Experimental study of a cooling jacket in renal transplantation.
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Biomedical subjects
Publications and source records attributed to P Teillac.
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OBJECTIVE: To assess telomerase activity (involved in cell immortalization and detectable in most malignant tumours but not in normal somatic tissues) as a marker in cancer diagnosis. PATIENTS AND METHODS: Tissue telomerase activity was assayed by two different techniques, the telomeric repeat amplification protocol-polymerase chain reaction (TRAP-PCR) and a telomerase PCR-enzyme linked immunosorbent assay. Malignant and inflammatory bladder lesions and their adjacent normal tissues were assessed for telomerase activity in a group of 18 patients, 14 of whom had urothelial carcinoma and four a nonspecific inflammatory lesion of the bladder. RESULTS: Eleven of the 14 tumour samples analysed were telomerase-positive and two of the three telomerase-negative tumour samples had a detectable 'telomerase inhibitor'. In the apparently normal tissues next to bladder tumours, four of the 14 specimens were telomerase-positive. Interestingly, these lesions were always next to high-grade muscle-invasive bladder tumours (pT2G3). Two of the four nonspecific inflammatory lesions (one of cystitis glandularis and one of severe dysplasia), known to be preneoplastic lesions, were also telomerase-positive. CONCLUSION: These results strongly suggest that the reactivation of telomerase may be an early event in bladder carcinogenesis, preceding morphological changes related to malignant transformation. Telomerase activity may therefore be useful both as an indicator of malignant potential in preneoplastic lesions, e.g. cystitis glandularis and severe dysplasia, and as a prognostic marker of bladder tumour relapse or progression.
OBJECTIVE: To assess the rationale for virus-mediated gene transfer into the urethra in vivo and in vitro, using a rabbit model, as this is an attractive approach to prevent recurrence after the endoscopic management of urethral strictures. MATERIALS AND METHODS: Primary cultures of rabbit urethral stromal cells were infected with adenoviral and retroviral solutions carrying a nucleus-targeted beta-galactosidase (beta-Gal) reporter gene (respectively 109 and 107 plaque-forming units/mL). In addition, to mimic the human clinical situation, a model was developed of thermally induced stricture in rabbit urethra which produced fibrotic stenosis within 15 days. Using a prototype channelled balloon catheter, these strictures were endoscopically dilated and then instilled with the beta-Gal adenoviral or retroviral constructs. RESULTS: The application of recombinant adenovirus and retrovirus harbouring a nucleus-targeted beta-Gal reporter gene to cultured rabbit urethral stromal cells resulted in a high transduction efficiency of up to 90% and 96%, respectively. Five days after infection, histochemical and immunohistochemical staining of the strictured urethrae showed a 3% rate of transfection targeted to stromal cells within the fibrosis, confirmed by polymerase chain reaction (PCR) analysis. Adjacent and distal spread of the virus was excluded by histochemistry, immunohistochemistry and PCR. CONCLUSION: These results represent the first report of endoscopic adenovirus and retrovirus-mediated gene transfer to the urethra. Although at a low rate, transduction reached stromal cells transmurally within the induced strictures and was site-specific.
OBJECTIVES: The objective of this study was to evaluate the efficacy and safety of a new prostatic stent (Trestle((R)), Boston Scientific Microvasive) for the treatment of BPH in patients with complete urinary retention and considered to be inoperable. METHODS: The efficacy of the stent was evaluated in terms of return of micturition, level of patient satisfaction, uroflowmetry and residual urine. Any stents removed were examined by infrared spectrophotometry for the presence of crystalline encrustations. RESULTS: From December 1997 to April 1999, 20 stents were inserted under local anaesthesia in 17 patients aged 54-90 years. Stents remained in place for an average of 3.5 months. Two migrations were reported. The mean maximum flow rate was 13.7 ml/s and the mean residual urine was 110 ml. The infrared spectrophotometry study revealed a glycoprotein film on stents in place for 1-6 months, accompanied by uric acid crystals on stents in place for 9 months. CONCLUSION: The Trestle prostatic stent is effective and constitutes a good alternative to surgical treatment in patients with a high operative risk.
