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Introduction: Our objectives were to evaluate the long-term renal function after radical cystectomy (RC) and ileal conduit diversion (ICD) and to analyze year-by-year the estimated glomerular filtration rate (eGFR) and morphologic upper urinary tract changes., Patients and Methods: We retrospectively identified 226 patients who had undergone RC and ICD from 1980 to 2008, with regular postoperative follow-up visits. The eGFR was calculated using the Modification of Diet in Renal Disease equation at baseline and during follow-up. A decrease in renal function was defined as > 1 mL/min/1.73 m(2) annually., Results: The median follow-up period after RC was 91 months (range, 61-235 months). The median eGFR decreased from 66 mL/min/1.73 m(2) (range, 17-139 mL/min/1.73 m(2)) to 59 mL/min/1.73 m(2) (range, 33-102 mL/min/1.73 m(2)). A rapid decline in renal function occurred during the first 2 postoperative years (-9 mL/min/1.73 m(2) and -4 mL/min/1.73 m(2) in the first and second year, respectively), with a moderate to slight decrease in the subsequent years. Urinary obstruction was diagnosed in 51 patients (23%). Among the patients who underwent prompt surgical treatment, we did not find any association with the eGFR decline (P = .8)., Conclusion: Patients with urinary ICD have a lifelong risk of chronic kidney disease. Regular monitoring of renal function and the morphologic upper urinary tract will permit early diagnosis and treatment of modifiable factors, avoiding irreversible kidney damage., (Copyright © 2015 Elsevier Inc. All rights reserved.)

Objectives: To retrospectively assess the long-term outcome of patients initially diagnosed with TaG1 non-muscle-invasive bladder cancer (NMIBC) with no immediate postoperative instillation of intravesical chemotherapy and evaluate the reproducibility of the European Organization for Research and Treatment of Cancer (EORTC) scoring system for predicting bladder cancer outcome., Methods and Materials: A retrospective analysis of 481 consecutive cases of initially diagnosed TaG1 NMIBC according to the 1973 World Health Organization classification between 1995 and 2008 in a single institution was performed. Time to first recurrence, time to progression to T1 or G3 bladder cancer, and time to progression to muscle-invasive bladder cancer were studied. Time to event distributions was estimated by means of cumulative incidence functions to accurately take into account the patients who died (competing risk) before recurrence or progression. The Harrell c statistic calculation was used for our study's data results as well the original data from EORTC to compare the predictive power of a survival model., Results: The median follow-up was 88 months (interquartile range: 51-135 mo). The 10-year recurrence-free, T1 or G3 NMIBC progression-free, and muscle-invasive bladder cancer progression-free survival rates were 64.2%, 96.6%, and 97%, respectively. In multivariate analysis, tumor size and number of lesions were prognostic variables of the risk of recurrence. In our study and EORTC data sets, the Harrell c values obtained were c = 0.85 (95% CI: [0.75, 0.93]) and c = 0.85 (95% CI: [0.75, 0.93]), respectively., Conclusion: Our study reports a detailed and extensive outcome of TaG1 NMIBC treated by TURB with no immediate postoperative intravesical instillation of chemotherapy. Our results suggest that the EORTC is a useful external validation scoring system for predicting bladder cancer outcome., (Copyright © 2014 Elsevier Inc. All rights reserved.)

Background: The detection of lymph node metastases in bladder cancer has a major impact on treatment decisions and patients prognosis. Due to limited value of conventional imaging, the place of molecular and functional imaging needs to be precised, particularly in the neoadjuvant setting., Methods: From June 2011 to June 2013, 102 patients with clinically localized BCa were simultaneously staged with (18)F-FDG PET/CT before RC. This study assessed the diagnostic accuracy of (18)F-FDG PET/CT for the detection of metastases in normal-sized lymph nodes using extended pelvic lymph node dissection and histopathology as the reference standard., Results: A total of 1211 LNs were examined histopathologically. Sixty-seven (5.5%) metastatic nodes were found in 26/102 patients (25.5%). Lymph node density was 22%. On patient-based analysis, sensitivity, specificity, predictive positive value (PPV), negative positive value (NPV) and accuracy for (18)F-FDG PET/CT were calculated as 50%, 96.2%, 80%, 86.2% and 85.3% respectively. On a field-based analysis, sensitivity, specificity, PPV, NPV and accuracy for (18)F-FDG PET/CT were calculated as 50.0%, 99.0%, 71.9%, 97.4%, and 96.5% respectively. The majority of missed metastases were micrometastasis <5 mm in long axis diameter., Conclusions: (18)F-FDG PET/CT improves diagnostic efficacy for lymph node staging in patients staged N0 with conventional cross-sectional imaging. (18)F-FDG PET/CT could be used as a surrogate marker for detection of metastases in non-enlarged pelvic lymph nodes and enhances management strategy guiding patients selection for neoadjuvant chemotherapy., (Copyright © 2014 Elsevier Ltd. All rights reserved.)

Objective: In accordance with the European Association of Urology guidelines, a second transurethral resection of the bladder (TURB) is recommended for high-grade or T1-category tumors. This practice brings into question the benefit of photodynamic diagnosis (PDD) in reducing the residual disease after TURB in patients with positive results on urine cytology showing high-grade cancer cells., Methods and Materials: A prospective, bicentric, randomized study comparing white light cystoscopy (WLC)+PDD with hexaminolevulinate arm with WLC alone (control arm) during the first TURB in patients with primary non-muscle-invasive bladder cancer and with positive results on urine cytology showing high-grade cancer cells. Patients underwent a first TURB with WLC and PDD or WLC alone, and then a second TURB with WLC and PDD, after 4 to 6 weeks. The number of tumors visualized in WLC and PDD and histology of the TURB specimen was recorded to perform a statistical analysis comparing both the 2 arms., Results: A total of 151 patients were enrolled (hexaminolevulinate, n = 72; control, n = 79). The number of visualized tumors did not increase with PDD in the first or second TURB. During the second TURB, the residual tumor rate was not reduced in patients who had PDD during the first TURB. No significant difference was observed regarding the pattern of category and grade, the size, and the recurrence and progression risks during either the first or the second TURB., Conclusions: In the setting of primary non-muscle-invasive bladder cancer with positive results on urine cytology, performing a second TURB allows to diagnose residual tumor in approximately half of the cases. This rate was not significantly reduced by the use of the PDD during the first TURB., (Copyright © 2014 Elsevier Inc. All rights reserved.)

