Alessandro Zucchi

Botulinum-A Toxin Injections Into the Detrusor Muscle Decrease Nerve Growth Factor Bladder Tissue Levels in Patients With Neurogenic Detrusor Overactivity

PURPOSE We investigated the effects of BTX-A on visceral afferent nerve transmission by measuring bladder tissue NGF levels in patients with neurogenic detrusor overactivity before and after intravesical treatment with BTX-A. We also compared the bladder tissue NGF content with clinical and urodynamic data. MATERIALS AND METHODS A total of 23 patients underwent clinical evaluation and urodynamics with detection of the UDC threshold, maximum pressure and maximum cystometric capacity before, and at the 1 and 3-month followups. Endoscopic bladder wall biopsies were also obtained at the same time points. NGF levels were measured in tissue homogenate by enzyme-linked immunosorbent assay (Promega, Madison, Wisconsin). RESULTS At 1 and 3 months mean catheterization and incontinent episodes were significantly decreased (p <0.05 and <0.001, respectively). On urodynamics we detected a significant increase in the UDC threshold and maximum cystometric capacity, and a significant decrease in UDC maximum pressure at the 1 and 3-month follow-ups compared to baseline (each p <0.001). At the same time points we detected a significant decrease in NGF bladder tissue content (each p <0.02). CONCLUSIONS BTX-A intravesical treatment induces a state of NGF deprivation in bladder tissue that persists at least up to 3 months. As caused by BTX-A, the decrease in acetylcholine release at the presynaptic level may induce a decrease in detrusor contractility and in NGF production by the detrusor muscle. Alternatively BTX-A can decrease the bladder level of neurotransmitters that normally modulate NGF production and release.

Simple Enucleation is Equivalent to Traditional Partial Nephrectomy for Renal Cell Carcinoma: Results of a Nonrandomized, Retrospective, Comparative Study

PURPOSE The excision of the renal tumor with a substantial margin of healthy parenchyma is considered the gold standard technique for partial nephrectomy. However, simple enucleation showed excellent results in some retrospective series. We compared the oncologic outcomes after standard partial nephrectomy and simple enucleation. MATERIALS AND METHODS We retrospectively analyzed 982 patients who underwent standard partial nephrectomy and 537 who had simple enucleation for localized renal cell carcinoma at 16 academic centers between 1997 and 2007. Local recurrence, cancer specific survival and progression-free survival were the main outcomes of this study. The Kaplan-Meier method was used to calculate survival functions and differences were assessed with the log rank statistic. Univariable and multivariable Cox regression models addressed progression-free survival and cancer specific survival. RESULTS Median followup of the patients undergoing traditional partial nephrectomy and simple enucleation was 51 ± 37.8 and 54.4 ± 36 months, respectively (p = 0.08). The 5 and 10-year progression-free survival estimates were 88.9 and 82% after standard partial nephrectomy, and 91.4% and 90.8% after simple enucleation (p = 0.09). The 5 and 10-year cancer specific survival estimates were 93.9% and 91.6% after standard partial nephrectomy, and 94.3% and 93.2% after simple enucleation (p = 0.94). On multivariable analysis the adopted nephron sparing surgery technique was not an independent predictor of progression-free survival (HR 0.8, p = 0.55) and cancer specific survival (HR 0.7, p = 0.53) when adjusted for the effect of the other covariates. CONCLUSIONS To our knowledge this is the first multicenter, comparative study showing oncologic equivalence of standard partial nephrectomy and simple enucleation.

Botulinum A toxin intravesical injection in patients with painful bladder syndrome: 1-year followup

PURPOSE We evaluated the 1-year efficacy and tolerability of botulinum A toxin intravesically injected in patients with painful bladder symptoms associated with increased urinary frequency, refractory to conventional treatments. MATERIALS AND METHODS Three men and 12 women were prospectively included in the study. Under short general anesthesia the patients were given injections of 200 U commercially available botulinum A toxin diluted in 20 ml 0.9% NaCl. Injections were performed submucosally in the bladder trigone and lateral walls under cystoscopic guidance. A voiding chart and the visual analog scale for pain were used, and urodynamics were performed before treatment, and 1, 3, 5 and 12 months later. RESULTS Overall 13 patients (86.6%) reported subjective improvement at the 1 and 3-month followups. The mean visual analog scale score, and daytime and nighttime urinary frequency were significantly decreased (p <0.05, <0.01 and <0.05, respectively). At the 5-month followup the beneficial effects persisted in 26.6% of cases but increased daytime and nighttime urinary frequency, and an increased visual analog scale score were observed compared to baseline. At 12 months after treatment pain recurred in all patients. Nine patients complained of dysuria 1 month after treatment. Dysuria persisted in 4 cases at the 3-month followup and in 2 at the 5-month followup. CONCLUSIONS Intravesically injected botulinum toxin A is effective for short-term management of refractory painful bladder syndrome. The beneficial effects decreased progressively within a few months after treatment. Thus, repeat injections of the neurotoxin are required for efficacious treatment in patients with the disease.