PURPOSE: We report the long-term outcome of our experience with percutaneous treatment of grade II upper urinary tract transitional cell carcinoma. MATERIALS AND METHODS: A total of 61 patients with transitional cell carcinoma of the upper urinary tract were treated percutaneously between 1984 and 1998. Of the patients 24 (39%) had grade II disease. Immediate nephroureterectomy was performed due to muscle invasive disease in 2 patients, bleeding in 1 and inability to resect the whole tumor in 1. Percutaneous resection was the actual treatment in 15 patients with stage Ta and 5 with stage T1 disease. RESULTS: Recurrence was noted in 5 patients (25%), including 3 (20%) with stage Ta tumors and 2 (40%) with stage T1 disease after a median followup of 48 months (range 9 months to 12 years). All stage Ta disease recurrences were superficial. In 1 patient with a stage T1 tumor invasive and metastatic disease developed. Disease specific survival was 95% overall, and 100% for stage Ta and 80% for stage T1 disease. No tumor seeding was detected along the percutaneous tract. CONCLUSIONS: Percutaneous surgery has proved safe and effective in treating superficial grade II upper tract transitional cell carcinoma. Offering an endoscopic approach electively to healthy individuals with a normal contralateral kidney seems viable.
OBJECTIVE: To evaluate the feasibility and complications of manually assisted laparoscopic live donor kidney harvesting. MATERIAL AND METHOD: Since June 1999, all related live donor kidney harvests have been performed by manually assisted laparoscopy. The patient is placed in the lumbotomy position and an 8 cm midline periumbilical incision is made. The assistant's hand is introduced through a watertight port (HandPort). Three trocars are used. The assistant presents the structures to be dissected and controls the ureter. The artery is clipped and the vein is stapled or clipped, depending on its diameter. The kidney is extracted via the midline incision and washed. RESULTS: Five kidney harvests were performed (three right kidneys and two left kidneys) with a mean operating time of 220 +/- 30 minutes. Conversion was necessary in one case following the intraoperative discovery of two right renal veins. Warm ischaemia lasted 5 minutes for the first patient and one to two minutes for the other four non-converted patients. Blood losses were minimal. The mean duration of major analgesia was 2.4 days and the mean length of hospital stay was 7.2 days. Complications were: bacteriuria in 2 cases and prolonged lymphorrhoea in 1 case. One transplanted kidney had to be removed because of immediate thrombosis of the recipient iliac artery. With a mean follow-up of 6 months (1 to 12 months), no ureteric or venous complications have been observed in the 4 evaluable transplanted kidneys. CONCLUSION: An intra-abdominal hand during laparoscopic live donor kidney harvesting simplifies dissection, ensures intraoperative security and allows rapid extraction of the kidney.
OBJECTIVE: Evaluation of the efficacy at 1 year of the Prostatron 2.5 in the treatment of BPH weighing more than 40 grams. MATERIAL AND METHODS: 46 patients over the age of 50 years presenting with BPH > 40 grams responsible for a maximum flow rate (MFR) < 9 ml/s and a mean IPSS score of 18 were prospectively included without randomization, by 5 French Urological Centres. These patients were reviewed at 3, 6 and 12 months. Primary endpoint: MFR; secondary endpoints: Madsen score and IPSS. RESULTS: No major complications were observed. The mean postoperative catheterization time was 10 days, causing discomfort with a mean score of 5 on a visual analogue scale from 0 to 10.. Maximum flow rate waas 13.4 ML/s at 3 months, 13.4 ml/s at 6 months and 14.7 ml/s at 12 months. The IPSS was improved by 75%. CONCLUSION: Treatment by Prostatron 2.5 improves the MFR and the patient's quality of life, which is maintained for at least 1 year after treatment.
OBJECTIVES: To develop an experimental model of endoscopic urethral stricture mimicking the human clinical situation. METHODS: Twenty-four New Zealand male rabbits were included. Eighteen animals (study group) underwent videourethroscopy with a pediatric resectoscope, and a 3 to 5-mm-long circumferential electrocoagulation of the bulbar urethra was performed, without postoperative urinary diversion. Six animals underwent the same procedure without application of electrocautery (control group). Each animal was assessed for urethral stricture on day 15 and day 30 by videourethroscopy and voiding cystogram. Among the study group, 8 animals were killed on day 15 and 10 on day 30 for histologic evaluation. All the control animals were killed on day 30 for histologic examination. RESULTS: Nine animals (50%) in the study group developed a significant bulbar stricture (reducing the lumen by more than 50%) at day 15. Histologic examination confirmed the presence of hyalin fibrosis mutilating the urethral wall. No spontaneous improvement of the stricture was observed on day 30. None of the controls developed urethral stricture, and histologic examination showed a normal urethra in each case. CONCLUSIONS: Endoscopic electrocoagulation of the urethral wall provides a reproducible model of stricture in the rabbit.
