[Prospective evaluation of intrasphincteric injections of autologous muscular cells in patients with stress urinary incontinence following radical prostatectomy]. / Évaluation prospective du traitement de l'incontinence urinaire post-prostatectomie par injections intrasphinctériennes de cellules musculaires autologues.

PURPOSE: Cell therapy for urinary incontinence management has been experienced in animals with encouraging results, but studies in human beings are lacking. Our primary objective was to assess the safety of intrasphincteric injections of autologous muscular cells in patients with postprostatectomy incontinence (PPI). Secondary objectives focused on complications efficacy. METHODS: We conducted an open, prospective study in a single center on 12 patients presenting PPI. Patients underwent intrasphincteric injections of autologous muscular cells isolated from a biopsy of deltoid muscle. The primary endpoint was the Q(max) variation at the three month visit in order to assess potential bladder outlet obstruction. Secondary endpoints assessed side effects and efficacy parameters based on symptoms, quality of life score, voiding diary, pad-test, and urethral pressure profile at one, two, three, six and 12 months after injection. RESULTS: No immediate complication occurred and no significant variation was noted on Q(max). The only side effects possibly product-related were three cases of urinary tract infection treated by antibiotics. An acceptable safety and tolerability of the procedure whatever the injected dose of muscular cells was demonstrated. Results on efficacy after one year were heterogeneous, with 4/12 patients describing reduced urine leakage episodes, 1/12 patient presenting increased maximal closure pressure, and 8/12 patients showing improvement on pad-test. CONCLUSIONS: Cell therapy consisting of intrasphincteric injections of autologous muscular cells in patients with PPI was a feasible and safe procedure. The results point out that some subjects may positively respond to this procedure, but clinical efficacy remains to be confirmed.

[Effect of wound infiltration of ropivacaine in postoperative pain after extraperitoneal laparoscopic radical prostatectomy]. / Effet de l'infiltration pariétale d'anesthésique local (ropivacaïne) sur la douleur postoperatoire après prostatectomie radicale laparoscopique sous-péritonéale.

PURPOSE: Evaluation of the efficiency of wound infiltration of ropivacaine in postoperative pain after extraperitoneal laparoscopic radical prostatectomy. MATERIAL AND METHODS: Prospective single institution study included 130 patients treated by extraperitoneal laparoscopic radical prostatectomy from January to March 2007. One hundred and two patients were included and randomised in two groups according to the year of birth (pair or impair). Only patients from the first group (year pair) had wound infiltration at the end of the procedure. The second group (year impair) was the control group. An analogic visual scale (EVA) permitted evaluation of pain at 30 minutes, 1, 6 and 12 hours after the procedure. Use of analgesics after procedure were noted for each patient. RESULTS: In the first group, the median of EVA was 1.44, 1.34, 1.72 and 1.51 respectively at 30 minutes, 1, 6 and 12 hours. In the second group, the median of EVA was 1.28, 1.36, 1.46 and 1.44. We found no statistically significant difference for pain and use of analgesic between the two groups (p=0.71, 0.96, 0.47 and 0.86 respectively at 30 minutes, 1, 6 and 12 hours). CONCLUSION: Ropivacaine in wound infiltration did not decrease significantly the postoperative pain and must not be used systematically.

[Erectile dysfunction and cavernosal endothelial cells]. / Dysfonction érectile et cellules endothéliales caverneuses.

The physiopathology of erectile dysfunction (ED) is multifactorial. The recent discovery of the precise role of cavernosal endothelium in the functional regulation of the smooth muscle cells allowed to understand the physiological bases of erection. The purpose of this article is to make a synthesis of the current knowledge on the endothelial function and to allow a better understanding of the pathological responsible mechanisms of ED. Endothelium provides cavernosal smooth muscle cells relaxation by two main pathways: the NO/cGMP pathway induced by production of neural nitric oxide (NO) in cavernosal nerve terminals, and the AC/cAMP pathway which by-passes the NO route by using other mediators. This action allows the initiation and maintenance of erection. Risk factor-associated cavernosal endothelial alterations (diabetes mellitus, hypertension, hypercholesterolemia) are mostly induced by unifying mechanisms, including oxidative stress and accumulation of reactive oxygen species, alteration of NO production, or decrease of VEGF expression. The same cellular mechanisms can also be observed during aging. To a comprehensive appraisal of physiological bases of viable endothelium in erectile function, it is crucial to understand its biological activities. The hemodynamic evaluation of endothelial function and the current therapeutic implications will be later approached.

