3-month formulation of goserelin acetate ('Zoladex' 10.8-mg depot) in advanced prostate cancer: results from an Italian, open, multicenter trial.

OBJECTIVES: To determine the endocrine effects, efficacy and tolerability of the 3-month formulation of goserelin acetate ('Zoladex' 10.8-mg depot; 'Zoladex' is a trade mark of the AstraZeneca group of companies) in the treatment of patients with advanced prostate cancer. METHODS: Between February 1996 and October 1997, this open, multicentre study enrolled 120 patients with locally advanced (T3/4) or metastatic (N+ or M1) disease, or an increase in prostate-specific antigen (PSA) level after radical prostatectomy. Patients received goserelin acetate 10.8-mg depot every 12 weeks until clinical progression or interruption for adverse events or other reasons. RESULTS: The mean testosterone concentrations were suppressed to the castration range (< or =2 nmol/l) after 4 weeks of treatment and remained suppressed throughout the study. In total, 99/115 (86%) patients had a serum PSA response, and the mean PSA value decreased significantly during treatment (p = 0.006). The mean PSA level at baseline was significantly lower in patients without disease progression compared to those who experienced disease progression (p = 0.0002). Goserelin acetate 10.8-mg depot was well tolerated and there were no injection site reactions. CONCLUSIONS: The goserelin acetate 10.8-mg depot is well tolerated with no injection site reactions. It produces PSA responses and provides reliable suppression of serum testosterone.

Urodynamic and clinical evidence of acute inhibitory effects of intravesical nociceptin/orphanin FQ on detrusor overactivity in humans: a pilot study.

PURPOSE: Management of neurogenic incontinence is complex and available treatments are not satisfactory. Nociceptin/orphanin FQ, a recently discovered neuropeptide, has been reported to inhibit the voiding reflex in the rat. These experimental results prompted us to investigate the urodynamic and clinical effects of intravesical instillation of nociceptin/orphanin FQ in humans. MATERIAL AND METHODS: Our study involved 5 normal subjects (group 1) with a mean age of 40.4 years (range 21 to 54) and 9 patients (group 2) 40.4 years (24 to 54). All patients in group 2 presented with detrusor hyperreflexia refractory to standard therapy. They were invited to undergo a filling cystometrogram with saline solution and after 30 minutes, a new one with a solution containing 1 microM. nociceptin/orphanin FQ. The urodynamic parameters that were recorded included bladder capacity, volume threshold for the appearance of detrusor hyperreflexia and maximum bladder pressure. Clinical and urodynamic followup was performed after 15 days. The data were statistically analyzed with 1-way analysis of variance followed by the Dunnett test for multiple comparison considered statistically significant with p <0.05. RESULTS: Intravesical instillation of 1 microM. nociceptin/orphanin FQ in group 1 did not produce significant functional changes. This infusion in group 2 produced a statistically significant increase in mean bladder capacity and volume threshold for the appearance of detrusor hyperreflexia from 164 plus or minus standard deviation (SD) 84 to 301 +/- 118 and 93 plus or minus SD 41 to 231 +/- 104 ml. (p <0.05, respectively). Mean maximum bladder pressure decreased from 79 plus or minus SD 25 to 54 +/- 44 cm. water but was not statistically significant (p = 0.19). After 15 days an absence of clinical improvement was noticed in group 2, and the urodynamic control did not show any significant changes compared to the values before nociceptin/orphanin FQ treatment. No severe symptomatic reactions were observed during infusion of 1 microM. nociceptin/orphanin FQ. CONCLUSIONS: Our results demonstrate that nociceptin/orphanin FQ is able to elicit a robust inhibitory effect on voiding reflex in group 2 but not 1. The ideal dosage, route of administration of nociceptin/orphanin FQ and treatment interval are not yet established.

Quality of life assessment in patients who undergo sacral neuromodulation implantation for urge incontinence: an additional tool for evaluating outcome.