This study was undertaken to evaluate the risk of haematogenous dissemination of epithelial cells induced by endoscopic resection and/or cystoprostatectomy for transitional cell carcinoma of the bladder. Thirty-three patients were studied. Thirty-one had different stages and grades of bladder cancer and two patients had benign bladder conditions. Twenty-five cancer patients required transurethral resection of their bladder tumour. Of those, 20 had superficial disease (pTaG1-G2: n = 19; pT1G2: n = 1) and five had muscle invasive tumours (pT2G3: n = 2; pT3aG3: n = 1; pT4G3: n = 2). Five patients underwent radical cystoprostatectomy for muscle invasive cancers (pT2G3: n = 3; pT3bG3: n = 1; pT4G3: n = 1) and one man received chemotherapy for metastatic disease. Venous blood (10 ml) was obtained from the antecubital fossa in each patient, before and 1-2 h after completion of surgery, and prior to treatment in the metastatic patient. An indirect immunocytochemical technique was used to detect circulating epithelial cells after centrifugation on Ficoll gradient and fixation of mononuclear cells on slides, using a monoclonal antibody directed against three cytokeratins: CK8, CK18 and CK19. Circulating epithelial cells were detected only in the patient with metastatic disease. None of the other patients had evidence of epithelial circulating cells before or after surgery. The results suggest that irrespective of disease stage and grade, neither endoscopic nor open bladder surgery leads to detectable dissemination of urothelial cells in the peripheral circulation. These procedures are therefore unlikely to increase the risk of progression and metastasis in transitional cell carcinoma of the bladder.
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OBJECTIVE: To evaluate the effect of the rectal administration of lidocaine gel on the tolerance of systematic sextant transrectal ultrasonography (TRUS)-guided prostatic biopsies. PATIENTS AND METHODS: From January to September 1997, patients undergoing initial biopsy mapping of the prostate (with six systematic TRUS-guided transrectal biopsies) were randomized using a pre-established randomization list into two groups. In group 1, 15 mL of 2% lidocaine gel (Astra, Södertälje, Sweden) was administered intrarectally 15 min before the biopsies. In group 2 (placebo), 15 mL of trans-sonic hydrophilic gel (Rivadis Laboratory, Thouars, France) was administered transrectally under the same conditions. Patients were randomized and the gel administered by a nurse; neither the patients nor the urologists were aware of which product was administered. At the end of the procedure, patients were asked to score the severity of discomfort of the biopsies, using a self-administered rating scale. RESULTS: In all, 109 patients were included, in either group 1 (56 patients) or group 2 (53 patients). Slight pain or no pain was experienced by the vast majority of patients in both groups. Moderate to severe pain was experienced in 12.5% of patients in group 1 and 11.3% of patients in group 2. There was no difference in patient tolerance between the groups (P=0.39). Only minor complications occurred and complication rates were not significantly different between the groups. CONCLUSION: The rectal administration of lidocaine has no impact on the tolerance to prostatic biopsy.
OBJECTIVE: To evaluate the conservative management of encrusted pyelitis (EP), an infectious disease caused by urea-splitting micro-organisms (Corynebacterium group D2 being the most common), and characterized by stone encrustation of the collecting system. PATIENTS AND METHODS: Four patients (aged 17-62 years) with EP caused by Corynebacterium group D2 were treated conservatively with intravenous vancomycin and percutaneous acidification of the renal collecting system. Percutaneous nephrostomy tubes were placed to allow irrigation with Thomas' acid solution, the outflow being ensured by ureteric catheters. Patients were monitored and the results of and tolerance to treatment evaluated clinically, by biological assays, and by imaging techniques (ultrasonography, computed tomography and pyelography). RESULTS: No kidneys were lost and in all patients with initial renal failure, creatinine levels recovered to previous values. The adverse effects were moderate, consisting of flank pain or discomfort, and low-grade fever. Three patients developed asymptomatic fungal urinary tract infections requiring antifungal agents. The encrustations were treated effectively and almost disappeared in two patients, while the other two had no residual calcification. One transplanted-kidney recipient developed a ureteric stricture requiring surgical repair. Within a mean follow-up of 16 months, there was no recurrence of EP and the residual encrustation remained small. CONCLUSION: The conservative treatment of EP can avoid surgery in many cases, although there are some adverse effects of irrigation. The long-term follow-up and prevention of recurrent EP are nevertheless required.
