[Pronostic value of parenchyma renal invasion of pT3 upper tract urinary carcinoma]. / Impact pronostique de l'envahissement du parenchyme rénal dans la population des tumeurs de la voie excrétrice urinaire supérieure de stade pT3.

INTRODUCTION: Upper tract urinary carcinoma (UTUC) pT3 tumors are a heterogeneous entity including tumors invading the renal parenchyma, tumors with peripelvic fat invasion or peri-ureteral fat invasion. The aim of this study was to evaluate the prognostic significance of these three different groups of pT3 tumors. PATIENTS AND METHODS: Between 1998 and 2012, 205 patients with UTUC were operated in two centers, including 52 patients with pT3 tumor stage. pT3 tumors were divided into three groups: peri-ureteral fat invasion (pT3U, n = 16), peripelvic fat invasion (pT3G, n = 21), and renal parenchyma invasion (pT3P, n = 15). The prognostic significance of the type of tumor infiltration was evaluated on specific and disease-free survival. RESULTS: Median follow-up was 18.9 months [6-133.4]. In univariate analysis, renal parenchyma invasion was associated with a better prognostic in both specific (P = 0.026) and disease-free survival (P = 0.031) compared with peripelvic or peri-ureteral fat invasion. Mutivariate analysis retained the pT3 subgroup as an independant prognostic factor in both specific and disease-free survival (P = 0.02). CONCLUSION: pT3 tumors with renal parenchyma invasion had a better prognosis than those with peripelvic or peri-ureteral fat invasion. The heterogeneity of the pT3 group should be taken into account to improve the care of patients.

[Pronostic value of ureteral location of upper tract urinary carcinoma]. / Impact pronostique de la localisation urétérale dans les tumeurs de la voie excrétrice supérieure.

OBJECTIVES: The aim of this study was to evaluate the prognostic significance of the ureteral location of the upper tract urinary carcinoma (UTUC). PATIENTS AND METHODS: Between January 1998 and December 2007, 161 patients with UTUC were operated in our center. Tumors were located on renal pelvis in 51% of cases, on the ureter in 34% of cases and in both locations in 15% of cases. Nephroureterectomy was performed in 79.5% of cases (128/161) whereas a conservative treatment was performed in 20.5% of cases (33/161). RESULTS: In our series, 29.8% of patients had primary bladder cancer and 14.3% had synchronous bladder tumor. At a median follow-up of 42.5 months, 38.6% of patients developed bladder recurrence and 4.8% developed controlateral upper tract tumor. In multivariate analysis, ureteral location and existence of synchronous bladder tumor were independent prognostic factors of bladder recurrence (P=0.009 and P=0.025, respectively). Multivariate analysis retained T-stage and ureteral location as independent prognostic factors in both overall and disease-free survival (P=0.002 and P=0.0008 respectively for ureteral location). CONCLUSION: Ureteral location was an independent prognostic factor of bladder recurrence and was associated with a poorer prognosis.

Hedgehog pathway activation in human transitional cell carcinoma of the bladder.

BACKGROUND: The Hedgehog (Hh) signalling pathway functions as an organiser in embryonic development. Recent studies have shown constitutive activation of this pathway in various malignancies, but its role in bladder cancer remains poorly studied. METHODS: Expression levels of 31 genes and 9 microRNAs (miRNAs) involved in the Hh pathway were determined by quantitative real-time RT-PCR in 71 bladder tumour samples (21 muscle-invasive (MIBC) and 50 non-muscle-invasive (NMIBC) bladder cancers), as well as in 6 bladder cancer cell lines. RESULTS: The SHH ligand gene and Gli-inducible target genes (FOXM1, IGF2, OSF2, H19, and SPP1) were overexpressed in tumour samples as compared with normal bladder tissue. SHH overexpression was found in 96% of NMIBC and 52% of MIBC samples, as well as in two bladder cancer cell lines. Altered expression of miRNAs supported their oncogene or tumour-suppressor gene status. In univariate analysis, high expression levels of PTCH2, miRNA-92A, miRNA-19A, and miRNA-20A were associated with poorer overall survival in MIBC (P=0.02, P=0.012, P=0.047, and P=0.036, respectively). CONCLUSION: We observed constitutive activation of the Hh pathway in most NMIBC and about 50% of MIBC. We also found that some protein-coding genes and miRNAs involved in the Hh pathway may have prognostic value at the individual level.

