Long-term Safety and Tolerability of Repeated Treatments With OnabotulinumtoxinA in Children With Neurogenic Detrusor Overactivity.

PURPOSE: OnabotulinumtoxinA is an approved treatment for neurogenic detrusor overactivity in adults inadequately managed with anticholinergics, and more recently was approved in children on the basis of a phase 3, 48-week, single-treatment study (NCT01852045). Given the paucity of long-term pediatric data, we report on the continued safety in these patients after repeated onabotulinumtoxinA treatment. MATERIALS AND METHODS: This was a multicenter, double-blind, repeat-treatment extension study (NCT01852058) in patients who entered from the preceding single-treatment study. Data were integrated across both studies. All patients (5-17 years) used clean intermittent catheterization and could receive dose escalations based on response to preceding treatment (50 U, 100 U, or 200 U onabotulinumtoxinA [not to exceed 6 U/kg]). RESULTS: Overall, 95, 90, 55, and 11 patients received 1, 2, 3, and 4 treatments with onabotulinumtoxinA, respectively, and median (quartiles) duration of follow-up was 82 (65, 94) weeks. The safety profile was similar across doses and after repeat treatments. The most common treatment-emergent adverse event during cycles 1, 2, and 3 was urinary tract infection (31%, 34%, 22%). Three serious treatment-emergent adverse events related to study treatment (3/95; 3.2%) were reported during the study, which were all cases of urinary tract infection. Annualized urinary tract infection rates post-treatment were similar to pre-screening rates. There were no cases of autonomic dysreflexia, neutralizing antibodies, and treatment-emergent adverse events related to distant spread of toxin. CONCLUSIONS: OnabotulinumtoxinA continued to be well tolerated after repeated treatments in pediatric neurogenic detrusor overactivity patients with similar safety profiles across dose groups. Treatment-emergent adverse events were primarily urological with no new safety concerns.

OnabotulinumtoxinA for the treatment of neurogenic detrusor overactivity in children.

AIMS: This study evaluated whether one (or more) of three doses of onabotulinumtoxinA were safe and effective to treat neurogenic detrusor overactivity (NDO) in children. METHODS: This was a 48-week prospective, multicenter, randomized, double-blind study in children (aged 5-17 years) with NDO and urinary incontinence (UI) receiving one onabotulinumtoxinA treatment (50, 100, or 200 U; not to exceed 6 U/kg). Primary endpoint: change from baseline in daytime UI episodes. Secondary endpoints: change from baseline in urine volume at first morning catheterization, urodynamic measures, and positive response on the treatment benefit scale. Safety was also assessed. RESULTS: There was a similar reduction in urinary incontinence from baseline to Week 6 for all doses (-1.3 episodes/day). Most patients reported positive responses on the treatment benefit scale (75.0%-80.5%). From baseline to Week 6, increases were observed in urine volume at first morning clean intermittent catheterization (50 U, 21.9 ml; 100 U, 34.9 ml; 200 U, 87.5 ml; p = 0.0055, 200 U vs. 50 U) and in maximum cystometric capacity (range 48.6-63.6 ml) and decreases in maximum detrusor pressure during the storage phase (50 U, -12.9; 100 U, -20.1; 200 U, -27.3 cmH2 O; p = 0.0157, 200 U vs. 50 U). The proportion of patients experiencing involuntary detrusor contractions dropped from baseline (50 U, 94.4%; 100 U, 88.1%; 200 U, 92.6%) to Week 6 (50 U, 61.8%; 100 U, 44.7%; 200 U, 46.4%). Safety was similar across doses; urinary tract infection was most frequent. CONCLUSIONS: OnabotulinumtoxinA was well tolerated and effective for the treatment of NDO in children; 200 U showed greater efficacy in reducing bladder pressure and increasing bladder capacity.

Male circumcision decreases penile sensitivity as measured in a large cohort.