[Permanent implant prostate cancer brachytherapy]. / La curiethérapie du cancer prostatique par implants permanents.

With an experience of more than 20 years for the pionneers (and more than 10 years in France), permanent implant brachytherapy using Iodin 125 seeds is now recognized as a valuable alternative therapy for localized low-risk prostate cancer patients. An extension of the indications of exclusive brachytherapy towards selected patients in the intermediate-risk group is presently under study. Moreover, for patients in the high-risk group, brachytherapy, as an addition to external radiotherapy, could represent one of the best way to escalate the dose for some patients. Various permanent implant brachytherapy techniques have been proposed; preplanning or real-time techniques, loose seeds or stranded seeds, manual or automatic injection of the seeds. The main point here is the ability to perfectly master the procedure and to comply with the dosimetric constraints which have been recently redefined by the Groupe européen de curiethérapie--European Society for Therapeutic Radiology and Oncology (GEC-ESTRO) group. Mid- and long-term results which are now available in the literature indicate relapse-free survival of about 90% at 5-10 years, the best results being obtained with satisfactory dosimetric data. Some comparative data have shown that the incontinence and impotence rates after brachytherapy seemed to be significantly inferior to what is currently observed after surgery. However, a risk of about 3-5% of urinary retention is usually reported after brachytherapy, as well as an irritative urinary syndrome which may be significant and last several months. In spite of those drawbacks, with excellent long-term results and low rates of incontinence and impotence, brachytherapy can be expected to be proposed to an increasing number of patients in France in the next future.

[Genetic determinants of anatomical variants of the prostate]. / Facteurs génétiques déterminant les variations anatomiques de la prostate.

INTRODUCTION: The determinants of macroscopic and microscopic anatomical variants of the prostate during ageing are poorly defined. The authors evaluated the correlation between specific gene polymorphisms involved in androgen and oestrogen synthesis and gross (prostatic weight) and microscopic anatomy (stroma/epithelium ratio) of the prostate during ageing. METHODS: The prostatic weight and stromal surface area of an autopsy series of 85 men over the age of 50 were measured, then compared as a function of gene polymorphisms involved in androgen or oestrogen regulation. The following polymorphisms were studied: number of CAG repeats of the androgen receptor (AR), number of TA repeats and the V89L variant of the 5-alpha-reductase gene (SRD5A2) for androgens, and the A1A2 variant of 17-alpha-hydroxylase (CYP17) and number of TTTA repeats of the aromatase (CYP19) for oestrogens. RESULTS: No correlation was observed between the number of TA repeats of the SRD5A2 gene or TTTA repeats of the CYP19 gene and anatomical parameters of the prostate. A statistically significant positive correlation was observed between age and prostate weight (r=0.21, p=0.05) and a statistically significant negative correlation was observed between prostate weight and number of CAG repeats (r=-0.32, p=0.003). The group with less than 20 CAG repeats was associated with a higher prostate weight than the other group. The stromal surface area was greater in the [20-23] CAG repeat group (p=0.02), and in the A2A2 group of CYP17 (p=0.016) than in the other groups. CONCLUSION: A small number of CAG repeats is associated with a higher prostate weight. The mean number of CAG repeats of the androgen receptor and the A2A2 variant of the CYP17 gene are associated with a larger stromal surface area.

High detection rate of circulating tumor cells in blood of patients with prostate cancer using telomerase activity.

