Enhanced visualization of female squirting.

INTRODUCTION: Squirting is the involuntary expulsion of fluid from the female urethra following stimulation of the anterior vaginal wall before or during orgasm. The mechanism underlying squirting has not been established. PURPOSE: To elucidate the mechanism of squirting. METHODS: The subjects in the current study were women who were able to squirt. They were not sex workers. A urethral catheter was inserted before sexual stimulation and the bladder was emptied. Then, a mixture of indigo carmine (10 ml) and saline (40 ml) was injected into the bladder. Sexual stimulation was provided to facilitate squirting, which was videotaped and verified. The secretions were collected in sterile cups, and prostate specific antigen (PSA) and glucose levels were measured. RESULTS: Five women (2 in the 30s, 2 in the 40s, and 1 in the 50s) participated in this study. All women were able to squirt; three squirted only with manual sexual stimulation and two with penetrative sexual stimulation. The discharged fluid was blue in all cases, confirming the bladder as the source. The fluid was PSA-positive in four patients. CONCLUSIONS: The main component of squirt fluid is urine, but may also contain fluid from Skene's glands (female prostate). This is the first report in which visualization of squirting was enhanced.

Comparison of Two Different Drugs for Overactive Bladder, Solifenacin and Mirabegron: A Prospective Randomized Crossover Study.

To assess the efficacy and safety of 2 drugs for overactive bladder (OAB), solifenacin and mirabegron. Fortyseven female OAB patients were randomized into 2 groups. Twenty-three patients were initially prescribed solifenacin for 4 weeks, followed by mirabegron for 4 weeks (group S). The other 24 patients were initially prescribed mirabegron for 4 weeks, followed by solifenacin for 4 weeks (group M). Evaluations included clinical determination of the OAB symptom score (OABSS), International Prostate Symptom Score (IPSS), and Visual Analog Scale. The IPSS significantly improved after the administration of solifenacin in both groups. The OABSS significantly improved in both groups after 4 weeks. In group M, the OABSS after eight weeks was significantly improved compared to that after 4 weeks. However, in group S, it was not significantly improved. Twelve patients experienced adverse events during the solifenacin treatment, while 2 patients experienced adverse events during the mirabegron treatment. Both solifenacin and mirabegron led to improved OAB symptoms. Switching from mirabegron to solifenacin significantly improved the OABSS. However, mirabegron led to fewer adverse events than solifenacin. We recommend that mirabegron be prescribed first for OAB patients. If patients are not satisfied with mirabegron, solifenacin should be used.

Clitoral Blood Flow Changes after Surgery with Tension-Free Vaginal Mesh for Pelvic Organ Prolapse.

We measured basal clitoral blood flow by Doppler sonography to determine whether tension-free vaginal mesh(TVM) affects the clitoral blood flow and sexual function in women with pelvic organ prolapse (POP). We performed a prospective study of 22 patients who underwent TVM for POP. Clitoral blood flow was measured by Doppler ultrasound. The resistance index (RI), pulsatility index (PI), peak systolic velocity (PSV), and end-diastolic velocity (EDV) of the clitoral arteries were measured preoperatively and at 1, 3, and 6 months postoperatively. Female sexual function was also investigated with the Female Sexual Function Index (FSFI). The mean PI and RI were increased at 1 month and significantly decreased at 6 months postoperatively (p<0.05). In contrast, the mean PSV and EDV decreased at 1 month postoperatively and increased at 6 months postoperatively. These four parameters recovered to baseline levels at 6 months following surgery. Total FSFI scores improved significantly from 10.2±7.9 at baseline to 18.2±8.9 at 6 months postoperatively. Color Doppler ultrasonography is potentially useful in measuring clitoral blood flow in patients treated with TVM for POP. Prospective long-term studies are needed to evaluate the utility of this modality as a diagnostic and prognostic tool for female sexual dysfunction.

[Linguistic validation of Japanese version of Prolapse/Urinary Incontinence Sexual Questionnaire, IUGA-Revised (PISQ-IR)].

