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The p15 gene which encodes a cyclin-dependent kinase inhibitor, is located in the 9p21 chromosomal region that is frequently deleted in human bladder transitional cell carcinomas (TCCs). The aim of the present paper is to study the potential involvement of thep15 gene in the evolution of TCCs. p15 mRNA expression was investigated by semi-quantitative RT-PCR in a series of 75 TCCs, 13 bladder cell lines and 6 normal bladder urothelia by semi-quantitative RT-PCR.p15 was expressed in the normal urothelium but p15 mRNA levels were significantly decreased in 66% of the superficial (Ta-T1) TCCs (P = 0.0015). In contrast, in muscle-invasive (T2-T4) TCCs, p15 expression differed widely between samples. p16 mRNA levels were also studied and there was no correlation between p15 and p16 mRNA levels, thus indicating that the two genes were regulated independently. Lower p15 expression in superficial tumours did not reflect a switch from quiescence to proliferative activity as normal proliferative urothelial controls did not present decreased p15 mRNA levels relative to quiescent normal urothelia. We further investigated the mechanisms underlyingp15 down regulation. Homozygous deletions of the p15 gene, also involving the contiguous p16 gene, were observed in 42% of the TCCs with decreased p15 expression. No hypermethylation at multiple methylation-sensitive restriction sites in the 5'-CpG island of p15 was encountered in the remaining tumours. Our data suggest that decreased expression of p15 may be an important step in early neoplastic transformation of the urothelium and that a mechanism other than homozygous deletions or hypermethylation, may be involved inp15 down regulation. [ABSTRACT FROM AUTHOR]

Résumé: L’ingénierie tissulaire est l’ensemble des méthodes ayant pour objectif de constituer des tissus fonctionnels proches de ceux de l’homme. Ces techniques composent avec deux éléments : les matrices et les cellules. La matrice est la structure sur laquelle l’architecture tissulaire doit s’organiser. Les cellules sont soit celles de l’hôte qui vont proliférer sur la matrice in vivo, soit les cellules de l’hôte cultivées in vitro sur la matrice puis secondairement autogreffées au patient. Les applications de l’ingénierie tissulaire concernent tous les domaines de la chirurgie reconstructrice. Ces techniques sont récemment entrées en pratique clinique. En urologie, le manque de tissu autologue donne un large champ d’application à l’ingénierie tissulaire. Deux techniques peuvent être distinguées : la thérapie cellulaire et l’ingénierie tissulaire proprement dite. Le nombre élevé d’études rapportées dans ce domaine souligne l’importance des implications cliniques futures en urologie. [Copyright &y& Elsevier]

Polyphenols extracted from many plants have shown antiproliferative and antitumor activities in a wide range of carcinogenesis models. The antiproliferative effects of polyphenols purified from the Brazilian aroeira plant (Schinus terebinthifolius, Raddi) were investigated on the androgen-insensitive DU145 human prostatic carcinoma cell line. A F3 fraction purified from leaf extract inhibited the DU145 cell proliferation more than 30-fold compared to the crude extract. By flow cytometric analysis, the polyphenol fraction was demonstrated to induce G0/G1 cell growth arrest and cell apoptosis. This apoptosis was evidenced by caspase 3 stimulation in F3-treated cells as compared to crude extract treated cells. The acid phosphatase activity of lysosomes was strongly activated in the lysosomal fraction of the F3-treated DU145 cells. This lysosomal activation, together with the appearance of autophagic vacuoles, suggests that "type 2 physiological cell death" was also involved in this antiproliferative effect. HPLC analysis of this F3 fraction showed 18 different subfractions. Among these subfractions, F3-3, F3-7 and F3-13 strongly inhibited DU145 cell proliferation in a dose-dependent manner. However, the nature of these polyphenols remains unknown since only one (Isoquercitrin) of the tested pure polyphenols co-migrated with F3-13. Since lysosomotropic drugs are considered as possible regulators of lysosome activity, aroeira polyphenols could target lysosomes of prostatic cancer cells to induce autophagic cell death.