Background: The purpose of this study was to determine health-related quality of life (HRQoL) among long-term disease-free survivors in women who underwent radical cystectomy (RC) for urothelial carcinoma and orthotopic ileal neobladder (ONB) reconstruction, using validated patient-reported outcome instruments., Methods: From 2000 to 2011, a total of 46 women with urothelial bladder carcinoma had RC and ONB at our institution; 31 (67 %) eligible women completed 3 validated questionnaires: the medical outcome study short form 12 (SF-12), the urinary symptom profile, and the Contilife, respectively evaluating general HRQoL, voiding function, and urinary incontinence specific HRQoL. Unadjusted analyses were performed to analyze standardized measures of HRQoL and voiding symptoms; p < 0.05 was considered significant., Results: The mean follow-up was 5.7 years; 24 women (77 %) considered their health as good, very good, or excellent. The SF-12 physical and mental scores were not significantly different between the population study and the general population (p > 0.05). A total of 20 women (65 %) declared to be fully continent. Daytime incontinence, nighttime incontinence, and hypercontinence were reported by 26, 29, and 31 % of women, respectively. On unadjusted analysis, incontinence was associated with age > 65 years at the time of surgery (p < 0.001). Hypercontinence was not associated with any variable., Conclusions: This study suggests that in the setting of radical cystectomy in women, ileal neobladder reconstruction provides long-term satisfaction with maintained HRQoL. For properly selected women, orthotopic neobladder can be considered an appropriate diversion choice.

Unlabelled: Study Type--Therapy (retrospective cohort) Level of Evidence 2b. What's known on the subject? and What does the study add? The more that bladder cancer progresses from the urothelium to the outside of the bladder the worse the prognosis. To date, the use of adjuvant chemotherapy has not been completely defined. The present study clarifies the prognosis and benefits of adjuvant chemotherapy for different stages of bladder cancer that invade perivesical fat., Objective: • To assess the prognosis of pT2b, pT3a and pT3b bladder cancers after radical cystectomy (RC) in order to define potential situations where chemotherapy may be of benefit., Patients and Methods: • Between 1985 and 2009, 903 patients underwent a RC and pelvic bilateral lymphadenectomy in an Institutional Referral Centre. • In all, 87 patients (9.6%) had a pT2b tumour, 111 patients (12.3%) a pT3a tumour, and 129 patients (14.3%) a pT3b tumour. • The median (range) overall follow-up was 23 (1-350) months. • Overall (OS), disease-specific (DSS), metastases-free (MFS) and local recurrence-free survival (LRFS) was estimated and compared using Kaplan-Meier plots and log-rank test., Results: • The 5-year survivals pT2b and pT3a were similar for LRFS (86% vs 84%), MFS (69% vs 63%), DSS (72% vs 70%) and OS (66% vs 61%), and the prognosis was better than for pT3b stage tumours (69%, 44%, 40%, and 31% respectively). • In pN0 disease, MFS differences between pT2b-pT3a and pT3b tumours were not significant in patients who had received adjuvant chemotherapy (MSF of 87%, 69% and 56%, respectively) while they were significant in patients without adjuvant chemotherapy (MFS of 70%, 68% and 42%, respectively)., Conclusions: • Bladder cancers invading perivesical tissue macroscopically have a greater propensity to produce lymph node metastases, local recurrence, and have lower MFS, DSS, and OS. In pN0 disease, pT3b tumours may receive more benefit from adjuvant chemotherapy. • Our results could be a useful for selecting patients for adjuvant chemotherapy., (© 2012 THE AUTHORS. BJU INTERNATIONAL © 2012 BJU INTERNATIONAL.)

Purpose: To describe the epidemiology, clinical features, and prognostic factors of local recurrence (LR) in a large case series of patients treated by radical cystectomy (RC) for bladder cancer., Methods: A retrospective study was conducted on 903 patients treated in a single tertiary reference center. All cases of LR were identified. Descriptive analysis was performed on the clinical features, evolution, and overall mortality of these patients. Prognostic factors of LR were assessed using the Mann-Whitney test for continuous variables and the χ(2) test for categorical variables., Results: Fifty-three patients were diagnosed with LR during follow-up (5.9 %). One patient had concomitant distant metastasis. Pain was the most frequent symptom leading to diagnosis. Mean time interval from RC to LR was 14.4 ± 13 months (1-64) with 50 % of cases diagnosed in the first postoperative year. Overall median survival of patients diagnosed with LR was 9 months [95 % confidence interval (6-11)]. Advanced pathological stage (T3 or T4) and lymph-node invasion were associated with increased LR rate in univariate and multivariate analysis. Presence of squamous cell carcinoma (SCC) was associated with a poorer prognosis after LR compared to pure urothelial carcinoma (p = 0.04). None of the parameters tested was associated with time interval between RC and LR diagnosis., Conclusions: LR is not uncommon, favored by high pathological stage (T3/T4), and has a very bad prognosis, particularly when SCC is present. LR must be carefully tracked during follow-up after RC, and optimal management of these cases remains to be determined.