Uterus preservation in pelvic organ prolapse surgery

Attitudes to sexuality and the psychological value of reproductive organs have changed in Western countries over the last few decades. Nevertheless, repair of pelvic support defects with concomitant hysterectomy is still considered the standard treatment for pelvic organ prolapse. Over the last 10 years, however, interest has been growing in uterus-sparing surgery, which can be divided into vaginal, abdominal, and laparoscopic procedures. The majority of studies on uterus-sparing surgery, with the exception of abdominal techniques, report few cases with short follow-up. Sacrospinous hysteropexy is the most studied vaginal technique for uterus preservation and favorable results have been demonstrated, although the majority of studies are flawed by selection and information bias, short follow-up and lack of adequate control groups. Abdominal and laparoscopic procedures are promising, providing similar functional and anatomical results to hysterectomy and sacrocolpopexy. Consensus is growing that the uterus can be preserved at the time of pelvic reconstructive surgery in appropriately selected women who desire it. The results of comparison trials and prospective studies confirm that uterus-sparing surgery is feasible and is associated with similar outcomes to hysterectomy, as well as shorter operating times. Surgeons should be ready to respond to the wishes of female patients who want to preserve vaginal function and the uterus.

Visually Directed Transrectal High Intensity Focused Ultrasound for the Treatment of Prostate Cancer: A Preliminary Report on the Italian Experience

PURPOSE High intensity focused ultrasound is a minimally invasive treatment option for prostate cancer. Data from the literature show promising early oncological outcomes and a favorable side effect profile. This study is a preliminary report of the Italian experience (Perugia and Turin) of patients treated with the Sonablate(R)500 high intensity focused ultrasound device. MATERIALS AND METHODS Between 2004 and 2007, 163 consecutive men with T1-T3 N0M0 prostate cancer underwent high intensity focused ultrasound with the Sonablate 500. Followup included prostate specific antigen tests at 1 month and then every 3 months after treatment, and a random prostate biopsy at 6 months. Failure was defined according to prostate specific antigen nadir, positive findings on followup biopsy and biochemical failure according to Phoenix criteria. RESULTS Median patient age was 72 years old, median baseline prostate specific antigen was 7.3 ng/ml, and disease stage was T1 in 44.1%, T2 in 42.5% and T3a in 13.4% of patients. Median followup was 23.8 months. After high intensity focused ultrasound treatment prostate specific antigen decreased to a median nadir of 0.15 ng/ml. Median prostate specific antigen at 3 and 6 months was 0.30 and 0.54 ng/ml, respectively. At 6 months the negative biopsy rate was 66.1%. There was no biochemical evidence of disease in 71.9% overall. On multivariate analysis prostate specific antigen nadir became the only independent predictor of no biochemical evidence of disease and positive biopsy at a cutoff of 0.40 ng/ml. CONCLUSIONS A favorable outcome of high intensity focused ultrasound is associated with lower baseline prostate specific antigen, lower prostate specific antigen nadir, lower Gleason score and lower tumor stage. As with any novel technology long-term data will be required before this technique gains widespread clinical acceptance.

Burch Colposuspension Does Not Provide Any Additional Benefit to Pelvic Organ Prolapse Repair in Patients With Urinary Incontinence: A Randomized Surgical Trial

PURPOSE We evaluated the impact of Burch colposuspension as an anti-incontinence measure in patients with urinary incontinence undergoing abdominal surgery for pelvic organ prolapse repair. MATERIALS AND METHODS A total of 47 women with pelvic organ prolapse and urinary incontinence were randomly assigned to abdominal pelvic organ prolapse repair and concomitant Burch colposuspension (24 patients, group A) or pelvic organ prolapse repair alone without an anti-incontinence procedure (23 patients, group B). They were followed up at 3, 6 and 9 months after surgery, and then annually. The primary outcome measures were anatomical outcome and changes in incontinence status as indicated by a bladder diary, the number of daily pads and the stress test. Secondary end points were changes in subjective symptoms and quality of life as measured by the Urogenital Distress Inventory and the Incontinence Impact Questionnaire. RESULTS In group A 13 of 24 patients (54.2%) were still incontinent after surgery compared with 9 of 23 (39.1%) in group B. The intragroup difference was significant (group A p = 0.003, group B p = 0.0001), but there was no significant intergroup difference (p = 0.459 for A vs B). No significant intergroup difference emerged in anatomical outcome. Urogenital Distress Inventory and Incontinence Impact Questionnaire scores improved in both groups (p = 0.0001) but the intergroup difference was not significant in either questionnaire (p = 0.769 and p = 0.327, respectively). CONCLUSIONS Burch colposuspension does not provide any additional benefit in pelvic organ prolapse repair in patients with urinary incontinence.

