Intermittent androgen suppression in patients with prostate cancer.

OBJECTIVES: To evaluate intermittent androgen suppression (IAS) in patients with prostate cancer and to try to define predictive factors for biochemical progression. PATIENTS AND METHODS: From 1989 to 2001, 146 patients received IAS as a primary treatment for localized, advanced or metastatic prostate cancer (72 men) or as a treatment for prostate-specific antigen (PSA) recurrence after radical prostatectomy (RP) and/or radiation therapy (74 men). Androgen-deprivation treatment (ADT) was continued up to 6 months after PSA became undetectable or a nadir PSA level was reached. ADT was then re-instituted when the PSA level was> 4 ng/mL for patients who had RP or> 10 ng/mL for the others. RESULTS: After a mean (range) follow-up of 45.6 (12-196.9) months, 24 patients had biochemical progression. These patients were younger than those with no biochemical progression (67 vs 72 years, P = 0.004) and had a statistically higher Gleason score (7.21 vs 6.52, P = 0.01) and PSA level (111.1 vs 32.1 ng/mL, P = 0.05), and a shorter first phase without treatment (7.6 vs 11.2 months, P = 0.05). Overall 5-year metastatic disease free survival of 91.3%. The overall 5-year biochemical recurrence-free survival was 68%. Using multivariate analysis, a Gleason score of >or= 8 (P = 0.021), first-phase duration with no treatment of < 1 year (P = 0.044), positive lymph nodes or metastatic disease at the time of starting IAS (P = 0.023) and age < 70 years (P = 0.037) were the strongest predictors of biochemical progression. CONCLUSION: IAS appeared to be a feasible treatment; the best candidates being those aged> 70 years with localized prostate cancer and a Gleason score of

Predictive factors of radiation therapy for patients with prostate specific antigen recurrence after radical prostatectomy.

OBJECTIVE: To assess the efficacy of salvage/adjuvant radiation therapy (RT) for patients with prostate-specific antigen (PSA) recurrence after radical prostatectomy (RP). PATIENTS AND METHODS: Between 1997 and 2001, 52 patients were treated in our institution with RT for PSA recurrence after RP. The mean (range) delay between RP and RT was 30.5 (0.16-105.6) months. Eighteen patients received no hormonal therapy before RT. The failure of RT was defined as three consecutive increases in PSA levels with intervals of > or = 6 weeks. RESULTS: Within a mean (range) follow-up of 27.7 (6-69) months, 18 patients presented with biochemical progression. The 3-year biochemical progression-free survival was 51%. Using univariate analysis, an age < 65 years (P = 0.0262), a Gleason score on the RP specimen of > or = 8 (P = 0.0024), stage pT3 (P = 0.02), a detectable nadir PSA after RT (P < 0.001) and the absence of hormonal therapy (P = 0.0359) were associated with a lower biochemical progression-free survival. However, only the Gleason score (P = 0.0395) and nadir serum PSA after RT (P = 0.028) remained independent predictive factors on multivariate analysis. CONCLUSION: Half of the present patients treated with RT for an isolated high serum PSA level after RP were free of biochemical relapse at 3 years of follow-up. RT may be proposed to selected patients with mild morbidity. However, definitive evidence of the beneficial effect of adjuvant RT for patients with PSA recurrence after RP awaits the conclusion of randomized clinical trials.

Image based renal stone tracking to improve efficacy in extracorporeal lithotripsy.

PURPOSE: We describe a method to reduce the number of shocks necessary to fragment renal stones during extracorporeal shock wave lithotripsy by automatically taking into account stone movements. MATERIALS AND METHODS: Echotrack computer software was developed and implemented on a lithotriptor. One software module uses image processing to detect instantaneous stone location based on ultrasound images generated by the lithotriptor. A second module uses the detected location to control the shock wave generator position, and automatically adjusts it to improve coincidence between the focal volume and stone. The reliability of the tracking algorithm was clinically tested in 65 patients with renal stones. These in vivo tests were qualitative and the goal was to assess software ability to track stones during actual treatments. A quantitative evaluation of the reduction in shocks necessary for fragmentation was performed in vitro. Artificial stones were moved according to computer generated trajectories. Each trajectory was applied once with and once without automatic adjustment of the generator position. RESULTS: The in vivo tests demonstrated software ability to track stones as far as they were visible in the images. During in vitro tests automatic adjustments of the generator position reduced the number of shocks necessary to fragment stones completely by a factor of 1.64. CONCLUSIONS: Image based renal stone tracking software that automatically adjusts the shock wave generator position according to the displacement of renal stones is useful during extracorporeal shock wave lithotripsy. Treatment time was significantly shorter with this software.