Tissue engineering refers to the techniques that are aimed at regeneration of human tissues and organs. Two elements are necessary for these techniques: matrix and cells. Matrix is the scaffold where tissues may organise. Cells are either autologous cells stimulated to regenerate in vivo, aided by implantation of matrix ("guided tissue regeneration"), or autologous cells cultured outside the body (in vitro) and later returned as auto-transplants. All types of conventional tissue reconstructive surgery need tissue engineering. These techniques have been introduced recently into the clinical practice. One of the main limitations of reconstructive surgery in genitourinary tract is the lack of autologous tissue. Two autotransplants could be distinguished: coherent tissue structure or cell suspensions. The great number of studies published in this area emphasizes the importance of the future clinical implication in urology.

Objective(s): The aim of our retrospective study was to determine if systematic placement of a posterior mesh, in addition to an anterior vesico-vaginal mesh, is necessary for laparoscopic treatment of pelvic organ prolapse., Methods: A laparoscopic promontory sacral colpopexy was performed in 108 patients, including 55 patients with a concurrent laparoscopic Burch procedure (50.9%). We compared 33 patients treated with a single anterior mesh (SAM) and 71 treated with a double, anterior and posterior, mesh (DM)., Results: The difference between the SAM and DM groups was statistically significant in terms of posterior compartment failure (rectocele and/or enterocele): 31.3% and 5.9%, respectively (p=0.0006). This significant difference persisted in the Burch (B) group (p=0.001), but not in the non-Burch (NB) group (p=0.98). Among the SAM group, this difference between the B and NB groups, was significant (57.1% versus 0%; p=0.0015) and above all not a single posterior failure was observed in the NB group., Conclusion(s): The placement of a posterior mesh, if highly effective, appeared unnecessary in the absence of an associated Burch procedure or a patent posterior prolapse. The posterior mesh also increased risk of postoperative complications and side effects.

Objectives: To demonstrate the feasibility of "complete solo" (CS) laparoscopic radical prostatectomy (LRP) performed solely with robotic manipulation of the laparoscope and without any human assistant at all. A comparison was made between CS LRP and the standard technique to identify the advantages and drawbacks., Methods: Sixteen consecutive patients undergoing CS LRP were compared with the last 16 patients undergoing standard LRP. The standard procedure was performed with five trocars and one human assistant. Therefore, the surgeon had three instruments immediately available and could switch quickly from one to another, while the assistant held the laparoscope and a retractor. The CS method used a voice-controlled robotic arm to manipulate the laparoscope and a mechanical arm for the assisting instrument., Results: The mean operative time in the CS and standard groups was 324 and 347 minutes, respectively (P >0.5). An additional human assistant was required, for 1 hour, in 3 patients of each group. No significant difference was noted between the two groups in terms of catheterization time, hospital stay, positive margin rate, complications, short-term cancer control, or functional results. The CS method has been demonstrated to be highly cost-effective compared with the standard technique., Conclusions: The CS LRP is feasible and compares favorably with the standard technique. It offers unique advantages in terms of direct control of the operative view, standardization of the assistance, and higher stability of the laparoscope, thus greatly enhancing the surgeon's comfort. The diminished need for human operative assistance provides significant economic and organizational benefits.

Transitional epithelium of the urinary bladder can be damaged during, for example, catheterization, overstretching due to obstructed voiding, or partial resection. The subsequent repair process can be stimulated by specific proteins such as epidermal growth factor (EGF) and transforming growth factor-alpha (TGFalpha). However, little is known about the role of EGF-like growth factors and their respective receptors in human urothelial repair. In this study, we examined the effects of EGF, TGFalpha, amphiregulin and heregulin-alpha (HRGalpha) on proliferation, wound closure, and the expression of their receptors c-erbB1-c-erbB4 in primary cultures of human urothelial cells in vitro. Under conditions representing intact urothelium, all EGF-like growth factors except HRGalpha induced proliferation. TGFalpha induced proliferation up to four times. Amphiregulin increased expression of c-erbB1. Treatment with either TGFalpha or amphiregulin resulted in higher c-erbB1 activation and c-erbB3 levels. None of the growth factors affected the constitutive expression of c-erbB2 and c-erbB4. In the repair model, both EGF and TGFalpha stimulated the wound closure most strongly. This was mainly achieved by increased cellular migration. Receptor expression was not affected by the addition of exogenous growth factor. The role of c-erbB2 in wound healing was further investigated with the use of antisense DNA. Wound closure could be delayed up to 50% by antisense c-erbB2 but not by mismatched or sense oligonucleotides. Excessive production (e.g. in bladder tumors) or application of EGF, TGFalpha or amphiregulin, but not HRGalpha may lead to either hyperplasia or a faster repair of damaged urothelium in vivo. These effects seem to be mediated not only via c-erbB1 but also via c-erbB2. Our results suggest that modified members of the EGF-EGFR family are potential targets for future therapies for bladder wound healing and malignancy.

