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Advancements in the diagnosis and treatment of prostate cancer (PC) have rapidly progressed through the past years. Various factors should be taken into account while treating individual patients to ensure optimal and careful decision making. The purpose of this consensus review is to summarize the current practice patterns when managing patients with advanced prostate cancer (APC) as there is still a lack of or very limited evidence on its clinical management in some areas. Pre-defined questions were shared with experts prior to the consensus session that took place in Cairo, Egypt in April 2019 during the 8th International gastrointestinal, liver and uro-oncology conference (IGILUC). Voting was based mainly on the expert opinions of the panel after a thorough discussion and review of available evidence from guidelines or best evidence available concerning the topic at hand. A strong consensus or unanimity was reached on 47% of the proposed questions. Notably, the panelists reached consensus on several topics based on high-level expert opinion. These findings contribute in several ways to our understanding of the management of PC and provide a basis for future recommendations. There was also a lack of consensus on other several topics, which suggests the need for further supporting data addressing these knowledge gaps. This review offers a thorough understanding of APC practice and offers insight on the various opinions shared amongst experts in the field that can serve as guidance regionally and deepens our understanding of disease management globally.

Introduction Women have been less represented in every NSTEMI clinical trial. Moreover, it has been observed that this group of patients have usually received less revascularization and evidence based treatment, therefore presenting with a greater long and short-term mortality. Purpose The purpose of our study is to analyze the presence of differences in baseline characteristics, management and outcome of women with NSTEMI during the last decade. Methods and results Retrospective study including 861 women admitted for NSTEMI between 2003 and 2015 in our center. We divided 2 groups according to hospitalization period (2003–2008 and 2009–2015) with a medium follow up of 4.5±2.9 years. Baseline characteristics and treatment at discharge are described on table 1. We noticed a greater use of statins and ACEI/ARB on the second period as well as a greater percentage of patients receiving early revascularization. It is remarkable on women a non-significant reduction of heart failure hospitalization at follow up (6.8% vs 4.5%; p=0.091), neither differences on 30-day mortality (1.3% vs 0,4%) or 1-year mortality (7.1% vs 5.8%). However, long-term mortality for the second group is reduced (HR 0.69; CI 95% 0.52–0.89), even after performing a multivariate analysis (HR 0.64; CI 95% 0.48–0.85). Characteristic Population (n=861) 2003–2008 (n=395) 2009–2015 (n=466) p-value Age (years) 73±12 73±12 72±12 0.316 Hypertension 629 (73.1%) 285 (72.2%) 344 (73.8%) 0.318 Hypercholesterolemia 414 (48.1%) 190 (48.1%) 224 (48.1%) 0.523 Killip class 0.292 I 664 (77.1%) 299 (75.7%) 365 (78.3%) II 143 (16.6%) 74 (18.7%) 69 (14.8%) III 47 (5.5%) 20 (5.1%) 27 (5.8%) IV 4 (0.5%) 2 (0.5%) 2 (0.4) GRACE score 129±32 130±37 128±33 0.897 Early PCI 249 (29.3%) 76 (19.2%) 173 (38.0%) Conclusions In recent years, early interventionist management and greater use of evidence-based therapies have been observed in women with NSTEMI. This has been associated with a lesser long-term mortality, although short-term events have remained the same.

Objective To assess changes in conditional disease-free survival (DFS) rates after radical prostatectomy (RP) and how the impact of well-known prognostic factors evolves over time. Materials and Methods There were 2813 patients treated with RP and postoperatively followed with clinical and prostate-specific antigen assessments. Estimation of conditional survival (CS) probabilities used the Kaplan-Meier method. Multivariable Cox regression model was used to calculate proportional hazard ratios for prediction of DFS after stratification by prognostics characteristics. Results The 5-year DFS rate was 71.2%. The DFS rate 5 years after RP increased to 77.4% (+8.7%), 82.1% (+15.3%), 88.0% (+23.6%), and 94.0% (+32.0%) for patients surviving without recurrence 1, 2, 3, and 4 years after RP, respectively. This represented a relatively stable survival gain per survived year ranging from 5.6% to 8.7%. The conditional 5-year DFS improves mainly for disease-free surviving patients with adverse pathologic factors. Among patients with pT3b-4 disease, the probability of surviving without recurrence to year 5 increased from 20.7% at the time of presentation to 78.9% for patients surviving 4 years without recurrence (+281%) as compared to +12.5% in pT2 disease. The impact of Gleason score and pT stage on CS estimates remained stable over time. Findings were confirmed upon multivariable analyses. Conclusion The period elapsed from RP is associated with DFS. The risk of recurrence decreases with increasing survivorship, mainly in patients with adverse pathologic factors. CS can provide relevant information for clinicians and patients giving an update of their risk of subsequent recurrence.

INTRODUCTION From 25% to 95% of those who have undergone radical prostatectomy (RP) report erectile dysfunction 12 months after surgery. We attempt a review of the available evidence regarding the anatomy of the cavernous nerves and the surgical refinements to enhance sexual function recovery after surgery. EVIDENCE ACQUISITION The PubMed/Medline database was searched. Duplicates were removed. Studies were selected by the authors according to the aim of the present review. EVIDENCE SYNTHESIS The cavernous nerves are deemed responsible for erections, but their exact function is still a matter of debate. They do not necessarily have the same distribution in all individuals: in most the cases, these nerves are located posterolaterally, however, it is not uncommon to find some fibers on the anterolateral aspects of the prostate, especially towards the apex. Several technical strategies were proposed in order to intraoperatively identify and spare the neurovascular bundles: despite all efforts, clinical results are still only partially satisfying. CONCLUSIONS The recovery of potency is one of the most unpredictable outcomes after RP. The advent of the robotic surgical system seems to have brought a trend towards a faster recovery of erectile function.

INTRODUCTION Prostate cancer (PCa) is the most common solid neoplasm and the second leading cause of cancer death in men. After the Partin tables were developed, a number of predictive and prognostic tools became available for risk stratification. These tools have allowed the urologist to better characterize this disease and lead to more confident treatment decisions for patients. The purpose of this study is to critically review the decision-making tools currently available to the urologist, from the moment when PCa is first diagnosed until patients experience metastatic progression and death. EVIDENCE ACQUISITION A systematic and critical analysis through Medline, EMBASE, Scopus and Web of Science databases was carried out in February 2016 as per the Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) statement. The search was conducted using the following key words: "prostate cancer," "prediction tools," "nomograms." EVIDENCE SYNTHESIS Seventy-two studies were identified in the literature search. We summarized the results into six sections: Tools for prediction of life expectancy (before treatment), Tools for prediction of pathological stage (before treatment), Tools for prediction of survival and cancer-specific mortality (before/after treatment), Tools for prediction of biochemical recurrence (before/after treatment), Tools for prediction of metastatic progression (after treatment) and in the last section biomarkers and genomics. CONCLUSIONS The management of PCa patients requires a tailored approach to deliver a truly personalized treatment. The currently available tools are of great help in helping the urologist in the decision-making process. These tests perform very well in high-grade and low-grade disease, while for intermediate-grade disease further research is needed. Newly discovered markers, genomic tests, and advances in imaging acquisition through mpMRI will help in instilling confidence that the appropriate treatments are being offered to patients with prostate cancer.