PURPOSE: We investigated the impact of sacral neuromodulation on quality of life and assessed the importance of quality of life for determining the success of sacral neuromodulation in patients with detrusor hyperactivity, including instability and hyperreflexia. We also compared it with parameters documented in a voiding diary. MATERIALS AND METHODS: From May 1998 to December 2000, 82 female and 31 male patients 17 to 79 years old (mean age 51.1) with urge incontinence (63), urgency/frequency (5), voiding disturbance (41) and pelvic pain (4) resistant to conservative treatment were enrolled in a national prospective registry after showing a positive response to percutaneous nerve evaluation testing. Of the patients 47 who were 32 to 79 years old (mean age 59.2) with urge incontinence due to detrusor instability and 16 who were 27 to 51 years old (mean age 51.5) with hyperreflexia were asked to complete a validated self-reporting incontinence domain specific quality of life questionnaire before, and 3, 6, 9, 12, 18, 24 and 36 months after implantation. RESULTS: Compared with baseline the quality of life index significantly improved at each followup, which strongly correlated with the decrease in the number of incontinence episodes. CONCLUSIONS: Evaluating quality of life may be an additional useful tool for assessing the results of sacral neuromodulation for urge incontinence. Our study confirms that sacral neuromodulation is effective therapy for urge incontinence that can have a positive effect on patient quality of life.

Neuromodulation for fecal incontinence: outcome in 16 patients with definitive implant. The initial Italian Sacral Neurostimulation Group (GINS) experience.

PURPOSE: Sacral nerve modulation appears to offer a valid treatment option for some patients with fecal incontinence and functional defects of the internal anal sphincter or of the striated muscle. METHODS: Sixteen patients with fecal incontinence (4 males; mean age, 51.4 (range, 27-79) years) with intact or surgically repaired (n = 1) anal sphincter underwent permanent sacral nerve stimulation implant. Cause was traumatic in two patients, and associated disorders included scleroderma (2 patients) and spastic paraparesis (1 patient); eight (50 percent) of the patients also had urinary incontinence, and two (12.5 percent) had nonobstructive urinary retention. All patients were selected on the basis of positive findings from at least one peripheral nerve evaluation. The stimulating electrode was positioned in the S2 (1 patient), S3 (14 patients), or S4 (1 patient) sacral foramen. RESULTS: Mean follow-up was 15.5 (range, 3-45) months. Mean preimplant Williams score decreased from 4.1 +/- 0.9 (range, 2-5) to 1.25 +/- 0.5 (range, 1-2) (P = 0.01, Wilcoxon test), and the number of incontinence accidents for liquid or solid stool in 14 days decreased from 11.5 +/- 4.8 (range, 2-20) before implant to 0.6 +/- 0.9 (range, 0-2) at the last follow-up. Important manometric data were an increase in mean maximal pressure at rest of 37.7 +/- 14.9 mmHg (implantable pulse generator 49.1 +/- 18.7, P = 0.04) and in mean maximal pressure during squeeze (prestimulation 67.3 +/- 21.1 mmHg, implantable pulse generator 82.6 +/- 21.0, P = 0.09). CONCLUSIONS: Neuromodulation can be considered an option for fecal incontinence. However, an accurate clinical and instrumental evaluation and careful patient selection are required to optimize outcome.

Chronic sacral neuromodulation in patients with lower urinary tract symptoms: results from a national register.

