[Screening for prostate cancer: synthesis]. / Dépistage du cancer de la prostate: synthèse.

Screening for prostate cancer (PCa) remains a matter of debate. Although the results of two ongoing randomised trials will be available in 2008, mass screening of PCa is already effective in the United States where PCa-related mortality has very significantly decreased. However, such screening is strongly suspected to induce "over-diagnosis". This results in the treatment of insignificant PCa, but in a significant complication rate. This situation finds an explanation in the low specificity of PSA, the screening tool for aggressive PCa. ALL of the debate is based on a misunderstanding between the pros and the cons of screening. On one hand, if diagnosis is considered a search for knowledge, then advocate an "over-diagnosis" would mean advocate an "over-knowledge", which is nonsense. On the other hand, if treatment is considered a search for action on the natural history of a disease, then advocate an "over-treatment" would mean advocate an "over-action", which is meaningful. The problem induced by screening is not to search for a disease, but what we do with it when we find it! Before recommending mass screening for PCa, we have to re-educate our patients in their understanding of the disease and re-educate ourselves in our treatment decision process. Waiting for a governmental decision about PCa screening policy, one should actually consider individual screening, which allows for personal education of patients.

Microsatellite instability and mutation analysis of candidate genes in urothelial cell carcinomas of upper urinary tract.

A subset of upper urinary tract urothelial cell carcinomas (UUC), arising sporadically or as a manifestation of hereditary non-polyposis colorectal cancer, displays microsatellite instability (MSI). MSI tumours are characterized by defective mismatch repair and accumulation of frameshift mutations in numerous genes harbouring repeats in their coding sequences. We have evaluated the incidence of MSI in UUC and the intratumoral distribution of mutations in 13 candidate target genes. A total of 58 unselected UUC were screened for MSI using the panel of five mononucleotide markers recently recommended by the National Cancer Institute for a precise MSI assessment. Four tumours displayed MSI (7%), among which at least three had alterations in the genes MSH3, BAX, MRE11, RAD50. Mutations in genes involved in key cellular pathways (ATR, DNA-PKcs, MBD4, TCF-4, MSH6, and BLM) were further detected. BAX and MRE11 mutations tend to present homogeneously within the three MSI UUC. Immunohistochemistry (MLH1, MSH2, MSH6) showed that loss of mismatch repair protein expression occurred in all MSI UUC defining the gene defect and that MRE11 and RAD50 mutations were associated with their concomitant loss expression. In conclusion, MSI UUC represent a small proportion of UUC in which BAX and MRE11 mutations are frequent and may play a role early in UUC tumorigenesis.

[Replacement enterocystoplasty in man (except Hautmann): principles and technical considerations]. / Entérocystoplastie de substitution chez l'homme (Hautmann exclu): principes et applications techniques.

Orthotopic urinary reservoir using a bowel segment has become the most favoured form of diversion after radical cystectomy. Ideal neobladder has to (i) store the urine with a low pressure bladder substitute, (ii) protect the upper urinary tract and (iii) provide a better quality of life enabling volitional voiding. A lot of techniques have bee described to construct a reservoir, however, all of them are based on the principle of intestinal loop detubulation. Many intestinal segments have been used, but ileum seems to be preferred in Europe. The upper urinary tract is mainly protected by a low neobladder pressure, rather than an additional antireflux flap-valve-type implantation technique which may increase the risk of uretero-enteric stricture. No significant difference in functional outcome can be observed among the several techniques. In selected cases, orthotopic bladder replacement is well tolerated and feasible and appears to be the gold standard after cystectomy.

[Renal cancer: what can we expect from emerging new technologies: radiofrequency and cryoablation?]. / Cancer du rein. Qu'attendre des nouvelles technologies: radiofréquence et cryoablation?