Aims To evaluate stress urinary incontinence (SUI), overactive bladder (OAB), and obstructive symptoms in patients with post-radical prostatectomy urinary incontinence (pRP-UI) treated with the bulbar compressive sling TOMS, and investigate the effect of each urinary symptom on urinary bother. Materials and Methods We prospectively followed 40 patients with pRP-UI before, and 6 and 12 months (T6 and T12, respectively) after implantation of the TOMS sling. Urinary symptoms were evaluated using the following questionnaires: USP, ICIQ, UCLA-PCI (urinary bother domain), PGI-I, and daily pad use. Success was defined as patients wearing no pads or using one security pad. Results Significant improvement of mean USP-SUI (6.97/9, 3.35, 3.02, P

Objectives To establish the rate of higher risk criteria in various definitions of an active surveillance population. Patients and Methods Over a period of 10 years, 1161 patients were diagnosed with prostate cancer and underwent radical prostatectomy at our institution. Statistical analysis was performed comparing the rates of upgrading, extracapsular extension, seminal vesical involvment and unfavourable disease (Gleason score upgrading >6 and/or T3 disease) for six groups of patients eligible for the University of Toronto, Royal Marsden, John Hopkins, University of California San Francisco, Memorial Sloan Kettering Cancer Center and Prospective Randomized International Active Surveillance. Results Active surveillance protocols including patients with biopsy Gleason score 3+4 (Royal Marsden) had significantly higher rates of extracapsular extension (P = 0.009), upgrading to pathological Gleason >3+4 (P = 0.004) and unfavourable disease (P = 0.001) compared to the most stringent John Hopkins criteria. Unfavourable disease was found in more than 40% of patients in all series with no significant difference between the Gleason 6 protocols. Biochemical recurrence-free survival at 5 and 10 years was 76.7% and 63.3% for the entire cohort. Positive margins (P < 0.001), pT3 tumours (P = 0.006) and unfavourable disease (P < 0.001) were significant predictors of biochemical recurrence. Conclusions Active surveillance in patients with Gleason 3+4 presents a risk of missing unfavourable disease and should be limited to older patients with comorbidities. The differences in inclusion criteria between Gleason 6 protocols did not have a significant impact on the pathological results.

Outcomes of continence, erectile function, and oncologic control are well-described in isolation especially for the retropubic open approach. However, only few series have yet reported combined results after radical prostatectomy. To determine the proportion of men who are continent, potent, and cancer-free (trifecta rate) 2 years after robot-assisted laparoscopic radical prostatectomy (RALRP).We included patients who underwent a RALRP at our department and who were followed during at least 2 years. Men who were impotent or incontinent before the surgery were excluded from the analysis. Overall, 500 men were included. All patients prospectively completed validated questionnaires (IIEF-5, ICS) before the medical visit and concerning their voiding and sexual disorders, preoperatively, 3, 6, 12, 18, and 24 months after RALRP. Biochemical recurrence was defined as any detectable serum PSA (≥ 0.2 ng/ml). The study end point was the trifecta rate (cancer control, continence, and potency) at 2 years of the surgery. Predictive factors of the trifecta outcome were assessed in univariate and multivariate analyses.Median age and PSA level were 62.2 years and 9.7 ng/mL. A trifecta outcome was achieved in 44% and 53% of men at 12 and 24 months, respectively. The 2-year trifecta rate reached 62% in men undergoing bilateral nerve-sparing surgery and 71% in men60 years. Age60 years, PSA level10 ng/ml, organ-confined disease, and bilateral nerve-sparing procedure were significantly associated with the 2-year trifecta outcome.Two years after RALRP, the trifecta outcome is achieved in 53% of preoperatively potent and continent men.

To report our surgical technique and outcomes after extraperitoneal robot-assisted laparoscopic radical prostatectomy (RALRP). At Henri Mondor’s Hospital, we performed the first RALRP in 2001 and started to perform routinely RALRP since 2006. Preoperative characteristics, perioperative parameters, functional and oncological outcomes were collected in a prospective database and studied. All parameters were tested in patients undergoing RALRP beyond the learning curve of each surgeon. The overall cohort included 792 patients. RALRP offers interesting results in terms of hospital stay, operative time, and blood loss. The overall rate of complications was low, especially concerning the rates of anastomosis’ complications. An extraprostatic extension was seen in 42.8 % of specimens. The overall rate of positive margins was 30.7 % of specimens. In our cohort, after a mean follow-up of 19 months, 8.7 % of PSA failure has been reported. The rate of continence was 77.4 % at 6 months and 96.8 % at 2 years. The rate of potency was 17 % at 3 months and 60.9 % at 2 years. The 2-year rate was 86.7 % in case of intrafascial dissection. A trifecta outcome was achieved in 44 and 53 % of men at 12 and 24 months, respectively. The extraperitoneal approach confers interesting results in terms of perioperative parameters as previously described in series using a transperitoneal approach. Functional outcomes in terms of continence and potency recovery after extraperitoneal seem equivalent to those reported after transperitoneal RALRP. Longer follow-up is warranted to confirm our favorable mid-term oncologic outcomes.

What's known on the subject? and What does the study add? Several criteria have been described to select patients with prostate cancer in active surveillance (AS) protocols; however, the risk of missing unfavourable disease remains. We report the risk of misclassification using the Prostate Cancer Research International: Active Surveillance (PRIAS) study in an analysis of pathological results after radical prostatectomy. We also define predictors of favourable disease that can be used to better select patients eligible for AS, as well as risk factors associated with disease progression. Objective To identify the risk of failure of active surveillance (AS) in men who had the Prostate Cancer Research International: Active Surveillance (PRIAS) criteria and had undergone radical prostatectomy (RP), by studying as primary endpoints the risk of unfavourable disease in RP specimens (stage >T2 and/or Gleason score >6) and of biochemical progression after RP. Patients and Methods We assessed 626 patients who had the PRIAS criteria for AS defined as T1c/T2, PSA level of ≤10 ng/mL, PSA density (PSAD) of T2) in 129 patients (20.6%), upgrading (Gleason score >6) in 281 (44.9%) and unfavourable disease in 312 patients (50%). There was a statistically non-significant trend for BFS at P = 0.06. Predictors of favourable tumours were age 12 (P = 0.005). Preoperative factors predicting disease progression were a PSAD of >0.15 ng/mL2 (P = 0.008) and biopsy core number of ≤12 (P = 0.017). Conclusions Even with stringent AS criteria, the rate of unfavourable disease remains high. Predictive factors of unfavourable disease and biochemical progression should be considered when including patients in AS protocols.

At the time of castration resistance, it is recommended to realize hormonal manipulations before chemotherapy. We evaluated the impact of a switch from GnRH agonist to antagonist in patients with castration-resistant prostate cancer on PSA and testosterone levels at 3 months.Retrospectively, 17 patients from 5 different centers undergoing androgen deprivation therapy and presenting rising PSA confirmed on 3 blood samples 2 weeks apart and despite a castrate testosterone level (0.5 ng/ml) were reviewed. Antiandrogen withdrawal syndrome had been tested before the switch. Degarelix was administered as followed: 240 mg for the first injection and then 80 mg every month, subcutaneously. We evaluated the PSA and testosterone level variation 3 months after the switch. Patients who experienced a variation in PSA of less than 10% compared to the baseline or who had a more than 10% PSA decrease were defined as responders.Mean PSA level at the switch was 34.3 ± 50.3 ng/ml, with a mean testosterone level of 0.21 ± 0.13 ng/ml. Three months after the switch, mean PSA level was 59.9 ± 81.6 ng/ml (P = 0.061), with a mean testosterone level of 0.19 ± 0.08 ng/ml (P = 0.086). At 3 months, 4 patients (23%) responded to therapy. Thirteen patients (77%) experienced a rise in PSA of more than 10% compared to baseline; 41% of patients decreased their testosterone level. The limitations of this study are its retrospective nature and the limited number of patients.Switch from an agonist to an antagonist of GnRH has a limited impact on PSA at 3 months in castration-resistant prostate cancer patients.

