First-in-man Safety and Efficacy of the ClearRing Implant for the Treatment of Benign Prostatic Hyperplasia.

BACKGROUND: Although effective for benign prostatic hyperplasia (BPH), transurethral resection of the prostate (TURP) can be associated with side effects including prolonged recovery, storage and voiding symptoms, and a risk of acute urinary retention. OBJECTIVE: To test a new minimally invasive device for the treatment of lower urinary tract symptoms (LUTS) due to BPH, involving implantation of a C-shaped nitinol ring (ClearRing) in a circular incision in the prostatic tissue using an electrocuting blade over a dilatation balloon. DESIGN, SETTING, AND PARTICIPANTS: This was a multicenter single-arm clinical trial involving 29 men with severe symptomatic BPH. INTERVENTION: Implantation of a ClearRing device under regional anesthesia. OUTCOME MEASUREMENTS AND STATISTICAL ANALYSIS: Effectiveness in alleviating LUTS was assessed in terms of International Prostate Symptom Score (IPSS) at baseline and 3, 6, and 12 mo after the procedure. To evaluate changes from baseline, a general estimating equation model was fitted to IPSS, the Quality of Life (QOL) scale, Benign Prostatic Hyperplasia Impact Index, maximum flow rate (Qmax), and postvoid residual volume. Statistical significance was defined as p<0.05. RESULTS AND LIMITATIONS: The average age was 71.4 yr, prostate size was 35-50cm3, and IPSS was 21.6. All procedures were successfully completed with one implant in 28 patients and two implants in one patient. No serious complications occurred. Patients experienced symptom relief by 3 mo that was sustained to 12 mo. Mean IPSS, QOL, and Qmax improved by 45%, 41%, and 40% by 3 mo, and 53%, 52%, and 49% by 12 mo, respectively (p<0.05). Adverse events were mild and transient. There were no reports of loss of antegrade ejaculation or any effects on erectile function. Implantation positioning failed in 11/29 patients, who then underwent uneventful TURP. After modification of the delivery device, the success rate for implant positioning improved from 5/13 patients to 13/16 patients. Study limitations include the single-arm nature and the low patient number. CONCLUSIONS: We demonstrated preliminary feasibility of the ClearRing device for minimally invasive treatment of BPH in men. Further studies are needed to confirm the safety and efficacy of this approach. PATIENT SUMMARY: In this study we tested outcomes after implantation of a ClearRing device in patients with benign prostatic hyperplasia. We found that the device was safe and effective. However, there was a high rate of implantation failure due to malpositioning, which was significantly improved following modification of the delivery device.

[MOLECULAR MARKERS FOR PROSTATE CANCER].

INTRODUCTION: Prostate cancer (PCa) is the most frequent malignancy and the second cause of death from malignancy in men in the Western world. Prostatic Specific Antigen (PSA) has been widely used as a possible marker for PCa for the last three decades, but its significant limitations are known, especially its lack of an exact cutoff level for diagnosis of PCa. Imprudent use of PSA has led to over-diagnosis and over-treatment in men with low risk PCa, not significant for survival. Therefore, researchers are looking for better and more accurate markers for diagnosis, treatment decisions and follow-up. In this article we review the various markers for PCa, especially two recent ones, their development process and validation results. The two markers are molecularbased and may provide an accurate and practical answer to important clinical questions: (1) In which patient with negative prostate biopsy should we repeat the biopsy? Can we locate the region of major risk? (2) Which patient diagnosed with low to moderate risk of PCa needs immediate treatment vs. active surveillance?

Long-term outcomes of a randomized controlled trial comparing thermochemotherapy with mitomycin-C alone as adjuvant treatment for non-muscle-invasive bladder cancer (NMIBC).

OBJECTIVE: • To present long-term efficacy data of intravesical thermochemotherapy vs chemotherapy alone with mitomycin-C (MMC) randomly administered to patients with non-muscle-invasive bladder cancer (NMIBC) as an adjuvant treatment after complete transurethral resection. PATIENTS AND METHODS: • In all, 83 patients with intermediate-/high-risk NMIBC, following complete transurethral resection, were randomly assigned to receive either intravesical thermochemotherapy by means of Synergo® (Medical Enterprises, Amsterdam, The Netherlands) or intravesical chemotherapy alone, for prophylaxis of tumour recurrence. • Two doses of MMC (20 mg dissolved in 50 mL distilled water administered throughout two consecutive sessions) was used as the chemotherapeutic agent in both arms. • In all, 75 patients completed the original study (35 of 42 in the treatment arm, 40 of 41 in the control arm), whose results at minimum 2-year follow-up have already been published. • Recently, the files of these patients have been updated for long-term outcome definition. Data on general health, follow-up examinations, tumour relapse or progression, and cause of death were collected and analysed. RESULTS: • Updated complete data collection was available for 65/75 (87%) of the original patients. • The median follow-up for tumour-free patients was 91 months. The 10-year disease-free survival rate for thermochemotherapy and chemotherapy alone were 53% and 15%, respectively (P < 0.001). • An intent-to-treat analysis performed to overcome the potential bias introduced by the asymmetrical discontinuation rate still showed a significant advantage of the active treatment over the control treatment. Bladder preservation rates for thermochemotherapy and chemotherapy alone were 86% and 79%, respectively. CONCLUSION: • This is the first analysis of long-term follow-up of patients treated with intravesical thermochemotherapy. The high rate (53%) of patients who were tumour-free 10 years after treatment completion, as well as the high rate (86%) of bladder preservation, confirms the efficacy of this adjuvant approach for NMIBC at long-term follow-up, even in patients with multiple tumours.