Efficacy and safety of transurethral alprostadil therapy in men with erectile dysfunction. MUSE Study Group.

OBJECTIVE: To examine the safety and efficacy of transurethral pharmacotherapy for erectile dysfunction, involving the use of a novel therapeutic system to administer alprostadil (prostaglandin E1) to the urethral mucosa in a double-blind, randomized, parallel, placebo-controlled study conducted in five countries in Europe. PATIENTS AND METHODS: In an outpatient setting, patients with primarily organic erectile dysfunction of at least 3 months' duration were treated with transurethral alprostadil, in an open-label, dose-escalating study. Testing stopped when the dose provided an erection sufficient for intercourse, as assessed by the patient and the investigator. Patients who achieved a sufficient response were then randomized to either active medication at the selected dose or to placebo for use at home for 3 months. After each home administration, patients recorded in diaries whether or not sexual intercourse occurred and any adverse reactions to the drug. RESULTS: A total of 249 patients were treated in an outpatient setting; of these patients, 159 (64%) achieved an erection sufficient for intercourse and were randomized (1:1) to either active medication or placebo for home treatment. Of the patients randomized to alprostadil for home treatment, 69% reported intercourse at least once, compared with 11% of patients randomized to placebo (P < 0.001). The most common adverse reaction, urethral pain/burning, was reported by 7% of patients in the clinic. Most patients (83%) graded transurethral alprostadil as causing minimal or no discomfort in the clinic. No patient reported priapism or developed penile fibrosis. CONCLUSION: Alprostadil delivered transurethrally by this system was well tolerated and effective in treating erectile dysfunction.

Endoscopic ureteroneocystostomy: palliative urinary diversion in advanced prostatic cancer.

Distal ureteral obstruction is a common complication in advanced prostatic cancer, secondary to direct compression at the ureterovesical junction and/or invasion of the ureteral orifice and/or of the intramural ureter by the tumor. The ureteral orifice may not be readily visible to the trigone-infiltrating tumor, but remains superficial as it is pushed upward by the tumoral tissue. The indications for palliative diversion in patients with pelvic malignant disease and renal failure from ureteral obstruction remain controversial. We present the results of our endoscopic ureteroneocystostomy technique by which the trigone is resected to restore continuity of the ureteral orifice and to place a double pigtail ureteral stent. Of the 31 operations performed for obstructive prostate cancer, continuity was restored in 76% of cases. Length of hospital stay was gradually reduced to a few days. Median survival after surgery was 8 months (0.25 to 27.5 months). Palliative diversion may be considered a reasonable option for many patients, even in the case of an apparently unpassable obstruction of the pelvic ureter, thereby prolonging survival and improving quality of life.

p53 status does not predict initial clinical response to bacillus Calmette-Guerin intravesical therapy in T1 bladder tumors.

PURPOSE: In superficial urothelial tumors of the bladder, p53 status is currently the most informative pretreatment parameter to define a population at higher risk for invasive carcinoma. Also, in T1 tumors, occurrence of muscular invasion is often related to an early relapse following BCG therapy. With the knowledge of biological parameters able to identify the group of initial BCG therapy non-responders, it would be possible to offer earlier treatment to the patients who need a more aggressive mode of therapy. The aim of this work was to study the predictive value of the p53 tumor status on the early BCG therapy response. MATERIALS AND METHODS: The population included a selected group of 43 patients presenting T1 bladder tumors with no carcinoma in situ (Tis), treated by transurethral resection (TUR) followed by intravesical BCG therapy. Clinical outcome was analyzed in relation to usual clinical and histopathological parameters, and pretreatment p53 tumor status was assayed by an immunohistochemical technique using DO7 monoclonal antibody. For 16 specimens, p53 gene was investigated using a Single Strand Conformation Polymorphism (SSCP) analysis and sequence determination. RESULTS: p53 anomalies were strongly correlated to smoking behavior (p = 0.003) and tumoral grade (p = 0.025). Univariate analysis revealed an absence of correlation between p53 immunostaining and initial, one and two years response-rate to BCG therapy. However, longterm followup revealed a trend between positive staining and disease progression. The p53 molecular study validated the use of DO7 immunostaining in detection of p53 anomalies. CONCLUSIONS: In T1 bladder tumors, pretreatment p53 determination was not useful to define a group of early BCG non-responders. Thus, p53 status and immunological response induced by BCG endovesical therapy are two independent events.