Study Type – Therapy (case series) Level of Evidence 4 OBJECTIVE • To assess the mid-term (3 years of follow-up) oncological control of laparoscopic radical cystectomy (LRC) for high-grade muscle-invasive bladder cancer in a well studied male population. PATIENTS AND METHODS • We assessed 40 men with bladder cancer (mean [range] age 66.5 [50–75] years) who underwent LRC and extended pelvic lymphadenectomy at our institution between April 2004 and September 2008. • Of the 40 patients, 13 (32.5%) had a complete laparoscopic procedure (ileal conduit: seven patients; neobladder: five patients; bilateral ureterostomy: one patient) and 27 (67.5%) had an LRC procedure only (ileal conduit: 15 patients; neobladder: 12 patients). RESULTS • No major complications were observed intraoperatively. • The mean operating time was 407 min and the mean blood loss was 720 mL. Four patients (10%) required conversion to open surgery. The mean (range) hospital stay was 10.2 (7–25) days. One patient died of myocardial infarction in the postoperative period. • Pathological analysis showed organ-confined tumours (stage pT0/pT1/pT2/pT3a) in 22 patients (55%) and extravesical disease (pT3/pT4) in 18 (45%). Of the 40 patients, six (15%) had lymph node involvement. The mean (range) number of nodes removed was 19.9 (5–40). • At a mean (range) follow-up period of 36 (0–72) months, 26 patients were alive with no evidence of disease (disease-free survival rate 67%). CONCLUSION • Laparoscopic radical cystectomy is a safe, feasible, and effective alternative to open radical cystectomy (ORC). The 3-year oncological efficacy was comparable with that of ORC.

We aimed to evaluate the impact of the primary Gleason pattern on biochemical recurrence-free survival (RFS) after radical prostatectomy (RP) in a single-center cohort of patients with Gleason 7 tumors.From 1998 to 2008, 2,239 consecutive patients underwent RP for a localized prostate cancer. A total of 1,248 patients with Gleason score (GS) 7 cancers were included. Follow-up was standardized for all patients and recorded into a prospective database. Median postoperative follow-up was 23.4 months. Biochemical recurrence was defined by prostate-specific antigen level0.2 ng/ml.In all, 721 patients (57.8%) had a final GS of 3 + 4 and 527 (42.2%) of 4 + 3. Patients with GS 4 + 3 had a significantly higher risk of biochemical progression than those with GS 3 + 4 (P0.001). The 3- and 5-year biochemical RFS for Gleason score 3 + 4 cancers was 84.6 and 76.4%, respectively, versus 69.9 and 61.1% in Gleason score 4 + 3 cancers. Multivariate analysis showed that the primary Gleason remained statistically predictive for PSA failure (P = 0.018). When analysis was stratified by both pathologic stage and margin status, predictive value of primary Gleason was significant in pT2R0, pT3-4R0, and pT3-4R1 cancers, whereas survival curves were not statistically different in pT2R1 cancers (P = 0.672).Primary Gleason 4 pattern is an independent predictor for PSA failure. Analysis of Gleason patterns provides clinically relevant prognostic information, which may assist in the management of patients with Gleason score 7 cancers.

Study Type – Therapy (case series) Level of Evidence 4 OBJECTIVE • To investigate the relationship between pretreatment testosterone levels and pathological specimen characteristics, by prospectively examining serum androgen concentrations in a well-studied cohort of patients who underwent radical prostatectomy (RP) for localized prostate cancer. PATIENTS AND METHODS • A total of 107 patients with clinically localized prostate cancer had an assay of total testosterone before laparoscopic RP at our institution. • The results were classified into two groups based on the total serum testosterone: group1, 7 and extraprostatic disease, pathological stage >pT2) in patients who underwent RP for localized prostate cancer.

The first objective of radical prostatectomy is cancer control. However, the success of RP should be also measured by the long-term morbidity outcomes and by the maintenance of quality of life. We performed a review of the literature for combined results of continence, erectile function, and cancer control after radical prostatectomy. Since 2003 and the first report of "trifecta," only 7 series have yet reported such combined results (trifecta rate range: 20%-76%). The preoperative risk (D'Amico) predicted for quality of life outcomes and biochemical recurrence is an aggregate endpoint, the trifecta.

Objectives To investigate the pathophysiology of postprostatectomy erectile dysfunction (pPED) in a rat model of bilateral cavernous nerve ablation (BCNA) and to assess the effects of local bone marrow mononuclear cell (BMMNC) injection on erectile dysfunction (ED) and cavernosal cellular abnormalities caused by BCNA. Design, setting, and participants This was an experimental study in Fisher rats with BCNA. Intervention Intervention included BNCA, electrical stimulation of the pelvic ganglion, and local BMMNC injection. Measurements Erectile responses to electric pelvic ganglion stimulation were studied. Cavernous tissue was examined to determine the cell types undergoing apoptosis and to detect changes in protein and gene expression of neuronal nitric oxide synthase (nNOS) and endothelial nitric oxide synthase (eNOS) using real-time quantitative polymerase chain reaction (RTQ-PCR) and Western blotting. The effects of local BMMNC injection on these parameters were studied. Results and limitations Diffuse apoptosis was noted in the connective tissue mesenchymal cells and vascular smooth muscle and endothelial cells. Compared with sham-operated controls, nNOS and eNOS levels were decreased after 3 wk and were normal (eNOS) or increased (nNOS) after 5 wk, suggesting spontaneous nerve regeneration. Despite nNOS recovery, erectile responses to electrical stimulation remained impaired after 5 wk, when mesenchymal cell apoptosis was the main persistent biologic abnormality. BMMNC injection decreased apoptotic cell numbers, accelerated the normalisation of nNOS and eNOS, and partially restored erectile responses at week 5. Conclusions Massive cell apoptosis may play a key role in the pathophysiology of pPED. In this animal model, apoptosis persisted despite spontaneous nerve regeneration, suggesting that the course of BCNA-induced cell dysfunction was independent of reinnervation. BMMNC improved erectile function by inhibiting apoptosis and may hold promise for repairing penile cell damage caused by radical prostatectomy (RP).

Occupational exposure to polycyclic aromatic hydrocarbons (PAH) is associated with an increased risk of urothelial carcinoma (UC). FGFR3 is found mutated in about 70% of Ta tumors, which represent the major group at diagnosis. The influence of PAH on FGFR3 mutations and whether it is related to the emergence or shaping of these mutations is not yet known. We investigated the influence of occupational PAH on the frequency and spectrum of FGFR3 mutations. We included on 170 primary urothelial tumors from five hospitals from France. Patients (median age, 64 yr) were interviewed to gather data on occupational exposure to PAH, revealing 104 non- and possibly PAH exposed patients, 66 probably and definitely exposed patients. Tumors were classified as follows: 75 pTa, 52 pT1, and 43 > or =pT2. Tumor grades were as follows: 6 low malignant potential neoplasms (LMPN) and 41 low-grade and 123 high-grade carcinomas. The SnaPshot method was used to screen for the following FGFR3 mutations: R248C, S249C, G372C, Y375C, A393E, K652E, K652Q, K652M, and K652T. Occupational PAH exposure was not associated with a particular stage or grade of tumors. Thirty-nine percent of the tumors harbored FGFR3 mutations. After adjustment for smoking, occupational exposure to PAH did not influence the frequency [OR, 1.10; 95% CI, 0.78-1.52], or spectrum of FGFR3 mutations. Occupational exposure to PAH influenced neither the frequency nor the spectrum of FGFR3 mutations and there was no direct relationship between these mutations and this occupational hazard.

Seeking insight into the possible role of estrogens in prostate cancer (PCa) evolution, we assayed serum E2, estrone (E1), and estrone sulfate (E1S) in 349 PCa and 100 benign prostatic hyperplasia (BPH) patients, and in 208 control subjects in the same age range (50-74 years). E1 (pmol/L+/-S.D.) and E1S (nmol/L+/-S.D.) in the PCa and BPH patients (respectively 126.1+/-66.1 and 2.82+/-1.78, and 127.8+/-56.4 and 2.78+/-2.12) were significantly higher than in the controls (113.8+/-47.6 and 2.11+/-0.96). E2 was not significantly different among the PCa, BPH, and control groups. These assays were also carried out in PCa patients after partition by prognosis (PSA, Gleason score (GS), histological stage, and surgical margins (SM)). Significantly higher E1S levels were found in PCa with: PSA10 ng/L (3.05+/-1.92) versus PSAor=10 ng/mL (2.60+/-1.55), stage pT3-T4 (2.99+/-1.80) versus pT2 (2.58+/-1.58), and positive (3.26+/-1.95) versus negative margins (2.52+/-1.48). E1 was higher in poor- than in better-prognosis PCa. E2 was significantly higher in PCa with GSor=4+3 (109.5+/-43.8) versus GSor=3+4 (100.6+/-36.5) and increased significantly when GS increased from 3+3 to 4+4. Estrogens, especially E1S appeared to be possible markers of PCa progression. Attempting to identify potential sources of E2 in PCa according to prognosis, as well as in BPH, we found a significant correlation coefficient between E1S and E2 (0.266-0.347) in poor-prognosis PCa and no correlation in BPH (0.026) and better-prognosis PCa (0.013-0.104). It is as though during progression of PCa from good to poor prognosis there were a shift in the E1 to E2 metabolic pathway from predominantly oxidative to predominantly reductive.