Objective: One of the priorities of the "Plan against the Cancer" in France is to ensure the discussion of all cancer cases in a multidisciplinary meeting staff (RCP). The multidisciplinary collaboration is proposed to guarantee a discussion between specialists in every cases, particularly in complex cases. The aim of this study was to compare the therapeutic decision taken in four RCP in Paris Île-de-France academic centres for three identical cases., Material: Three cases of urological oncology (prostate cancer [PCa], renal cell carcinoma [RCC] and bladder tumour) were selected by a single urologist, not involved in further discussion. These cases were blindly presented in four academic urology department from Paris: Pitié-Salpêtrière Hospital, Mondor Hospital, the Georges-Pompidou European Hospital and Foch Hospital., Results: The four centres met the criteria of quality of RCP in terms of multidisciplinarity, frequency and standardization. The therapeutic suggestions were similar in the RCC cases, there were differences in the surgical approaches and preoperative work-up in the PCa case and, lastly, the proposals were different for the bladder cancer case., Conclusion: The decisions relies on clinical data and preoperative work-up but also on the experience and habits of the centre of excellence. For complex cases that does not fit with current guidelines, the panel discussion can lead to different therapeutic options from a centre to another and is largely influenced by the local organisation of the RCP., (Copyright © 2012 Elsevier Masson SAS. All rights reserved.)

Purpose: To assess the postsurgical survival of patients with urothelial carcinoma of the bladder with pT0 tumor at pathologic examination of cystectomy specimens., Methods: A multi-institutional, retrospective database was analyzed with data from 4758 radical cystectomy (RC) patients who underwent RC without neoadjuvant chemotherapy and who were diagnosed with pT0 on the basis of the pathologic specimen. Survival curves were estimated. A multivariate Cox model was used to evaluate the association between prognosis factors and disease recurrence or survival., Results: Overall, 258 patients (5.4%) were included in the study. The median age was 64 years. At last resection, 171 tumors were invasive (at least pT2), and 87 were not. Median follow-up was 51 months. At multivariate analysis, initial location of the tumor and absence of lymphadenectomy were associated with tumor recurrence (P = 0.03 and P = 0.005, respectively) and specific mortality (P = 0.005 and 0.001, respectively). The main limitation of the study is its retrospective design, which is due to the rarity of this situation. Cancer-specific and recurrence-free survival rates were 89 and 85%, respectively, at 5 years and 82 and 80%, respectively, at 10 years., Conclusions: Despite acceptable oncological outcomes, patients with a pT0 tumor at the time of RC are still at risk of recurrence and progression and should not be considered to be entirely cured. In this population, stringent follow-up according to current recommendations should be effective.

Unlabelled: Study Type - Therapy (case series)., Level of Evidence: 4., Objective: To evaluate the results in terms of functional results and morbidity of Z-shaped ileal neobladder performed in a single center., Patients and Methods: 329 consecutive male patients who had an orthotopic bladder replacement using the Z-shaped ileal neobladder between May 1990 and January 2009., Results: The mean age of the patients was 64.4 ± 9.6 years, with a mean follow-up of 59.4 ± 55 months. Eighty-three early complications in 80/294 patients (27.2%) occurred. The average Clavian rate of these early complications was 2.24. Among these, 12 complications in 12 patients (4.1%) were pouch-related, and 3 reoperations were required. Two patients died from cardiac complications. Sixty-three late complications in 60/294 patients (20.4%) were recorded. The average Clavian rate of these late complications was 2.98. Among these, 47 complications in 45/294 patients (15.3%) were pouch-related, and 18 reoperations were required, essentially for ureteral anastomosis stricture. Satisfactory daytime urinary continence was achieved in 92% of patients. Daytime continence was obtained within, on average, 6.8 ± 16.4 months. The interval between each daytime urination was 2.6 ± 0.8 h (median = 2.5 [1-5] h). Forty-four (15%) patients developed metabolic acidosis which only required oral medication. Satisfactory nocturnal urinary continence was achieved in 87% of patients. Night-time continence was obtained within, on average, 10.8 ± 22.4 months. Hyper-continence with subsequent need for CISC was observed in 4%., Conclusion: In our series of 329 patients, compared with the other techniques, the Z-shaped ileal neobladder had an 'expected' complication rate for this high risk surgery with satisfactory daytime and night-time continence in nine out of ten patients., (© 2011 THE AUTHORS. BJU INTERNATIONAL © 2011 BJU INTERNATIONAL.)

Objectives: Although Bacillus Calmette-Guérin (BCG) instillations are considered as the adjuvant treatment of choice for stage Ta-T1 grade G3 bladder tumours, there is no consensus for a predictive factor to assess BCG success. This study attempted to evaluate if heat shock proteins (HSPs) could be useful predictive markers in BCG responses., Methods: Thirty-three primary resected G3 superficial bladder tumours were included in the study. All patients received adjuvant BCG instillations. The mean follow-up was 56 mo (range: 24-132 mo). HSP expression was evaluated by immunochemistry., Results: In the 33 patients, 18 had no recurrence (group 1), 9 had recurrence with no muscular invasion (group 2), and 6 had an invasive recurrence (group 3). A significant correlation was found between lack of expression of HSP90 and BCG response: the mean HSP expression was 92.7%, 84.4%, and 26.7% for groups 1, 2 and 3 tumours, respectively (p<0.0001). For the 6 patients who did not positively respond to BCG, HSP expression was <40%. All the tumours with a HSP90 expression >40% positively responded to BCG, corresponding to group 1 or 2 patients. In contrast, HSP60 expression was not correlated to the BCG response., Conclusions: HSP90 could be considered as a very promising marker to assess BCG treatment response. Low HSP90 expression (<40%) could be useful to predict BCG failure and early stage cystectomy could be proposed for these selected patients with primary high-risk grade 3 superficial bladder tumours.

