Intravesical electromotive drug administration of mitomycin-C for non-muscle invasive bladder cancer

This article reviews intravesical application of electromotive drug administration (EMDA) for the treatment of bladder cancer and the evidence in support of intravesical passive diffusion chemotherapy in the management of non-muscle invasive bladder cancer. Two recently published randomised trials adopting protocols that use EMDA to enhance urothelial transport of intravesical mitomycin-C showed it provided a therapeutical advantage and suggested that intravesical passive diffusion administration of chemothera-peutic drugs may be suboptimal. Further studies are required to demonstrate feasibility and advantage of intravesical EMDA of mitomycin-C in the wider uro-oncological community

Localised prostate cancer and hemophilia A (AHA): Case report and management of the disease.

Acquired Hemophilia A (AHA) is a rare bleeding diathesis characterized by the development of autoantibodies against factor VIII (FVIII). About half of the cases are idiopathic and the other half are associated with autoimmune diseases, postpartum problems, infections, inflammatory bowel disease, drugs, lymphoproliferative disorders or solid tumors . AHA is associated with malignancies in 7-15% of cases. We report a case of AHA in a 65 year old patient with prostatic carcinoma, who underwent retropubic radical prostatectomy (RP)

The efficacy and safety of duloxetine in a multidrug regimen for chronic prostatitis/chronic pelvic pain syndrome.

OBJECTIVE To evaluate the efficacy and safety of duloxetine hydrochloride in the treatment of patients affected by chronic prostatitis/chronic pelvic pain syndrome (CP/CPPS). METHODS Thirty-eight CP/CPPS patients completed the National Institutes of Health Chronic Prostatitis Symptom Index (NIH-CPSI) and International Index of Erectile Function-Erectile Function-5 (IIEF-5) questionnaires, uroflowmetry, and evaluation of psychologic status using Hamilton Anxiety Scale (HAM-A) and Hamilton Depression Scale (HAM-D). Patients were randomly assigned to 2 treatments groups. Treatment in group 1 consisted of a simultaneous oral administration of tamsulosin (0.4 mg/d, 60 mg/d), saw palmetto (320 mg/d), and duloxetine (60 mg/d). Treatment in group 2 consisted of tamsulosin (0.4 mg/d) and saw palmetto (320 mg/d). NIH-CPSI and IIEF-5 questionnaires, uroflowmetry, and evaluation of the psychological status were repeated at 16 weeks of follow-up. RESULTS At 16 weeks, a significant improvement in NIH-CPSI pain subscore, NIH-CPSI quality of life subscore, and NIH-CPSI total score were observed in group 1 patients compared with those in group 2 (P <.01, respectively), together with a significant improvement in HAM-A and HAM-D scores (P <.01, respectively). Patients in group 2 showed a significant improvement in NIH-CPSI total score, in the urinary symptoms subscore, and in the HAM-A total score. No significant differences were observed in IIEF-5 scores in the 2 groups. Maximum flow rate significantly increased in both groups. In group 1, 20% of patients stopped the study due to adverse effects. CONCLUSION The use of duloxetine in a multimodal treatment with an alpha-blocker medication and a saw palmetto extract allowed better results in controlling clinical symptoms, psychologic status and quality of life patients affected by CP/CPPS

Pelvic floor muscle behavior during Valsalva leak point pressure measurement in males and females affected by stress urinary incontinence.

PURPOSE: We evaluated pelvic floor muscle (PFM) behavior during Valsalva leak point pressure (VLPP) measurement in males and females affected by stress urinary incontinence and investigated whether VLPP results are influenced by PFM contraction. MATERIALS AND METHODS: A total of 25 females and 14 males underwent surface electromyographic (EMG) recording of PFM activity while performing VLPP. We investigated 2 conditions, VLPP during spontaneous strain (test A), and with simultaneous relaxation of the pelvic floor (test B). We analyzed average EMG activity (microV) at rest and during VLPP in tests A and B, the increasing EMG activity during tests A and B (the difference between average EMG activity during tests A and B and at rest), and the mean duration (seconds) of EMG activity during tests A and B. RESULTS: We detected a significant increase in EMG activity during tests A and B as compared to activity at rest (p <0.0001). Increasing EMG activity during test B was significantly reduced in females (p <0.05) but not in males. During test A patients reporting urinary incontinence showed a significantly lower EMG activity than that of continent patients (p <0.05). A significant reduction in maximum abdominal pressure was detected in test B compared to test A, but there was no difference in VLPP values between tests A and B. CONCLUSIONS: PFM activity significantly increases during VLPP measurement. Eliminating muscular contraction of the pelvic floor does not significantly alter VLPP results

Type V phosphodiesterase inhibitor treatments for erectile dysfunction increase testosterone levels.