OBJECTIVE: To evaluate the safety and efficacy of holmium:YAG laser vaporization v transurethral electroresection (TURP) for benign prostatic hyperplasia. PATIENTS AND METHODS: Thirty-six patients were randomized. Two laser procedures (60 to 80 W) were performed for one TURP. Symptom Score, peak flow rate, potency, and ejaculation status were measured at baseline and at 1, 3, 6, and 12 months. RESULTS: The mean operative time was 75 minutes for laser and 56 minutes for TURP (P = 0.0407). With a mean laser energy delivered of 103.6 kJ, hemostasis was satisfactory during vaporization. The mean catheterization time was 1.7 and 2.1 days in the laser and TURP group, respectively. For the laser and TURP groups, the mean AUA Score improved from 20 preoperatively to 7 and from 24.1 to 5, respectively, at 12 months. The mean peak flow increased from 8.4 to 19.5 mL/sec and from 7.6 to 16.8 ml/sec, respectively, at 12 months. These results are not statistically different. No significant initial dysuria occurred. No significant difference between the groups appeared in potency or ejaculatory status during the follow-up. One patient in the laser group (Day 5) and two in the TURP group (2nd and 6th month) had to undergo a second procedure to relieve obstruction. CONCLUSION: Although taking slightly longer to accomplish, holmium:YAG laser vaporization of BPH provides early results very similar to those of TURP with a shorter catheterization time and no initial dysuria or pain.
PURPOSE: To establish a reliable model of iatrogenic ureteral stricture mimicking the human clinical situation in order to experiment with new site-specific endourologic treatment concepts. MATERIALS AND METHODS: After cystoscopic insertion of a 7F right ureteral catheter, we induced external thermal radiofrequency injury to the right upper third ureter at low power setting (10 W) using an open surgical approach in 13 pigs. Three pigs considered as controls underwent the same procedure without application of electrocautery. All 16 animals were initially assessed at 8 days; 3 study animals and the 3 controls were followed for 6 weeks. RESULTS: No control animals had strictures. Significant upper third ureteral strictures with marked hydronephrosis where achieved in all study animals after a mean interval of 9 days, as evidenced by ultrasound examination and retrograde ureteropyelography. Endoscopic retrograde access to these strictures was always possible (mean length 1.4 cm.). Histologic examination displayed severe disorganization of the muscular layer by dense fibrosis composed of collagen bundles with few scattered fibroblasts. No spontaneous improvement of the stricture was observed in the 3 animals reassessed at 6 weeks. CONCLUSIONS: Externally applied radiofrequency energy to porcine ureter provides a reproducible model of fibrous stricture resembling its clinical counterparts.
PURPOSE: Additional trocars and retractor instruments may enhance the risk of iatrogenic injuries during laparoscopic nephrectomy. We describe a modified technique of laparoscopic nephrectomy requiring only 3 ports of entry and no extra instruments instead of the 5 ports, 2 of which are used for retractors, usually required. MATERIALS AND METHODS: With the patient in full flank position a 10 mm. trocar is inserted between the umbilicus and subcostal margin, a 5 mm. trocar is placed subcostal in the midclavicular line and a 12 mm. trocar is inserted over the iliac crest in the anterior axillary line. The first step is incision of the line of Toldt and medial reflection of the colon. During the second step of vascular controls the posterosuperior attachments of the kidney are left untouched, keeping the renal vessels stretched, with no need for an extra instrument. The third step consists of severing the remaining posterior and superior attachments of the kidney followed by specimen retrieval. A total of 14 consecutive patients underwent laparoscopic nephrectomy with this technique. RESULTS: All 14 procedures were completed without an additional port. There were no intraoperative or postoperative complications, except 1 abdominal wall hematoma. Mean operating time was 120 minutes (range 70 to 230) and mean hospital stay was 5 days (range 3 to 7). CONCLUSIONS: Transperitoneal laparoscopic nephrectomy with laparoscopic access limited to 3 trocars is a reliable and safe technique.