Radiofrequency and cryoablation are both minimally invasive techniques applied to the treatment of renal cell carcinoma. These techniques allow in situ destruction of neoplasm. Although cryotherapy is the most studied, radiofrequency is the most currently used technique. Indications mostly accepted as elective indication are the less than 4 cm in diameter exophytic tumors. Radiofrequency and cryoablation can also be proposed in patients with solitary kidney, multiple bilateral tumors and patients with contraindication for surgical resection. The radiofrequency parietal tract can be coagulated at the time of radiofrequency electrode withdrawal reducing the rare risk of parietal tumor dissemination. Preliminary oncological results in exophytic small renal tumors are promising with only few complications. A longer follow-up is however mandatory to better define the place of these two new technologies in the treatment of renal cancer.

[Hand-assisted laparoscopy for kidney sampling in living donors: the surgical technique]. / Prélèvement de rein chez le donneur vivant par laparoscopie assistée manuellement: technique chirurgicale.

Hand-assisted laparoscopic surgery bridges the gap between open and Laparoscopic surgery. It involves introduction of the surgeon's hand into the insufflated abdomen. Hand-assisted laparoscopy is clearly advantageous for those laparoscopic procedures that require removal of relatively large amount of tissue intact as living donor nephrectomy is. Technically, a short midline incision is performed to introduce the non dominant operators'hand. Trocars are placed. The colon is then reflected, the ureter dissected with its surrounding vascularization and divided. The renal vein is controlled, by transecting the surrenal vein on the left side, and the genital vein in both sides. Then the artery is dissected close to the aorta on the Left side, behind the vena cava on the right side. An endoscopic stapler is used to transect the renal artery and the renal vein. The kidney is quickly removed through the midline incision and immediately washed with a cooled preservation solution. The different incisions are closed.

Clinical relevance of genetic instability in prostatic cells obtained by prostatic massage in early prostate cancer.

We investigated whether genetic lesions such as loss of heterozygosity (LOH) are detected in prostatic cells obtained by prostatic massage during early diagnosis of prostate cancer (CaP) and discussed their clinical relevance. Blood and first urine voided after prostatic massage were collected in 99 patients with total prostate-specific antigen (PSA) between 4 and 10 ng ml(-1), prior to prostate biopsies. Presence of prostatic cells was confirmed by quantitative RT-PCR analysis of PSA mRNA. Genomic DNA was analysed for LOH on six chromosomal regions. One or more allelic deletions were found in prostatic fluid from 57 patients analysed, of whom 33 (58%) had CaP. Sensitivity and specificity of LOH detection and PSA free to total ratio <15% for positive biopsy were respectively 86.7 and 44% (P=0.002) for LOH, and 55 and 74% (P=0.006) for PSA ratio <15%. Analysis of LOH obtained from prostatic tumours revealed similar patterns compared to prostatic fluid cells in 86% of cases, confirming its accuracy. The presence of LOH of urinary prostatic cells obtained after prostatic massage is significantly associated with CaP on biopsy and may potentially help to identify a set of patients who are candidates for further prostate biopsies.

Evaluation of the transurethral ethanol ablation of the prostate (TEAP) for symptomatic benign prostatic hyperplasia (BPH): a European multi-center evaluation.

OBJECTIVE: We prospectively conducted a European multi-center study to assess the safety and efficacy of injecting dehydrated ethanol using a specialized injection system for the treatment of BPH. METHODS: Patients with symptomatic BPH were enrolled and evaluated to undergo transurethral ethanol ablation of the prostate for their BPH condition. Procedures were performed using the ProstaJect device. Treatment dosages were based on prostate volume, prostatic urethral length and median lobe involvement. Follow-up evaluations were done at four days and one, three, six and 12 months. RESULTS: One-hundred fifteen symptomatic patients underwent the transurethral ethanol ablation procedure and ninety-four patients have been followed and evaluated for the entire 12-month post-treatment period. The average prostate volume was 45.9 g, and average ethanol injected was 14 ml. Post-operatively, 98% of patients voided spontaneously four days following treatment. Significant reduction in reported lower urinary tract symptoms was evidenced at the one-month follow-up visit and maintained through 12 months follow-up, with International Prostate Symptom (IPSS) and Quality of Life (QoL) scores decreased by more than 50%. Peak flow rates (Q(max)) improved by 35% by the three-month evaluation and these results were sustained through to 12-months follow-up. The average prostate volume reduction was 16%. Adverse events included discomfort or irritative voiding symptoms in 26% of patients, hematuria in 16%, with retrograde ejaculation, and erectile dysfunction reported in less than 3% of patients. The majority of these events required no intervention. Two patients experienced serious adverse events (bladder necrosis) and underwent open surgery that included a urinary diversion and a ureteral implantataion. During the one year follow- up, 7% of patients required a trans-urethral resection of prostate (TURP). CONCLUSIONS: This preliminary multi-center data, representing the largest reported cohort to date, suggests that TEAP may be considered an effective minimally invasive treatment option for lower urinary tract symptoms secondary to BPH. Analyses of safety lead to a procedure modification for needle placement more distal from the bladder neck. Objective reduction in symptoms was not correlated in prostate volume reduction suggesting a non-purely mechanical effect.