Long-term follow-up of patients with Stage T1 high-grade transitional cell carcinoma managed by Bacille Calmette-Guérin immunotherapy.

OBJECTIVES: To report the long-term outcome of patients with Stage T1 high-grade transitional cell carcinoma of the bladder treated initially by transurethral resection and adjuvant intravesical bacille Calmette-Guérin. METHODS: From June 1984 to November 1995, 78 consecutive patients with Stage T1 high-grade bladder cancer underwent transurethral resection and adjuvant intravesical bacille Calmette-Guérin therapy. The results at the interim follow-up (median 56 months) were reported in 1998. The median duration of follow-up for the present study was 107 months (range 16 to 238). The endpoints were tumor recurrence (Stage Ta, T1, or Tis), tumor progression (to T2 or greater), and disease-specific survival. RESULTS: Of the 78 patients, 34 (44%) were alive for the present analysis and 44 (56%) had died, 12 (16%) of transitional cell carcinoma and 32 (72%) of other causes. Recurrence was documented in 27 patients (35%) at a median of 8.5 months (range 5 to 129) after treatment, and progression in 14 patients (18%) at a median of 31.4 months (range 5 to 88) after treatment. The 2, 5, and 10-year recurrence-free survival and progression-free survival rates were 76%, 72%, and 62% and 92%, 82%, and 80%, respectively. The corresponding disease-free survival rates were 99%, 90%, and 85%. Disease progression occurred in 10 (37%) of 27 patients with recurrence, of whom 9 died. Of the 14 patients with disease progression, 12 died of their disease. CONCLUSIONS: Bacille Calmette-Guérin is an effective conservative treatment for patients with Stage T1 high-grade bladder cancer. More than one half the recurrences appeared within the first year, but a small risk remains throughout the patient's life. Progression during follow-up appears to carry a high risk of cancer-specific death.

Treatment program for erectile dysfunction in patients with cardiovascular diseases.

The present study assesses the effectiveness of our progressive treatment program for erectile dysfunction in patients with cardiovascular diseases. The study sample included 453 patients aged 36 to 91 years. Therapy in all patients was begun with sildenafil citrate 25 to 100 mg. Those with contraindications, drug adverse effects, or a negative response (erection insufficient for vaginal penetration) were given intracavernous injections of a cocktail of vasoactive drugs (dimix, trimix, or quadmix), followed by the addition of sildenafil citrate to the trimix in case of failure, and then a penile prosthesis. Patients were followed for 2 years; in cases of treatment ineffectiveness during follow-up, drug dosages were increased or a penile prosthesis was suggested. Sildenafil citrate was offered to 417 patients of whom 205 (49.2%) responded positively. The remaining 248 patients received intracavernous injections: 135 (54.4%) had a positive response to the dimix, 85 (75.2%) to the trimix, and 16 (57.1%) to the quadmix. Four of the other 12 patients (0.9%) responded to sildanefil citrate + trimix, and 2 (0.4%) agreed to a penile prosthesis. At the 2-year follow-up of 447 patients, 131 (29.3%) were successfully treated with sildanefil citrate, 92 (20.6%) with dimix, 122 (27.3%) with trimix, 12 (2.7%) with quadmix, and 2 (0.4%) with sildanefil citrate + trimix; 5 patients (1.1%) had a penile implant. Forty-eight patients (10.7%) achieved spontaneous erection, of whom 46 were taking aspirin. Twenty-six patients (5.8%) stopped treatment because of health and family reasons and 9 (2%) had a negative response. Our progressive treatment program for erectile dysfunction has a high success rate in patients with cardiovascular disease: Overall, 98.7% achieved an erection sufficient for vaginal penetration immediately after the trial and 92.2% on follow-up; 10.7% achieved spontaneous erections.

Urinary tract infection in men younger than 45 years of age: is there a need for urologic investigation?

OBJECTIVES: To determine in a prospective study whether urinary tract infection (UTI) in men younger than 45 years of age is associated with anomalies of the genitourinary tract that necessitate additional urologic evaluation. UTI in young men is uncommon. In these patients, it is customary to follow the same policy as that for children or older men and to routinely perform urologic investigations. METHODS: Twenty-nine consecutive, otherwise healthy, male patients aged 16 to 45 years (mean 30.5) were hospitalized for a first event of acute UTI. All patients underwent an imaging evaluation, including ultrasonography and intravenous urography. Those with macroscopic hematuria underwent cystoscopy. Uroflowmetry was performed at least 1 month after recovery, and patients with a maximal flow rate of less than 15 mL/s underwent a pressure flow study. RESULTS: Significant urethral stricture was excluded in all patients. Twenty-seven patients (93%) had a postvoid residual urine volume of less than 20 mL, and only two had values of 120 and 200 mL. The imaging and cystoscopic evaluation demonstrated a normal urinary tract in all patients. The maximal urinary flow rate was greater than 15 mL/s in 22 patients (76%) and lower than 15 mL/s in 7 patients (24%). In the latter group, urodynamic investigations, including free flowmetry and/or pressure flow study, revealed normal lower urinary tract function in 6 patients and a bladder outflow obstruction in 1 (3%). CONCLUSIONS: A first event of UTI in men younger than 45 years is usually not associated with significant structural or functional urinary tract abnormalities. Therefore, no radiologic, endoscopic, or urodynamic investigation is required.