UNLABELLED: WHAT'S KNOWN ON THE SUBJECT? AND WHAT DOES THE STUDY ADD?: The sensitivity of the foreskin and its importance in erogenous sensitivity is widely debated and controversial. This is part of the actual public debate on circumcision for non-medical reason. Today some studies on the effect of circumcision on sexual function are available. However they vary widely in outcome. The present study shows in a large cohort of men, based on self-assessment, that the foreskin has erogenous sensitivity. It is shown that the foreskin is more sensitive than the uncircumcised glans mucosa, which means that after circumcision genital sensitivity is lost. In the debate on clitoral surgery the proven loss of sensitivity has been the strongest argument to change medical practice. In the present study there is strong evidence on the erogenous sensitivity of the foreskin. This knowledge hopefully can help doctors and patients in their decision on circumcision for non-medical reason. OBJECTIVES: To test the hypothesis that sensitivity of the foreskin is a substantial part of male penile sensitivity. To determine the effects of male circumcision on penile sensitivity in a large sample. SUBJECTS AND METHODS: The study aimed at a sample size of ≈1000 men. Given the intimate nature of the questions and the intended large sample size, the authors decided to create an online survey. Respondents were recruited by means of leaflets and advertising. RESULTS: The analysis sample consisted of 1059 uncircumcised and 310 circumcised men. For the glans penis, circumcised men reported decreased sexual pleasure and lower orgasm intensity. They also stated more effort was required to achieve orgasm, and a higher percentage of them experienced unusual sensations (burning, prickling, itching, or tingling and numbness of the glans penis). For the penile shaft a higher percentage of circumcised men described discomfort and pain, numbness and unusual sensations. In comparison to men circumcised before puberty, men circumcised during adolescence or later indicated less sexual pleasure at the glans penis, and a higher percentage of them reported discomfort or pain and unusual sensations at the penile shaft. CONCLUSIONS: This study confirms the importance of the foreskin for penile sensitivity, overall sexual satisfaction, and penile functioning. Furthermore, this study shows that a higher percentage of circumcised men experience discomfort or pain and unusual sensations as compared with the uncircumcised population. Before circumcision without medical indication, adult men, and parents considering circumcision of their sons, should be informed of the importance of the foreskin in male sexuality.

Erectile implants in female-to-male transsexuals: our experience in 129 patients.

BACKGROUND: The combination of a neourethra and erection prosthesis in a single neophallus in the female-to-male transsexual remains a challenge. No good data are available on this subject. OBJECTIVE: To report the outcome in 129 female-to-male transsexuals with a neophallus after the implantation of an erectile prosthesis. DESIGN, SETTING, AND PARTICIPANTS: From March 1996 until October 2007, 129 female-to-male transsexuals with a neophallus underwent the implantation of an erectile prosthesis. The mean follow-up was 30.2 mo (range: 0-132 mo). INTERVENTION: A Dynaflex prosthesis was implanted initially in 9 patients, a three-piece hydraulic device (AMS CX or AMS CXM) in 50 patients, and a CX Inhibizone, Ambicor, and Coloplast/Mentor prosthesis in 17, 47, and 6 patients, respectively. MEASUREMENTS: Data on outcome in these patients were retrospectively evaluated. RESULTS AND LIMITATIONS: Of 129 patients, 76 patients (58.9%) still have their original implant in place. Fifty-three patients (41.1%) needed to undergo either removal or revision of the prosthesis due to infection, erosion, dysfunction, or leak. Forty-one patients underwent a replacement of the prosthesis, nine needed a second revision, five needed a third revision, and one patient needed a fourth revision of prosthesis. Malposition of prosthesis was corrected by surgical repositioning so that removal or revision could be avoided. Of 185 prostheses used in 129 patients, 108 (58.4%) still remain in place, with a total infection rate of 11.9%, a total protrusion rate of 8.1%, a total prosthesis leak rate of 9.2%, a total dysfunction rate of 13%, and a total malposition rate of 14.6%. The period of follow-up in the more recent types of prostheses (Ambicor, Coloplast/Mentor) is much shorter; therefore, comparison with earlier types is difficult to make. CONCLUSIONS: Despite high complication rates, implantation of a hydraulic erectile prosthesis remains the best option for achieving the possibility of sexual intercourse in female-to-male transsexuals.

One-stage penectomy and phalloplasty for epithelioid sarcoma of the penis in an adolescent.

Epithelioid sarcoma (ES) of the penis is a rare tumour. We present a case of ES of the penis in a 16-yr-old boy, for which penectomy and immediate reconstruction with a free forearm phalloplasty, including a urethral reconstruction, was performed. Because total penectomy is a dramatic life event for any patient, the option of immediate penile reconstruction is presented. It can help to prevent major psychological problems after this kind of surgery.