BACKGROUND: Circulating tumor cells (CTCs) cannot be readily detected with currently available methods in the majority of patients with prostate cancer. Telomerase activation, one of the major immortalization events, is found in most cases of prostate cancer. We attempted to develop a method using telomerase activity to isolate CTCs in patients with prostate cancer. PATIENTS AND METHODS: Peripheral blood mononuclear cells (PBMCs) were isolated from whole blood using Ficoll-Hypaque. Immunomagnetic beads coated with an epithelial cell-specific antigen antibody (BerEP4) were used to harvest epithelial cells from PBMCs. Telomerase activity was detected in harvested epithelial cells using the telomerase-PCR-enzyme-linked immunosorbent assay method. RESULTS: Blood samples from 107 patients with prostate cancer were studied. CTCs were detected in 19 of 24 (79%) patients with advanced prostate cancer. In contrast, CTCs were not detected in blood samples from 22 healthy male volunteers. CTCs were even identified in patients with an undetectable (<0.1 ng/ml) serum prostate-specific antigen (PSA). CTCs were detected in 55 of 70 (79%) patients with localized prostate cancer before radical prostatectomy (n = 30) or brachytherapy (n = 40). CTCs were also detected in 3 of 13 patients (23%) with an undetectable serum PSA measured at least 1 year after radical prostatectomy, which is consistent with the expected relapse rate in this setting. CONCLUSION: CTCs can be detected using telomerase activity in a large majority and a wide variety of patients with prostate cancer, including those with localized disease.

[Renal angiomyolipoma complicated by extension to the renal vein and inferior vena cava]. / Angiomyolipome rénal compliqué d'une extension à la veine rénale et à la veine cave inférieure.

Renal angiomyolipomas are renal hamartomas. They are usually found incidentally, presenting as well-defined echogenic masses on sonography and fat containing tumors on CT and MRI. We report a case of angiomyolipoma with sonographic and CT evidence of extension to the renal vein and inferior vena cava.

[Vesico-urethral anastomosis during total laparoscopic prostatectomy]. / Anastomose urétrovésicale lors de la prostatectomie radicale laparoscopique.

Vesico-urethral anastomosis is the last step of radical prostatectomy. Whatever the approach, radical prostatectomy remains a difficult surgical intervention. The dissection steps are similar whatever the selected access, open or laparostopic. Laparoscopic anastomosis requires specific skills that must be adequately mastered by the surgeon before starting any laparoscopic radical prostatectomy program. Pelvi-trainers allow training on the anastomosis technique, with reproducible results. This chapter presents the key points for laparoscopic vesico-urethral anastomosis.

Age, comorbidity and hypertensive co-medication do not affect cardiovascular tolerability of 10 mg alfuzosin once daily.

PURPOSE: We assessed in real-life practice the impact of age, cardiovascular comorbidity and co-medication on the tolerability and efficacy of 10 mg alfuzosin OD in men with lower urinary tract symptoms suggestive of benign prostatic obstruction. MATERIALS AND METHODS: A total of 6,523 men with a mean age of 64.7 years were enrolled in a 6-month open label study of 10 mg alfuzosin OD. They were stratified by age quartile (younger than 60, 60 to 64, 65 to 70 and older than 70 years), comorbidity (hypertension, ischemic heart disease and diabetes) and antihypertensive co-medication (diuretics, beta-blockers, angiotensin converting enzyme inhibitors, angiotensin II inhibitors and calcium channel antagonists). RESULTS: Alfuzosin was effective and well tolerated. Despite an increased prevalence of cardiovascular comorbidity and antihypertensive co-medication with age changes in blood pressure did not significantly differ among age groups. In controls, ie those with no cardiovascular comorbidity or co-medication, alfuzosin produced minimal decreases in sitting systolic (mean -2.6 to -2.8 mm Hg) and diastolic (mean -1.7 to -1.8 mm Hg) blood pressure. In men with cardiovascular comorbidity mean decreases in systolic (-3.5 to 5.8 mm Hg) and diastolic (-2.0 to -3.3 mm Hg) blood pressure remained marginal. Of the 6,523 exposed patients 19.3% withdrew from the study, mainly for adverse events (6.4%) or a lack of efficacy (5.3%), while 229 (3.5%) experienced serious adverse events and 1,558 (23.9%) reported at least 1 treatment emergent adverse event. The most commonly reported adverse event was dizziness/postural dizziness (4.8%). Hypotension/postural hypotension was uncommon (0.7%). Age, cardiovascular comorbidity and antihypertensive co-medication had no impact on the safety profile of 10 mg alfuzosin OD. CONCLUSIONS: Alfuzosin (10 mg) OD is effective and well tolerated, and it has marginal effects on blood pressure, including in elderly patients and those with hypertension, ischemic heart disease or diabetes and those receiving antihypertensive agents.