PURPOSE: Direct gene transfer to the ureter is an attractive approach to prevent restenosis after endourologic management of ureteral strictures. We therefore assessed the rationale for adenovirus-mediated gene transfer in the ureter in vitro and in vivo using a porcine model. MATERIALS AND METHODS: Primary cultures of porcine ureteral epithelial and stromal cells were infected with an adenoviral solution carrying a nucleus-targeted beta-Galactosidase (beta-Gal) reporter gene (6.5 10(8) pfu/ml.). In addition, in order to mimic the human clinical situation, we have devised a model of thermally-induced stricture in porcine ureter which produced tight fibrotic stenosis within 8 days. Using a purposely designed channelled balloon catheter prototype, these strictures were endoscopically dilated and then instilled with the same beta-Gal adenoviral construction. RESULTS: Application of recombinant adenovirus harboring a nucleus-targeted beta-Gal reporter gene to cultured porcine urothelial and stromal cells resulted in high transduction efficiency of up to 99% and 84% respectively. Seven days after infection, X-Gal staining of the strictured ureters demonstrated transfection up to 2 mm. depth within the fibrosis, confirmed by polymerase chain reaction (PCR) analysis. Adjacent and distal spread of the virus was excluded by histochemistry (X-Gal staining) and PCR. CONCLUSION: This data represents the first report of adenovirus-mediated gene transfer to the ureter. It remained site specific by endourologic retrograde clinically applicable techniques.
OBJECTIVES: (1) To determine the frequency of familial (at least 2 cases) and hereditary forms of prostate cancer (CaP), (2) to define the results according to the patient's age at diagnosis, as various epidemiological studies have demonstrated a possible familial aggregation of CaP in about 15 to 25% of cases. Carter's familial segregation study (P.N.A.S. 1992, 89, 3367-71) showed that a genetic predisposition, with autosomal dominant transmission, could be responsible for 9% of all cases of prostate cancer. MATERIAL AND METHODS: We conducted a systematic genealogy study of patients suffering from newly diagnosed CaP or followed for known CaP in 3 French urological centres, by means of questionnaires completed by the patients. Subsequently, a national collection of families with at least 2 cases of CaP identified families with hereditary forms of CaP. Hereditary cases were considered to be those presenting at least: one CaP in three 1st degree relatives, or 3 cases over 3 generations in the same branch of the family (paternal or maternal), or finally 2 early cases before the age of 55 years. Statistical analysis used the univariate logistic regression test between family status and the medical centre or the patient's age at diagnosis. RESULTS: From July 1994 onwards, we included 801 patients (all stages combined) in the systematic study and 110 patients (13.7%) were excluded (refusal to participate, advanced age). For 691 of the families studied (Brest: 225, Nancy: 249, Paris St Louis: 217), we observed 32 (14.2%), 29 (11.6%), 37 (17.1%) of familial forms (mean: 14.2%) and 11 (4.9%), 6 (2.4%), 8 (3.7%) of hereditary forms (mean: 3.6%), respectively (no significant differences between centres). Analysis of the results according to age at diagnosis of CaP also showed a higher incidence of familial (significant difference) and hereditary forms (limit of significance) for CaP occurring at a younger age (before 65 years). The national collection collected a total of 624 familial forms of CaP, including 236 (37.8%) cases of hereditary forms; 115 families were informative for the genetic linkage study. CONCLUSION: These results confirm the data of earlier studies, revealing about 15 to 25% of familial forms of CaP and 5 to 10% of hereditary forms. Similarly, the systematic study confirmed the earlier onset of CaP in patients with a genetic predisposition. These data therefore encourage systematic questioning of patients for a family history of CaP in order to propose targeted screening of high-risk subjects in the families concerned and to intensify identification of hereditary forms in order to investigate the genes involved.
Loss of heterozygosity (LOH) and alterations in microsatellite DNA markers have been reported in bladder-cancer tumors. We have studied, in a blinded fashion, using PCR-based microsatellite analysis, genetic alterations of cells exfoliated in urine of 59 Caucasian patients and control patients; 31 with initially confirmed bladder transitional-cell carcinoma (TCC), 17 with signs and symptoms suggestive of bladder cancer, 6 control patients who underwent renal transplantation, and 5 control patients with urolithiasis. Microsatellite analysis of cells exfoliated in the urine allowed the diagnosis of 83% (10/12) of patients with bladder TCC recurrence confirmed by cystoscopy, while 100% of patients followed up for transitional-cell carcinoma of the bladder for up to 12 months without evidence of tumor recurrence upon routine cystoscopy showed no microsatellite alterations. None of the patients without neoplasia (negative controls) had any microsatellite alterations, whereas all patients who underwent renal transplantation had additional new alleles corresponding to contamination with donor's renal and urothelial cells (positive controls). No control patients had any evidence of transitional-cell carcinoma by cystoscopy. Our results provide objective evidence that non-invasive molecular detection of bladder TCC by microsatellite analysis is reproducible with a sensitivity of 83% and a specificity of 100% in Caucasian patients. This non-invasive procedure represents a potential clinical tool for the detection and the screening of bladder TCC.