PURPOSE: To translate the Prolapse/Urinary Incontinence Sexual Questionnaire, IUGA-Revised (PISQ-IR) into Japanese and evaluate the linguistic validation of the translated PISQ-IR. METHODS: The translation and evaluation of PISQ-IR were performed through 3 steps: forward translation based on 2 urologists and discussed by another 4 urologists, 1 pharmacoeconomist and 1 nurse; the community review process consists of conducting one-on-one cognitive interviews with 20 patients by a professional interviewer; backward translation by a native English speaker, which was negotiated with the PISQ-IR Working Group comprised original authors in International Urogynecological Association (IUGA). RESULTS: The PISQ-IR Working Group generally approved our translation and had 2 major concerns in the Japanese version; 1) "disagree" in every sentence of English version was not translated into Japanese, and 2) the Japanese expression in "sexual desire" should be more emotional. The former concern was approved by explaining that Japanese does not have the word which is the equivalent of "disagree", and "don't agree" is always used instead of "disagree". The latter concern was compromised by switching to a translation using emotional words. CONCLUSION: The Japanese version of PISQ-IR was translated in a linguistically valid manner. It would be equivalent to the original English questionnaire. It may provide a tool to assess sexual function for Japanese women with prolapse, urinary incontinence and/or fecal incontinence in an internationally harmonized fashion.

The interaction of the ErbB4 intracellular domain p80 with α-enolase in the nuclei is associated with the inhibition of the neuregulin1-dependent cell proliferation.

We have shown that the receptor tyrosine kinase ErbB4 signals neuregulin1-stimulated proliferation of human cells. Some isoforms of ErbB4 are cleaved to release the soluble intracellular domain p80; however, the function of p80 in cell proliferation remained unclear. Here we propose the possibility for p80 as a negative feedback modulator of ErbB4-mediated cell proliferation. Cells exposed to lower doses of neuregulin1 displayed a stimulated proliferation and contained ErbB4 but barely p80. By contrast, cells exposed to its higher doses displayed a suppressed proliferation and contained p80 but barely ErbB4. Analyses with cells overexpressing the p80 wild type and mutants indicated that nuclear p80 inhibits cell proliferation independently of the tyrosine kinase activity. A screen for a novel protein that interacts with p80 identified α-enolase, which is reported as a transcriptional inhibitor for the proliferation-associated c-myc gene. The c-myc mRNA expression was induced by lower doses of neuregulin1 but was suppressed by its higher doses. Subcellular fractionation demonstrated the localization of not only p80 and α-enolase but also the decrease of the functional c-myc amount in the nuclei of cells exposed to higher doses of neuregulin1. These results suggested that p80, which is generated from ErbB4 and translocates to the nuclei, interacts with α-enolase and inhibits neuregulin1-dependent ErbB4-mediated cell proliferation by impairing the c-myc gene transcription.

Effect of stone Spa bathing and hot-spring bathing on pulse wave velocity in healthy, late middle-aged females.

OBJECTIVES: The purpose of this study was to clarify the effect of stone spa bathing (Ganban-yoku) and hot-spring bathing on brachial-ankle pulse wave velocity (baPWV) in healthy, late middle-aged females. METHODS: The subjects were 13 females (mean age, 47.3 years). The skin and tympanic temperatures, blood pressure, and baPWV were measured before and after stone spa bathing and hot-spring bathing. For the stone spa bathing, the subjects lay down three times for approximately 10 min each time over warm stone beds. RESULTS: Although body weight showed no change after the hot-spring bathing, it significantly increased after the stone spa bathing. The increase was significantly related to the amount of water intake. The skin and tympanic temperatures increased to a smaller degree after the stone spa bathing than after the hot-spring bathing. The diastolic blood pressure decreased to a smaller degree after the stone spa bathing. BaPWV showed no significant change after bathing both in the stone spa and in the hot-spring. The results of multiple regression analysis showed that the factors significantly related to the change in baPWV after the stone spa bathing were the changes in skin and tympanic temperatures and habit of smoking, and that after the hot-spring bathing was the change in skin temperature. CONCLUSIONS: The results suggest that, compared with the hot-spring bathing, stone spa bathing causes less strain on the body. The stone spa bathing and hot-spring bathing showed no marked effect on baPWV. However, there is a possibility that the stone spa bathing may be used as a load for investigating arterial stiffness.

Laparoscopic-assisted tension-free vaginal mesh: an innovative approach to placing synthetic mesh: transvaginally for surgical correction of pelvic organ prolapse.

