High-intensity focused ultrasound and localized prostate cancer: efficacy results from the European multicentric study.

PURPOSE: To describe the safety and efficacy of high-intensity focused ultrasound (HIFU) for the treatment of prostate cancer as assessed in a Phase II/III prospective multicentric clinical trial. PATIENTS AND METHODS: Patients (N = 402) presenting with localized (stage T(1-2)N(0-x)M(0)) prostate cancer between 1995 and 1999 at six European sites who were not candidates for radical prostatectomy were treated with HIFU under general or spinal anesthesia. Their mean age was 69.3 +/- 7.1 (SD) years, the mean prostate volume 28.0 +/- 13.8 cc, and the mean serum prostate specific antigen (PSA) concentration 10.9 +/- 8.7 ng/mL. Nearly all (92.2%) of the patients had one to four positive biopsy samples at baseline. The Gleason scores were 2 to 4 for 13.2% of the patients, 5 to 7 for 77.5%, and 8 to 10 for 9.3%. During the follow-up, random sextant biopsies and serum PSA measurements were performed. Any positive sample in biopsies performed after the last treatment session resulted in a "HIFU failure" classification. RESULTS: The patients received a mean of 1.4 HIFU sessions. The mean follow-up duration was 407 days (quartile 1 135 days, median 321 days, quartile 3 598 days). The negative biopsy rate observed in the T1-2 primary-care population was 87.2%. These results were also stratified according to the usual disease-related risk classification, and as much as a 92.1% negative biopsy rate was observed in low-risk patients. Nadir PSA results correlated with prostate size and the clinical procedure. CONCLUSION: These short-term results obtained on a large cohort confirm that HIFU is an option to be considered for the primary treatment of localized prostate cancer.

Microsatellite instability in urothelial carcinoma of the upper urinary tract.

PURPOSE: Transitional cell carcinoma (TCC) of the upper urinary tract (TCC-UUT) may develop with high frequency in patients with hereditary nonpolyposis colorectal cancer syndrome. Tumors in patients with this syndrome show genomic lesions in DNA mismatch repair genes that are detectable as microsatellite instability (MSI). Because little is known about genetic lesions in TCC-UUT compared with bladder TCC, we determined the genetic profiles (MSI and allelic loss) in a series of 26 upper urinary tract tumors using 5 informative microsatellite markers. MATERIALS AND METHODS: A total of 26 paraffin embedded samples from 24 patients with clinically diagnosed TCC-UUT (renal pelvis and/or ureter) were tested for loss of heterozygosity (LOH) and MSI with the dinucleotide markers D9S171 (9p21) and D5S346 (5q22), and the mononucleotide repeats BAT25 (4q12), BAT26 (2p16) and BAT40 (1p13.1). RESULTS: MSI was detected at 1 or more microsatellite loci in 12 of the 26 tumors (46%). The markers BAT40, BAT25, BAT26, D9S171 and D5S346 showed instability in 7, 4, 4, 2 and 3 tumor samples, respectively. LOH at D9S171 was detected in 58% of the cases and 10 of the 14 tumors showing LOH were superficial. LOH at D5S346 occurred in 27% of the cases and it was a feature of invasive high grade TCC-UUT. CONCLUSIONS: Frequent LOH at D9S171 in TCC-UUT confirms that LOH at 9p21 is not only observed in bladder TCC, but rather in whole urinary tract TCC. Furthermore, our study indicates a high level of MSI in TCC-UUT, although it is a rare event in bladder cancer. The establishment of distinct genetic profiles between upper and lower urinary tract tumors could provide an additional tool to improve diagnosis, disease monitoring and prediction of prognosis.

[Use of a previously transplanted kidney for second transplantation]. / Utilisation d'un rein déjà greffé pour une seconde transplantation.

The constant shortage of renal transplants has led to the selection of unusual donors. We report a case of renal transplantation using a renal transplant that had already been transplanted 29 months previously. To our knowledge, this constitutes the first case of retransplantation of the same organ after long-term implantation in a first recipient.

Non-invasive molecular detection of bladder cancer recurrence.

Transitional cell carcinoma (TCC) is the most common bladder tumor and approximately 90% of bladder TCC are superficial at initial diagnosis. High recurrence rate and possible progression to muscle invasive disease that is eventually indicated for radical cystectomy are established features of these tumors. Therefore, reliable predictors of tumor recurrence are of critical importance for management of superficial bladder TCC. Successful molecular diagnosis of bladder cancer by detecting genetic lesions: loss of heterozygosity (LOH) or microsatellite instability (MSI) in cells exfoliated in urine has been reported by several groups including ours. The aim of our study was to evaluate the predictive potential of microsatellite analysis of cells exfoliated in urine in the detection of superficial bladder TCC recurrence. We studied 47 Caucasian patients with confirmed superficial bladder TCC (37 pTa, 10 pT1) at initial diagnosis. Blood samples were obtained once from every patient whereas urine samples were collected before each cystoscopy (initial and follow-up). Matched DNAs from blood and urine were subjected to microsatellite analysis in a blinded fashion. The follow-up period ranged 12-48 months after tumor resection. Microsatellite analysis correctly identified 94% (44/47) of primary tumors and 92% (12/13) of tumor recurrences. Interestingly enough, 75% (9/12) of tumor recurrences were molecularly detected 1-9 months before cystoscopic evidence of recurrent disease. This study demonstrated clearly that not only urine microsatellite analysis reliably detected superficial bladder tumors, but also was a reliable test for detecting and predicting tumor recurrence in Caucasian patients. These results warrant multicenter randomized trials.

[Role of uropontin in calcium oxalate lithogenesis]. / Rôle de l'uropontine dans la lithogénèse des calculs oxalocalciques.

The formation of calcium oxalate stones involves four phases: nucleation, growth, aggregation and retention. Stone formation is a complex, multifactorial phenomenon involving, among other factors, proteins, some of which play an inhibitory role, while others play a promoting role. The authors studied the role of uropontin. Uropontin is the urinary form of osteopontin. Osteopontin is essentially involved in the mineralisation of bone tissue. Uropontin is secreted in the kidney by epithelial cells of the distal convoluted tubule and loop of Henle. Uropontin has an inhibitory action on the four phases of calcium oxalate crystal formation and is also one of the main constituents of the calcium oxalate stone matrix. A reduction of uropontin expression in epithelial cells induces a reduction of calcium oxalate stone formation. Uropontin is a protein largely involved in the lithogenesis of urinary stones, but its mechanism of action has not yet been fully elucidated.