Management of prostate-specific antigen relapse in prostate cancer: a European Consensus.

A European Consensus on the management of prostate-specific antigen (PSA) relapse in patients with prostate cancer has been formulated. The key recommendations proposed are that total PSA is the best detection tool for prostate cancer, with free and complexed PSA having a role in the PSA range 1-4 ng/ml. PSA relapse after radical prostatectomy (RP) has been defined as a value of 0.2 ng/ml with one subsequent rise, while the ASTRO definition should be used after radiotherapy. A PSA level of less than 0.4 ng/ml after hormonal therapy can be considered an indicator of a positive response. Continuous assessment using nomograms or artificial neural networks will help to determine whether progression after local therapy is distant or local, which is the basis for treatment decisions. Secondary treatment after local failure of RP should be initiated when PSA levels reach 1.0-1.5 ng/ml and salvage radiotherapy can be considered with or without hormonal therapy. Local failure after radiotherapy can be treated with a choice of high-intensity-focused ultrasound, salvage RP (only in highly selected patients), cryotherapy or external beam radiation. Treatment of distant failure involves hormonal manipulation, the type and the timing of which is based on both physician and patient preferences.

[Benign prostatic hyperplasia: patients' perception of medical treatment and their expectations. Results of a french survey involving patients treated with finasteride]. / Hypertrophie bénigne de la prostate: attentes des patients et perception du traitement. Résultats d'une enquête menée en France auprès de patients traités par finastéride.

Benign prostatic hyperplasia (BPH) is increasingly common in medical practice, as a result of the inevitable aging of the population. The current therapeutic strategy includes three alternatives: watchful waiting, medical treatment and invasive therapy. Finasteride is one of the pharmacological options available. Many clinical studies have demonstrated its efficacy and good safety profile in patients with BPH. The survey we report provides new insights into what has to date been a purely therapeutic approach by taking into consideration patients' expectations and their perception of finasteride treatment. Results indicate that the main preoccupation for patients with BPH is that the pharmacological treatment will reduce the risk of major urological complications and the need for surgery (treatment characteristics considered as very or extremely important by 88 and 93% of patients, respectively). Decreasing symptoms and improving quality of life take second place after these primary concerns. Patient perception of finasteride is excellent. Nearly all patients are satisfied by the efficacy of the treatment, 89% of them reporting good to extremely good improvement of symptoms, the rapid onset of relief being particularly important. The efficacy of finasteride is not hindered by any tolerability issues and is further strengthened by its ease of use. Although this novel survey includes a number of biases, it nevertheless demonstrates that treatment of BPH with finasteride is well accepted by patients and satisfies their expectations. In addition, it provides a mass of general epidemiological data on patients with BPH, as well as on current medical practice regarding this condition.

Percutaneous implantation of subcutaneous prosthetic ureters: long-term outcome.