Disseminated intravascular coagulation (DIC) revealing a prostatic adenocarcinoma is rare. Most of the case are limited to biological abnormalities. We report a case of a 73 year old man with metastatic prostatic carcinoma and CIVD. The patient consulted for epistaxis and ecchymosis with thrombocytopenia and low coagulate factors. The prostatic specific antigen was 2200 ng/ml and fine needle aspiration of bone marrow biopsy detected metastatic cells. The patients received hormonotherapy, heparine and antithrombine III with a good follow up. About this case, we discuss the management of the patient with metastatic prostatic cancer and CIVD.

Simultaneous pancreas kidney transplantation has become an accepted therapy for the treatment of patients with insulino-dependant diabetes and renal chronic failure. The arterial arrangement of the pancreatic graft is necessary in order to avoid surgical complications of vascular thrombosis. We reported three cases of simultaneous pancreas kidney, a simple procedure using aortic arterial patch preleved with the superior mesenteric artery and detubulated, than the splenic artery is directly anastomosed to the patch.

The efficacy of Bacillus Calmette-Guérin (BCG) in the treatment of superficial bladder cancer was first reported by Morales in 1976. Several authors have since demonstrated the efficacy of BCG in the prophylaxis and treatment of high-risk superficial bladder tumors (pT1G3, CIS). Although BCG is now recommended as an adjunctive treatment for superficial bladder tumors, the optimal treatment schedule remains to be defined. Results reported by Lamm suggest that an initial induction cycle of six weekly intravesical BCG instillations is suboptimal unless maintenance therapy (three consecutive weekly instillations) is given 3, 6, 12, 18, 24, 30 and 36 months later. However, the use of maintenance therapy is hindered by troublesome adverse reactions. This article reviews adverse reactions associated with BCG treatment, proposed a classification and discusses their prevention and treatment.

Objective: To examine whether the outcome of cystectomy for invasive transitional cell carcinoma (TCC) of the bladder was influenced by the type of disease at initial presentation., Patients and Methods: The charts of 76 patients treated for TCC by radical cystectomy from 1987 to 1997 in our unit were reviewed. The patients were divided into three groups: group 1 comprised 43 patients with primary invasive disease; group 2 included 12 patients with progression of an initial superficial bladder tumour after failure of conservative treatment; and group 3 comprised 21 patients who had a radical cystectomy for superficial TCC, with a high risk of progression after attempts at conservative treatment. The pathological findings on transurethral resection and cystectomy specimens, cancer-specific survival and the time to progression were compared among the three groups., Results: The rate of pT0 in cystectomy specimens was 16%, 41% and 24% in groups 1, 2 and 3, respectively. Under-staging occurred in 24% of cases in group 3. The 10-year cancer-specific survival rates were 48%, 47% and 82% in groups 1, 2 and 3, respectively. The cancer-specific survival rate and progression rate were not significantly different between groups 1 and 2, but were significantly lower/higher in these patients than in group 3 (P < 0.01)., Conclusions: These data suggest that the prognosis of superficial TCC which progresses despite conservative management is no better than that of invasive TCC at initial presentation, despite the closer follow-up received by the former patients. Early identification of this group of patients may improve the cancer-specific survival, as early cystectomy for high-risk superficial TCC yields better results.

Objective: To determine whether muscle precursor cells (MPCs) harvested from limb skeletal muscle can enhance the regeneration process of the striated urethral sphincter after injury., Material and Methods: Striated urethral sphincters of male mice were injured by an injection of a myotoxic substance (notexin). In the experimental group, 2 days after injury, MPCs were enzymatically harvested from striated muscles of the lower limbs and labelled with PKH 26, then immediately re-injected into the injured urethral sphincter of the same animal. In the control group, saline buffer was injected instead of MPCs. Animals were killed 7 days or 1 month after injury and the sphincters removed for histological study (the presence of PKH 26-labelled myofibres, measurement of myofibre diameter and total number of myofibres)., Results: MPC autografting accelerated sphincter muscle repair, as shown by a higher myofibre diameter (P = 0.03) and number (P = 0.01) in the experimental group than in the controls at 7 days. One month after their injection MPCs were still detectable in the regenerating sphincters and participated in the formation of new myofibres., Conclusion: This study provides the experimental basis for a new therapeutic approach to urethral sphincter insufficiency after surgical or obstetrical injury, based on MPC autografting.