PURPOSE: The Italian Register was created in February 1997 to collect the national results of sacral neuromodulation. All Italian centers at which sacral neuromodulation is performed were invited to participate in our study. We present the results from retrospective and prospective registers. MATERIALS AND METHODS: A total of 196 patients underwent permanent implantation of sacral neuromodulation and were enrolled in the Italian register. There were 18 males and 75 females in the retrospective, and 28 males and 75 females in the prospective studies. Student's t test was used to compare paired values, and the Wilcoxon rank sum and nonparametric tests were used when necessary. RESULTS: Mean incontinent episodes daily plus or minus standard deviation for patients with detrusor instability went from 5.4 +/- 3.9 to 1.1 +/- 1.6 (median 5 and 0, respectively) at 12-month followup (p <0.001). For idiopathic retention average residual volume decreased from 277 to 108 cc (median 287 and 80, respectively), and 50% of patients stopped catheterization and another 13% catheterized once daily at 1-year after implantation. With neurogenic voiding disturbances, the results fluctuated with time from a minimum of 33% to a maximum 66% of patients who did not catheterize at 6-month followup and 12 months after implantation, respectively. At 12-month followup, 50% of patients with hyperreflexia had less than 1 incontinent episode daily. The problem was completely solved in 66% of patients in the retention group. Of patients in the urge incontinent population 39% were completely dry and 23% had less than 1 incontinent episode daily. CONCLUSIONS: Sacral neuromodulation is effective therapy for treating lower urinary tract symptoms resistant to less invasive therapy.

Intravesical resiniferatoxin for the treatment of hypersensitive disorder: a randomized placebo controlled study.

PURPOSE: Present therapeutic approaches to control hypersensitive disorder of the lower urinary tract and bladder pain are clinically and scientifically unsatisfactory. We performed a randomized placebo controlled study with followup after 1 and 3 months using intravesical resiniferatoxin to treat hypersensitive disorder and bladder pain. MATERIALS AND METHODS: We prospectively randomized 18 patients into 2 groups to receive a single dose of 10 nM. resiniferatoxin intravesically (group 1) or a placebo saline solution only (group 2). All patients had at least a 6-month history of frequency, nocturia, urgency and symptoms of pelvic pain as well as no urinary tract infection within the last 3 months, functional disorders of the lower urinary tract, or other vesical or urethral pathology. Pretreatment voiding pattern and pain score were recorded. Patients were evaluated after 30 days (primary end point) and 3 months (secondary end point). RESULTS: The 2 groups were adequately homogeneous in regard to patient age, sex ratio, disease duration, voiding pattern and pain score. At the primary end point mean frequency plus or minus standard error of mean was decreased from 12. 444 +/- 0.70 voids to 7.111 +/- 0.67 and nocturia from 3.777 +/- 0. 27 to 1.666 +/- 0.16 (p <0.01). We observed a lesser significant improvement in mean frequency in group 1 at the secondary end point to 10.444 +/- 0.94 voids (p <0.05). No significant modification was noted in patients assigned to placebo. Mean pain score significantly decreased in group 1 at the primary end point from 5.555 +/- 0.29 to 2.666 +/- 0.23 (p <0.01) but not at the secondary end point (4.777 +/- 0.66, p >0.05). No statistically significant improvement in mean pain score was observed in placebo group 2. During resiniferatoxin infusion 4 group 1 patients noticed a light warm or burning sensation at the suprapubic and/or urethral level. CONCLUSIONS: Intravesical resiniferatoxin may significantly improve the voiding pattern and pain score in patients with hypersensitive disorder and bladder pain. Because resiniferatoxin did not cause a significant warm or burning sensation at the suprapubic and/or urethral level, it may be considered a new strategy for treating hypersensitive disorder and bladder pain. However, further studies are necessary to confirm our results and define the resiniferatoxin mechanism of action, dose and necessary treatment schedule.

Urodynamic assessment during intravesical infusion of capsaicin for the treatment of refractory detrusor hyperreflexia.