Objective: After endoscopic resection of high-grade superficial urothelial neoplasms (Ta, T1 or Tis), adjuvant bacillus Calmette-Guérin (BCG) therapy is performed routinely to avoid recurrence and/or progression. Vesical biopsies often are performed to assess the efficacy of treatment. The aim of our study was to evaluate the usefulness of these biopsies., Materials and Methods: During this retrospective bi-centre study, 130 patients who had undergone vesical high-grade tumour resection were included. There were 40 Ta associated with Tis in three cases, 87 T1 associated with Tis in 13 cases, and three isolated Tis. After BCG treatment, the following parameters were studied: cytoscopic findings, urine cytology and the histologic results of systematised biopsies., Results: Urine cytology was positive (high-grade) for 26 patients and negative (normal or low-grade) for 104 patients. For the 26 patients with positive cytology, vesical flexible cystoscopy findings were considered suspicious in 18 patients and normal in eight patients. As for the 104 patients who presented negative cytology, cystoscopic findings were considered negative in 76 patients and suspicious in 28 patients. In the present study, the sensitivity of cytology and cystoscopy in the detection of recurrence after BCG treatment was 56% and 87.5%, respectively; specificity was 56% and 81.6%, respectively. When the two examinations were combined, sensitivity was 100%, and specificity was 76%., Conclusions: After BCG therapy, the association of negative flexible cystoscopy findings and normal urine cytology made it possible to avoid routine biopsies. Patients could therefore avoid the morbidity of this procedure.

Objective: To test different approaches of evaluation of the ErbB2 status in a large series of human transitional cell carcinoma (TCC) of the bladder with the prospect of finding targeted therapies., Methods: ErbB2 status of 73 human TCC samples was analyzed by both immunohistochemistry (IHC) and by quantification of mRNA levels of expression using real-time reverse transcription-polymerase chain reaction (RT-PCR). Additionally, 18 bladder samples were studied for ERBB2 gene amplification by real-time quantitative PCR., Results: Twenty-five tumors (34.2%) overexpressed ERBB2 mRNA compared to normal bladder samples; this alteration appeared in low-grade and low-stage tumors (pTaG1). Twenty-four (32.9%) tumors showed moderate (++) or strong (+++) immunostaining. A very strong agreement was found between the two methods (kappa = 0.97, 95% confidence interval, 0.90-1). ErbB2 status was not associated with tumor stage. Of the 18 bladder samples tested for ERBB2 gene amplification, only one showed ERBB2 DNA amplification., Conclusions: ErbB2 overexpression occurs in about one third of bladder TCCs. This overexpression can be detected by RT-PCR with a very good correlation with IHC. RT-PCR can therefore be used for cases considered doubtful on IHC rather than gene amplification studies because, in TCC, gene amplification is not the predominant mechanism of both mRNA and protein overexpression. Accurate quantification of ErbB2 status is mandatory for the use of anti-ErbB2-targeted therapies in bladder TCC.

Purpose: The ErbB driven growth pathway has been implicated in most human epithelial malignancies. Therefore, its blockade is a promising therapeutic strategy and several candidate drugs are currently undergoing clinical trials. Paradoxically little is known of the expression pattern or clinical significance of the 4 ErbB receptors and their 11 ligands in TCC of the bladder., Materials and Methods: To obtain further insight into the molecular pathogenesis of TCC we used quantitative real-time reverse transcriptase-polymerase chain reaction assay to quantify mRNA expression of the 4 ERBB and their 11 known ligand genes, including recently described EPGN/epigen, in 73 tumor samples., Results: The level of mRNA of 4 ligand genes (EGF, NRG1, NRG2 and NRG3) was extremely low, that is detectable but not quantifiable. Six genes were over expressed (ERBB2, TGFA, HB-EGF, AREG, EREG and EPGN), 3 were under expressed (ERBB1, ERBB4 and NRG4) and 2 were over or under expressed (ERBB3 and BTC). ERBB2 and AREG expression differed between early stage tumors (pTa grade 1) and normal samples. The most marked differences in expression were ERBB3, EREG and NRG4 between superficial and muscle invasive tumors (p = 0.0069, 0.00007 and 0.0000001, respectively), and TGFA and NRG4 between low and high grade superficial tumors, and between pT1 or greater and pTa tumors., Conclusions: This study shows the involvement of the ERBB family and ligand genes in TCC. Most receptor and ligand genes are deregulated at different stages of carcinogenesis, implying that they should be studied simultaneously. Quantitative real-time reverse transcriptase-polymerase chain reaction could be used to determine ErbB signaling pathway status in individuals with a view to tailored therapy.

Among the surgical options for bladder replacement proposed after cystectomy, the ileocaecal pouch system has been abandoned for twenty years because of its poor gastrointestinal tolerance. Colonic enterocystoplasty is useful because of the reduced risk of degeneration and fewer repercussions on gastrointestinal absorption. However, replacement with the ileum is today the reference cystoplasty with three main techniques: Hautmann bladder, Studer pouch and Foch Z-shaped pouch. According to the data in the literature, these techniques offer similar overall performances and the results therefore remain mainly operator-dependent. Efficacy in terms of urinary continence is optimized by the preparation of a detubularized neobladder with a "physiological" functional capacity, the preservation of the sphincter as well as perineal-abdominal re-education which is started immediately after surgery. Direct ureteral reimplantation in the detubularized bladder is today an effective and sufficient technique to prevent vesico-renal reflux. Tumor recurrences do not seem be dependent on the type of ureteral reimplantation, nor on the type of initial bladder tumor. Extemporaneous examination of the cross-section of normal urethral section (no tumor, dysplasia, or carcinoma in situ) makes it possible to exclude the risk of urethral recurrence.

