Federico Nelli

Treating erectile dysfunction and central neurological diseases with oral phosphodiesterase type 5 inhibitors. Review of the literature.

INTRODUCTION Erectile dysfunction (ED) is reported in a high percentage of patients with central neurological disorders (CND). AIM   An up-to-date review on oral phosphodiesterase 5 inhibitors (PDE5): sildenafil, tadalafil, and vardenafil for individuals with CND and ED. MAIN OUTCOME MEASURES Various questionnaires on ED, such as the International Index of Erectile Function composed of 15 questions. METHODS Internationally published clinical studies evaluating the efficacy and safety of PDE5 on subjects with CND and ED were selected. RESULTS Overall, 28 articles on PDE5 used to treat patients with CND and ED were included. With each of the three PDE5 compared to placebo or erectile baseline, literature reported significant statistical improvement (P < 0.01; P < 0.05) only in patients with spinal cord injury (SCI). PDE5 efficacy was documented for SCI patients up to 10 years. The most frequent predicable factor for PDE5 success was the presence of upper motoneuron lesion. Each of the three clinical sildenafil studies documented statistically significant improvement on erectile function in Parkinsons patients (P < 0.01; P < 0.05). Two studies reported discordant results about sildenafils effectiveness on multiple sclerosis (MS) patients; one on tadalafil showed significant statistical efficacy on erection versus baseline (P < 0.01; P < 0.05). The only spina bifida article determined that sildenafil remarkably improved erectile function. Overall, drawbacks were mostly slight-moderate, except in subjects with multiple system atrophy where sildenafil caused severe hypotension. CONCLUSIONS PDE5 represent first line ED therapy only for SCI patients, though treatment results through meta-analysis were not possible. Encouraging results are reported for Parkinsons and MS patients. PDE5 use for other CND patients is limited for various reasons, such as ED and concomitant libido impairment caused by depression and/or sexual endocrinology dysfunctions, and because PDE5 may cause a worsening of neurological illness. Medical centers staffed by health professionals able to counsel patients on the possible use of PDE5 are needed.

Clinical concomitant benefits on pelvic floor dysfunctions after sacral neuromodulation in patients with incomplete spinal cord injury

Objectives:To assess the concomitant clinical improvement in incomplete spinal cord injury patients (SCIPs) suffering from neurogenic bowel symptoms (NBSs), neurogenic lower urinary tract symptoms (NLUTSs) and neurogenic erectile dysfunction (NED) using sacral neuromodulation (SNM) for NBSs and NLUTSs.Methods:Seventy-five SCIPs were selected. Before and during the follow-ups post-SNM, NLUTSs and NBSs were detected mainly through specific diaries. Erectile function was assessed using the International Index of Erectile Function composed of 5 questions (IIEF5). Quality of life (QoL) was measured with the Short Form 36 Health Survey questionnaire (SF-36). During the first stage, in which a permanent electrode was inserted percutaneously into the third sacral foramina and stimulated using an external generator, patients with NBSs or NLUTSs were required to improve their symptoms by at least 50% compared with baseline before proceeding to the second stage in which the generator was placed in the patients buttock. NED patients needed to increase their IIEF5 score by at least 25% compared with baseline (evaluated initially 3 months after the second stage) in order to continue follow-up.Results:Fourteen out of 37 subjects who manifested two functional pelvic dysfunctions at baseline maintained notable clinical improvement in two pelvic functions (median follow-up >3 years). Six had non-obstructive retention (NOR) and NED, six double incontinence, and two constipation with NOR. In the general and mental health domains of the SF-36, all patients improved their scores by at least 20% compared with baseline.Conclusions:SNM may be beneficial to selected incomplete SCIP with concomitant pelvic functional disturbances.

Controversy over the pharmacological treatments of storage symptoms in spinal cord injury patients: a literature overview

Study design:Our aim was to locate research and communicate the evidence found from scientific studies pertaining to the treatment of neurogenic detrusor overactivity (NDO) in the chronic stage of spinal cord injury (SCI).Objective:To address the controversy over the traditional (antimuscarinics) and the ‘new’ treatments for NDO and try to offer an insight on the rationale underlying the development of new drugs such as botulinum toxin (BTX), vanilloids, nociceptin/orphanin FQ. As a final point, to provide information on a new class of cation channels, the Degenerin/Epithelial Na+Channel (Deg/ENaC) Family that could be future targets for the management of NDO.Setting:International.Methods:Overview of English literature on drug management of NDO.Results:Agents that block the ‘efferent’ function of micturition reflex, such as antimuscarinics, are currently first-line therapy for NDO. They reach the highest level of evidence (1a) and grade of recommendation (A). However, many patients and physicians believe that the ‘efferent’ pharmacological management of NDO is not completely satisfactory. Consequently, research is trying to address issues of efficacy, tolerability and convenience of new therapeutic strategies targeting the ‘afferent’ function.Conclusion:Antimuscarinic therapy increases the bladder capacity and delays the initial urge to void. However, in some patients they fail to achieve the patients therapeutic goals. New interesting approaches have been investigated in the last few years. BTX seems to be very promising in treating neurogenic overactive bladder (OAB), but other compounds are now on the horizon.