Resume But Evaluer le risque de diagnostiquer un cancer de la prostate sur des biopsies iteratives chez des patients ayant des valeurs de PSA fluctuantes, compare a des patients ayant des valeurs de PSA stables ou en augmentation reguliere. Materiel Etude retrospective menee sur les bases de donnees 2000 - 2003 de 2 CHU. Les patients selectionnes avaient eu une premiere biopsie prostatique negative, puis au minimum une nouvelle serie de biopsies prostatiques. Le PSA “en dents de scie” (DdS) etait definie par une valeur de PSA inferieure a la valeur du dosage precedent. Dans les autres cas, il s’agissait d’un PSA “en escalier” (ESC). Resultats Parmi les 191 patients inclus, 79 etaient dans le groupe DdS et 112 dans le groupe ESC. Un cancer de prostate a ete diagnostique chez 53 patients (27.7%), dont 39 lors de la deuxieme biopsie prostatique. Parmi les 79 patients du groupe DdS, un cancer a ete retrouve chez 17 (21.5%). Cette proportion n’etait pas significativement differente (p=0.14) de celle retrouvee chez les patients du groupe ESC, soit 36/112 (32.1%). Il n’y avait pas de difference significative quant a l’âge, le stade, le score de Gleason et le PSA initial entre les patients ayant eu le diagnostic de cancer dans les groupes DdS et ESC. Conclusion Dans notre etude, le risque de decouverte d’un cancer sur des biopsies prostatiques iteratives n’etait pas plus important chez les patients ayant un PSA en escalier par rapport aux patients ayant un PSA en dents de scie.

To prospectively evaluate the diagnostic yield of a 21-sample ultrasound-guided needle biopsy protocol as the initial diagnostic strategy for detection of prostate cancer.Between December 2001 and October 2005, 1000 consecutive patients underwent 21-sample needle biopsies under local anesthesia, comprising sextant biopsies, 3 additional posterolateral biopsies in each peripheral zone, 3 biopsies in each transition zone (TZ), and 3 biopsies in the midline peripheral zone. Each prostate core was numbered and analyzed separately. The patients were divided into subgroups according to the result of digital rectal examination (DRE), serum prostate-specific antigen (PSA), and prostate volume. We evaluated the cancer detection rate overall and in each subgroup. We compared the results of our biopsy protocol to those from 6-, 12-, and 18-core biopsy protocols by analyzing only those cores from our protocol that would correspond to these biopsy schemes.Cancer detection rates using 6 biopsy samples (sextant biopsies only), 12 samples (sextant plus lateral biopsies), 18 samples (sextant, lateral, and TZ biopsies), and 21 samples (sextant, lateral, TZ, plus midline biopsies) were 31.7%, 38.7%, 41.5%, and 42.5%, respectively. The 12-sample procedure improved the cancer detection rate by 22% compared with the 6-sample procedure (p=0.0001). The improvement in the diagnostic yield was most marked in patients with a prostate volumeor =55 ml (36.9%), in patients with normal DRE (26.6%), and in patients with PSA4 (37.5%). The addition of TZ biopsies to a 12-biopsy scheme increased the diagnostic yield by 7.2% overall (p=0.023). Only 10 of 425 (2.3%) patients were diagnosed on the sole basis of midline biopsies.Patients with suspected localized prostate cancer should be offered at least 12 biopsies in the peripheral zone and far lateral peripheral zone (statistically significant). TZ biopsies have to be considered, because these biopsies improve the diagnostic yield. For patients with abnormal DRE and/or PSAor =20 ng/ml, the 6-biopsy scheme seems sufficient (statistically), but 6 far lateral peripheral zone biopsies as well as the TZ biopsies add little incremental value (not significant). Evidence does not support the use of routine midline peripheral zone needle biopsies in the initial biopsy to enhance the detection of prostate cancer.

To analyse through a large multicentre series, morbidity of nephron-sparing surgery (NSS) in relation to tumour size and surgical indication.The study included patients from eight international academic centres. Age, sex, TNM stage, tumour size, Fuhrman grade, Eastern Cooperative Oncology Group performance status (ECOG-PS), surgical margins, local and distant recurrences, and overall and cancer-specific survival rates were collected and analysed. Indication for elective or mandatory NSS, medical and surgical complication rates, mean blood loss, blood transfusion, and length of hospital stay were specifically recorded for the purpose of this study. Groups were compared for qualitative and quantitative variables by using chi(2) (Fischer exact test) and Student t tests, respectively.A total of 1048 NSS procedures were included in this study. Mean tumour size was 3.4+/-2.1cm. In 730 elective procedures mean operative time (p=0.002), mean blood loss (p=0.01), the need for blood transfusion (p=0.001), and urinary fistula rate (p=0.01) were significantly increased for tumours4 cm. However, these differences did not result in significantly increased medical (p=0.4), surgical complication rates (p=0.6), or length of hospital stay (p=0.9). Finally, in elective procedures for malignant tumours, positive surgical margins, local or distant recurrence rates, and cancer-specific survival were not significantly different in tumoursor =4 cm and4 cm.Excellent cancer control and outcomes can be achieved with NSS in carefully selected patients with tumours4 cm. Expanding the size indication of elective NSS results in an increased but acceptable morbidity.

We investigated a new method of muscle precursor cell transfer in the urethra for the treatment of urinary incontinence, consisting of implanting myofibers with their satellite cells.In preliminary experiments to test the regenerative capacities of satellite cells histological analysis was performed on days 7 and 30 after the implantation of myofiber cores in the urethra of 6 female pigs. In the main experiments 11 pigs underwent baseline urodynamics, followed by endoscopic destruction of the striated urethral sphincter located around the distal urethra (day 0). On day 30 circular myofiber strips in 7 experimental cases and adipocytes in 4 controls were implanted in the proximal urethra. Seven days later (day 37) 1 case was sacrificed to verify satellite cell activation. On day 60 urodynamics were performed without and with curarization. Urethral cryosections were immunostained for desmin (activated satellite cells), fast myosin heavy chain/bungarotoxin (myotubes/acetylcholine receptors), neurofilament/vesicular acetylcholine transporter (nerve endings) and CD45/CD68 (inflammatory response).Preliminary histological studies revealed a myogenic process consisting of myofiber degeneration and satellite cell activation (day 7), followed by myotube formation replacing parental myofibers (day 30). In the main experiments endoscopic injury abolished striated urethral sphincter activity. Implantation of myofiber strips generated a pressure peak that decreased after curarization (mean+/-SEM 71.5+/-17.8 vs 33.5+/-14.8 cm H2O, p=0.031) and reappeared 60 minutes later, revealing that this action was tonic and under neural control. Nerve endings connected to the acetylcholine receptors of myotubes were observed on day 60. An inflammatory response was observed only on day 7 in the myofiber implantation group. Adipocyte implantation resulted in no significant intraurethral pressure changes.Urethral implantation of myofibers regenerates as myotubes that exert tonic activity under neural control. This has potential clinical value as a means to create an additional striated urethral sphincter.

