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Thierry Lebret

Publications and source records attributed to Thierry Lebret.

27 records · Page 2Linked to original sources

[Detection of telomerase activity by semi-quantitative and in situ assays and quantification of hTERT expression in bladder carcinomas].

OBJECTIVES: Several studies have reported the important role played by telomerase, an enzyme which maintains the length of telomeres, during carcinogenesis. The objective of this study was to detect telomerase activity by semiquantitative in situ methods and to quantify expression of the hTERT subunit in a group of bladder cancers in order to assess its diagnostic and prognostic value. MATERIAL AND METHODS: Telomerase activity (TA) was detected by the TRAP method ("telomeric repeat amplification protocol") on a series of 29 bladder cancers and 3 samples of healthy mucosa. Levels of expression of the hTERT gene were studied by real-time quantitative RT-PCR. In situ detection of TA was performed by using the same kit as the TRAP method, applied to frozen tissue sections exclusively for cases with discordant results between TA detection and hTERT mRNA. RESULTS: TA was detected by TRAP in 15 of the 29 bladder cancers. hTERT mRNA was detected and quantified in all tumour samples. A significant correlation was observed between TA and the level of hTERT mRNA expression. In situ detection of TA demonstrated heterogeneous TA in tumour tissue. A significant correlation was observed between the level of hTERT mRNA expression and tumour histological grades and stages. CONCLUSION: hTERT mRNA detection by real-time quantitative RT-PCR appears to be a sensitive method for the diagnosis of bladder cancer with a good correlation with tumour grade and stage. Quantitative evaluation of hTERT mRNA could therefore be a useful marker of tumour progression for the early diagnosis and follow-up of bladder cancers.

DNA-Binding Proteins↗

[Bladder tumors and molecular markers. Current status and perspectives].

With 15,000 new cases each year, bladder tumors are the second leading urological cancer in France, after prostate carcinoma. In spite of advances in surgical techniques and therapeutic protocols based on trans-urethral resection associated with additive treatment (immunotherapy or endovesical chemotherapy), the natural course of superficial bladder tumors remains marked by two risks: recurrence and progression. In spite of the impressive efforts developed by molecular biologists searching for new specific markers, none of the markers can currently replace histological features such as stage and grade. Although detection of microsatellite instability is a promising approach, numerous difficulties limit the use of these markers and prevent their application in routine practice. Let us hope that the new techniques for tissue analysis such as DNA or tissue-arrays developed for simultaneous analysis of hundreds or even thousands of tumors will allow identification and validation of biological and even therapeutic markers. Among the various biological markers, only the proliferative index given by the expression of Ki67, the expression of p53 and EGFR have been examined in comparative studies. Ki67 seems to be the best marker for progression, its expression and the interpretation of results being more reproducible than for p53.

Biomarkers, Tumor↗

[Superficial grade G2 tumors of the bladder: recurrence, progression, prognosis].

OBJECTIVE: The primary objective of this study was to describe the course of a series of grade 2 noninvasive urothelial carcinomas and to determine their prognosis by establishing recurrence, progression and mortality rates The initial histological and endoscopic characteristics were analysed in order to identify risk factors for recurrence and progression towards detrusor invasion. MATERIAL AND METHODS: This retrospective study was conducted on 75 patients with initially grade 2 superficial bladder tumours. Tumours were initially multifocal in 47% of cases and were classified as follows: 52 pTa tumours (69%) and 23 pT1 tumours (31%). The mean follow-up was 58 months. RESULTS: After the initial endoscopic resection, 26 patients (3.9%) received adjuvant therapy by intravesical instillations. The overall recurrence and progression rates in this series were 67% and 7%, respectively. Twelve patients (16%) underwent cystectomy. The specific mortality rate was 2.6%. Among the initial prognostic criteria, only the multifocal nature was identified as a risk factor for recurrence and progression towards detrusor invasion. CONCLUSION: This study confirmed the uncertain prognosis of grade 2 superficial bladder tumours. These tumours have a high recurrence risk with a cystectomy rate of 16%. These tumours require surveillance identical to that of high-grade tumours, at least half-yearly for the first 3 years then annually thereafter.

Adult↗

[Treatment of bladder tumors].

The bladder tumour treatment closely depends on initial diagnosis. For superficial bladder tumour a conservative treatment is required using endoscopic resection. Adjuvant instillations (BCG or mitomycine C) can be proposed for high grade tumour. In case of muscular layer invasion or in case of frequent non controlled recurrence, cystectomy is necessary. Progress in anaesthesia, surgery and postoperative care permitted to enteroplasty to be much less morbid, it must be considered as the urinary diversion of choice. To prevent recurrence, both (superficial or infiltrating) tumour require very strict follow-up for many years.

Administration, Intravesical↗

Extracorporeal shock wave therapy in the treatment of Peyronie's disease: experience with standard lithotriptor (siemens-multiline).