PURPOSE: Parameters to predict outcome and the urodynamic effects during infusion of capsaicin, seem not to have been assessed in patients with chronic cord injury. We monitored bladder activity urodynamically during infusion of high dosage of capsaicin. MATERIAL AND METHODS: Thirty patients, 18 women and 12 men (average age 29 years, range 20-59 years), suffering from chronic spinal myelopathy, who presented a refractory detrusor hyperreflexia, were studied. They received saline solution containing 10(-3) M capsaicin at a flow rate of 2 ml min(-1) for 15 min (total volume 30 c.c.). The detrusor activity was monitored by a real-time cystometrogram during infusion and 15 min after the end of the infusion itself. New filling cystometrograms were recorded after 30 days and after 6 months. RESULTS: We obtained a clinical and significant urodynamic improvement in 15 of the 30 patients (50%), confirming that intravesical capsaicin may represent a therapeutic option for a selected group of patients suffering from refractory detrusor hyperreflexia due to chronic spinal upper motor neuron lesion. Best results were observed in patients who showed, during the infusion of capsaicin, early uninhibited bladder contractions which disappeared within 10-12 min from the beginning of the infusion (desensitisation). The patients of this group presented a significant increase of mean cystomanometric capacity after 6 months (from 190.7 to 396.7 ml). No significant clinical or urodynamic improvement was observed in the group of patients in whom uninhibited activity of detrusor was recorded for all the time of infusion. CONCLUSION: Our results support the idea of a major complexity of spinal reflex in paraplegic patients and may offer a clue to explain the failure of therapy with capsaicin. The present results support a new approach in the treatment of detrusor hyperreflexia. The ideal dosage and treatment interval are not at present established and further studies are needed to explain substantial differences in the outcome according to different urodynamic responses.

Intravesical resiniferatoxin for the treatment of detrusor hyperreflexia refractory to capsaicin in patients with chronic spinal cord diseases.

OBJECTIVE: Resiniferatoxin (RTX), a substance isolated from some species of Euphorbia, a cactus-like plant, shows pharmacological effects similar to those of capsaicin. We have studied the possibility of treating detrusor hyperreflexia refractory to intravesical capsaicin in patients with chronic spinal cord injuries, thereby providing insight into the mechanism of action of RTX on sensory neurons and its possible future pharmacological and clinical use. MATERIALS AND METHODS: RTX saline solution (30 ml at a concentration of 10(-5) M) was instilled into the bladder of 7 patients with detrusor hyperreflexia, refractory to intravesical capsaicin therapy, and left in place for 30 min. Effects on bladder function were monitored during the treatment and at follow-up (15 days and 4 weeks later). RESULTS: Fifteen days after RTX, the mean cystomanometric capacity increased significantly from 190 ml +/- 20 ml to 407.14 ml +/- 121.06 (p < 0.01), and it remained high four weeks later (421.66 +/- 74.40 p < 0.01). After 15 days, four patients had a pharmacologically induced detrusor areflexia. They emptied their bladders by clean intermittent catheterization. After four weeks, only two patients still had a pharmacologically induced detrusor areflexia. Clinically, three patients remained dry, and the other three reported a significant improvement in their incontinence and symptoms (frequency, urgency and nocturia). CONCLUSIONS: By interfering with sensory unmyelinated fibers, intravesical RTX seems to be a promising treatment option for selected cases of detrusor hyperreflexia. The ideal dosage and treatment interval have not yet been established, and further studies are necessary to confirm our preliminary results.

[Malformations of the scrotum and its contents]. / Le malformazioni dello scroto e del suo contenuto.

To introduce we report the embryological origin of the male genitals and we present the endocrine control of the sex phenotypic differentiation and the most important features of the sexual differentiation abnormalities (ambiguous genitalia of newborn, gonadal dysgenesis, chromosome anomalies). Subsequently we report the classification of cryptorchidism and its correlation with hormonal and histological abnormalities. Furthermore we tried to expose the various different thoughts about testicular descent, anomalies associated with cryptorchidism and implications with malignant degeneration and infertility. Finally we describe the Magenta hospital experience from 1972 to 1998 reporting the surgical procedures for undescended testicle and for scrotal anomalies.