Intravesical electrostimulation versus sacral neuromodulation for incomplete spinal cord patients suffering from neurogenic non-obstructive urinary retention

Objectives:To compare the efficacy of intravesical electrostimulation (IVES) versus sacral neuromodulation (SNM) in patients with incomplete spinal cord lesions (SCL) and neurogenic non-obstructive urinary retention (N-NOR).Methods:In this retrospective study, 77 N-NOR patients underwent IVES (minimum 28 sessions), then after returning to voiding baseline symptoms, percutaneous first stage of SNM (lasting for minimum 4 weeks). After the two neuromodulation treatments, responders were categorized as patients experiencing both a 50% reduction of volume per catheterization per ml and a 50% reduction in number of catheterizations per day when comparing the 7-day voiding diaries at the end of both procedures to baselines. New urodynamics were performed subsequently. Responders to first stage of SNM underwent permanent SNM.Results:Forty-eight patients responded to neither of the treatments, whereas 29 responded to both IVES and first-stage SNM. No significant statistical differences (P>0.05) were detected in the voiding diaries. Following the two procedures, the first sensation of bladder filling was either maintained or recovered by all responders, whereas the same 11 patients reached a bladder contractility index of >100. The 29 IVES responders lost their clinical benefits in a mean follow-up of 9.6 months. Only 10 out of the 29 patients became nonresponsive to permanent SNM, in a mean follow-up of 54 months.Conclusion:A strict correlation in terms of clinical and urodynamic patterns was demonstrated in patients with incomplete SCL and N-NOR, following IVES and first stage of SNM. However, voiding improvement through IVES was short-term when compared with the effects of permanent SNM.

Clinical efficacy of intravesical electrostimulation on incomplete spinal cord patients suffering from chronic neurogenic non-obstructive retention: a 15-year single centre retrospective study.

Objective:To evaluate the clinical and urodynamic impact of intravesical electrostimulation (IVES) on incomplete spinal cord injury (SCI) patients suffering from chronic neurogenic non-obstructive urinary retention (N-NOR).Methods:One-hundred and two patients underwent at least 28 consecutive daily IVES sessions because objective evidence of detrusor acontractility instead of hypocontractility was detected. Diary entries written at various stages by each patient were compared (7 days before the IVES cycle, 15–21 days into the cycle and 7 days before its end). Responders were patients with a mean 50% reduction in both the number of daily catheterizations and post-void residual urine. Responders underwent further urodynamics at the end of the IVES cycle; patients experiencing first sensation of bladder filling, and the mean volume of first sensation of bladder filling per ml, Qmax ml s−1, among others, were evaluated. Nineteen individuals who repeated another IVES round were included in this study.Results:Thirty-eight subjects (37.2%) responded to IVES and of those, 83.3% recovered the first sensation of bladder filling after the IVES round. Nineteen responders repeated IVES within 1 year, owing to loss of efficacy. They obtained similar voiding symptoms improvement and urodynamic results as after the first IVES cycle. A timespan of <2 years from SCI to IVES, and the presence of first sensation of bladder filling at baseline represented significant predictive parameters for IVES success (P<0.05) using χ2-test.Conclusions:IVES represents a possible therapeutic option for incomplete SCI patients with N-NOR.

A retrospective study on female urological surgeries over the 10 years following spinal cord lesion

Objectives:To evaluate the efficacy and safety over a 10-year period of any urological operations required by female patients with spinal cord lesions (SCLs).Methods:Retrospective study of urological surgeries from our database performed on females with SCLs from 2001 to 2002. Surgery efficacy for neurogenic lower urinary tract dysfunctions (N-LUTDs) was evaluated by comparing 7-day voiding diaries pre- and post-surgeries, while individual investigations were done pre- and post-surgery to evaluate urological complications. Drawbacks were assessed.Results:Thirty-eight out of 69 patients underwent one or more urological procedures. Twenty-one out of 42 patients with suprasacral lesions underwent interventions for N-LUTD. The main surgical treatment was endoscopic detrusor infiltration of botulinum-A (Botox 300 UI or Dysport 750 UI) performed 107 times on 15 subjects using aseptic intermittent catheterizations for neurogenic overactive bladder. Mean efficacy duration was 9.2 months. Six females with infrasacral lesions underwent at least one intervention for N-LUTD. Two females in each group underwent tension-free vaginal tape for stress urinary incontinence (SUI), reducing episodes per week of SUI by >90% after 5 years. The most serious urological complication was active vesico-ureteral reflux (VUR) in three patients, treated endoscopically with submucosal injection of Macroplastique. No VUR recurrence was detected during a 6-year follow-up. All bladder stones (five cases) and renal calculi (five cases) were treated with endoscopic transurethrally electrohydraulic lithotripsy and extracorporeal shock-wave lithotripsy, respectively. Overall, no serious drawbacks were observed.Conclusions:Mini-invasive surgeries were exclusively used to address urological issues in chronic SCL patients.