Polypropylene mesh implants for the correction of pelvic organ prolapse (POP) are now available in Japan. We developed an innovative approach for correcting POP by placing polypropylene mesh transvaginally with laparoscopic assistance. From June 2007 through March 2010, sixteen consecutive patients with symptomatic stage 2 or 3 pelvic organ prolapse underwent the laparoscopic-assisted tension-free vaginal mesh procedure at Okayama University Hospital. All patients were evaluated before and at 1, 3, 6, and 12 months after surgery. Female sexual function was also evaluated with the Female Sexual Function Index (FSFI). The procedure was performed successfully without significant complications. Fifteen of 16 patients were considered anatomically cured (93.8%) at 12 months postoperatively. One patient with a recurrent stage 3 vaginal vault prolapse required sacral colpopexy six months postoperatively. Total FSFI scores improved significantly from 10.3 ± 1.3 at baseline to 18.0 ± 1.2 at 12 months after surgery. The laparoscopic-assisted trans-vaginal mesh is a safe, effective, and simple procedure for POP repairs. The procedure not only restores anatomic relationships but also improves sexual function.

Impact of overactive bladder and lower urinary tract symptoms on sexual health in Japanese women.

INTRODUCTION AND HYPOTHESIS: This study aims to assess whether lower urinary tract symptoms (LUTS) affect sexual function in Japanese females. METHODS: A multi-component questionnaire was mailed to 576 female hospital workers. It contained the Female Sexual Function Index (FSFI) and a self-administered questionnaire pertaining to LUTS. RESULTS: Of the 276 responses (overall response rate, 47.9%), 146 questionnaires were evaluable. LUTS had been experienced by 72 (49.3%) of the respondents, 17 (11.6%) had urge urinary incontinence, and 35 (24.0%) had stress urinary incontinence (SUI). The mean overall FSFI score was 22.4 ± 9.0. The mean FSFI score was not significantly different between women with LUTS and women without LUTS (23.2 ± 9.3 and 21.6 ± 8.8, respectively; P = 0.057). However, the mean FSFI score of women with SUI was significantly lower than that of women without it (P = 0.04). No other symptoms showed significant differences in FSFI scores. CONCLUSIONS: Our results suggest that sexual dysfunction is related to SUI.

Cell-penetrating D-isomer peptides of p53 C-terminus: long-term inhibitory effect on the growth of bladder cancer.

OBJECTIVES: To investigate whether a single application of the membrane-permeable D-isomer of the p53 C-terminus connected with a retro-inverso version of the NH(2)-terminal 20-amino acid peptide of the influenza virus hemagglutinin-2 protein (riHA2) inhibited the growth of bladder cancer cells. The transduction of p53 using poly-arginine is useful for targeting and suppressing the growth of bladder cancer cells. However, the protein's intracellular half-life is short, and repeated application is necessary to achieve an anti-tumor effect. METHODS: The p53 carboxyl-terminal peptides covalently coupled with cell-penetrating peptides were synthesized with D- or L-amino acids. Moreover, the peptides were connected with riHA2 by a disulfide bridge. Human bladder cancer cell lines were incubated with each peptide and cell viability was assessed with the WST assay. Apoptotic cells were confirmed by Hoechst and active capase-3 staining. The p53 peptides were injected into severe combined immunodeficiency disease mice transplanted with J82 cells to investigate their anti-tumor effect on bladder tumors. A survival curve was plotted using the Kaplan-Meier method. RESULTS: A single application of cell-penetrating D-isomer peptides of the p53 C-terminus connected with riHA2 (d11R-p53C'-riHA2 and dFHV-p53C'-riHA2) inhibited the growth and induced the apoptosis of bladder cancer cells. The tumor-bearing mice treated only with vehicle had a mean survival time of 12 days, whereas treatment with d11R-p53C'-riHA2 resulted in a long-term survival rate of 50%. CONCLUSIONS: Peptide transduction therapy using the D-isomer p53 C-terminal peptide with riHA2 may be an innovative method for the treatment of bladder cancer.

Use of Doppler ultrasound for non-invasive urodynamic diagnosis.