Resume Introduction Le Plan Cancer souligne l’importance de la prise en charge en hospitalisation a domicile (HAD). Depuis 5 ans, notre service a developpe ce mode d’hospitalisation pour les patients atteints de cancer urologique afin de realiser des chimiotherapies ou pour les patients en soins palliatifs. Le but de cette etude est d’etablir l’evolution du nombre de patients depuis 5 ans hospitalises en HAD et d’evaluer pour les patients hospitalises en 2005 leur satisfaction par un auto-questionnaire. Methodes Une etude retrospective a ete realisee afin de colliger les patients hospitalises entre 2001 et 2005 en HAD. Pour 58 patients hospitalises en 2005, un questionnaire de satisfaction a ete adresse visant a evaluer le degre de satisfaction, la prise en charge et la bonne coordination de tous les intervenants medicaux et paramedicaux et les avantages ressentis par les patients. Resultats Entre 2001 et 2005,178 patients ont ete hospitalises en HAD. La chimiotherapie representait 59% des hospitalisations et les traitements symptomatiques 41%. Dans 56% des cas, les patients etaient suivis pour cancer de la prostate. Parmi les 58 patients interroges, 44 questionnaires ont ete renvoyes (taux de reponse 76%): 43 patients sont globalement satisfaits de leur prise en charge (28 tres satisfaits, 13 satisfaits et 2 moyennement satisfaits) et recommanderaient l’HAD a un de leurs proches. Aucune difficulte n’a ete rapportee pour joindre l’infirmiere, l’oncologue ou l’urologue referent. Les avantages soulignes par les patients sont le maintien dans son environnement habituel (92%) qui permet la poursuite des activites quotidiennes (85%), la limitation des trajets en ambulance pour se rendre a l’hopital et l’attente dans les hopitaux (90%) ainsi que l’implication du medecin traitant, librement choisi par le malade, dans le suivi (62.5%); 98% des patients n’auraient pas souhaite etre pris en charge en hospitalisation traditionnelle pour le traitement recu. Conclusion L’HAD pour chimiotherapie ou soins palliatifs apparait comme une alternative efficace a l’hospitalisation “classique” necessitant une adequation de la relation ville-hopital.

Resume Objectifs Comparer les techniques de nephrectomie partielle (NP) par voie ouverte (NPO) et laparoscopique (NPL) au travers d’une serie multicentrique francaise. Materiel et methodes Les donnees correspondant a 741 NP (91 laparoscopies et 650 voies ouvertes) ont ete comparees, incluant les indications, les tailles des tumeurs, les donnees operatoires, les taux de complications et les durees d’hospitalisation. Resultats Les tumeurs etaient de plus petite taille dans le groupe NPL (2,7 vs 3,4 cm, p:0,001). Il y avait moins de tumeurs malignes dans le groupe NPL (71,1% vs 80% p: 0,05) et moins de NP de necessite (20,9% vs 31,4%, p: 0,04). Il y avait moins de tumeurs hilaires dans le groupe NPL que dans le groupe NPO (NPL: 4% vs NPO:14,8%, p: 0,03). Il a ete realise moins de clampage pediculaire dans le groupe NPL (33% vs 50,2%, p: 0,002) mais pour des durees significativement plus elevees (35 minutes vs 19 minutes, p: 0,0001). La duree operatoire moyenne etait plus elevee dans le groupe NPL (163 vs 150 minutes, p: 0,02). Les taux de complications chirurgicales (17,6% vs 14,3%), de transfusion (6,6% vs 10,5%) et les pertes sanguines moyennes (363 vs 434 ml) n’etaient pas significativement differents dans les 2 groupes. Il y a eu significativement plus de fistules uri-naires (12,1% vs 2,5%, p Conclusion II ressort de cette serie comparative refletant une experience initiale que la nephrectomie partielle laparoscopique a des resultats operatoires et peri-operatoires proches de ceux de la nephrectomie partielle ouverte. Cependant, les indications de la voie laparoscopique restent selectionnees, les durees de clampage pediculaire et les complications medicales sont superieures en chirurgie laparoscopique. L’experience et les progres techniques de la nephrectomie partielle laparoscopique devraient pouvoir rendre la technique operatoire comparable a celle de la chirurgie ouverte.

New treatments are currently under investigation for intrinsic sphincter insufficiency. However, animal models in which to study the resting urethral tone generated by the striated urethral sphincter are still lacking. We describe the striated urethral sphincter in the pig. We investigated its participation in resting urethral tone with the aim of developing new tools for evaluating therapies for sphincter insufficiency.A total of 15 female pigs were used in this study. Anatomy of the striated urethral sphincter was described via transpubic and endoscopic approaches. Participation of the striated urethral sphincter in resting urethral tone was assessed by analysis of urethral pressure profilometry (maximum urethral closure pressure, functional urethral length and area under the curve) before and after curare injection or by destruction of the striated urethral sphincter by endoscopic electrocautery. Serial urethral cross sections were immunostained for slow/fast myosin and digitalized for 3-dimensional reconstructions to determine striated urethral sphincter volume.The striated urethral sphincter was Omega-shaped and it encircled the distal third of the urethra. A mean peak intraurethral pressure +/- SEM of 58.9 +/- 13.4 cm H(2)O was noted in front of the striated urethral sphincter. Curare injection and endoscopic injury decreased maximum urethral closure pressure by 48.4% and 51.1%, functional urethral length by 10.3% and 15.3%, and area under the curve by 47% and 64%, respectively. The striated urethral sphincter consisted of 52% slow and 48% fast myofibers. Its mean volume was 0.87 cm.The striated urethral sphincter of the female pig shows the morphological and functional features of a tonic muscle. Methods of measuring resting urethral tone generated by the striated urethral sphincter represent original tools for evaluating therapies for intrinsic sphincter insufficiency.

Genetic and epigenetic alterations have been identified that lead to transcriptional deregulation in cancers. Genetic mechanisms may affect single genes or regions containing several neighboring genes, as has been shown for DNA copy number changes. It was recently reported that epigenetic suppression of gene expression can also extend to a whole region; this is known as long-range epigenetic silencing. Various techniques are available for identifying regional genetic alterations, but no large-scale analysis has yet been carried out to obtain an overview of regional epigenetic alterations. We carried out an exhaustive search for regions susceptible to such mechanisms using a combination of transcriptome correlation map analysis and array CGH data for a series of bladder carcinomas. We validated one candidate region experimentally, demonstrating histone methylation leading to the loss of expression of neighboring genes without DNA methylation.

Purpose: Abnormally high levels of epidermal growth factor receptor (EGFR) protein are associated with advanced tumor stage/grade. The objective of this study was to evaluate the effects of the specific EGFR tyrosine kinase inhibitor gefitinib on activation of the Akt and mitogen-activated protein kinase (MAPK) pathways in human urothelial cell carcinoma (UCC) cell lines and to identify potential markers of gefitinib responsiveness in biopsy samples of UCC. Experimental Design: Changes in markers of UCC growth and invasion after exposure to gefitinib were studied in six human UCC cell lines expressing various levels of EGFR. The findings were related to activation of Akt and MAPK. We studied the influence of gefitinib on intraepithelial expansion of the responsive 1207 cell line. EGFR, Akt, and MAPK activation was studied by Western blot analysis of a panel of 57 human UCC. Results: Gefitinib had a growth-inhibitory and anti-invasive effect in two of six UCC cell lines (i.e., 647V and 1207). Gefitinib was also able to block the expansion of 1207 at the expense of normal urothelial cells. These effects did not depend on the level of expression of EGFR but they were associated with the down-regulation of MAPK and Akt activity; in 1207 cells, gefitinib activity was associated with p27 up-regulation and p21 and matrix metalloproteinase-9 down-regulation. Similarly, the Akt and MAPK pathways were found to be strongly phosphorylated in association with EGFR activation in a subset of human UCC specimens. Conclusions: Activation of EGFR, Akt, and MAPK defines a subset of UCC which might provide information for the identification of gefitinib responders.