OBJECTIVE Lack of sexual activity due to erectile dysfunction (ED) decreases testosterone (T) levels through a central effect on the hypothalamic-pituitary axis. In this paper we studied the effect of different type V phosphodiesterase (PDE5) inhibitor treatments for ED on the reversibility of this endocrine pattern. DESIGN Open-label, retrospective study. PATIENTS Seventy-four consecutive patients were treated on demand with sildenafil (Sild) (50 mg) and tadalafil (Tad) 20 mg. MEASUREMENTS The success in sexual intercourse was recorded and total (tT) and free testosterone (fT) levels were studied before and after 3 months of treatment. RESULTS Basal level of tT and fT were at the bottom of the normal range and LH levels were at the top of the high normal range. After treatments, this endocrine pattern was reversed in both groups. However, the T increase in Sild-treated patients was significantly lower than in those treated with Tad (4.7 +/- 2.7 vs. 5.1 +/- 0.9, P < 0.001). fT levels followed a directly proportional pattern, while the inverse was found when LH production was studied. The intercourse rate reflected this effect: in fact, the Sild group showed a 4.9 +/- 2.9/month full sexual intercourse rate while in the Tad group a significantly higher rate of sexual intercourse was found (6.9 +/- 4.6/month, P = 0.04). However, drug consumption was comparable between the groups (Sild 4.9 +/- 2.9 vs. Tad 4.4 +/- 2.8 pills/month, P = 0.72). CONCLUSIONS As it is unlikely that the two drugs have a different direct effect on the pituitary-testis axis, this effect is probably due to the higher frequency of full sexual intercourse in the Tad-treated group, because of the drug's longer half-life

Intravesical oxybutynin: mode of action assessed by passive diffusion and electromotive administration with pharmacokinetics of oxybutynin and N-desethyl oxybutynin.

PURPOSE: A proportion of patients with detrusor hyperreflexia who are unresponsive to oral oxybutynin often benefit from intravesical oxybutynin instillation. To our knowledge the precise mode of action of this method is obscure. MATERIALS AND METHODS: In 12 patients with detrusor hyperreflexia who were previously unresponsive to oral and intravesical passive diffusion of 5 mg. oxybutynin we administered 5 mg. oxybutynin orally as well as increased doses of 15 mg. oxybutynin intravesically with passive diffusion and with 15 mA. associated electric current. Each administration mode per patient was associated with an 8-hour urodynamic monitoring session during which oxybutynin and N-desethyl oxybutynin plasma levels, and intravesical oxybutynin uptake were measured. RESULTS: A dose of 5 mg. oxybutynin orally induced no urodynamic improvement with an area under the plasma concentration time curve of combined N-desethyl oxybutynin plus oxybutynin of 16,297 ng./8 hours and an area under the curve ratio of N-desethyl oxybutynin-to-oxybutynin of 11:1. Passive diffusion oxybutynin resulted in 12 mg. oxybutynin intravesical uptake and significant improvement in 3 of 8 urodynamic measurements, although the area under the curve of combined N-desethyl oxybutynin plus oxybutynin was only 2,123 ng./8 hours and the N-desethyl oxybutynin-to-oxybutynin ratio was 1.1:1.0. Electromotive administration of oxybutynin resulted in almost complete intravesical uptake of the 15 mg. dose, significant improvement in all 8 urodynamic measurements and an increased oxybutynin level versus oral and passive diffusion, although the area under the curve of combined N-desethyl oxybutynin plus oxybutynin was 4,574 ng./8 hours and the N-desethyl oxybutynin-to-oxybutynin ratio was inverted at 1.0:1.4. The oral dose of 5 mg. oxybutynin caused anticholinergic side effects in 8 of the 12 patients. Neither intravesical passive diffusion nor electromotive administration caused side effects with an uptake of 12 and 15 mg., respectively. CONCLUSIONS: A large proportion of intravesical oxybutynin is sequestered, probably in the urothelium. Intravesical oxybutynin administration confers therapeutic benefits via localized direct action within the bladder wall. Comment in Intravesical treatment of bladder dysfunction. [J Urol. 2001

Intravesical electromotive mitomycin C versus passive transport mitomycin C for high risk superficial bladder cancer: a prospective randomized study.

