Henry Botto

Dosage effect on uropathogenic Escherichia coli anti-adhesion activity in urine following consumption of cranberry powder standardized for proanthocyanidin content: a multicentric randomized double blind study

BackgroundIngestion of cranberry (Vaccinium macrocarpon Ait.) has traditionally been utilized for prevention of urinary tract infections. The proanthocyanidins (PACs) in cranberry, in particular the A-type linkages have been implicated as important inhibitors of primarily P-fimbriated E. coli adhesion to uroepithelial cells. Additional experiments were required to investigate the persistence in urine samples over a broader time period, to determine the most effective dose per day and to determine if the urinary anti-adhesion effect following cranberry is detected within volunteers of different origins.MethodsTwo separate bioassays (a mannose-resistant hemagglutination assay and an original new human T24 epithelial cell-line assay) have assessed the ex-vivo urinary bacterial anti-adhesion activity on urines samples collected from 32 volunteers from Japan, Hungary, Spain and France in a randomized, double-blind versus placebo study. An in vivo Caenorhabditis elegans model was used to evaluate the influence of cranberry regimen on the virulence of E. coli strain.ResultsThe results indicated a significant bacterial anti-adhesion activity in urine samples collected from volunteers that consumed cranberry powder compared to placebo (p < 0.001). This inhibition was clearly dose-dependent, prolonged (until 24 h with 72 mg of PAC) and increasing with the amount of PAC equivalents consumed in each cranberry powder regimen. An in vivo Caenorhabditis elegans model showed that cranberry acted against bacterial virulence: E. coli strain presented a reduced ability to kill worms after a growth in urines samples of patients who took cranberry capsules. This effect is particularly important with the regimen of 72 mg of PAC.ConclusionsAdministration of PAC-standardized cranberry powder at dosages containing 72 mg of PAC per day may offer some protection against bacterial adhesion and virulence in the urinary tract. This effect may offer a nyctohemeral protection.

Heat shock proteins HSP27, HSP60, HSP70, and HSP90: expression in bladder carcinoma.

Heat shock proteins (HSPs) are synthesized by cells in response to various stress conditions, including carcinogenesis. The expression of HSPs in neoplasia has been implicated in the regulation of apoptosis, and HSPs also can act by increasing immunity. In the current study, the authors attempted to clarify the significance of HSPs in bladder carcinoma and their effect on tumor behavior.

Electrovaporization of the Prostate with the Gyrus Device

PURPOSE To assess the efficacy and the safety of a new transurethral endoscopic device using bipolar electrocautery, the Gyrus system. This system permits rapid prostate tissue removal by endoscopic vaporization with little bleeding and no pad return using saline irrigation and therefore eliminating TURP syndrome. PATIENTS AND METHODS Forty-two patients (mean age 70; range 49-90 years) with symptomatic benign prostatic hyperplasia (BPH) without suspected cancer, confirmed by digital rectal examination and PSA tests, were treated between October 1998 and February 1999 with the Gyrus and evaluated at 1 and 3 months postoperatively by the International Prostate Symptom Score (IPSS) and maximum urinary flow rate. RESULTS No postoperative bleeding necessitating catheterization for postoperative retention occurred. The duration of the procedure was < or = 30 minutes in 12 patients, 30 to 60 minutes in 27 patients, and >60 minutes in 3 patients. The mean time of postoperative continuous bladder irrigation was 1.2 days (0.5-3 days). The mean catheterization time was 1.4 days (range 0.5-5 days). Urethral stricture requiring treatment occurred in two patients. Dysuria was reported by four patients (mild two, severe two). The postoperative hospitalization was a mean of 2.2 days. The mean peak flow rate increased from 7.9 to 19.7 mL/sec at 3 months, and the IPSS decreased from 16 to 9 at 3 months. CONCLUSION Our preliminary results with a bipolar electrode for electrovaporization of the prostate using the Gyrus suggest that it is a useful and safe endoscopic device. It appears to be an effective treatment for BPH; however, long-term results (i.e., 1-year follow-up) should be evaluated. This pilot series permits a comparative study with TURP to assess the benefits for patients and the health care system.

Impact of Symptoms of Prostatism on Level of Bother and Quality of Life of Men in the French Community

The impact of symptoms of prostatism on level of bother and quality of life of French men was assessed nationwide, in a representative community sample of 2,011 subjects 50 to 84 years old. Bothersome level and quality of life associated with 12 urinary symptoms were assessed by face-to-face interviews, using a previously validated questionnaire for benign prostatic hyperplasia (BPH). The international prostate symptom score and the American Urological Association (AUA) bothersome index were also computed. Urgency was by far the most bothersome symptom in French men. Nocturia and wetting underclothes ranked second in subjects who did not undergo prostate surgery and among symptomatic patients, respectively. Overall, symptom frequency accounted for 72% of the variability of symptom bother but the form and strength of this correlation varied among symptoms from 0.18 to 0.43. Among the symptomatic subjects who had not yet undergone prostate surgery 11%, 10% and 79%, respectively, were dissatisfied, neutral and satisfied with the current urinary condition. Satisfaction with the urinary condition was positively linked to symptom frequency (p < 0.001) and symptom bother level (p < 0.001). Nocturia, dysuria, daytime repeat voiding, wetting clothes and urgency, when severely bothersome, were independent predictors of decreased satisfaction with the urinary condition (p = 0.01). Approximately half of the patients with severe BPH symptoms expressed serious worries and concerns with the urinary condition, and sizable levels of interference by the symptoms with daily activities, which are potentially affected by urinary troubles. The AUA bother index was the best determinant of subject level of worry about the urinary condition and of interference with daily life. This study supported the concomitant use of the international prostate symptom score and the AUA bother index in further research studies of BPH related impairments in quality of life.