[Diagnostic test for bladder cancer: the NMP22®]. / Actualités urologiques concernant les tests diagnostiques utilisés pour les tumeurs de vessie: le NMP22.

INTRODUCTION: Diagnosis and follow-up of bladder cancer is based on cytology and cystoscopic exams. Cytology is highly specific but remains with a highly variable sensitivity. Cystoscopy is an invasive exam and has shown specific limits. Urinary test, highly specific and highly sensitive, might be ideal to replace the couple cytology-cystoscopy. MATERIAL AND METHODS: Through a literature review, using MeSH system and Pubmed system (keywords: NMP22 and bladder cancer), authors pointed to the value of NMP22 to replace cystoscopy and cytology. RESULTS: Between 1996 and 2010, 193 publications were identified with these keywords. Seventeen original articles have been selected based on their quality and methodology. NMP22 was more sensitive than cytology for follow-up and screening of bladder cancer. As screening test, NMP22 has shown positive predictive value between 0 and 70%. As follow-up test, NMP22 has shown more stable positive predictive value close to 70%. Coupled to cytology, NMP22 has shown predictive positive value up to 90%. CONCLUSION: For screening test, NMP22 should be the referent test for best selection cases (tobacco, hematuria) and for systemic elimination of false positive cases (ureteral stent, lithiasis). For follow-up test, NMP22-cytology should be the new reference. Moreover, when NMP22 is positive with negative cystoscopy, follow-up may be carefully proposed (recurrence risk×10).

[Healing and targeted therapies: Management in perioperative period?]. / Cicatrisation et thérapies ciblées : quelles précautions en période périopératoire ?

INTRODUCTION: In the era of new-targeted therapies and neoadjuvant strategies, this article highlights the role of angiogenesis in the process of physiological wound healing with a review of literature about parietal complications under anti-angiogenic therapies. METHODS: Research on Medline was carried out using the terms renal cell carcinoma, angiogenesis, wound healing, targeted therapies, and complications. RESULTS: The frequency of these complications varies between 5 and 50% in recent series. These results depend on half-lives of each drug and perioperative management (before and after surgical procedure). CONCLUSION: In the absence of current recommendations, it is advised to stop bevacizumab at least five weeks before a surgical intervention and to take it back 4 weeks later. For the tyrosine kinase inhibitors, the treatment can be stopped 24-48 hours before the surgery and taken back 3-4 weeks later. Finally, for the mTOR inhibitors, it is advised to stop the treatment 7-10 days before and to take back it at least 3 weeks later.

[What's new in 2009 about urothelial tumors? Live from EAU, AUA and ASCO, ASCO-GU]. / Avancées et synthèse des derniers congrès: ASCO-GU, EAU, AUA, ASCO concernant la prise en charge médicale des cancers urothéliaux.

During the EAU and AUA congress in 2009, major work about the urothelial carcinoma was interested in the classification T1a / b and its therapeutic consequences, the last results of BCG therapy and photodynamic diagnosis. At ASCO congress, the main studies presented focused on the systemic treatment, in adjuvant situation, in first line treatment of metastatic bladder cancer, particularly with the addition of anti-angiogenic to chemotherapy, and in conservative treatment in association with radiotherapy.

[Checkup and management of upper urinary tract tumours in 2010: An update from the committee of cancer from the French National Association of Urology]. / Bilan et prise en charge d'une tumeur de la voie excrétrice urinaire supérieure en 2010 : mise au point du comité de cancérologie de l'Association francaise d'urologie.