Transperitoneal or extraperitoneal approach for laparoscopic radical prostatectomy: a false debate over a real challenge.

PURPOSE: With our extensive experience of transperitoneal laparoscopic prostatectomy, we evaluated the advantages and disadvantages of the extraperitoneal approach by comparing 2 consecutive series of each procedure. MATERIALS AND METHODS: We reviewed 200 consecutive procedures performed by 2 surgeons. A total of 100 transperitoneal procedures (designated group 1) were compared to the first 100 extraperitoneal cases (designated group 2). RESULTS: Mean operating time was 173 minutes in group 1 and shorter in group 2 at 163 minutes (p = 0.003). Mean blood loss (360 ml in group 1,375 ml in group 2) and transfusion rates (4% in group 1, 3% in group 2) were equivalent. There were no major complications. Minor complications were 10% in group 1 and 9% in group 2. There was no statistical difference in positive margin rate between groups 1 and 2. CONCLUSIONS: The 2 procedures are equivalent in terms of operative, postoperative and pathological data. Each surgeon has to choose considering personal experience, training and standardization.

Feedback from operative performance to improve training program of laparoscopic radical prostatectomy.

PURPOSE: We report our preliminary experience identifying factors that contribute to differences in operative performance in laparoscopic radical prostatectomy (LRP) between trainees and experienced laparoscopic urologists based on objective and subjective feedback. MATERIALS AND METHODS: Between December 2001 and May 2002, six trainees at the Institut Montsouris and Ecole Européenne de Chirurgie, Paris, were evaluated to identify the factors contributing to differences in operative performance in LRP between them and experienced laparoscopic urologists, both objectively and subjectively. Objective evaluation was done by an independent observer who was well versed in laparoscopic surgery, while all the trainees evaluated themselves subjectively. All the trainees had in vitro, in vivo, and didactic training sessions during the evaluation period. RESULTS: The following deficiencies were noted objectively in the trainees compared with experienced laparoscopic urologists: (1) lack of perfect knowledge of each step, (2) lack of synchronized movements of the nondominant hand; and (3) easy physical fatigue. The trainees took a long time to dissect the vas deferens, seminal vesicles, and bladder neck because they did not have perfect knowledge of each step. It was difficult for them to pass the needle for ligation of dorsal venous complex because they tried to hold the needle far away from the needle tip at the wrong angle, and the direction of movement was not correct. For the urethrovesical anastomosis, they struggled to find the right angle to pass the needle on the urethral side. CONCLUSION: Lack of synchronized movement of the nondominant hand, easy physical fatigue, and lack of perfect knowledge of operative steps are crucial limitations for live operative performance of trainees in LRP. Incorporation of intensive well-planned in vitro training into the curriculum to correct these deficiencies and feedback from the operative performance can make a significant contribute to shortening the learning curve.

Laparoscopic [correction of laproscopic] management of rectal injury during laparoscopic [correction of laproscopic] radical prostatectomy.

PURPOSE: Rectal injury is a potential complication of radical prostatectomy. Because laparoscopic radical prostatectomy is still a challenging procedure, we review the incidence and management of rectal injury in 1,000 cases of consecutive laparoscopic radical prostatectomy performed at our institution. MATERIALS AND METHODS: Of the first 1,000 laparoscopic transperitoneal radical prostatectomies performed between January 1998 and April 2002, 13 (1.3%) were complicated by rectal injury. Mean patient age was 66.5 years (range 58 to 76) and mean prostate specific antigen was 12.9 ng./ml. (range 2.9 to 26). Clinical stage was T1c, T2a and T2b in 5, 7 and 1 patient, respectively. Mean preoperative Gleason score was 5.8 (range 3 to 8). Once recognized the rectal defect was closed laparoscopically in 2 layers and tested for the absence of leakage. Broad-spectrum intravenous antibiotics were given for 7 days. Oral liquids were started the day after surgery with a low residue diet, and a regular diet was started on postoperative day 5. Healing of the vesicourethral anastomosis was confirmed by voiding cystourethrogram on postoperative day 5. RESULTS: All patients underwent a non-nerve sparing procedure except 1 in whom unilateral neurovascular bundle preservation was done. Of 13 injuries 11 were diagnosed and repaired intraoperatively, and 2 were diagnosed postoperatively. Of the 11 cases of intraoperative diagnosis and repair 9 healed primarily without colostomy and peritonitis was diagnosed in the remaining 2 on days 3 and 4, respectively. Of the latter 2 patients 1 required repair of a small rectal defect without colostomy while the other required colostomy. Colostomy was performed in the 2 patients with delayed diagnosis on days 3 and 4 but even then a rectourethral fistula developed in 1, necessitating secondary repair. Average urethral catheterization time was 8.6 days for the 9 patients with an uneventful immediate postoperative course and mean hospital stay was 6.8 days. For the remaining 4 patients urethral catheterization duration was 12, 13, 15 and 120 days, and hospital stay was 7, 16, 21 and 27 days, respectively. There was no perioperative mortality. CONCLUSIONS: Rectal injury during laparoscopic radical prostatectomy requires meticulous intraoperative repair in 2 layers, which allows primary healing without diversion colostomy. For injury prevention scrupulous attention is required during non-nerve sparing radical prostatectomy, particularly at the posterior surface of the prostatic apex.