OBJECTIVES: A totally non-invasive transperineal urodynamic technique using Doppler ultrasonography has been developed. METHODS: Since normal urine does not have blood cells, urine was thought not to produce the Doppler effects. However, basic studies confirmed that the decrease of pressure at high velocity (Bernouilli effect) caused dissolved gas to form microbubbles, which are detected by Doppler ultrasonography. Subjects sat and the probe was advanced via remote control to achieve gentle contact with the perineal skin. The digital uroflow data signals and the color Doppler ultrasound video images were processed on a personal computer. The flow-velocity curves from two sites; the distal prostatic urethra just above the external sphincter (V1) and the sphincteric urethra (V2) were plotted against time. The parameters of both the pressure-flow studies and the Doppler ultrasound urodynamic studies were compared in men who had various degrees of obstruction. RESULTS: Functional cross-sectional area at prostatic urethra (A1), calculated by Q(max)/V1, was lower in the group of bladder outlet obstruction (BOO) vs. control group. Velocity ratio (VR), which was calculated by V1/V2, was the parameter having the best correlation with BOO index, though A1 had a similar correlation. This method is viable to diagnose the degree of BOO. CONCLUSIONS: The development of non-invasive Doppler ultrasound videourodynamics (Doppler UDS) will dramatically expand the information on voiding function.

p53 protein transduction therapy: successful targeting and inhibition of the growth of the bladder cancer cells.

INTRODUCTION: Virus-mediated gene therapy for bladder cancer has some problems, such as efficiency of gene delivery and safety issues. We have reported that poly-arginine peptide (11R) has the ability to increase protein transduction in cells. Here, we show that p53 protein transduction using 11R is useful for targeting to bladder tumors and suppressing the growth of bladder cancer cells. MATERIALS AND METHODS: An 11R-fused p53 protein (11R-p53) was transduced in bladder cancer cell lines (J82 and T24) to evaluate the anti-tumor effect. Cell viability was assessed by performing the 4-[3-(4-iodophenyl)-2-(4-nitrophenyl)-2H-5-tetrazolio]-1,3-benzene disulfonate (WST) assay. To investigate whether 11R-p53 enhanced the effect on anti-cancer drug-dependent apoptosis of bladder cancer cells, the cell lines were cotreated with 11R-p53 and cis-diaminedichloroplatinum (CDDP). Apoptotic cells were identified using Hoechst staining. To investigate the efficiency of protein transduction mediated by 11R in bladder tumors in vivo, SCID mice were transplanted with J82 cells in the bladder and 11R-GFP was transurethrally transduced into the bladder. The transduction of 11R-GFP in the tumor was examined by confocal microscopy. RESULTS: 11R-p53 inhibited the growth of both J82 and T24 cells in a dose-dependent manner. The transduction of 11R-p53 enhanced CDDP-dependent induction of apoptosis. Transurethral application of 11R-GFP resulted in transduction of GFP in bladder tumors but not in the normal bladder epithelium or subepithelial tissues. CONCLUSION: The present results suggest that p53 protein transduction therapy may be a promising method for the treatment of bladder cancer.

Tolerability and morbidity of urodynamic testing: a questionnaire-based study.

OBJECTIVES: To determine the tolerability and morbidity rate of multichannel urodynamics (UDS). METHODS: A total of 154 consecutive patients were included in the present study; 87 men and 67 women underwent UDS and completed a questionnaire. All patients undergoing UDS were given a two-part questionnaire. The first part, given immediately after UDS, contained four questions regarding pain, embarrassment, and physical burden (assessed with a visual analogue scale on which 0 = not at all, 10 = unbearable), as well as willingness to undergo UDS again. The second part, given within 2 weeks after UDS, contained five questions regarding micturition pain, gross hematuria, dysuria, cloudy urine, and fever episodes after UDS. Urine specimens were also analyzed. RESULTS: The mean (+/-SD) degrees of pain, embarrassment, and physical burden were 2.27 +/- 2.53, 2.59 +/- 2.69, and 1.76 +/- 2.43, respectively, and 73.6% of men and 80.6% of women were willing to repeat UDS. The most common complaint after UDS was micturition pain. Two men and 1 woman had fever after UDS; there was no relationship between fever and urinary tract infections. Urinalysis showed that 4.6% of men and 7.5% of women had leukocyturia after the investigation. CONCLUSIONS: The complication rates of UDS were relatively low. For most patients, UDS were tolerable and acceptable. Proper informed consent is necessary.

Preliminary results of the effect of extracorporeal magnetic stimulation on urinary incontinence after radical prostatectomy: a pilot study.