Purpose To analyze to what extent histologic subtype is of prognostic importance in renal cell carcinoma based on a large, international, multicenter experience. Patients and Methods Four thousand sixty-three patients from eight international centers were included in this retrospective study. Histologic subtype (1997 International Union Against Cancer [UICC] criteria of tumor response), age, sex, TNM stage, Fuhrman grade, tumor size, Eastern Cooperative Oncology Goup performance status (ECOG PS), and overall survival were determined in all cases. The prognostic values of clear cell, papillary, and chromophobe histologic features were assessed by uni- and multivariate analysis using the Kaplan-Meier method and Cox model, respectively. Results Clear cell, papillary, and chromophobe carcinomas accounted for 3,564 (87.7%), 396 (9.7%) and 103 (2.5%) cases, respectively. In univariate analysis, a trend toward a better survival was observed when clear cell, papillary, and chromophobe histologies were considered prognostic categories (log-rank P = .0007). However, in multivariate analysis, TNM stage, Fuhrman grade and ECOG PS, but not histology, were retained as independent prognostic variables (P < .001). Conclusion The stratification in three main renal cell carcinoma histologic subtypes as defined by the 1997 UICC–American Joint Committee on Cancer consensus should not be considered a major prognostic variable comparable to TNM stage, Fuhrman grade and ECOG PS.

Measuring health-related quality of life (QoL) after surgery is essential for decision making by patients, surgeons, and payers. The aim of this consensus conference was twofold. First, it was to determine for which diseases endoscopic surgery results in better postoperative QoL than open surgery. Second, it was to recommend QoL instruments for clinical research. An expert panel selected 12 conditions in which QoL and endoscopic surgery are important. For each condition, studies comparing endoscopic and open surgery in terms of QoL were identified. The expert panel reached consensus on the relative benefits of endoscopic surgery and recommended generic and disease-specific QoL instruments for use in clinical research. Randomized trials indicate that QoL improves earlier after endoscopic than open surgery for gastroesophageal reflux disease (GERD), cholecystolithiasis, colorectal cancer, inguinal hernia, obesity (gastric bypass), and uterine disorders that require hysterectomy. For spleen, prostate, malignant kidney, benign colorectal, and benign non-GERD esophageal diseases, evidence from nonrandomized trials supports the use of laparoscopic surgery. However, many studies failed to collect long-term results, used nonvalidated questionnaires, or measured QoL components only incompletely. The following QoL instruments can be recommended: for benign esophageal and gallbladder disease, the GIQLI or the QOLRAD together with SF-36 or the PGWB; for obesity surgery, the IWQOL-Lite with the SF-36; for colorectal cancer, the FACT-C or the EORTC QLQ-C30/CR38; for inguinal and renal surgery, the VAS for pain with the SF-36 (or the EORTC QLQ-C30 in case of malignancy); and after hysterectomy, the SF-36 together with an evaluation of urinary and sexual function. Laparoscopic surgery provides better postoperative QoL in many clinical situations. Researchers would improve the quality of future studies by using validated QoL instruments such as those recommended here.

Objective: To examine the kinetics of growth, differentiation and senescence of normal human urothelium in an organoid-like culture model. Materials and Methods: Micro-dissected normal human urothelium explants were grown on porous membranes pretreated with various matrix components. Between 5 and 30 days of culture, cell proliferation was assessed by BrdU incorporation. Differentiation was evaluated on the basis of cytokeratin (Ck) and uroplakin (UP) expression. Epidermal growth factor family mRNA expression was monitored during explant outgrowth. Senescence was assessed by measuring endogenous β-galactosidase activity and p16INK4a mRNA expression. Results: Collagen IV was the most efficient matrix component for urothelial cell expansion. BrdU incorporation by urothelial cells was 5% between 15 and 30 days, corresponding to steady-state urothelium in vivo. Heparin-binding EGF (HB-EGF), Amphiregulin (AR) and Transforming Growth Factor α (TGFα) expression correlated with increased cell proliferation. UPII expression was stable throughout culture. P16INK4a mRNA expression and β-galactosidase activity increased on day 25, giving signs of senescence. Conclusions: This model retains many characteristics of the urothelium in vivo. It can be used for pharmacological studies between 15 to 25 days and to study mechanisms such as wound healing, proliferation and senescence.

Objectives: To understand the clinical behavior of renal oncocytoma in a retrospective analysis of a European multicentric nephrectomies database. Methods: The records of 891 patients who underwent surgical resection of renal neoplasm were reviewed. Relevant clinical and pathological data for each patient were retrieved in a database. Results: Thirty-two (3.6%) cases of renal oncocytoma were identified. Twenty patients (62.5%) were asymptomatic. No case of lymphatic invasion or metastatic disease, nor any evidence of vascular or fat tissue invasion was found. Thirty-one cases (96%) exhibited low mitotic activity. In one case the presence of renal clear cell carcinoma (diameter: 1.5cm) was found. After a median follow-up of 42 months, 87.5% of patients were alive with no evidence of tumor, while 9.3% of patients had died for non-malignant causes. One patient had not treated the tumor surgically and was disease-free at a 27-month follow-up. Conclusions: Renal oncocytoma is a benign neoplasm, characterized by slow growth and excellent prognosis after surgery. Nephron sparing techniques may be adequate for tumor removal.

We evaluated the clinical significance of Th1(IL-2)/Th2(IL-10) urinary profiles during a weekly induction course lasting 6 weeks, followed by a weekly maintenance therapy schedule for 3 weeks. Urinary IL-2 and /IL-10 were measured by ELISA in 39 patients receiving BCG for superficial bladder cancer or carcinoma in situ. Measurements were made after each instillation of 81 mg of BCG Connaught (Immucyst) during the induction course and the 3-week maintenance therapy (given at 3, 6, 12, 18, 24, 30 and 36 months). Cytokine levels were correlated with the risk of recurrence, progression, leukocyturia and adverse events. Median follow-up was 35 months (range 7-72 months). Complete responses to BCG were obtained in 30 patients (77%); the remaining 9 patients relapsed (23%), and 4 of these patients progressed (10.2%). Failure to detect urinary IL-2 during BCG induction course and the first extended induction cycle (6+3 schedule) correlated with time to recurrence (p = 0.01) and progression (p = 0.01). During the extended induction cycle, the first instillation was associated with an IL-2 cytokine profile, whereas the second and third instillations were associated with a switch to an IL-10 cytokine profile. This switch was associated with leukocyturia (p = 0.0001) and adverse events (p = 0.03). The 6+3 schedule is associated with urinary IL-2 overproduction and improved recurrence- and progression-free survival. During the BCG extended induction cycle, the favorable IL-2 urinary cytokine pattern gradually switches to an IL-10 profile, suggesting that the schedule based on 3 weekly instillations may be unsuitable for some patients and that the dose and frequency of maintenance BCG instillations may be adapted to individual urinary cytokine levels.

Objective: To review prognostic factors identified in clinical trials for remission versus relapse after intravesical adjuvant Bacillus Calmette–Guerin (BCG) immunotherapy for superficial bladder cancer (Ta, T1, and carcinoma in situ). Materials and Methods: Information was retrieved by a MEDLINE search of the English literature. Indexing terms comprised bladder cancer, bladder neoplasm, BCG vaccine, superficial bladder cancer, immunotherapy, intravesical therapy, prognostic marker, and Bacillus Calmette–Guerin. Fifty clinical studies were assessed for the strength of their results on the therapeutic response to BCG instillation. Emphasis was placed on clinical trials that assessed tumor and/or host characteristics, immunological reactions, recurrence rates, progression rates and disease-specific survival after BCG. Results: The predictive value of host factors is extremely controversial, but marked adverse reactions to BCG instillation appear to be associated with a better tumor response. Traditional pathological tumor characteristics, molecular markers (p53) and immunological status (PPD skin test) do not appear to have prognostic value in this setting. There is increasing evidence that immunologic markers are predictive of the BCG response, but most of them have not yet been assessed in large prospective studies. Histologic/cytologic response criteria are the critical determinant of post-BCG outcome. Conclusions: After a quarter century of clinical research, no independent prognostic factor for the bladder tumor response to BCG has yet been identified. Sophisticated individual therapeutic approaches (SITA) appear to be the most promising. Nomograms based on host, tumor and immunological characteristics may help with clinical decision-making and with rationalized BCG schedule design.