Objective: To evaluate the oncological outcome and functional results of prostate-sparing cystectomy (PSC), proposed for treating bladder cancer, used since 1999 in our institution in an attempt to preserve male sexuality and to increase continence after cystectomy., Patients and Methods: Between January 1999 and December 2001, 111 men were candidates for cystectomy; 42 were selected for a prostatic capsule- and seminal-sparing cystectomy with orthotopic urinary diversion. All patients had clinically organ-confined tumours (clinical stage

Background: Heat shock proteins (HSPs) are synthesized by cells in response to various stress conditions, including carcinogenesis. The expression of HSPs in neoplasia has been implicated in the regulation of apoptosis, and HSPs also can act by increasing immunity. In the current study, the authors attempted to clarify the significance of HSPs in bladder carcinoma and their effect on tumor behavior., Methods: Expression levels of the 27-kilodalton HSP (HSP27), HSP60, HSP70, and HSP90 were studied using immunohistochemistry on tissue sections from 42 transitional cell carcinomas of the bladder (14 Grade 1 tumors; 13 Grade 2 tumors; 15 Grade 3 tumors, including 3 tumors associated with carcinoma in situ; 30 Stage Ta tumors; 7 Stage T1 tumors; and 5 Stage T2 tumors). Bladder specimens from 10 healthy patients were used as controls in the study. The selected patients had a mean follow-up of 52 months (range, 24-78 months). Among the 37 patients with superficial bladder carcinoma, 17 patients did not have any recurrence after undergoing primary resection, and 20 patients developed recurrent disease, including 4 recurrences with muscle invasion. HSP expression was evaluated according to the percentage of positively stained cells, and loss of expression was defined as < 80% of stained cells., Results: In normal bladder specimens, all four HSPs (HSP27, HSP60, HSP70, and HSP90) were expressed strongly in the cytoplasm and membrane from the basal cell layer to the superficial cell layer. Loss of expression was detected in tumors: respectively, 45.2%, 38.1%, 69.0% and 23.8% of tumors showed a loss of immunostaining for HSP27, HSP60, HSP70, and HSP90. No correlation between HSP expression and grade was found. Low expression levels of HSP27 and HSP60 were correlated with higher tumor stage (87% vs. 6% [P < 0.001] and 78% vs. 9% [P < 0.01], respectively). HSP60 and HSP90 expression levels were correlated with final outcome for patients with superficial bladder carcinoma: loss of expression was associated with the risk of developing an infiltrating recurrence (97% vs. 6.0% [P < 0.001] and 88.2% vs. 52.5% [P = 0.02] for HSP60 and HSP90, respectively)., Conclusions: HSPs were expressed in normal urothelium, and the current results indicated that loss of HSP60 and HSP90 expression may have prognostic relevance in patients with bladder carcinoma. The authors believe that HSP60 may be a very useful marker for patients with superficial bladder carcinoma and may be used for predicting disease progression. If these data are confirmed, low HSP60 expression levels may be usable as a prognostic marker to identify patients for whom local treatment would be insufficient., (Copyright 2003 American Cancer Society.)

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

Objective: To investigate whether telomerase activity could be used as a diagnostic and/or prognostic marker of bladder carcinoma, by assessing telomerase activity using semiquantitative and in situ methods, and quantifying telomerase reverse transcriptase (hTERT) mRNA expression in a series of bladder carcinomas., Material and Methods: Telomerase activity was detected by the telomeric repeat amplification protocol (TRAP) assay using a telomerase polymerase chain reaction (PCR) enzyme-linked immunosorbent assay (ELISA) kit on a series of 29 bladder carcinomas and on three normal bladder samples. hTERT mRNA levels were quantified using real-time quantitative reverse transcription (RT)-PCR. For the in situ detection of telomerase activity, the same telomerase PCR ELISA kit was used and applied to frozen-tissue sections only for discordant cases between telomerase activity and hTERT mRNA status., Results: Telomerase activity was positive in 15 of the 29 bladder carcinomas (52%) and negative for the three normal bladder samples. hTERT was detected and quantified in all tumour samples, with major differences in hTERT values. None of the three normal bladder samples had quantifiable hTERT mRNA, giving complete sensitivity and specificity for the method in diagnosing bladder carcinoma. Comparing the results of RT-PCR and TRAP assay showed a significant association between the enzyme activity and levels of hTERT mRNA expression, with only five discordant cases, most of them being TRAP-negative and hTERT-positive. Among these cases the in situ results of telomerase activity were concordant with hTERT mRNA levels by RT-PCR and not with TRAP assay results, as nuclear fluorescence of malignant epithelial cells. The semiquantitative evaluation of positive cell numbers showed a heterogeneity of telomerase activity within the tumour tissue. There was a significant correlation between RT-PCR and histopathological variables (grade and stage), and a significant correlation between TRAP assay results and histopathological grade., Conclusion: Detecting hTERT mRNA by RT-PCR seems to be a promising method, with a much better sensitivity than the TRAP assay in diagnosing bladder carcinomas, and a better correlation with histopathological variables. False-negative cases on the TRAP assay are explained by the heterogeneity of telomerase activity within tumour cells. Thus evaluating hTERT gene expression levels could be used as a marker of malignant progression, useful in the early diagnosis and follow-up of bladder carcinomas.

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

Purpose: After cystectomy for bladder cancer, when pelvic lymph nodes are positive, bladder replacement remains controversial. The aim of this study was to evaluate the outcome of patients who underwent neobladder replacement despite bladder cancer metastasis to the regional lymph nodes., Materials and Methods: From 1981 to 1997, a total of 504 consecutive cystectomies for bladder cancer were performed at our institution. For 150 patients, pelvic lymphadenectomy were positive, nevertheless 71 patients underwent a neobladder replacement (50 N1 and 21 N2). The distribution of patients by clinical stage, according to the TNM 97 classification, was 4 T1, 14 T2, 32 T3 and 21 T4. No patient showed signs of metastasis on diagnosis., Results: Five-year disease specific survival rate of the entire group (71 patients) was 46%. With a mean follow-up of 8.3 years (3.2-20 years), 25 patients (35%) were alive and free of disease (72% with day continence), five patients were alive with recurrence (three bone metastasis, one chest metastasis and one with local recurrence), 41 patients died, (three non-cystectomy related). Of the 46 patients who recurred, a total of eight patients had local recurrence. For five patients, a severe dysfunction of the plasty appeared: two needed definitive bladder drainage until they died, one patient became totally incontinent, one patient needed a conversion of the plasty to Bricker ileal conduit. For the remaining patient the tumor involvement provoked recto-plasty-cutaneous fistula. All these five patients died in the 6 months after the plasty dysfunction appeared., Conclusions: Although prognosis in bladder cancer metastasis to the regional lymph nodes has been reported to be poor, this study demonstrates that after cystectomy, it is justified to propose a neobladder replacement to well selected patients. Local recurrence only occurred in 11% of patients and there was no damage to enteroplasty function for nearly half of the patients, and considering benefit to the quality of life, orthotopic bladder substitution should be considered as the preferential diversion in this patient population., (Copyright 2002 Elsevier Science B.V.)