Purpose: Interleukin (IL)-2 and interferon-gamma are released during T helper 1 lymphocyte responses and IL-10 is released during T helper 2 lymphocyte responses. We have previously reported that a T helper 1 lymphocyte urinary cytokine profile is associated with a favorable prognosis after bacillus Calmette-Guerin (BCG) treatment. We evaluated the T helper 1/2 lymphocyte cytokine profiles during courses 1 and 2 of 6 weekly BCG instillations., Materials and Methods: Urinary interferon-gamma, IL-2 and IL-10 were measured by enzyme-linked immunosorbent assay after each of 6 weekly instillations of 150 mg. BCG, Pasteur strain, in 19 patients with superficial stages Ta and T1 bladder cancer, and carcinoma in situ. The 11 patients who did not respond to course 1 were re-treated according to the same schedule and reevaluated., Results: During course 1 interferon-gamma was higher than during course 2 (p <0.001), which was associated with nonrecurrence (p <0.001). In contrast, IL-2 cytokine was higher after course 2 (p <0.01), which was associated with a BCG response (p = 0.01). Interferon-gamma and IL-10 correlated during courses 1 and 2 (p = 0.04 and 0.0004, respectively). We distinguished groups 1-immediate T helper 1 lymphocyte profile consisting of responders to course 1 with high interferon-gamma, IL-2 and IL-10, 2-delayed T helper 1 lymphocyte profile consisting of responders to course 2 with early high IL-2 and 3-consisting of nonresponders to the 2 courses with low interferon-gamma, IL-2 and IL-10., Conclusions: A T helper 1 lymphocyte urinary cytokine profile was associated with a clinical response to BCG. A repeat BCG course induces a favorable immune response in a subset of patients, suggesting that maintenance therapy may be beneficial.

The p15 gene which encodes a cyclin-dependent kinase inhibitor, is located in the 9p21 chromosomal region that is frequently deleted in human bladder transitional cell carcinomas (TCCs). The aim of the present paper is to study the potential involvement of the p15 gene in the evolution of TCCs. p15 mRNA expression was investigated by semi-quantitative RT-PCR in a series of 75 TCCs, 13 bladder cell lines and 6 normal bladder urothelia by semi-quantitative RT-PCR. p15 was expressed in the normal urothelium but p15 mRNA levels were significantly decreased in 66% of the superficial (Ta-T1) TCCs (P = 0.0015). In contrast, in muscle-invasive (T2-T4) TCCs, p15 expression differed widely between samples. p16 mRNA levels were also studied and there was no correlation between p15 and p16 mRNA levels, thus indicating that the two genes were regulated independently. Lower p15 expression in superficial tumours did not reflect a switch from quiescence to proliferative activity as normal proliferative urothelial controls did not present decreased p15 mRNA levels relative to quiescent normal urothelia. We further investigated the mechanisms underlying p15 down regulation. Homozygous deletions of the p15 gene, also involving the contiguous p16 gene, were observed in 42% of the TCCs with decreased p15 expression. No hypermethylation at multiple methylation-sensitive restriction sites in the 5;-CpG island of p15 was encountered in the remaining tumours. Our data suggest that decreased expression of p15 may be an important step in early neoplastic transformation of the urothelium and that a mechanism other than homozygous deletions or hypermethylation, may be involved in p15 down regulation.