PURPOSE: We have used an extra-anatomic subcutaneous alloplastic ureteral replacement initially to bypass ureteral obstruction secondary to advanced pelvic malignancies in patients with a short life expectancy. Following the encouraging preliminary results, our list of indications has broadened to include complex benign ureteral strictures. We herein report the long-term outcome. PATIENTS AND METHODS: A series of 35 subcutaneous prosthetic ureters were implanted percutaneously in 27 patients (19 unilateral and 8 bilateral) to bypass extrinsic ureteral obstructions. The nature of obstruction was neoplastic in 22 patients and benign in 5. A composite prosthesis, consisting of two coaxial tubes--internal pure smooth silicone covered by coiled e-PTFE--has been designed to serve as the ureteral replacement. This tube is inserted percutaneously into the renal pelvis, tunnelled subcutaneously, and introduced through a small suprapubic incision in the bladder. All patients were followed to date or until death from tumor. The mean follow-up was 6.3 months for the deceased patients and 47 months for the surviving ones, the longest follow-up being 84 months. RESULTS: No operative or immediate postoperative deaths were observed. Initial difficulty in placing the prosthesis was encountered in 5 of the 27 patients (19%). Secondary parietal complications occurred in 8.5% of cases (3/35). The prosthetic ureter had to be removed in one patient because of skin erosion. Return to a standard percutaneous nephrostomy was needed in two patients because of local tumor progression with bladder fistulae. Five patients are alive with the prosthesis in place and a follow-up as long as 84 months without encrustation, infection, obstruction, or skin problems and with normally functioning kidneys. CONCLUSION: The subcutaneous urinary diversion using a silicone-PTFE prosthesis is an efficient and minimally invasive way to bypass malignant or complex benign obstructions of the ureters that otherwise would necessitate permanent nephrostomy drainage.

[Hand-assisted laparoscopic bi-nephrectomy for refractory arterial hypertension in kidney transplantation]. / Bi-néphrectomie laparoscopique assistée manuellement pour hypertension artérielle réfractaire chez le transplanté rénal.

OBJECTIVE: The authors report their preliminary experience of a manually assisted laparoscopic bilateral nephrectomy technique for refractory hypertension in renal transplant recipients. MATERIAL AND METHODS: Between April and May 1999, 2 laparoscopic bilateral nephrectomies were performed with manual assistance using the Hand-Port. One patient was operated 4 months before renal transplantation and the other was operated 13 months after renal transplantation. Both patients presented severe hypertension refractory to several antihypertensive drugs. An 8 cm midline supra-umbilical incision and 3 trocars were necessary. One hand was introduced into the abdominal cavity via the Hand-Port at the beginning of the operation. The intra-abdominal hand assisted all phases of dissection of the kidney and control of vessels. The renal vessels and ureter were clipped. The kidneys were removed by the intra-abdominal hand through the supra-umbilical incision. RESULTS: Operating times were 200 min and 130 min. Blood loss was 220 ml. No conversion was performed. The duration of major postoperative analgesics was 3 days. Length of hospital stay was 6 days and 7 days. There were no complications. Blood pressure was controlled by bilateral nephrectomy in both cases, with significant reduction of antihypertensive therapy. One year after the operation, both patients were satisfied with the aesthetic result. CONCLUSIONS: Laparoscopic bilateral nephrectomy manually assisted by the Hand-Port is an alternative to open bilateral nephrectomy. Larger series are necessary to evaluate the morbidity of this technique.

Noninvasive detection of genetic instability in cells from prostatic secretion as a marker of prostate cancer.

We present a clinical and molecular study of a series of specific loss of heterozygosity (LOH) indicators which, together with PSA, increase the predictability of cancer in early prostate cancer patients. Considering a positive biopsy as the standard reference, the testing parameters for LOH testing are better than the PSA F/T ratio (<25%), suggesting that this noninvasive approach to detecting early prostate cancer could be very useful as a new tool to optimize the indications for iterative prostate biopsies.

In vivo model mimicking natural history of dog prostate cancer using DPC-1, a new canine prostate carcinoma cell line.