INTRODUCTION: Radical prostatectomy is a common procedure for the treatment of clinically localized prostate cancer. However, urinary incontinence is a significant potential source of morbidity following surgery. Extracorporeal magnetic stimulation (ExMS) is a new technology used for pelvic muscle strengthening in the treatment of stress urinary incontinence. We investigated the clinical effects of ExMS on urinary incontinence after retropubic radical prostatectomy. PATIENTS AND METHODS: Ten patients who had suffered from urinary incontinence for more than 12 months following radical prostatectomy were enrolled in this study. The Neocontrol system was used. Treatment sessions were for 20 min, twice a week for 2 months. The frequency of the pulse field was 10 Hz for 10 min, followed by a second treatment at 50 Hz for 10 min. Objective and subjective measures included voiding diaries, 1-hour pad weight testing, and a quality of life survey at 1, 2, 3, and 6 months after starting the treatment. Urodynamic studies were performed before and after treatment. RESULTS: Three patients became dry (30%), 3 patients improved (30%), and 4 patients showed stationary symptoms (40%). In the 1-hour pad weight testing, the mean pad weight decreased from 25 to 10.3 g, and the quality of life scores had improved from 70.5 to 84.9 2 months after treatment. The frequency of leak episodes per day was reduced from 5.0 times before to 1.9 times after treatment. In the urodynamic study, mean maximum cystometric capacity and Valsalva leak point pressure increased from 197 +/- 53.2 to 309 +/- 85.3 ml and from 67.3 +/- 22.6 to 97.1 +/- 22.7 cm H2O after treatment, respectively (p < 0.05). 3 of 6 patients who showed improvement returned to the baseline values within 12 months after treatment and requested maintenance ExMS therapy. No side effects were observed. CONCLUSIONS: ExMS therapy offered a new option for urinary incontinence treatment after radical prostatectomy. Further studies are required to determine how long the benefits of treatment last and whether maintenance therapy is necessary.

Extracorporeal magnetic innervation treatment for urinary incontinence.

BACKGROUND: Extracorporeal magnetic innervation (ExMI) is a new technology used for pelvic muscle strengthening for the treatment of stress urinary incontinence. We explored whether this new technology is effective for patients with urge incontinence, as well as those with stress urinary incontinence. METHODS: We studied 20 patients with urge incontinence and 17 patients with stress urinary incontinence. The Neocontrol system (Neotonus Inc., Marietta, GA) was used. Treatment sessions were for 20 min, twice a week for 8 weeks. Evaluations were performed by bladder diaries, one-hour pad weight testing, quality-of-life surveys and urodynamic studies. RESULTS: Of the urge incontinence cases, five patients were cured (25.0%), 12 patients improved (60.0%) and three patients did not show any improvement (15.0%). Leak episodes per day reduced from 5.6 times to 1.9 times at 8 weeks (P < 0.05). Eight patients with urge incontinence recurred within 24 weeks after the last treatment (47.1%). Of the stress incontinence cases, nine patients were cured (52.9%), seven patients improved (41.1%) and one patient did not show any improvement (6%). In one-hour pad weight testing, the mean pad weight reduced from 7.9 g to 1.9 g at 8 weeks (P < 0.05). Three patients returned to the baseline values within 24 weeks after the last treatment (17.6%). No side-effects were experienced by any of the patients. CONCLUSION: Although the results for urge incontinence were less effective than for stress urinary incontinence, ExMI therapy offers a new option for urge incontinence as well as stress urinary incontinence.

Role of C afferent fibers and monitoring of intravesical resiniferatoxin therapy for patients with idiopathic detrusor overactivity.

PURPOSE: Resiniferatoxin (RTX) is a specific C fiber neurotoxin which produces desensitization. In this study we performed intravesical RTX therapy in patients with idiopathic detrusor overactivity. In addition we measured the current perception threshold of C and A delta fibers before and after treatment to evaluate clinical significance. MATERIALS AND METHODS: The protocol involved an RTX solution (100 ml of 50 nM) instilled in the bladder for 30 minutes. Four men and 6 women 59 to 75 years old were treated. Effects on bladder function were evaluated before and 30 days after treatment by cystometry and Neurometer (Neurotron, Inc., Baltimore, Maryland). Subjective and objective measures included bladder diaries and quality of life before treatment, and 7, 30 and 90 days subsequently. RESULTS: Of the 10 patients 5 noted improvement and 2 of them became dry. The other 5 patients were considered to have stationary symptoms. Mean maximal cystometric capacity +/- SD increased from 229 +/- 108 ml at baseline to 271 +/- 99.5 ml at 30 days (p = 0.04). The mean number of daily episodes of urinary incontinence decreased from 3.5 +/- 2.2 to 2.0 +/- 1.6 (p = 0.008) at 7 days, to 1.9 +/- 1.6 (p = 0.018) at 30 days and to 2.5 +/- 1.7 (p = 0.018) at 90 days. Mean current perception threshold values of C and A delta fibers did not change significantly, from 46.9 +/- 35.2 to 56.4 +/- 32.1 (p = 0.161) and from 66.9 +/- 31.7 to 66.4 +/- 25.2 (p = 0.952), respectively. However, values of C fibers increased in all patients who showed improvement from 46.2 +/- 33.2 to 64.0 +/- 36.8 (p = 0.043). CONCLUSIONS: Intravesical RTX improved bladder capacity and leak episodes in patients with idiopathic detrusor overactivity. Intravesical RTX is a promising treatment for this condition.