The muscle changes related to pelvic floor disorders are poorly understood. We conducted an anatomical and histological study of the perineum of the normal mouse and of a transgenic mouse strain deficient in urokinase-type plasminogen activator (uPA-/-) that was previously reported to develop a high incidence of rectal prolapse. We could clearly identify the iliococcygeus (ILC) and pubococcygeus (PC) muscles and anal (SPA) and urethral (SPU) sphincters in male and female mice. The bulbocavernosus (BC), ischiocavernosus (ISC) and levator ani (LA) muscles could be found only in male mice. Histochemical analysis of the pelvic floor muscles revealed a majority of type IIA fibres. Rectal prolapses were observed only in male uPA-/- mice. The most obvious finding was an irreducible evagination of the rectal mucosa and a swelling of the entire perineal region corresponding to an irreducible hernia of the seminal vesicles through the pelvic outlet. The hernia caused stretching and thinning of the ISC, BC and LA. Myopathic damage, with degenerated and centronucleated myofibres, were observed in these muscles. The PC, ILC, SPA and SPU were not affected. This study provides an original description of a model of pelvic floor disorder and illustrates the differences existing between the perineum of humans and that of a quadruped species. In spite of these differences, the histopathologic changes observed in the pelvic floor muscles of uPA-/- mice with rectal prolapse suggest that prolonged muscular stretching causes a primary myopathic injury. This should be taken into account in the evaluation of pelvic floor disorders.

Objective: To compare the immunological status of normal and peritumoral bladder walls, and to characterize immunocompetent cells before and during intravesical instillations of bacillus Calmette-Guérin (BCG)., Patients and Methods: Twenty-three patients with superficial urothelial bladder carcinoma (stages pTa to pT1, grades 1-3) were treated with six weekly instillations of 150 mg of BCG (Pasteur strain). Biopsies of cystoscopically normal bladder wall were taken before, 3 weeks and 3 months after BCG instillation. The controls comprised bladder biopsy specimens from 13 brain-dead ventilated kidney donors. Local infiltrating cell types, i.e. lymphocyte infiltrates (CD4, CD8, CD20, CD3, interleukin-2-receptor-positive, natural killer, gammadelta), macrophages and dendritic cells, adhesion and costimulatory molecules (ICAM-1 and B7-BB1) and major histocompatibility complex (MHC) class I and class II antigens were assessed using semi-quantitative immunohistochemical analysis., Results: Before BCG the peritumoral bladder wall had fewer macrophages than control bladder wall. BCG treatment restored normal numbers of macrophages and enhanced T helper lymphocytes, B lymphocytes, natural killer cells, activated lymphocytes, dendritic cells, normal MHC class I, adhesion (ICAM-1) and costimulatory (B7-BB1) expression. The enhancement of these immunological variables was transient, with a return to baseline 3 months after BCG instillation., Conclusions: These results support the concept that there is a host-immune escape associated with bladder cancer. BCG therapy may temporarily restore impaired tumour rejection mechanisms in the peritumoral bladder wall, suggesting a need for maintenance therapy after the first course of BCG.

Purpose: To analyze the retroperitoneal approach to laparoscopic radical nephrectomy in terms of feasibility, safety, morbidity, and cancer control., Patients and Methods: We reviewed the records of 50 consecutive patients with renal cancer underwent radical nephrectomy via the retroperitoneal laparoscopic approach from 1995 through 1999., Results: The mean operative time was 139 minutes (range 60-330 minutes) with a mean of 149.78-mL operative blood loss (0-1500 mL). The mean renal size was 100 mm (70-150 mm) with a mean tumor size of 38.6 mm (20-90 mm). The postoperative hospital was 6 days (2-13 days). Three open conversions were necessary: one for laparoscopically uncontrolled bleeding and two because obesity interfered with surgery. We noted two major complication and two minor complications. Two disease progression have been noted to date. One patient with a pT3 grade 2 renal-cell carcinoma had a local recurrence with liver metastasis 9 months after the procedure and died 19.7 months after radical nephrectomy. Another patient with a pT3aN+M+ cancer died 23.1 months after the procedure., Conclusion: Retroperitoneal laparoscopic nephrectomy for kidney cancer requires further assessment. It seems to have several advantages over open radical nephrectomy and to be effective and safe for small (<50-mm) renal tumors.

Obesity: Studies attempting to establish an epidemiological link between body mass index and the risk of cancer of the prostate have been contradictory. ENERGY INTAKE: No straightforward relationship between energy intake and cancer of the prostate has been identified. FAR INTAKE: According to epidemiology studies, there is a correlation between high-fat diet and the incidence of cancer of the prostate. It has thus been demonstrated that men whose diet contains more than 30 to 40% fat have a higher risk of developing cancer of the prostate than those whose diet contains less than 30% fat. In addition, high-fat diets favor progression of tumors in elderly subjects. ROLE OF SATURATED FAT: Saturated fat has been implicated most often in the development of cancer of the prostate, high intake being correlated with shorter survival after diagnosis of cancer.