To analyze the association between Gleason score, stage and status of surgical margins with tumor volume in prostate cancer progression after radical prostatectomy.200 consecutive radical prostatectomy specimens were analyzed. Preoperative clinical stage, PSA, results of prostate biopsies as well as pathological results were noted. A biochemical recurrence was defined as a single, postoperative detectable PSA level (0.2 ng/ml). Tumor volume was compared to postoperative staging, Gleason score, and surgical margin status to predict tumor progression. Univariate and multivariate analysis using stepwise logistic regression were used to identify parameters with additional prognostic value.Pathological results of the prostatectomy specimens showed 149 (74.5%) pT2a-b, 29 (14.5%) pT3a and 22 (11%) pT3b tumors. Tumor volume was 0.57 cc for pT2a, 1.2cc for pT2b, 1.7cc for pT3a and 2.9cc for pT3b, respectively (p0.05). Taken together, mean volume for pT2 and pT3 were 1.06 and 2.2 cc, respectively (p0.0001). Five-year progression-free actuarial survival was 69.7%. Using univariate analysis, tumor progression correlated with final Gleason score (p0.0007), positive surgical margins (p=0.02), tumor volume (p=0.009) and stage (p0.0001). In a multivariate analysis, tumor progression correlated only with the final Gleason score (p=0.04) and stage (p=0.0002).Gleason score and pathological stage are independent factors to predict prostate cancer progression after radical prostatectomy. When these parameters are known, tumor volume does not provide additional information.

Objective: To report a multicenter analysis after laparoscopic radical nephroureterectomy for pathologically confirmed upper tract transitional cell carcinoma. Materials and Methods: A total of 116 patients (72 males; mean age 68 years) underwent laparoscopic radical nephroureterectomy at five international institutions: 51 transperitoneally, 65 retroperitoneally. Location of the primary tumor was pelvicalyceal in 70 patients (60%), ureteral in 27 (23%), and multifocal in 19 (17%). In 18 patients (15%), transurethral resection was performed for concomitant bladder tumor. The median follow-up time was 25 months (range 3–93). A minimum follow-up of 1 and 2 years was available in 77 and 41 patients, respectively. Results: Five patients (4%) were converted to open surgery. The specimen was extracted intact in all 116 patients: using an Endocatch bag in 78 patients, a Lapsac in 5, and manually in 33. Pathologic staging was pTis in 5 (4%), pTa in 41 patients (35%), pT1 in 31 (26%), pT2 in 18 (15%), pT3 in 16 (13%), and pT4 in 5 (4%). Pathological grade was grade I in 26 patients (23%), grade II in 41 (35%), grade III in 34 (29%) and grade IV in 15 (12%). Histopathology revealed a positive surgical margin in five patients (4.5%): renal hilum (one), periureteral soft tissue (two), distal edge of the ureter/ bladder cuff (two). Local recurrence was noted in two patients (1.7%). Bladder recurrence was noted in 28 patients (24%) with a mean time to recurrence of 13.9±11.5 months. Distant metastases occurred in 11 patients (9%): lung (5), liver (3), bones (2), adrenal (1); mean time to metastasis was 13 months. Overall, 23 patients (20%) died. One-year and 2-year cancer-specific survival was 92% and 87%, respectively. Two-year cancer-specific survival according to pathologic stage was 89% for patients with pT1 disease, 86% for pT2, 77% for pT3, and 0% for pT4 ( p =0.0001). Two-year survival according to pathologic grade was 88% for grade I, 90% for grade II, 80% for grade III, and 90% for grade IV ( p >0.05). Conclusion: Laparoscopic radical nephroureterectomy appears to be an effective minimally invasive treatment for select patients with upper tract transitional cell carcinoma. Although the 2-year survival data reported herein are encouraging, longer follow-up is needed before laparoscopy can be considered as a standard treatment.

Due to the nephrotoxicity of cyclosporin A (CsA), its benefit on long-term graft survival remains controversial, especially in low-risk patients. Here we report the 12-year results of a calcineurin-inhibitor-free regimen. One hundred and seventeen low-risk kidney recipients were prospectively randomized to maintenance therapy with either a combination of azathioprine and prednisone (group NoCsA, n=58), or with cyclosporine, azathioprine, and prednisone (group CsA, n=59). Both groups received induction therapy with anti-lymphocyte globulins (ALG). Twelve-year patient survival was 75% and 82.5% in the CsA and NoCsA groups, respectively [ P= not significant (NS)]. Twelve-year graft survival was 59% and 56% ( P=NS) in the CsA and NoCsA groups, respectively (NS). Transplant rejection rates were similar in both groups. Mean serum creatinine levels after 10 years were 161 and 136 micromol/l in the CsA and NoCsA groups, respectively. Rejection-free patients of the CsA group had poorer renal function (168 micromol/l) than those of the NoCsA group (121 micromol/l; P=0.0060). We concluded that a 12-year graft survival of 56% and a graft half-life of 15 years can be achieved without the primary use of a calcineurin inhibitor in low-risk patients receiving ALG. Patients treated with CsA had poorer graft function at 12 years.

Purpose: Interleukin (IL)-2 and interferon-γ are released during T helper 1 lymphocyte responses, while IL-10 is released during T helper 2 responses. We evaluated the prognostic value of urinary IL-2, interferon-γ and IL-10 levels in patients with superficial bladder cancer treated with bacillus Calmette-Guerin (BCG) instillationMethods: Urinary IL-2, interferon-γ and IL-10 were measured by enzyme-linked immunosorbent assay in 37 patients receiving BCG for stages Ta/T1 superficial bladder cancer, and carcinoma in situ. Measurements were made after instillations 5 and 6 during a course of 6 weekly instillations of 150 mg. BCG, Pasteur strain. Correlations of cytokine levels with the clinical outcome were evaluated using the log rank testResults: Median followup was 29 months. Patients with urinary IL-2 less than 27 pg./μmol. creatinine were significantly more likely to have recurrences than those with higher values (log rank test p = 0.0009). Urinary IL-10 and interferon-γ levels had no apparent impact on...

Objectives. To study the influence of adverse reactions on adherence to an immunotherapy maintenance schedule and the recurrence rate of bladder cancer. Bacille Calmette-Guerin immunotherapy has documented efficacy in the management of high-risk superficial bladder cancer. However, the optimal duration of intravesical bacille Calmette-Guerin therapy and the risk/benefit ratio of maintenance therapy are controversial. Methods. From April 1996 to April 2000, 72 patients with superficial bladder cancer were treated with Immucyst (six consecutive weekly instillations of 81 mg) and then received maintenance therapy consisting of three consecutive weekly instillations 3, 6, 12, 18, 24, 30, and 36 months later. Adverse reactions, studied during 518 instillations, were classified in four categories using a scale based on the World Health Organization recommendations, and their impact on the adherence to therapy was analyzed. Results. After an average follow-up of 24 months, a durable disease-free response was observed in 84.9% of the patients; 12.5% of patients had a relapse and 2.6% had disease progression. The response rate was similar in patients with and without adverse reactions. Only 14 patients (19%) received all the scheduled maintenance instillations. The dose was reduced in 41 patients (57%), and treatment was stopped in 28 patients (39%). In multivariate analysis, an adverse event score of 1.5 or greater during induction therapy was significantly associated with cessation or modification of maintenance therapy ( P = 0.01). Conclusions. The scale developed in this study to monitor the adverse reactions to bacille Calmette-Guerin and their impact on the adherence to maintenance therapy may be helpful for tailoring maintenance regimens or implementing protective measures (dose reduction or treatment postponement).