BACKGROUND: Dog prostate cancer is usually considered to be highly relevant to human prostate cancer. We report the isolation of a new canine prostate cancer epithelial cell line designated DPC-1. METHODS: Primary cultures were established from a canine poorly differentiated prostatic adenocarcinoma. Population doubling time was determined by counting nuclei after cell lysis. Tumorigenicity was assessed in nude mice and in one adult immunodeficient dog. Immunoscintigraphy was performed in both models using a monoclonal antibody (mAb) raised against the [44-62] sequence of human PSMA. RESULTS: DPC-1 cells have a rapid growth in vitro (doubling time, 27 hr) which is not stimulated by androgens. In addition, DPC-1 displays immunoreactivity to human PSA and PSMA. DPC-1 was found to be highly tumorigenic not only in nude mice but also for the first time after orthotopic seeding in an immunodeficient dog. This allograft mimicked, in a compressed form, the aggressive biological behavior of spontaneous dog prostate adenocarcinoma. Immunoscintigraphy using a (131)Iodine-labeled PSMA mAb clearly visualized induced tumors in nude mice and in the dog allograft. CONCLUSIONS: This study suggests that DPC-1 may constitute a powerful model for assessing new diagnostic and/or therapeutic tools in the management of prostate cancer.

[Esthetic and functional results of the transperitoneal laparoscopic approach in nephrectomy]. / Conséquences esthétiques et fonctionnelles de l'abord laparoscopique transpéritonéal pour la néphrectomie.

OBJECTIVE: To evaluate the aesthetic and functional sequelae of laparoscopic transperitoneal nephrectomy. MATERIAL AND METHODS: Twenty-one laparoscopic transperitoneal nephrectomies were performed between 1996 and 1999. Four trocars were used in 9 patients and 3 trocars were used in 12 patients. In all patients of the series, nephrectomy was performed without manual assistance and the kidney was extracted from the iliac fossa after enlarging a trocar orifice. A questionnaire evaluating the aesthetic sequelae of the operation, resumption of everyday activities and the patient's general satisfaction was sent to each patient by mail. RESULTS: 17 patients completed the questionnaire after a mean follow-up of 12.2 months (range: 2 to 33 months). Scars were cosmetically satisfactory in 100% of cases, painless in 100% of cases and were considered to be invisible in 58.8% of cases. All patients were satisfied with the operation, but only 70.6% would have recommended this procedure to a friend or relative. 57.1% of the patients hospitalised for less than 5 days considered the hospital stay to be too brief and 42.9% considered it to be barely sufficient. Time to resumption of everyday activity varied considerably (7 to 70 days) with a mean of 32 days and was not correlated with operative complications. CONCLUSION: Laparoscopic transperitoneal nephrectomy achieves good aesthetic and functional results, but patients are not satisfied with the short hospital stay. Resumption of everyday activity does not appear to depend on the postoperative course.

A new prostatic stent for the treatment of benign prostatic hyperplasia in high-risk patients.

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.

Early onset and familial predisposition to prostate cancer significantly enhance the probability for breast cancer in first degree relatives.

Genetic predisposition accounts for >/=10% of all cancer of the prostate (CaP) and is therefore considered a major risk factor, together with age and ethnic origin. Several epidemiological studies have suggested that familial clustering of CaP may be associated with an increased frequency of breast and other cancers among relatives. In order to correlate the incidence of CaP with prevalence of breast and other cancers, we have performed uni- and multi-variate analyses on 691 complete pedigrees including probands, who were consecutive patients with confirmed CaP treated in three French urological departments. We have shown a significantly higher risk (RR = 2.3, p = 0.01) to develop breast cancer in families with multiple than in those with a single CaP. Risk of observing other types of cancer within these families was not significant. We then calculated the breast cancer risk in early onset prostate cancer families, and observed a relative risk that is even more significant (RR = 5.5, p = 0.002). Furthermore, the risk was >30 times that a proband's mother have breast cancer if CaP occurred below 55 years of age, rather than after 75 years (p = 0.003). This study has therefore shown for the first time, the relatively high penetrance for breast cancer in relatives of early onset CaP patients.

Gene transfer to urethral strictures in rabbits: a preliminary report.

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.

Percutaneous management of grade II upper urinary tract transitional cell carcinoma: the long-term outcome.

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.