[Orthotopic urinary diversions: the Paduan ileal neobladder. Experience at the Urologic Division of Magenta]. / Derivazioni urinarie ortotopiche: la neovescica ileale padovana. Esperienza della Divisione Urologica di Magenta.

We refer our experience about continent ileal orthotopic bladder in male patient with bladder tumor we report our selections criteria, with particular attention about technical point of view. We show the results, early and late complications.

[Management of sexual dysfunction in spinal cord injury]. / Come gestrie le disfunzioni sessuali nel mieloleso.

In this paper we tried to report the sexual life aspect of spinal cord injury (SCI) patients and to explain how it should be treated in diagnostic and therapeutic pathways. We explain the sexual life alterations of male and female SCI patient and we report some dates about our experience.

Urolume in urethral stenosis: Italian Club of Minimally Invasive Urology experience.

A multicenter study of the patients in whom the Urolume has been implanted has been among the actions undertaken by the Italian Club of Minimally Invasive Urology (UMICLUB). For each patient, a computer information format has been prepared containing evaluation data related to the preoperative period, the endoscopic procedure, and follow-up. The collected data were computerized through unifunctional and multifunctional analysis. Of the 82 patients recruited, 76 were followed for a period ranging from 1 to 40 months. Urinoflow results dramatically improved after implantation of the endoprosthesis: peak flow rates increased by 310%, while mean flow rates increased by 294%. Incontinence and dribbling were found in 4% and 20% of the patients, respectively, and were independent of the distance between the external sphincter and the Urolume prosthesis and of the stent number and length. The cross-data elaboration seems to indicate a statistically significant relation between urethral preparation before Urolume implantation and stricture recurrence, with recurrence being more frequent after dilation. Significant correlations have not been noticed between stenosis etiology, urinary infection, type of anesthesia, and recurrence; between the type of anesthesia, stent length, and duration of hospitalization; or between stent number and position and pain. The impact of the Urolume prosthesis on sexual activity was marginal by all three measures considered (pain during erection, coitus, and ejaculation).

[Post-traumatic penoscrotal avulsion: cosmetic and uro-andrologic evaluation after surgical reconstruction]. / Scuoiamento penoscrotale post-traumatico: valutazione plastica e uro-andrologica post-intervento ricostruttivo.

A case of surgical reconstruction after penoscrotal skin avulsion is described. Penile coverage was gained by two full thickness grafts helicoidally placed to avoid retractions. Scrotal reconstruction was carried out in two steps, after testis subcutaneous implantation, with axial flaps expanded in abdominal region. The procedure has the advantage of flaps sure vitality, avoids patient discomfort produced by a perineal expansion with satisfactory cosmetic appearance and restore of a normal sexual function.

[Anti-sperm antibodies in dysspermia in spinal cord injury patients]. / Anticorpi antispermatozoo nelle dispermie di pazienti mielolesi.

A relatively uninvestigated area of reproductive physiology is the changes of sperm quality in the anejaculatory man. The retention of sperm cells may result in increased pressure in the genital tract, initiating an autoimmune response to sperm as seen in cases of congenital absence of the vas deferens and vasectomy. Reports on this matter are very contradictory. We evaluated antisperm antibodies in two groups of anejaculatory men with SCI. In the first group of 16 patients there was no clinical and laboratory urogenital infection. In the second group of 13 patients there was clinical and laboratory evidence for urogenital infection. Sperm antibodies were found in 12% of the patients of the first group and in 38% of the patients of the second group.

Transcutaneous minoxidil in the treatment of erectile dysfunctions in spinal cord injured men.

We have tested the erectile effect of a topical applied drug (Minoxidil) in 15 spinal cord injured men. Minoxidil exerts a direct relaxant effect on arterial smooth muscles. This topical vasodilatory agent (1 ml of a 2% solution) was applied on the skin of the penile shaft. Increases in diameter and rigidity were measured with the RigiScan device (Dacomed Minneapolis, Minnesota). A total of 4 paraplegic men with a complete dorsal level lesion reported a positive erectile response. 3 of these 4 patients preferred to continue with this noninvasive treatment compared to prostaglandin E1 intracavernous injections. In our study no side effects were emerged and minoxidil proved to be well tolerated at the cutaneous level of the penis. Our results indicate that this treatment should be tested in spinal cord injured men before a invasive therapy is initiated.

