNORs were greater than two(p<0.05). The patients with a low p AgNORs(less than 8%) have a better prognosis than those with a high p AgNORs. These results suggest that number of AgNORs may be a clinically useful prognostic marker for patients with RCC.

Comparative Analysis of Conventional Transurethral Resection of the Prostate and Laser Induced Prostatectomy / 대한비뇨기과학회지

BACKGROUND AND PURPOSE: Laser induced prostatectomy(LIP) has recently been considered as safe alternative to conventional transurethral resection of the prostate(TURP) in the surgical treatment of BPH. However, the value of LIP remains incompletely defined. We herein have performed a prospective study to compare TURP and LIP in treatment efficacy, safety and costs to define the value of LIP. MATERIALS AND METHODS: 113 patients with BPH who were candidates of TURP were randomized to undergo TURP or LIP and were adequately followed up for more than 1 year. There were no significant differences in preoperative clinical characteristics between 55 patients who underwent TURP and 58 patients who underwent LIP. For the LIP procedure, Nd:YAG was used in 42 patients and diode laser in 16 patients, respectively. 37 patients were treated by contact LIP only, and 21 with hybrid procedures of contact LIP and noncontact LIP using side firing laser fiber or interstitial laser fiber. Seven patients underwent LIP under local anesthesia at the outpatient department. RESULTS: International prostate symptom score(IPSS) and peak urinary flow rate(Qmax) were significantly improved at 3 months, 6 months, and 1 year after LIP as well as after TURP. There were no significant difference between TURP group(85.4%) and LIP group(87.9%) in treatment success rate as defined by improvement of IPSS and Qmax as well as patient's content for the surgical outcome. Nine(16.4%) and two(3.6%) of the patients who underwent TURP and none of the patients who LIP underwent developed ignificant bleeding and electrolyte imbalance, respectively. There were no significant difference in postoperative incidence of retrograde ejaculation, infection and urethral stricture between the two groups. Compared to TURP, the LIP procedure required significantly shorter hospitalization(6.8 vs 4.5 days) and catheterization(4.1 vs 2.6 days, all p<0.0l). There was no significant difference in total treatment cost between the two groups. CONCLUSIONS: LIP may be comparable to TURP in terms of short term treatment efficacy and cost effectiveness. LIP may be better than TURP in terms of safety and shortened hospitalization and catheterization. Further studies are necessary on long-term outcomes of LIP."

The Role of nm23-H1 Gene in Urologic Cancer (II): Expression and Mutation of nm23-H1 Gene in Urothelial Cancer / 대한비뇨기과학회지

BACKGROUND AND PURPOSE: We had previously demonstrated by immunohistochemical study (IHS) that nm23-H1 gene may play an important role in disease prognosis as well as its participation in metastasis of urothelial cancer. The purpose of present study was 1) to reexamine the role of nm23-H1 gene in urothelial cancers at molecular level, 2) to identify the molecular mechanism of decreased immunoreactivity for nm23-H1 protein in metastatic urothelial cancers, and 3) to identify whether IHS is reliable in studying the expression of nm23-H1. MATERIALS AND METHODS: We studied expression level and mutation profiles of nm23-H1 gene in 25 fresh surgical specimens of urothelial cancer by reverse transcription polymerase chain reaction(RT-PCR)-Southern blotting analysis, and PCR of genomic DNA followed by single strand conformation polymorphism and sequencing analysis. The results of RT-PCR-Southern blotting were comparatively analyzed with those of IHS. RESULTS: mRNA transcript levels of nm23-H1 gene were significantly decreased in tumor tissues with metastasis as compared with those without metastasis. The transcript levels of nm23-H1 gene were also significantly decreased in metastatic tumor tissues as compared with primary tumor tissues. Point mutation of nm23-H1 gene was detected in only 1 of 13 urothelial cancer tissues with metastasis, whereas, mutation was observed in none of those without metastasis. The results of IHS corresponded with those of RT-PCR-Southern blotting analysis in 23 of 25 specimens. CONCLUSIONS: The nm23-H1 gene may play an important role in metastasis of urothelial cancer. Decreased transcription at mRNA level may be a major molecular mechanism of loss of immunoreactivity for nm23-H1 protein in urothelial cancer. IHS used in the present study may be a clinically useful method to study the expression of nm23-H1 and to predict metastasis potential and prognosis of urothelial cancers.

The Immunohistochemical Study for Angiogenesis of Bladder Cancer / 대한비뇨기과학회지

All solid tumors require the induction of new blood vessel to grow. The neovascularization of tumor tissue(angiogenesis) is considered essential for tumor growth, proliferation and eventually metastasis. Recent reports have demonstrated that the intensity of tumor angiogenesis in prostate and other tumors may be of prognostic value. We analyzed the prognostic significance of microvessel quantitation in bladder carcinoma. Microvessels were identified by immunohistochemistry using antibodies to endothelial marker, factor VIII-related antigen. The three most vascular area within a tumor were selected, and the microvessels within a x200 microscopic field of each area were counted by an investigator. The significant relationship was observed between microvessel counts and recurrence rate in 17 patients with superficial bladder cancer. Microvessel counts correlated with stage, grade, lymph node and distant metastasis, and 2 year disease free survival rate in 28 patients with invasive bladder cancer. In 15 patients with invasive cancer who were not showed distant metastasis, tumors from patients who experienced distant metastasis had higher microvessel counts than did tumors from patients who were disease- free(75.7118.59 and 61.7517.78), these values were not significantly different(p=0.081). These findings suggest that assessment of angiogenesis by microvessel quantitation may be a valuable method to predict metastatic potential of tumors, survival and the candidates for adjuvant therapy in patients with invasive bladder cancer.

Prognostic Significance of E-cadherin Expression in Renal Cell Carcinoma / 대한비뇨기과학회지

E-cadherin is one of intercellular adhesion molecules, and it has been demonstrated that E- cadhedrin acts as an invasion suppressor in vitro and loss of its expression is an important prognostic factor in human malignancies. However the prognostic value of loss of expression of E-cadhedrin in renal cell carcinoma (RCC) remains to be defined. We herein immunohistochemically examined the expression of E-cadhedrin in paraffin- embedded tissues of 43 patients with RCC to investigate the prognostic value of loss of expression of E-cadherin. Twenty three of 43 patients (54.5%) showed loss of expression of E- cadherin. There were significant correlations between loss of expression of E-cadherin and histopathologic grade, Robson stage, T stage, N stage and M stage (all p<0.05). Patients with loss of expression of E-cadherin showed significantly decreased 2 year disease free survival as compared with those with normal expression of E-cadherin (p<0.001). These results suggest that loss of expression of E-cadherin has a ominous prognostic value in patients with RCC.