Objectives: Cystectomy is the reference treatment for invasive bladder cancer and superficial tumours with a high risk of recurrence. However, the long-term results of this treatment remain controversial. Progress in anaesthesia-intensive care and surgical techniques appear to have improved the prognosis of this disease over the last two decades. The availability of numerous adjuvant therapies (radiotherapy and chemotherapy) and the development of alternative conservative management therefore require a re-evaluation of the long-term results of cystectomy for bladder cancer performed over the last 20 years., Material and Methods: The case files of 504 consecutive patients undergoing cystectomy for bladder cancer in our department from 1981 to 1997 were reviewed. The operative and postoperative morbidity and actuarial survival by stage were studied. Histological prognostic factors and the influence of adjuvant therapies were also studied., Results: According to the TNM 97 classification, 55% of tumours (on the cystectomy specimen) were intravesical (< T3), and 70% of patients had negative lymph nodes (N0). The perioperative mortality was 1.56%. The overall survival at 2 years, 5 years and 10 years for the total patient population was 83.1%, 52.3% and 46.6%, respectively. The 5-year survival of tumours confined to the bladder (< T3) was 79.4% versus 27.5% when the tumour extended beyond the bladder (> T3). The lymph node status considerably influenced survival. N0, N1 and N2-3 patients had 5-year survival rates of 64%, 48% and 14%, respectively. Neoadjuvant chemotherapy or radiotherapy did not appear to improve survival., Conclusions: Survival after cystectomy for bladder cancer essentially depends on pathological stage and lymph node status. Patients with a localized tumour have a 5-year survival greater than 80%. Prospective studies are required to determine the real benefit of adjuvant chemotherapy, as its value has not yet been formally demonstrated.

Purpose: Proliferation rate is an important determinant of bladder tumor progression. However, this factor has not yet been correlated to bacillus Calmette-Guérin (BCG) therapy response in a selected high-risk population of patients with stage T1 grade G3 bladder cancer. To assess the predictive value of the proliferation rate, an immunoreactivity test with monoclonal antibodies MIB-1 was carried out. The aim of this study was to evaluate the prognostic value of an MIB-1 labeling index by selecting a group of responsive patients prior to intravesical therapy., Materials and Methods: After complete transurethral resection, 35 patients with T1G3 bladder carcinoma received 6 weekly installations of BCG (intravesical Pasteur strain: 75 mg in 50 ml course of BCG therapy). After treatment a cystoscopy and randomized biopsies of the bladder mucosa were carried out and all recurrences were systematically resected. All tissue samples were fixed in Bouin's solution, embedded in paraffin and stained with hematoxylin-eosin-safran. Pathologists had sufficient material to perform immunomarking in 25 patients using peroxidase-antiperoxidase (PAP) technique, with antiprotein monoclonal antibody MIB-1 (Immunotech, Marseilles, France) to study MIB-1 expression before BCG therapy. Consensus was obtained from three independent pathologists for all sections. The results were expressed in a percentage of marked nuclei. Ten percent increment thresholds were established from 10 to 60%. Contingency tables were established, chi2 (p1) and Fisher exact test (p2) were performed for each threshold of 10%., Results: Median follow-up was 57.3 months (range 25-144). Of the 25 patients, 8 (32%) did not respond to BCG therapy, 17 (68%) responded positively. With a 20% threshold, there was a statistical difference (p1 = 0.03, p2 = 0.04) between responder (R) and nonresponder (NR) patients. All the 7 patients with less than 20% of nuclear activity positively responded to BCG. At this threshold level, sensitivity was high but specificity low (positive predictive value = 0.44). If we consider other reactivity thresholds there were no statistical differences between R and NR patients (10%) threshold p1 = 0.13, p2 = 0.19; 30% p1 and p2 = 0.20; 40% p1 = 0.82, p2 = 0.61; 50% p1 = 0.57, p2 = 0.55)., Conclusion: Our study indicates that the proliferation rate, assessed by MIB-1 immunoreactivity in Bouin's solution-fixed primary tissue, could be a useful predictive marker of outcome in T1G3 bladder carcinoma. With a 20% reactivity cut-off, a negative MIB-1 immunomarking appears to predict a positive response to BCG instillations. However, on the other hand, MIB-1 is of limited clinical use because the low specificity of this test cannot predict failure and then select candidates for cystectomies.