Localized prostate cancer treated with intensity-modulated radiotherapy.

Aims and background The development and use of new radiotherapy techniques, especially 3D conformal radiotherapy or intensity-modulated radiotherapy, has allowed the safe application of high doses of external beam radiotherapy without increasing toxicity. The aim of this analysis was to describe the acute and when possible late toxicity and the feasibility on using intensity-modulated radiotherapy into our routine work. Patients and methods From June 2003 to December 2004, 60 patients with prostate cancer underwent high dose (80 Gy) radiotherapy treatment with intensity-modulated radiotherapy at the University of Florence. In the current analysis, we included patients without clinical or radiographic evidence of distant disease at the time of the first evaluation in the radiotherapy unit. Results Intensity-modulated radiotherapy treatments were delivered successfully without any interruption or technical problem. High-dose intensity-modulated radiotherapy was well tolerated acutely. Four patients (10%) developed grade 1 late rectal toxicity after completion of intensity-modulated radiotherapy and 8 patients (20%) developed grade 1 late urinary symptoms. Conclusions Intensity-modulated radiotherapy is the approach of choice for high-dose radiotherapy delivery. No patient had severe toxicity (grade 3) despite the high dose delivered. From a cost-benefit point of view, our experience shows that delivery of intensity-modulated radiotherapy requires only minor corrections to the ordinary activity schedule.

γEpithelial Na+ Channel (γENaC) and the Acid‐Sensing Ion Channel 1 (ASIC1) expression in the urothelium of patients with neurogenic detrusor overactivity

To investigate the expression of two types of cation channels, γEpithelial Na+ Channel (γENaC) and the Acid‐Sensing Ion Channel 1 (ASIC1), in the urothelium of controls and in patients affected by neurogenic detrusor overactivity (NDO). In parallel, urodynamic parameters were collected and correlated to the immunohistochemical results.

Unusual asymptomatic presentation of bladder cancer metastatic to the penis

Penile metastasis is an extremely rare event and mainly originate from primary pelvic tumor sites such us urinary bladder, gastro-intestinal tract and prostate and more rarely from respiratory system, bone tumors and melanoma. Here we describe the unusual presentation of two bladder urothelial cancer metastatic to the penis with no relevant clinical symptoms. Namely, a 69 years-old man with a warthy lesions of the foreskin and the glans misunderstood for a condylomata that at histological and immunohistochemical analysis showed a bladder urothelial carcinoma; and a 71 years-old man with reddish skin lesion of the glans, a previous history of bladder and urethral carcinoma and histological pagetoid spread of urothelial cancer to the glans. Recurrent bladder urothelial carcinoma is usually a visceral disease that rarely presents as a superficial asymptomatic skin lesion. The two reported cases were asymptomatic superficial penis metastases with a relatively slow growth and a fairy good prognosis after conservative surgical approach. Accurate clinical examination of the penis is mandatory for males with history of bladder cancer.

γEpithelial Na+ Channel and the Acid-Sensing Ion Channel 1 expression in the urothelium of patients with neurogenic detrusor overactivity

Both Epithelial Na+ Channel (γENaC) and the Acid-Sensing Ion Channel 1 (ASIC1) belong to Degenerin/Epithelial Na+ channel family that represents a new class of cation channels [1]. Increasing evidences show an involvement of these channels in the control of bladder afferent excitability under physiological and pathological conditions [2]; however, data available on their expression in human urothelium are controversial. Pathogenesis of the neurogenic detrusor overactivity (NDO), one of the most severe disabilities reported in patients with spinal cord lesions (SCL), has been attributed to bladder afferent dysfunction. Therefor, the aim of the present study was to investigate the expression of γENaC and ASIC1 in control urothelium and NDO patients. Controls and SCL patients with a clinical diagnosis of NDO underwent to urodynamic measurements and cystoscopy. Cold cup biopsies were processed for immunohistochemistry and western blots. In controls, γENaC and ASIC1 were expressed in the urothelium with different cell distribution and intensity. In NDO patients, both markers showed consistent changes in their cell distribution and intensity. Moreover, a significant correlation between the higher intensity of γENaC expression in urothelium of NDO patients and lower values of bladder compliance was found. In conclusion, the present findings show important changes in the expression of γENaC and ASIC1 in NDO human urothelium. Of note, while the changes in γENaC might impair the mechanosensory function of urothelium, the increase of the ASIC1 might represent an attempt to compensate excess in local sensitivity.