The effect of transurethral alprostadil on the quality of life of men with erectile dysfunction, and their partners. MUSE Study Group.

OBJECTIVE: To evaluate the impact of treatment for erectile dysfunction on the quality of life of men and their partners. PATIENTS AND METHODS: The study included 249 men with organic erectile dysfunction of more than 3 months' duration who self-administered transurethral alprostadil in an open-label, dose-escalating manner in an outpatient medical setting. Patients with a sufficient response (159) were randomly assigned in a double-blind protocol to either active medication or placebo for 3 months at home. Patients and partners each completed quality-of-life questionnaires before and after treatment. RESULTS: In the clinic 159 of the 249 men (64%) had an erection sufficient for intercourse when using transurethral alprostadil. At home, 46 of 67 men (69%) reported intercourse at least once on transurethral alprostadil, compared with eight of 73 (11%) on placebo (P < 0.001). Patients on alprostadil showed a 34% improvement in their 'relationship with partner', a 5% improvement in 'personal wellness', and a 71% improvement in 'quality of erection' domains, compared with a decline of 11%, 8% and 1%, respectively, in patients on placebo (P < 0.005 for each comparison). Partners of patients on alprostadil showed a 35% improvement in the 'relationship with partner' domain, compared with a 12% improvement in the placebo group (P = 0.028). There was a trend toward improvement in other partner domains. Urogenital pain was reported by 14% of patients during home treatment. CONCLUSION: The resumption of sexual intercourse with the use of transurethral alprostadil was accompanied by an improvement in several important quality-of-life domains in patients and their partners.

Positive prostate-specific antigen circulating cells detected by reverse transcriptase-polymerase chain reaction does not imply the presence of prostatic micrometastases.

OBJECTIVES: Detection of circulating tumor cells may improve the preoperative local staging of prostate cancers. The aim of this study was to perform enhanced reverse transcriptase-polymerase chain reaction (RT-PCR) of prostate-specific antigen (PSA) mRNA to define the predictive value of PSA-positive circulating cells in a large series of patients. METHODS: The study included 46 patients with Stage T1 to T2 prostate cancer, 94 with benign prostatic hyperplasia (BPH), and 51 (including 9 women) with nonprostatic disease. PSA-positive cells from peripheral blood samples were detected by Southern blot analysis of the RT-PCR products. Original oligonucleotide primers were defined to exclusively detect the three PSA mRNA splices. RESULTS: Circulating PSA-positive cells were observed in 8 (8.5%) of 94 patients with BPH, 10 (22%) of 46 with Stage T1 to T2 prostate cancer, and 9 (17.6%) of 51 with nonprostatic disease. The detection rate of PSA-positive circulating cells was significantly increased in patients with prostate cancer versus patients with BPH (P = 0.03). Among clinically localized prostate cancers with a Gleason score less than 8, a correlation was observed between PSA-positive circulating cells and Stage pT3 cancer (P = 0.038), capsular penetration (P = 0.04), and a positive margin (P = 0.038). The specificity of the assay for Stage pT3 cancer detection was 84.6%, with a positive predictive value of 60%. CONCLUSIONS: Although RT-PCR assay may have a role in preoperative local staging, this study demonstrated the absence of tissue and tumor specificity of PSA-positive circulating cells, accounting for the weak positive predictive value of this technique.