BACKGROUND To determine the mechanism by which prostate volume increases during the development of BPH and to evaluate the effect of LSESr (Permixon®), a phytotherapeutic agent, we investigated apoptosis and cell proliferation in the stroma and epithelium of normal prostate and of BPH tissues from patients treated with or without LSESr. METHODS MIB-1 staining and the in situ end-labeling assay were used to evaluate the proliferative-apoptotic balance in normal prostates and in BPH tissues. Quantitative assessment was performed using an image analysis system. RESULTS In normal prostates, there was no significant difference between apoptotic and proliferative indices. Cell numbers and proliferative indices were higher in BPH than in normal prostates, while apoptosis values were similar. In the BPH treated group, LSESr significantly inhibited proliferation and induced cell death in both epithelium and stroma. CONCLUSIONS Induction of apoptosis and inhibition of cell proliferation are likely to be the basis for the clinical efficacy of LSESr. Prostate 45:259–266, 2000. © 2000 Wiley-Liss, Inc.

Retropubic and perineal radical prostatectomy are used for curative treatment of localized prostate cancer. More complex urological procedures are now being done with laparoscopy. We present our initial results of transperitoneal laparoscopic radical prostatectomy.Twenty laparoscopic radical prostatectomies were performed between May 1998 and May 1999. The mean age at the time of surgery was 64.2 years. There were 14 stage T1c, 5 stage T2a and 1 stage T2b tumors. The preoperative PSA was 9. 3 ng/ml (normal4 ng/ml). The Gleason score for positive specimens in 6 random echo-guided endorectal biopsies was 5.7. Four trocars were used. Insufflation pressure was 15 mmHg. The seminal vesicles were first dissected. The prostate was dissected free from the anterior face of the rectum to the prostate apex. Then the peritoneum was incised to find the apex of the prostate. The puboprostatic ligaments were isolated and cut, and the dorsal vein complex was ligated and cut to expose the urethra. The bladder neck was opened and dissected free from the prostate. The lateral pedicles were coagulated before sectioning the urethra. The radical prostatectomy specimen was left along the sigmoid colon, the bladder neck was reconstructed, and a urethrovesical anastomosis was performed with 6 interrupted sutures. The prostatectomy specimen was removed intact in a sack by enlarging the umbilical trocar port. All the prostatectomy specimens were processed according to the Standford protocol. Prostate weight, tumor weight, the Gleason score, and the tumor status of the capsule, seminal vesicles, lymph nodes and surgical margins were studied.The operating time was 385 min. Two patients were transfused. The mean hospital stay was 7. 8 days. The Foley catheter was removed 10.7 days after the operation. Specimen weight was 61 (28-126) g, the Gleason score was 5.9, and tumor volume was 1.4 ml. There were 18 stage pT2, 1 stage pTa (capsular effraction) and 1 stage pT3b (seminal vesicle invasion) tumors. There were four positive surgical margins (2 at the apex and 2 at the bladder neck). All the patients had a postoperative PSA level0.1 ng/ml at 1 month. The first patient had urethrovesical anastomotic leakage, and required Foley catheterization for 21 days. There was 1 colostomy for rectal injury and 1 urinoma because of urethrovesical anastomotic leakage that required an open surgical procedure. One month after surgery, 15 (75%) patients were fully continent. Six patients had erections, and 5 stated having sexual intercourse.These preliminary results show that radical prostatectomy can be performed laparoscopically. Laparoscopy offered excellent vision of all the anatomical structures of the pelvis, permitting precise dissection. Long-term follow-up and further studies are required to confirm and improve these results.

After initial regression in response to androgen deprivation, most prostate cancers develop resistance to endocrine therapy. Identification of cellular and molecular changes occurring during endocrine therapy-induced regression and subsequent hormone insensitivity may point to mechanisms underlying the transition to hormone-independent prostate cancer. A series of untreated (n = 24), regressed (n = 15), and endocrine therapy-resistant (n = 10) prostatic adenocarcinomas were analyzed using immunohistochemistry with regard to cytokeratin 5 and 18, androgen receptor (AR), and epidermal growth factor receptor (EGF-R) expression in tumor cells. Using semiquantitative reverse transcription-polymerase chain reaction, the amount of AR mRNA also was determined. In regressed and therapy-resistant prostate cancers, an increase in cytokeratin 5-positive tumor cells was noted when compared with untreated carcinomas. Similarly, the proportion of EGF-R-positive tumor cells increased in the treated cases, whereas the proportion of AR-positive tumor cells dropped in regressed carcinomas and increased in hormone-refractory cancers. In the latter group, an eightfold higher level of AR mRNA was observed when compared with the other cases. Changes in the proportion of cytokeratin 5 and EGF-R-positive tumor cells suggests that during androgen deprivation an enlarged subpopulation of tumor cells with combined features of basal and secretory phenotypes arises. The increased proportion of AR-positive tumor cells during the transition from the regression phase to the hormone escape phase points to an important role of AR overexpression in this process.

Local immunotherapy with bacillus Calmette-Guerin (BCG) can prevent recurrences and progression of superficial bladder cancer, but the antitumoral mechanism of BCG is still unclear. The first event seems to be binding of BCG to urothelial cells via fibronectin, and processing of mycobacterial antigens by antigen-presenting cells. Experimental data suggest that bacterial antigens can also be processed by urothelial cells. CD4 lymphocytes subsequently recognize antigenic peptides presented by HLA class II molecules. The most common profile of urinary cytokines is interleukin-2 and interferon-gamma, suggesting the predominant involvement of the Th1 lymphocyte subpopulation. Natural killer cells, lymphocyte-activated killer cells, BCG-activated killer cells and macrophages are able to kill bladder tumor cells in vitro, but there is no evidence that a major histocompatibility complex (MHC)-restricted specific T cytotoxic response is involved in BCG antitumor activity.

Purpose: Prostate specific antigen (PSA), prostatic acid phosphatase and alkaline phosphatase were analyzed in 2 large prospective multicenter and multinational trials to assess their correlation with time to progression and overall survival after hormonal therapy for metastatic carcinoma of the prostate.Materials and Methods: A total of 868 patients who underwent medical or surgical castration was randomized to receive an oral antiandrogen (nilutamide) or placebo. The serum markers under study were measured at baseline and at 1, 3, 6 and every 6 months thereafter.Results: At baseline the strongest predictive factor was serum alkaline phosphatase. Patients with an alkaline phosphatase of 2 or less times normal lived almost twice as long as those with a level of more than 2 times normal (p

The predictive value of the abnormality side during digital rectal examination (DRE) has never been studied, suggesting that physicians examined the left lobe of the gland as well as the right lobe. We aimed to assess the predictive value of the side of DRE abnormality for prostate cancer (PCa) detection and aggressiveness in right-handed urologists.An analysis of a prospective database was carried out that included all consecutive men undergoing prostate biopsies between 2001 and 2012. The main end point was the predictive value of the abnormality side during DRE for cancer detection in clinically suspicious unilateral T2 disease. The diagnostic performance of left- versus right-sided abnormality was also assessed in terms of sensitivity, specificity and negative/positive predictive values.Overall, 308 patients had a suspicious unilateral clinical disease (detection rate 57.5%). The cancer detection rate was significantly higher in case of left-sided compared with right-sided clinical T2 stage (odds ratio 2.1). In case of left-sided disease, the number of positive cores, the rate of perineural invasion, the rate of primary grade 4 pattern and the percentage of cancer involvement per core were significantly higher compared with those reported for right-sided disease. The predictive value of abnormality laterality for cancer detection and aggressiveness remained statistically independent in multivariate models. The positive predictive value for cancer detection was 64.6 in case of suspicious left-sided disease versus 46.9 in case of right-sided disease.The risks of detecting PCa and aggressive disease on biopsy are significantly higher when DRE reveals a suspicious left-sided clinical disease as compared with right-sided disease. Right-handed physicians should be aware of this variance in diagnostic performance and potential underdetection of left-sided clinical disease, and should improve their examination of the left lobe of the gland by conducting longer exams or changing the patient's position.