Urethral Recurrence of Transitional Cell Carcinoma of the Bladder

Objective: The management of the male urethra after cystectomy for bladder cancer continues to be a dilemma. Patients who undergo a cystectomy require either urinary diversion or bladder substitution. Therefore, the use of the urethra to ensure voiding is important. On the other hand, the probable risk of urethral carcinoma recurrence is generally estimated at approximately 10%. The aim of this study was to assess the predictive value of preoperative urethral biopsies, and of frozen sections during cystoprostatectomy, in patients with invasive bladder cancer. Methods: From 1982 to 1986, 118 male patients underwent a cystoprostatectomy for transitional cell carcinoma of the bladder. All patients underwent endoscopic latero-montanal biopsies 2 weeks preoperatively and urethral frozen cut section during radical prostatocystectomy. Results: Carcinoma was observed in 12 patients on both examinations. All patients underwent en bloc urethrectomy during cystectomy. In the remaining 106 patients, the frozen cut margin was negative (including 9 with positive latero-montanal biopsies), and these patients had the urethra preserved. After a 10-year minimum follow-up, no recurrence was observed in these patients with negative frozen cut section. No significant risk factors for urethral recurrence were found. Latero-montanal biopsies did not reveal a positive specificity, and this procedure was later abandoned in our institution (in 1986). Conclusions: The urethral frozen section was the only guideline used for simultaneously performing the urethrectomy. All male patients with negative frozen cut sections should be considered candidates for bladder substitution. A prophylactic urethrectomy is only indicated in patients with carcinoma (minimum carcinoma in situ) in the frozen urethral margin section during cystectomy.

Evaluation of Tension–Free Vaginal Tape Procedure

Introduction and Objectives: The aim of this study was to evaluate preliminary results of tension–free vaginal tape (TVT), a new surgical procedure, performed during the learning phase for the treatment of stress urinary incontinence. Material and Methods: One–hundred consecutive patients underwent surgery, between June 1998 and December 1999, by six different senior surgeons. Indications were socially annoying urinary stress incontinence which persisted after complete physical therapy education. Preoperative examination included a urodynamic evaluation program. Surgical procedure was performed according to Ulmsten technique under local, regional or general anaesthesia. Results were evaluated by self–evaluation questionnaire and the patients were followed for at least 1 year. Results: Perioperative complications were: 14 bladder injuries and one urethral perforation without sequelae (except prolonged bladder drainage up to 3 days). Postoperative complications were: 13 retentions including 3 persistent after 1 month. During the learning phase (50 first patients) bladder injuries, retention and dysuria were more frequent. Progressively, local anesthesia was abandoned while most of the 50 remaining patients had TVT performed under epidural anesthesia. Functional results were divided into 3 groups according to preoperative urethral closure pressure (UCP) and eventual concomitant prolapse repair (PR): (1) UCP >25 cm H2O no PR (59 patients): 39 were totally dry without any instability, 13 dry with de novo (4) or persistent (7) instability and 5 were moderately improved. (2) UCP <25 cm H2O no PR (25 patients): 11 were dry without instability, 5 dry with instability, 6 were improved and 4 failed. (3) PR (15 patients): 9 were dry, 4 were improved and 2 failed. For 2 patients a bladder erosion due to the tape occurred (7 and 11 months) after the TVT procedure. Conclusions: During the learning phase, bladder perforation (22%) and retention (20%) were much more frequent than previously reported. Nevertheless, our results confirm that TVT appears to be an efficient procedure: 97% of patients were cured or improved when UCP >25 cm H2O, 85% when UCP <25 cm H2O and 87% when a PR was associated.

Treatment of Postprostatectomy Stress Urinary Incontinence Using a Minimally Invasive Adjustable Continence Balloon Device, ProACT: Results of a Preliminary, Multicenter, Pilot Study