Comparative study of effects of extracorporeal magnetic innervation versus electrical stimulation for urinary incontinence after radical prostatectomy.

OBJECTIVES: To perform a randomized comparative study to investigate the clinical effects of extracorporeal magnetic innervation (ExMI) and functional electrical stimulation (FES) on urinary incontinence after retropubic radical prostatectomy. METHODS: Thirty-six patients with urinary incontinence after radical prostatectomy were randomly assigned to three groups (12 patients each in the FES, ExMI, and control groups). For FES, an anal electrode was used. Pulses of 20-Hz square waves at a 300-micros pulse duration were used for 15 minutes twice daily for 1 month. For ExMI, the Neocontrol system was used. The treatment sessions were for 20 minutes, twice a week for 2 months. The frequency of the pulse field was 10 Hz for 10 minutes, followed by a second treatment at 50 Hz for 10 minutes. For the control group, only pelvic floor muscle exercises were performed. Objective measures included bladder diaries, 24-hour pad weight testing, and a quality-of-life survey, at 1, 2, and 4 weeks and 2, 3, 4, 5, and 6 months after removing the catheter. RESULTS: The leakage weight during the 24 hours after removing the catheter was 684, 698, and 664 g for the FES, ExMI, and control groups, respectively. At 1 month, it was 72, 83, and 175 g (FES versus control, P <0.05) and at 2 months was 54, 18, and 92 g (ExMI versus control, P <0.05) in the FES, ExMI, and control groups, respectively. Finally, 6 months later, the average 24-hour leakage weight was less than 10 g in all groups. Quality-of-life measures decreased after surgery, but gradually improved over time in all groups. No complications were noted in any of the groups. CONCLUSIONS: ExMI and FES therapies offered earlier continence compared with the control group after radical prostatectomy. We consider ExMI and FES to be recommendable options for patients who want quick improvement of postoperative urinary incontinence.

[A clinical study of renal pelvic and ureteral cancer: prognosis and frequency of subsequent bladder cancer following surgical treatment].

PURPOSE: A retrospective investigation of patients presenting with renal pelvic and ureteral cancer was performed. This study focused on the prognostic factors and frequency of subsequent bladder cancer following surgical treatment. MATERIALS AND METHODS: Forty-five patients presenting with transitional cell carcinoma, who had undergone nephroureterectomy at the Department of Urology, Okayama Central Hospital, from March 1990 to November 2000, were reviewed. Various factors were evaluated according to survival and non-bladder cancer occurrence rates. The Kaplan-Meier method was used in the analyses. RESULTS: Patients consisted of 33 males and 12 females (mean age was 71.7). Seventeen patients exhibited renal pelvic cancer, 25 cases displayed ureteral cancer and three subjects presented with multiple cancers. Eleven patients had received treatment for precedent or coexistent superficial bladder cancer by transurethral resection. The overall 5-year survival rate was 71.9%. Ten patients died as a result of the disease; in all cases, lymph node or distant metastasis had progressed. Pathological T factor, tumor grade and pN factor demonstrated a significant effect on survival; however, sex, age, tumor localization and incidence of subsequent bladder cancer had no influence on survival. The 5-year non-bladder cancer occurrence rate was 38.8%; additionally, all subsequent bladder cancer was disclosed within three years. Tumor multiplicity exclusively in the upper urinary tract significantly affected occurrence of bladder cancer. T factor and tumor grade revealed no correlation to occurrence. CONCLUSIONS: Adjuvant chemotherapy for prevention of clinical metastasis should be considered in cases involving pT3 or higher stage, grade 3, or in instances of pathologically confirmed lymph node metastasis. The significant occurrence of subsequent bladder cancer in the case of tumor multiplicity suggested that prophylactic therapy such as intravesical BCG instillation or chemotherapy might be beneficial.