Purpose: Bacillus Calmette-Guerin (BCG) therapy is considered to be an effective prophylactic and therapeutic agent for high risk superficial transitional cell carcinoma of the bladder. Nevertheless, in a select uncommon population of stage Ta grade 3 superficial lamina-free tumors the results of this treatment have not yet been well established. We evaluated recurrence and progression rates, and the success of BCG therapy in a population with stage Ta grade 3 transitional cell carcinoma of the bladder., Materials and Methods: Of the 605 patients treated at our institution from 1982 to 1996 for the histopathological diagnosis of primary bladder cancer 32 (5.3%) with stage Ta grade 3 noninvasive primary bladder tumor were treated with intravesical instillations of 75 mg. Pasteur strain BCG in 50 ml. saline weekly for 6 weeks. At a followup of 2 to 13 years (mean 58.4 months) patients were evaluated with urinary cytology, cystoscopy, transurethral resection and random mucosal biopsies. Recurrence, grade and stage progression, death and causality were analyzed., Results: Of the 32 patients 9 (28%) responded positively to BCG without recurrence, while disease recurred as stage Ta in 8 (25%) and T1 in 7 (22%), and progressed to muscle layer infiltration in 8 (25%). Four patients (12%) died of bladder cancer. The number of tumors at primary resection, gross examination, the mitotic index or an association with carcinoma in situ did not appear to be predictive factors of progression to muscle invasion. Urine cytology (I to II versus III to IV) appeared to correlate highly with progression and BCG response (p<0.001) with excellent sensitivity (1) but low specificity (0.67)., Conclusions: Our study demonstrates the high progression potential of stage Ta grade 3 tumors, since nearly 50% recurred and 25% progressed to invasive disease. These results may be closely compared with the results of previous trials of stage T1 grade 3 disease. We suggest that recurrence should be detected at an early stage using long-term followup with strict observance of the surveillance protocols during a minimum 5-year tumor-free period.

The role of radical cystectomy as the standard treatment of localised infiltrating bladder malignancy is challenged by the development radiotherapy and chemotherapy combinations. The published studies are difficult to compare because of large differences in the patients selection criteria and in the assessment of local involvement (only clinical in combined treatment, based on pathology and therefore unquestionable in surgical series). The advantages of radical surgery are its precedence and a well-established technique, simplified follow-up procedures and seemingly higher survival rates acquired after 3 years. Conversely, the combination of radiotherapy and chemotherapy allows bladder preservation in about 40% of the patients (at 5 years), but only in 23% without bladder relapses. A complete initial endoscopic resection is the best and only prognostic factor of these results which nevertheless needs a very carefully and endless follows. The comparison of the quality of life achieved by both treatment modalities remains insufficiently documented.

Purpose: The aim of this study was to determine if p53 status, assessed before intravesical bacillus Calmette-Guerin (BCG) therapy, can predict clinical outcome in a high risk population of patients with stage T1, grade G3 bladder cancer and if it can be used to select patients responsive to therapy., Material and Methods: After complete transurethral resection 35 patients with T1G3 bladder carcinoma received 6 weekly instillations of BCG and nonresponsive patients received a second course. After treatment cystoscopy and randomized biopsies of the bladder mucosa were performed. Pathologists had sufficient material to perform immunomarking in 25 cases using the peroxidase-antiperoxidase technique with antiprotein monoclonal antibody p53. The results were expressed in percentage of marked nuclei. We established 5% increment thresholds from 0 to 60%. Contingent tables were established, and chi-square and Fisher's exact test were performed for each 5% threshold., Results: Median followup was 51.3 months (range 25 to 144). Of the 25 patients 8 (32%) did not respond to BCG therapy and 17 (68%) did. Immunomarkings were not statistically different between BCG responsive and nonresponsive patients for 0, 5, 10, 20, 35, 40, 45, 55 and 65 thresholds. Chi-square and Fisher's exact test were 0.91 and 0.83, 0.40 and 0.20, 0.58 and 0.29, 0.96 and 0.81, 0.80 and 0.88, 0.67 and 0.73, 0.91 and 0.83, 0.80 and 0.38, 0.69 and 0.32, respectively., Conclusions: Our results indicate that the percentage of p53 immunomarked cell cannot currently be used to predict clinical response to BCG therapy and, therefore, p53 over expression is not a viable indicator of T1G3 recurrence when using this treatment.

Objective: The management of the male urethra after cystectomy for bladder cancer continues to be a dilemma. Patients who undergo a cystectomy require either urinary diversion or bladder substitution. Therefore, the use of the urethra to ensure voiding is important. On the other hand, the probable risk of urethral carcinoma recurrence is generally estimated at approximately 10%. The aim of this study was to assess the predictive value of preoperative urethral biopsies, and of frozen sections during cystoprostatectomy, in patients with invasive bladder cancer., Methods: From 1982 to 1986, 118 male patients underwent a cystoprostatectomy for transitional cell carcinoma of the bladder. All patients underwent endoscopic latero-montanal biopsies 2 weeks preoperatively and urethral frozen cut section during radical prostatocystectomy., Results: Carcinoma was observed in 12 patients on both examinations. All patients underwent en bloc urethrectomy during cystectomy. In the remaining 106 patients, the frozen cut margin was negative (including 9 with positive latero-montanal biopsies), and these patients had the urethra preserved. After a 10-year minimum follow-up, no recurrence was observed in these patients with negative frozen cut-section. No significant risk factors for urethral recurrence were found. Latero-montanal biopsies did not reveal a positive specificity, and this procedure was later abandoned in our institution (in 1986)., Conclusions: The urethral frozen section was the only guideline used for simultaneously performing the urethrectomy. All male patients with negative frozen cut sections should be considered candidates for bladder substitution. A prophylactic urethrectomy is only indicated in patients with carcinoma (minimum carcinoma in situ) in the frozen urethral margin section during cystectomy.