Laparoscopic radical prostatectomy: oncological evaluation after 1,000 cases a Montsouris Institute.

PURPOSE: We performed a prospective oncological evaluation of laparoscopic radical prostatectomy in regard to local tumor control and biochemical recurrence. MATERIALS AND METHODS: Between January 1998 and March 2002, 1,000 consecutive patients with a mean age +/- SD of 63 +/- 6.2 years and clinically localized prostate cancer underwent laparoscopic radical prostatectomy at 1 institution. Preoperative 1997 TNM clinical stage was T1a in 6 patients (0.6%), T1b in 3 (0.3%), T1c in 660 (66.5%), T2a in 304 (30.4%) and T2b in 27 (2.7%). Mean preoperative prostate specific antigen (PSA) +/- SD was 10 +/- 6.1 ng./ml. (range 1.5 to 55). Postoperatively, surgical specimens were assessed and positive surgical margins recorded. Factors that could influence the surgical margins status were evaluated. Irrespective of pathological stage or surgical margin status, no adjuvant treatment was proposed before an increasing PSA. PSA recurrence was defined as PSA greater than 0.1 ng./ml. and was confirmed by a second increase. Recurrence time was defined as the time of the first increase in PSA. RESULTS: Postoperative pathological stage was pT2aN0/Nx in 203 patients (20.3%), pT2bN0/Nx in 572 (57.2%), pT3aN0/Nx in 142 (14.2%), pT3bN0/Nx in 77 (7.7%) and pT1-3 N1 in 6 (0.6%). Positive surgical margin rate was 6.9%, 18.6%, 30% and 34% for pathological stages pT2a, pT2b, pT3a and pT3b, respectively (p <0.001). The main predictors of a positive surgical margin were preoperative PSA (p <0.001), clinical stage (p = 0.001), pathological stage (p <0.001) and Gleason score (p = 0.003). The overall actuarial biochemical progression-free survival rate was 90.5% at 3 years. According to the pathological stage, the progression-free survival rate was 91.8% for pT2aN0/Nx, 88% for pT2bN0/Nx, 77% for pT3aN0/Nx, 44% for pT3bN0/Nx and 50% for pT1-3N1 (p <0.001). Of the patients 94% with negative surgical margins and 80% with positive margins had progression-free survival (p <0.001). Preservation of the neurovascular bundles in patients with localized tumors had no significant effect on the subsequent risk of positive surgical margins or progression-free survival. CONCLUSIONS: Based on followup, our evaluation confirms that laparoscopic radical prostatectomy provides satisfactory results in regard to local tumor control and biochemical recurrence.

Laparoscopic partial nephrectomy for renal tumor: single center experience comparing clamping and no clamping techniques of the renal vasculature.