Pelvic Organ Prolapse Repair With and Without Prophylactic Concomitant Burch Colposuspension in Continent Women: A Randomized, Controlled Trial With 8-Year Followup

PURPOSE We reevaluated and brought up to date the 8-year followup of a previous published, randomized, controlled trial of the impact of Burch colposuspension as a prophylactic anti-incontinence procedure in patients without urinary incontinence who underwent abdominal pelvic organ prolapse repair. MATERIALS AND METHODS A total of 66 continent women with pelvic organ prolapse were randomly assigned to abdominal pelvic organ prolapse repair and concomitant Burch colposuspension in 34 (group 1) or pelvic organ prolapse repair alone without an anti-incontinence procedure in 32 (group 2). Primary study end points were the anatomical outcome and changes in incontinence status. Secondary end points were changes in subjective symptoms and quality of life. RESULTS Median followup was 97 months (range 72 to 134). Three group 1 and 1 group 2 patients were lost to followup. Three group 1 patients had a stage I rectocele and 1 had a stage I cystocele. Four group 2 patients had a stage I rectocele and 3 had a stage I cystocele. Nine of 31 group 1 patients (29%) were incontinent compared with 5 of 31 (16%) in group 2 (p = 0.553). In group 1 all except 1 patient were successfully treated for voiding dysfunction. Storage symptoms had disappeared in 1 patient and de novo storage symptoms had developed in 2 since the previous followup. De novo incontinence developed in 2 group 2 patients after midterm outcomes were reported. Median Urogenital Distress Inventory-6 and Incontinence Impact on Quality of Life-7 scores were improved in all groups at last followup (p 0.0001). CONCLUSIONS Long-term results cast doubt on whether Burch colposuspension should be done during pelvic organ prolapse repair in continent women.

Surgical Treatment of Peyronie's Disease by Plaque Incision and Grafting with Buccal Mucosa

BACKGROUND Plaque incision and tunical grafting is widely used to correct penile curvatures secondary to Peyronies disease (PD), but there is no consensus on the ideal graft to be used. OBJECTIVE To evaluate the efficacy, safety, and reproducibility of plaque incision and buccal mucosa grafting (BMG) in the correction of severe penile curvatures secondary to PD. DESIGN, SETTING, AND PARTICIPANTS Fifteen patients reporting normal erections and stable curvature (>12-mo duration) entered this prospective study carried out at two university hospitals. INTERVENTION All patients underwent plaque incision and BMG. MEASUREMENTS Preoperative evaluation included the International Index of Erectile Function (IIEF-5) and penile duplex ultrasounds with measurement of curvature and length of affected side. Follow-up visits were scheduled at 1, 3, 6, and 12 mo postoperatively, then yearly. Three-mo postoperative evaluation included IIEF-5, patient and partner satisfaction, and intracavernous injection test with evaluation of penile rigidity, straightness, and length; patient and partner satisfaction was recorded at all subsequent visits. RESULTS AND LIMITATIONS Mean patient age was 56.3 yr and mean penile curvature 72 degrees ; five patients had a two-sided curvature with mean second curvature of 37 degrees . There were no complications. All patients resumed unassisted intercourse 1 mo after surgery. Three-mo postoperative evaluation showed 100% penile straightening, 1.8-cm mean increase in length of affected side, no curvature recurrence or de novo erectile dysfunction, 1.6 mean increase in IIEF-5 score, and patient and partner satisfaction of 93.3% and 100%, respectively. Although results remained stable at subsequent follow-up (mean 13.1 mo), a greater number of patients and longer follow-up are needed before drawing any definite conclusions. CONCLUSIONS BMG provided excellent short-term results, probably because its prompt revascularisation, suggested by the fast return of spontaneous erections, prevented shrinkage, which is the main cause of graft failure. It also proved to be safe and reproducible, thus representing a valuable treatment option for PD.

Open Prostatectomy in Benign Prostatic Hyperplasia: 10-Year Experience in Italy

This study reports the experience of 47 Italian urology units together with the urology unit at the University of Perugia concerning open surgery in the management of benign prostatic hyperplasia (BPH). Until 20–25 years ago, open surgery was the most common approach. In the late 1970s the development of endoscopes and their methodology has led to a gradual reduction in open surgery operations, which decreased rapidly with the introduction of mini-invasive endoscopic techniques. Therefore, open surgery for BPH is declining, though still performed. Skill in traditional surgery is mandatory because, until an alternative is devised, indications for open surgery still exist and cannot be ignored. The survey shows the indications and contraindications, complications and results of a 10-year nationwide experience. Guidelines for open surgery in patients with BPH have been drawn up.

Lichen Sclerosus of the Male Genitalia and Urethral Stricture Diseases

Introduction: The true incidence of urethral involvement in patients with genital lichen sclerosus (LS) is unknown. We review the epidemiology and discuss the pathogenesis of LS and urethral stricture diseases. Materials and Methods: During the period 1991–2002, of 925 patients who underwent urethroplasty for anterior urethral stricture, 130 patients (14%) received the diagnosis of LS. In all patients with LS the histology was re-examined to confirm the clinical diagnosis. Retrograde and voiding urethrography was used to establish urethral involvement in the disease. Results: In 106 patients (82%) the histology provided the classical features of LS, and 24 patients (18%) showed some histological variations. In 49 patients (37%) the LS involved the pendolous urethra (meatus-navicularis-penile), and in 53 cases (41%) a panurethral stricture was evident. Conclusions: LS urethral involvement appears to be a much more common and extensive disease than previously reported, and requires particular care in its early diagnosis.