OBJECTIVES To evaluate the safety and efficacy of a new minimally invasive device, Adjustable Continence Therapy (ProACT) for patients with postprostatectomy stress urinary incontinence (SUI). METHODS Sixty-two patients with urodynamic SUI after prostate surgery were evaluated according to daily pad count and a specific validated evaluation for persons with urinary incontinence. RESULTS All patients were successfully implanted in a single procedure using general or spinal anaesthesia. Procedural time was 37 minutes (range, 18 to 80 minutes). Daily pad usage decreased from 4.6 pads per day to 1.06 pads per day at 12 months. Mean quality-of-life index score increased from 48 to 67 at 12 months.Fifty-nine percent of patients without adjuvant radiation were improved (greater than 50% reduction in pad use), and 30% were cured (no pads), whereas 83% of postirradiated patients failed intervention. Fifty-five patients (88%) required percutaneous balloon adjustments. The mean optimal volume after adjustments for all 45 improved patients was 3.8 mL per balloon. Complications necessitating removal occurred in 19 patients and included erosion, infection, migration, and failure to respond. Of these, 4 were successfully reimplanted. All complications occurred in the first postoperative month. CONCLUSIONS Implantation of postoperatively adjustable balloons in postprostatecomy men is technically feasible, with an improvement in continence particularly in patients with nonirradiated periurethral tissues. Optimal urethral resistance is achieved, with easy postoperative adjustment. Implantation of ProACT balloons may represent a promising development in the treatment of postprostatectomy SUI.

RECURRENCE, PROGRESSION AND SUCCESS IN STAGE TA GRADE 3 BLADDER TUMORS TREATED WITH LOW DOSE BACILLUS CALMETTE- GUERIN INSTILLATIONS

PURPOSE Bacillus Calmette-Guerin (BCG) therapy is considered to be an effective prophylactic and therapeutic agent for high risk superficial transitional cell carcinoma of the bladder. Nevertheless, in a select uncommon population of stage Ta grade 3 superficial lamina-free tumors the results of this treatment have not yet been well established. We evaluated recurrence and progression rates, and the success of BCG therapy in a population with stage Ta grade 3 transitional cell carcinoma of the bladder. MATERIALS AND METHODS Of the 605 patients treated at our institution from 1982 to 1996 for the histopathological diagnosis of primary bladder cancer 32 (5.3%) with stage Ta grade 3 noninvasive primary bladder tumor were treated with intravesical instillations of 75 mg. Pasteur strain BCG in 50 ml. saline weekly for 6 weeks. At a followup of 2 to 13 years (mean 58.4 months) patients were evaluated with urinary cytology, cystoscopy, transurethral resection and random mucosal biopsies. Recurrence, grade and stage progression, death and causality were analyzed. RESULTS Of the 32 patients 9 (28%) responded positively to BCG without recurrence, while disease recurred as stage Ta in 8 (25%) and T1 in 7 (22%), and progressed to muscle layer infiltration in 8 (25%). Four patients (12%) died of bladder cancer. The number of tumors at primary resection, gross examination, the mitotic index or an association with carcinoma in situ did not appear to be predictive factors of progression to muscle invasion. Urine cytology (I to II versus III to IV) appeared to correlate highly with progression and BCG response (p<0.001) with excellent sensitivity (1) but low specificity (0.67). CONCLUSIONS Our study demonstrates the high progression potential of stage Ta grade 3 tumors, since nearly 50% recurred and 25% progressed to invasive disease. These results may be closely compared with the results of previous trials of stage T1 grade 3 disease. We suggest that recurrence should be detected at an early stage using long-term followup with strict observance of the surveillance protocols during a minimum 5-year tumor-free period.

Correlation between p53 over expression and response to bacillus Calmette-Guerin therapy in a high risk select population of patients with T1G3 bladder cancer.

PURPOSE The aim of this study was to determine if p53 status, assessed before intravesical bacillus Calmette-Guerin (BCG) therapy, can predict clinical outcome in a high risk population of patients with stage T1, grade G3 bladder cancer and if it can be used to select patients responsive to therapy. MATERIAL AND METHODS After complete transurethral resection 35 patients with T1G3 bladder carcinoma received 6 weekly instillations of BCG and nonresponsive patients received a second course. After treatment cystoscopy and randomized biopsies of the bladder mucosa were performed. Pathologists had sufficient material to perform immunomarking in 25 cases using the peroxidase-antiperoxidase technique with antiprotein monoclonal antibody p53. The results were expressed in percentage of marked nuclei. We established 5% increment thresholds from 0 to 60%. Contingent tables were established, and chi-square and Fishers exact test were performed for each 5% threshold. RESULTS Median followup was 51.3 months (range 25 to 144). Of the 25 patients 8 (32%) did not respond to BCG therapy and 17 (68%) did. Immunomarkings were not statistically different between BCG responsive and nonresponsive patients for 0, 5, 10, 20, 35, 40, 45, 55 and 65 thresholds. Chi-square and Fishers exact test were 0.91 and 0.83, 0.40 and 0.20, 0.58 and 0.29, 0.96 and 0.81, 0.80 and 0.88, 0.67 and 0.73, 0.91 and 0.83, 0.80 and 0.38, 0.69 and 0.32, respectively. CONCLUSIONS Our results indicate that the percentage of p53 immunomarked cell cannot currently be used to predict clinical response to BCG therapy and, therefore, p53 over expression is not a viable indicator of T1G3 recurrence when using this treatment.

Prostatic capsule- and seminal-sparing cystectomy for bladder carcinoma: initial results for selected patients.

To evaluate the oncological outcome and functional results of prostate‐sparing cystectomy (PSC), proposed for treating bladder cancer, used since 1999 in our institution in an attempt to preserve male sexuality and to increase continence after cystectomy.