PURPOSE: In laboratory studies electromotive mitomycin C (MMC) demonstrated markedly increased transport rates compared with passive transport. We performed a prospective study in patients with high risk superficial bladder cancer to assess the efficacy of intravesical electromotive vs passive MMC using bacillus Calmette-Guerin (BCG) as a comparative treatment. MATERIALS AND METHODS: Following transurethral resection and multiple biopsies 108 patients with multifocal Tis, including 98 with T1 tumors, were randomized into 3 equal groups of 36 each who underwent 40 mg electromotive MMC instillation with 20 mA electric current for 30 minutes, 40 mg passive MMC with a dwell time of 60 minutes or 81 mg BCG with a dwell time of 120 minutes. Patients were scheduled for an initial 6 weekly treatments, a further 6 weekly treatments for nonresponders and a followup 10 monthly treatments for responders. Primary end points were the complete response rate at 3 and 6 months. MMC pharmacokinetics were assessed. RESULTS: The complete response for electromotive vs passive MMC at 3 and 6 months was 53% versus 28% (p = 0.036) and 58% versus 31% (p = 0.012). For BCG the responses were 56% and 64%. Median time to recurrence was 35 vs 19.5 months (p = 0.013) and for BCG it was 26 months. Peak plasma MMC was significantly higher following electromotive MMC than after MMC (43 vs 8 ng/ml), consistent with bladder content absorption. CONCLUSIONS: Intravesical electromotive administration increases bladder uptake of MMC, resulting in an improved response rate in cases of high risk superficial bladder cancer

Hexaminolevulinate hydrochloride in the detection of nonmuscle invasive cancer of the bladder

Clinical trials have shown that hexaminolevulinate (HAL) fluorescence cystoscopy improves the detection of bladder tumors compared with standard white-light cystoscopy, resulting in more efficacious treatment. However, some recent meta-analyses report controversially on recurrence-free rates with this procedure. A systematic review of literature was performed from December 2014 to January 2015 using the PubMed, Embase and Cochrane databases for controlled trials on photodynamic diagnosis (PDD) with HAL. A total of 154 publications were found up to January 2015. Three of the authors separately reviewed the records to evaluate eligibility and methodological quality of clinical trials. A total of 16 publications were considered eligible for analysis. HAL-PDD-guided cystoscopy increased overall tumor detection rate (proportion difference 19%, 95% confidence interval [CI] 0.152-0.236) although the benefit was particularly significant in patients with carcinoma in situ (CIS) lesion (proportion difference 15.7%, 95% CI 0.069-0.245) and was reduced in papillary lesions (Ta proportion difference 5.9%, 95% CI 0.014-0.103 and T1 proportion difference 1.2%, 95% CI 0.033-0.057). Moreover, there were 15% of patients (95% CI 0.098-0.211) with at least one additional tumor seen with PDD. With regard to recurrence rates, the data sample was insufficient for a statistical analysis, although the evaluation of raw data showed a trend in favor of HAL-PDD. This meta-analysis confirms the increased tumor detection rate by HAL-PDD with a most pronounced benefit for CIS lesion

Measurement of the thickness of the urethrovaginal space in women with or without vaginal orgasm

Introduction. The physiology and anatomy of female sexual function are poorly understood. The differences in sexual function among women may be partly attributed to anatomical factors. Aim. The purpose of this study was to use ultrasonography to evaluate the anatomical variability of the urethrovaginal space in women with and without vaginal orgasm. Methods. Twenty healthy, neurologically intact volunteers were recruited from a population of women who were a part of a previous published study. All women underwent a complete urodynamic evaluation and those with clinical and urodynamic urinary incontinence, idiopathic detrusor overactivity, or micturition disorders, as well as postmenopausal women and those with sexual dysfunction were excluded. The reported experience of vaginal orgasm was investigated. Main Outcome Measure. The urethrovaginal space thickness as measured by ultrasound was chosen as the indicator of urogenital anatomical variability. Designated evaluators carried out the measurements in a blinded fashion. Results. The urethrovaginal space and distal, middle, and proximal urethrovaginal segments were thinner in women without vaginal orgasm. A direct correlation between the presence of vaginal orgasm and the thickness of urethrovaginal space was found. Women with a thicker urethrovaginal space were more likely to experience vaginal orgasm (r = 0.884; P = 0.015). A direct and significant correlation between the thickness of each urethrovaginal segment and the presence of vaginal orgasm was found, with the best correlation observed for the distal segment (r = 0.863; P < 0.0001). Interobserver agreement between the designated evaluators was excellent (r = 0.87; P < 0.001). Conclusions. The measurement of the space within the anterior vaginal wall by ultrasonography is a simple tool to explore anatomical variability of the human clitoris-urethrovaginal complex, also known as the G-spot, which can be correlated to the ability to experience the vaginally activated orgasm