[Transurethral vaporization of the prostate for benign hypertrophy: preliminary clinical and histological study]. / Vaporisation trans-urétrale de la prostate pour hypertrophie bénigne: étude préliminaire clinique et histologique.

Twenty five patients with symptomatic BPH and normal PSA underwent electrovaporization. The mean IPSS was 21.5 before and 7.8 three months after treatment while the mean peakflow was 7.1 ml/s and became 16.9. With a short hospital stay (3 days) and a very low morbidity, electrovaporization seems to be a good alternative to TURP. A longer follow-up is necessary.

Lack of efficacy of low-dose subcutaneous recombinant interleukin-2 and interferon-alpha in the treatment of metastatic renal cell carcinoma.

OBJECTIVE: To evaluate the efficacy and toxicity of subcutaneous immunotherapy using a combination of recombinant interleukin-2 (r-IL2) and interferon-alpha (IFN-alpha) for the treatment of patients with metastatic renal cell carcinoma (RCC). PATIENTS AND METHODS: Initially a maximum of 45 patients with advanced RCC were to be included in the study, according to a Fleming three-stage procedure. To be included patients had to have measurable metastasis. Of a potential 45 patients with advanced RCC, 15 patients were included in the study (10 men and five women, mean age 51 years, range 25-69). From the first week of treatment r-IL2 was given subcutaneously on day 1 to 5, at 18 x 10(6) units once a day and then 9 x 10(6) units once a day for the following 5 weeks. IFN-alpha was given three times a week for the last 5 weeks. Minimum follow-up was 6 months. RESULTS: All patients initially underwent radical nephrectomy. Seven patients were found to have metastases at the time of diagnosis. All patients received ambulatory therapy, except for the first 5 days of treatment. Overall, 80% of the patients received more than 75% of the complete dose of r-IL2. One patient suffered toxicity greater than the World Health Organization (WHO) grade 2 (neutropenia). No patient had a complete or partial response, two patients had a minor response, two patients had stable disease and 11 patients had disease progression. CONCLUSIONS: Subcutaneous r-IL2 and IFN-alpha had no beneficial effect on the first 15 patients and the study was discontinued, in accordance with the Fleming rules. The dose, administration and combination of r-IL2 and IFN-alpha may explain the lack of efficacy. Other studies have shown that low doses of r-IL2 are not effective and the superiority of the combination of r-IL2 and IFN-alpha has not been proven. Therefore, a high dose of r-IL2, in association with other cytokines, chemotherapy and adoptive immunotherapy, may be the only way to improve the response rate of metastatic RCC.

Electroconductive lithotripsy: principles, experimental data, and first clinical results of the Sonolith 4000.

The electroconductive lithotripter (ECL) is a new concept for shockwave generation in which a highly conductive solution channels the discharge between the anode and cathode. In vitro experiments showed a linear relation between the voltage setting and the pressure at F2. In vitro stone disintegration studies showed a considerable reduction in shockwave pressure variability, improved energy transfer to the stone, and a unique linear relation between fragmentation and electrode voltage without a saturation effect. This new concept has been used clinically in the Sonolith 4000 lithotripter. In 142 evaluable treatments with a 3-month follow-up, the overall stone-free rate was 82%, and the retreatment rate in stone-free patients was 10%. For stones equal or less than 10 mm, the 3-month stone-free rate, retreatment rate, and secondary procedure rate were 85%, 5%, and 0%, respectively. For stones between 11 and 20 mm, these figures were 83%, 4%, and 2%, respectively. The efficiency quotient was found to be 81% for stones equal or less than 10 mm and 78% for stones between 11 and 20 mm. These clinical results confirm the improvements in efficacy observed in vitro with very satisfactory tolerance.

Complete ureteral transection associated with percutaneous lumbar disk nucleotomy.

A case of complete ureteral transection complicating percutaneous nucleotomy for disk herniation is reported. The ureteral lesion was contralateral to the percutaneous approach and was treated by intubated ureteroureterostomy, since complete section precluded endourological management.

Localized hyperthermia versus the sham procedure in obstructive benign hyperplasia of the prostate: a prospective randomized study.