The aim of this retrospective study was to evaluate the effects and results of low-dose bacillus Calmette-Guérin (BCG) therapy on a selective high-risk population of stage T1, grade 3 (G3) bladder tumours. Recurrence and progression were also analysed. Thirty-five consecutive patients presenting with T1 G3 tumours were treated with intravesical BCG. All patients underwent complete transurethral tumour resection. A course of BCG 75 mg Pasteur strain was begun 4 weeks after the first resection of the diagnosed tumour and continued for a 6-week period. At the end of treatment, a complete urological evaluation was routinely carried out: urine cytology test, cystoscopy with bladder biopsies randomly performed, and any recurrences were resected. In cases of abnormal cytology and/or recurrence an additional course of BCG was initiated, followed by the same tests. Follow-up examination and cystoscopy or fibroscopy were conducted every 3 months for 1 year, semiannually and annually thereafter. Median follow-up was 45 months (range 10-120); 7 patients (20%) did not respond to BCG instillations. Of these patients, 5 underwent cystectomy and in 2 patients the bladder was left in place in spite of recurrence because of age (+80 years). Twenty-eight patients (80%) responded positively, 24 after one single course of BCG, and 4 patients after two courses. During follow-up, recurrence was observed in 8 cases: stage T1 G3 in 4 patients, T1 CIS (carcinoma in situ) in 2 patients, Ta G2 and Ta G1 in 2 patients. Three of these patients were treated by cystectomy and the remaining patients with transurethral resection alone or combined with additional courses of BCG. Overall, 25 patients (71%) were considered free of tumour occurrence after low-dose BCG therapy. Ten patients underwent cystectomy (29%) or remained in occurrence and 2 patients died of the disease. These results can be closely compared to the results of other trials conducted on stage T1 G3 and BCG treatment, using a different dosage and BCG protocol therapy. BCG is an effective prophylactic and therapeutic agent for T1 G3 carcinoma of the bladder responders. The identification of these responders before beginning instillations still remains a challenge.

Between January 1987 and January 1991, 110 detubularized U-shaped ileocystoplasties (Camey II) following radical cystectomy were carried out in our Department of Urology (CMC Foch Suresnes, France). Our first evaluation of this procedure was carried out in 1989 and reviewed initial 57 patients operated on. These data were compared with those of the Camey I operation. The improvement in neobladder capacity as well as nighttime urinary control achieved by the detubularization required in the Camey II operation was obvious. In this article we review the first 110 patients treated by Camey II bladder replacement following cystectomy.

Forty eight patients with T1 G3 bladder cancer were treated between 1975 and 1991. An associated carcinoma in situ in one third of cases. Twenty six patients received intravesical BCG instillations (an average of 2.5 courses of 6 instillations) with no local recurrence or metastases in 50% of cases (mean follow-up: 54 months). Thirteen patients developed recurrence after a mean disease-free interval of 8 months (range: 3 to 18 months: 7 with disease progression, 5 at an identical stage and 1 Ta. Six cystectomies were performed in this group over the following two years: 3 patients were cured with a mean follow-up of 33 months, 2 died from their cancer, 1 patient is alive with an urethral redux. In view of age and/or clinical context, 7 patients were treated by repeated resections and other local treatments: 3 relapsed without progression, 2 died from their cancer and 2 have been lost to follow-up. Twenty one cystectomies were performed as first-line treatment: 20 patients are recurrence-free with a mean follow-up of 47 months and one patient died from cancer within 6 months. T1 G3 bladder cancer should be considered to be a lesion with a poor prognosis, requiring active treatment. First-line BCG therapy is effective in 50% of cases, but cystectomy is required in the absence of response to BCG.

After the completion of the radical cystoprostatectomy and a thorough survey of the dissected pelvis, a small bowel segment 50 to 60 cm long is resected, 20 cm proximal to Bauhin's valve. The small bowel resected is left as it is and as we find it, without rotation folding or twist, forming a Z. It is incised at its antimesenteric border and then the ileal plate is formed with running 3/0 vicryl sutures. The urethra is anastomosed in the lower part of the pouch and there after each ureter is implanted directly in a very simple way. The ureteral catheters are brought directly through the anterior abdominal wall lateral to the rextus muscle. When the omentum is large enough and covers all the dissected pelvis, drainage of the operative site will not be necessary.

Chemotherapy of bladder cancer is based on the methotrexate-vinblastine-cysplatinum (M-VAC) protocole. The neo-adjuvant therapy sterilizes 20% of the bladders, but the criteria of effectiveness are not precise enough to recognize the patients. Surgical indications have not been modified by this chemotherapy. The effectiveness of adjuvant chemotherapy has not yet been firmly established; it seems therefore reasonable to reserve it for cancers with poor prognosis. Intravesical chemotherapy has been abandoned to be replaced by BCG.

Small tumors of the mobile portion of the bladder may be treated by means of interstitial irradiation by iridium-192 wiring. Twenty-six tumors (mostly T1, but also T2 and T3) were treated by this procedure. Good results are attained in 89 per cent of 19 cases followed over three years. This method has the benefit of avoiding irradiation to the surgeon's hands, and of delivering to a specific site a dose of 6,000 rads. No bladder contraction was observed.

Small tumors of the mobile portion of the bladder may be treated by means of interstitial irradiation by iridium-192 wiring. Forty-four tumors (mostly T1, but also T2 and T3) were treated by this procedure and followed over five years. Good results are attained in 66 per cent of the cases. This method has the benefit of avoiding irradiation to the surgeon's hands, and of delivering to a specific site a dose of 6,000 rads. No bladder contraction was observed. Supplementary treatment by irradiation has to be considered in view of frequent recurrences of malignant bladder tumors after transurethral resection of partial cystectomy. In small cancers slightly infiltrating the bladder wall, many attempts have been made to replace tele-irradiation by interstitial irradiation. The latter delivers specifically high rad dosage to the involved area. Radium needles has been used in France by Darget before 1951 but evaluation of accurate dosage proved difficult. This material was dangerous to the surgeon's hands, and the procedure lead frequently to bladder sclerosis. This technique is currently used by Van der Werf-Messing in Rotterdam. She strongly advises preoperative tele-irradiation (3 X: 350 rads) to prevent tumor implants in the scar. An intravesical balloon filled with fluid radioisotope of gold-198 or cobalt-60 has been used for diffuse malignant papillary epithelioma. It was discontinued because of radiation cystitis and subsequent contraction of the bladder. Recently in well-limited tumors, Bloom and Wallace have used Tantalum-182 needles which have interesting physical properties (high energy and short half-life period) (2).