PURPOSE: We performed a nonrandomized retrospective comparison of 2 techniques for laparoscopic partial nephrectomy, that is without and with clamping the renal vessels. MATERIALS AND METHODS: Between December 1997 and February 2002, 28 consecutive patients underwent transperitoneal laparoscopic partial nephrectomy for renal tumor. In group 1 (12 patients) partial nephrectomy was performed with ultrasonic shears and bipolar cautery without clamping the renal vessels, while in group 2 (16 patients) the renal pedicle was clamped before tumor excision. In group 2 patients intracorporeal kidney cooling was achieved by a ureteral catheter connected to 4C solution. Intracorporeal freehand suturing techniques were used to close the collecting system when opened and approximate the renal parenchyma. RESULTS: All procedures were successfully completed laparoscopically. Mean renal ischemia time +/- SD was 27.3 +/- 7 minutes (range 15 to 47) in group 2 patients. Mean laparoscopic operating time was 179.1 +/- 86 minutes (range 90 to 390) in group 1 compared with 121.5 +/- 37 minutes (range 60 to 210) in group 2 (p = 0.004). Mean intraoperative blood loss was significantly higher in group 1 than in group 2 (708.3 +/- 569 versus 270.3 +/- 281 ml., p = 0.014). Three patients in group 1 and 2 in group 2 required blood transfusions. Immediately postoperatively mean creatinine was 1.26 +/- 0.36 and 1.45 +/- 0.61 mg./dl. in groups 1 and 2, respectively (p = 0.075). Surgical margins were negative in all specimens. Pathological examination revealed renal cell cancer in 18 cases (stages pT1 in 17 and pT3a in 1), oncocytoma in 4, angiomyolipoma in 5 and renal adenoma in 1. CONCLUSIONS: Laparoscopic partial nephrectomy represents a feasible option for patients with small renal masses. Clamping the renal vessels during tumor resection and suturing the kidney mimics the open technique and seems to be associated with less blood loss and shorter laparoscopic operative time.

Complications of transperitoneal laparoscopic surgery in urology: review of 1,311 procedures at a single center.

PURPOSE: The development of laparoscopic surgery in urology is increasing rapidly. We describe our experience with complications during and after transperitoneal laparoscopic surgery after 9 years of practice. MATERIALS AND METHODS: A total of 1,311 laparoscopic procedures were performed by 5 senior urologists in the same department since 1992, of which 72% were classified as difficult or very difficult (prostatectomy, nephrectomy for cancer, nephroureterectomy, partial nephrectomy, cystectomy, para-aortic lymph node dissection), 27.5% as moderately difficult (nephrectomy for benign disease, adrenalectomy, genitourinary prolapse, ureteropelvic junction, pelvic and ureteral stones, ureterovesical reimplantation, pelvic lymph node dissection) and 0.5% as easy (lymphocele, renal cyst and so forth). RESULTS: There was no mortality or anesthetic complications. The overall transfusion rate was 2.4%. Complications were serious in 0.7% of cases, all of which required reoperation, intermediate in 1.8% of which 1% required reoperation and minor in 1.1%. The main complications were bowel (1.2%), vascular (0.5%) and ureteral injuries (0.8%). The conversion rate was 1.2% and the reoperation rate was 2.4%. Of the patients 1.2% had to be admitted to the intensive care unit. Postoperative complications were observed in 19% of cases. Laparoscopic surgery is associated with essentially the same complications as open surgery, and they, particularly bowel injuries and bleeding, can be diagnosed and often treated with repeat laparoscopy. CONCLUSIONS: Complications during and after transperitoneal laparoscopy remain low and are not superior to those observed during and after open surgery. As laparoscopy becomes more widely used, urologists wishing to learn this technique must realize that the learning process is long but essential.

Gene expression profiles of bladder cancers: evidence for a striking effect of in vitro cell models on gene patterns.

In order to assess the effect of in vitro models on the expression of key genes known to be implicated in the development or progression of cancer, we quantified by real-time quantitative PCR the expression of 28 key genes in three bladder cancer tissue specimens and in their derived cell lines, studied either as one-dimensional single cell suspensions, two-dimensional monolayers or three-dimensional spheroids. Global analysis of gene expression profiles showed that in vitro models had a dramatic impact upon gene expression. Remarkably, quantitative differences in gene expression of 2-63-fold were observed in 24 out of 28 genes among the cell models. In addition, we observed that the in vitro model which most closely mimicked in vivo mRNA phenotype varied with both the gene and the patient. These results provide evidence that mRNA expression databases based on cancer cell lines, which are studied to provide a rationale for selection of therapy on the basis of molecular characteristics of a patient's tumour, must be carefully interpreted.