Hyperthermia was shown to cause improvement in 50 to 60% of the patients with benign prostatic hyperplasia (BPH) without considering placebo effects. We studied 68 patients randomly assigned to a treatment group (38) and a sham group (30) who underwent the same manipulation but without applying radio frequency power. The Biodan Prostathermer was used. Criteria for inclusion were based on objective and subjective symptoms. Treatment was performed 6 times at 43 +/- 0.5C for the treatment group. Followup evaluation was performed at 3 months, and the same objective and subjective symptoms were recorded. We observed a statistically significant subjective improvement in the sham group (33%) that was not accompanied by any significant objective improvement. In the treatment group the subjective response was significantly better regarding number of patients (68%) and response rate, and was substantiated by a significant improvement in all objective symptoms (53% of the patients) except voided volume. Therefore, hyperthermia treatment had a definite therapeutic effect on BPH in excess of placebo.

Laser treatment of obstruction from incrusted ureteral catheter.

Incrustations may develop on ureteral catheters and cause obstruction. We report a case in which obstruction was relieved by laser lithotripsy inside the lumen of the catheter. This completely noninvasive technique may prove to be useful in selected cases.

Extracorporeal shock-wave lithotripsy to remove calcified ureteral stents.

A patient was seen with a large calcification of the renal end of a silicone catheter placed to intubate a cutaneous ureterostomy. Because of the stone, withdrawal of the catheter was impossible, and the patient presented with obstruction and dilatation of the renal cavities along with febrile bacteriuria and renal failure. Extracorporeal shock-wave lithotripsy, done under intravenous sedation, was found to be an effective noninvasive method to treat such a complication of long-term urinary drainage.

Immunohistochemical markers defined by monoclonal antibodies and response to bacillus Calmette-Guérin endovesical immunotherapy for superficial bladder tumors.

As bacillus Calmette-Guérin (BCG) immunotherapy is highly effective for most but not all superficial bladder tumors, there is a need to define predictors of response to this mode of treatment. We have investigated a panel of markers defined by monoclonal antibodies, directed against tumor-associated transitional cell carcinoma antigen (G4 and E7), epidermal growth factor receptor, cytokeratin (CK) 18 and blood group antigens A, B and H, using an indirect immunoperoxidase staining on paraffin sections. Twenty superficial bladder tumors (T1) treated with intravesical BCG therapy (10 responders and 10 nonresponders) were tested with this panel. Among the responders, expression of CK18 antigen was positive in 7 and negative in 3, whereas in the nonresponder group it was positive in 2 and negative in 8. The difference was statistically significant (p less than 0.05). Loss of expression of CK18 antigenicity was associated with recurrence or progression of superficial bladder tumors following BCG therapy, indicating that changes in CK patterns should be investigated as potential predictive markers for response to BCG.

Experimental study of hollow, absorbable polyglycolic acid tube as stent for vasovasostomy.

Bilateral vasovasostomy in 16 rats permitted evaluation of a microsurgical technique using an original absorbable hollow stent made of polyglycolic acid. Advantages of this stent included ease of anastomosis, maintenance of luminal patency, satisfactory approximation of vasal ends, and reduction of perivasal inflammation possibly due to reduction of extravasation of sperm. Absorbable stents were eliminated within four weeks of placement, and patency was confirmed by histologic studies performed two, four, and six weeks after vasovasostomy.

[2 cases of testicular seminoma associated with HIV infection. Analysis of treatment tolerance]. / Deux cas de séminomes testiculaires associés à une infection HIV. Analyse de la tolérance du traitement.

Two homosexuals with advanced HIV infection and testicular seminoma stage IIb and IIc were treated with irradiation associated with chemotherapy in one patient. Subdiaphragmatic irradiation was followed by moderate diarrhoea. Initial chemotherapy consisted of cisplatinum, vinblastine, bleomycin replaced by cyclophosphamide after radiotherapy. The use of cyclophosphamide was discontinued after 2 courses due to neutropenia (less than 1500/mm3). Complete tumor remission was achieved in both patients without infection in spite of an aggravation of the CD4 deficit (5/mm3, 52/mm3). The patients died of opportunistic infections 14 and 12 months after terminating treatment. We conclude that cytotoxic and radiation treatment can be administered safely if carefully monitored in these severely immunodepressed patients.