[Intracavernous injections of prostaglandin E1 in the treatment of erection disorders]. / Le iniezioni intracavernose di prostaglandina E1 nel trattamento dei disturbi erettivi.

Vasoactive drugs have been widely used for the treatment of impotence in the last years. Recently Prostaglandin E1 has been employed with success as a therapy in erection problems. The Authors have treated with Prostaglandin E1 209 patients complaining erection failure. Positive results were obtained in 155 patients (74,16%). No complications or side effects occurred. 129 patients of the 155 in which the test resulted positive were proposed a self-injection program and 115 accepted. Until now no side effects or complications occurred.

[Anamnestic criteria for sexual evaluation in the andrological field]. / Criteri anamnestici di valutazione sessuologica in campo andrologico.

What is the cause for impotence? In the recent years psychological studies have accredited some insights and modern neurological and vascular technologies have identified some previously idiopathic or misdiagnosed causes. The postulated ratio of psychogenic to organic dysfunction varies from 20:1 to 1:7 and this ratio may vary form one cultural area to the next. The authors underline that the main characteristic of the groups of males complaining of erectile dysfunction is heterogeneity and that the diagnostic procedure for finding the correct etiology may be rather cumbersome. Of primary importance is the patient's history to obtain a precise description of the dysfunction. Graber has suggested a more systematic approach to create a scientific nosology in the area of erectile failure. The phenomenon of morning erections must be inquired as well as the evaluation of the genital reflexes. A series of new diagnostic procedures has been developed but the Authors underline that it is preferable to use noninvasive techniques.

Nerve conduction velocity of dorsal nerve of penis: a modified technique.

The dorsal nerve of the penis is involved in sexual function. Until now, the nerve conduction velocity (NCV) of the dorsal nerve of the penis has been measured by dividing the distance between the stimulating and the recording electrodes by the latency to the negative peak of the action potential. With the penis stretched with a 1 lb weight, the NCV in normal men was 33 m/sec +/- 3.8. Measuring the NCV in this way, we became aware that when we decreased the distance between the stimulating and the recording electrodes, the velocity decreased. Furthermore these different measurements were linearly related. Taking this into account, we calculated the NCV with mathematical formula. In normal people, it turned out to be faster than reported previously.

Office treatment: intracavernous injections of prostaglandin E1 (PG E1) and improvement of spontaneous erections.

The Authors evaluated 48 patients with erectile dysfunctions, either psychogenic or neurologic or with vascular etiology. The experience confirms that PG E1 is able ti improve erection, mainly in case of psychological and vascular problems. The drug used is useful for the office treatment, since it has such a low incidence of side effects.

[Renal adenocarcinoma: 20 years of surgical experience, 1970-1990]. / Adenocarcinoma renale: un ventennio d'esperienza chirurgica 1970-1990.

Epidemiology, diagnostics, staging, surgical procedure and survival data of 219 patients with renal cells carcinoma are reported (1970-1990). Diagnosis is based on Tc and angiography. Possibly in the future high sensitivity methods like Magnetic Resonance could limit the use of invasive techniques. 207 patients underwent radical nephrectomy and 68 of these lymphadenectomy too (para and pre aortic and/or caval). In 41 patients the tumor had involved the venous system and 9 cavatomies, 2 caval resections and 1 atriotomy have been performed. In the stage T1-T2-T3 NoMoVo the survival rate (at. 5 years) is 87%, 80%, and 75% respectively. The survival in N+MoVo patients is 17% (at 5 y.) and in V+NoMo patients 57%.