OBJECTIVES: To assess in a prospective study whether extracorporeal shock wave therapy (ESWT) using a standard radioscopic location lithotriptor is effective in the treatment of Peyronie's disease. METHODS: Fifty-four patients were included in this prospective study. Before and after treatment, the angulation was calculated by auto-photography. Pain severity was assessed by a visual analog pain scale. A self-evaluation questionnaire (International Index of Erectile Function) was used. All patients had symptoms (35 had pain during erection and 51 angulation greater than 20 degrees ). The mean disease duration was 16 months. The mean angulation before treatment was 48 degrees (range 10 degrees to 100 degrees ). Twenty-four patients had erectile dysfunction (questionnaire score less than 18). The Multiline Siemens lithotriptor was used. The plaque was located by palpation, and 1 mL of contrast agent was injected. Scopic visualization was used. Each patient received a minimum of one session of ESWT (3000 shock waves, 7 kJ) applied to a flaccid penis. RESULTS: All patients completed the protocol. The tolerance and safety were excellent. Of the 35 patients with pain on erection, 31 (91%) noticed relief immediately after ESWT (mean reduction 2.9 on the visual analog pain scale) (P <0.00001). For 29 patients (53.7%), an improvement in angulation (greater than 10 degrees ) was observed, with a mean reduction of 31 degrees (P <0.001). For patients with erectile dysfunction, only 6 (25%) had an increased questionnaire score (greater than 4). Twenty-five patients thought the plaque was smoother. CONCLUSIONS: ESWT with a standard lithotriptor (without the mobile arm) in Peyronie's disease is a feasible, safe, and effective treatment for pain on erection and significantly improves the penile angle.

Adult↗

Efficacy and safety of a novel combination of L-arginine glutamate and yohimbine hydrochloride: a new oral therapy for erectile dysfunction.

PURPOSE: The goal of this double-blind, placebo-controlled, three-way crossover, randomized clinical trial was to compare the efficacy and safety of the combination of 6g of L-arginine glutamate and 6 mg of yohimbine hydrochloride (AY) with that of 6 mg of yohimbine hydrochloride (YP) alone and that of placebo (PP) alone, for the treatment of erectile dysfunction (ED). MATERIALS AND METHODS: Forty-five patients were included in this study. During each of the 2-week, crossover periods, drug was administered orally, one to two hours before intended sexual intercourse. The primary endpoint was change in the Erectile Function Domain score of the International Index of Erectile Function (IIEF). The secondary endpoints were patient and investigator assessments of treatment success. RESULTS: At the end of each treatment period, the Erectile Function Domain scores for AY, YP and PP were 17.2+/-7.17, 15.4+/-6.49 and 14.1+/-6.56, respectively. The difference between AY and PP was statistically significant (p=0.006). When stratified according to baseline scores over 14, those patients with mild to moderate MED had a better Erectile Function Domain response to treatment (AY=22.2+/-4.99, YP=18.2+/-5.59, PP=16.9+/-6.91, respectively) than those with scores 14 and below (AY=12.4+/-5.48, YP=12.7+/-6.25, PP=11.4+/-5.02, respectively). Investigators' and patients' assessment of efficacy was significantly improved by YP over PP. CONCLUSIONS: This pilot study shows that the on-demand oral administration of the L-arginine glutamate 6g and 6 mg yohimbine combination is effective in improving erectile function in patients with mild to moderate ED. It appears to be a promising addition to first-line therapy for ED.

Administration, Oral↗

After cystectomy, is it justified to perform a bladder replacement for patients with lymph node positive bladder cancer?

PURPOSE: After cystectomy for bladder cancer, when pelvic lymph nodes are positive, bladder replacement remains controversial. The aim of this study was to evaluate the outcome of patients who underwent neobladder replacement despite bladder cancer metastasis to the regional lymph nodes. MATERIALS AND METHODS: From 1981 to 1997, a total of 504 consecutive cystectomies for bladder cancer were performed at our institution. For 150 patients, pelvic lymphadenectomy were positive, nevertheless 71 patients underwent a neobladder replacement (50 N1 and 21 N2). The distribution of patients by clinical stage, according to the TNM 97 classification, was 4 T1, 14 T2, 32 T3 and 21 T4. No patient showed signs of metastasis on diagnosis. RESULTS: Five-year disease specific survival rate of the entire group (71 patients) was 46%. With a mean follow-up of 8.3 years (3.2-20 years), 25 patients (35%) were alive and free of disease (72% with day continence), five patients were alive with recurrence (three bone metastasis, one chest metastasis and one with local recurrence), 41 patients died, (three non-cystectomy related). Of the 46 patients who recurred, a total of eight patients had local recurrence. For five patients, a severe dysfunction of the plasty appeared: two needed definitive bladder drainage until they died, one patient became totally incontinent, one patient needed a conversion of the plasty to Bricker ileal conduit. For the remaining patient the tumor involvement provoked recto-plasty-cutaneous fistula. All these five patients died in the 6 months after the plasty dysfunction appeared. CONCLUSIONS: Although prognosis in bladder cancer metastasis to the regional lymph nodes has been reported to be poor, this study demonstrates that after cystectomy, it is justified to propose a neobladder replacement to well selected patients. Local recurrence only occurred in 11% of patients and there was no damage to enteroplasty function for nearly half of the patients, and considering benefit to the quality of life, orthotopic bladder substitution should be considered as the preferential diversion in this patient population.

Adult↗

Major complex pelvic arteriovenous malformation in a patient with Down syndrome.

Pelvic arteriovenous malformations (AVM) are rare, and the treatment of this condition presents an interesting challenge. We report the first case of a major AVM in a patient with Down syndrome which was revealed by a massive hematuria. Arteriography showed a bilateral complex iliac artery malformation. The first proximal embolization (unilateral) did not prevent bladder hemorrhage, and the second distal (bilateral) immobilization produced bladder necrosis. However, the patient died despite an emergency cystectomy.

Arteriovenous Malformations↗