Urothelial carcinoma of the upper urinary tract (UUT-UCC) are rare tumours and represent about 5 % of urothelial tumours. There is a history of bladder cancer in 30 % of patients with UUT-UCC but less than 2 % of patients with bladder cancer have a location in the upper urinary tract. The main prognostic factors are age, grade and tumour stage. A High-MSI status is predictive of improved survival, especially in patients under 70years with invasive tumour. During the preoperative assessment, improved staging of UUT-UCC is now essential. The couple urine cytology and uro-CT is an element of staging that underestimates or overestimates some UUT-UCC. The diagnostic ureteroscopy has become a fundamental step in the preoperative evaluation of the tumour. Ureteroscopy allows to explore visually at least 95 % of the upper urinary tract and to perform biopsies of the tumour that help to determine the grade cell. It can also detect a possible secondary location unnoticed with imaging. An exhaustive preoperative assessment, including a systematic diagnostic ureteroscopy, should allow to explore UUT-UCC in a better manner and to increase the number of potential candidates for conservative treatment. The treatment of choice is currently nephroureterectomy with open approach. Superficial and/or low-grade UUT-UCCs have favourable outcomes similar to noninvasive tumours of the bladder (80 % specific survival at five years). Their surgical management is gradually evolving towards the maximum preservation of the upper urinary tract and of the renal parenchyma. The good oncologic results obtained after conservative endoscopic treatment (ureteroscopy, percutaneous treatment) make it a credible alternative to the radical surgery for the management of tumours with non-aggressive behaviour. However, the high cost of endoscopy equipment and supplies currently remains a factor limiting their distribution in France.

[Analysis of anatomopathological results of radical prostatectomy specimen of patients who answer to criteria for active surveillance of prostate cancer]. / Analyse des résultats anatomopathologiques des pièces de prostatectomie radicale des patients répondant aux critères de surveillance active du cancer de prostate.

OBJECTIVE: To analyze pathological data of the radical prostatectomy specimen in patients operated for clinically-localized prostate cancer and who meet strict criteria for active surveillance. PATIENTS AND METHODS: The data of patients who underwent a radical prostatectomy by a single surgeon between 2002 and 2007 were reviewed. We only included the patients that met the usual criteria for active surveillance: clinical stage T1-2a tumor, PSA< or =10 ng/mL, biopsy Gleason sum inferior or equal to 6 with no pattern of grade 4 or 5, cancer involvement inferior or equal to two biopsy cores, inferior to 50% of malignant tissue in each positive biopsy core and a PSA density inferior or equal to 0.15 ng/ml/cc. RESULTS: Two hundred and seventy-three patients were operated, including 25 (9.2%) who met all the criteria for active surveillance. Mean age was 61 years (55-68). The mean preoperative PSA was 6.6 ng/mL (2.5-10). Clinical stage of the tumor was T1c in 84% of patients and T2a in 16%. Biopsy Gleason score was 3+3 in 92%, 2+3 in 4% and 2+2 in 4%. Pathological study of the surgical specimen showed that 28% of the tumors were pT2a, 8% pT2b, 40% pT2c and 20% pT3a. One tumor was pT0. The pathological Gleason score was 3+3 in 68% of patients and 3+4 in 28%. Surgical specimen showed a higher Gleason score in 44% of cases, but there were no cases of predominant grade 4. After a mean follow-up of 19.2 months, there was no clinical or biological recurrence. CONCLUSION: In our experience, 20% of patients who meet the criteria for active surveillance show an extracapsular extent of the tumor on pathological analysis. Active surveillance is still under evaluation. Its main risk is to underestimate the aggressiveness of the tumor at the time of diagnosis.

[Use of double J ureteral stent as an alternative to prevent ureteroileal anastomosis stricture in orthotopic bladder substitution]. / Etude comparative du drainage urétéral par sonde double J ou sonde urétérale après cystectomie-entéroplastie.

OBJECTIVE: The aim of the study was to compare ureteroileal anastomosis strictures rates in patients receiving either double J stent or open-ended ureteral stent, after bladder replacement for cancer. METHODS: Medical charts from 75 patients who underwent cystectomy and Z pouch bladder substitution for bladder cancer, between 2001 and 2005, were retrospectively reviewed. Ureteroileal anastomosis was direct, spatulated end-to-side fashioned in all patients. Double J stents were used in 39 patients (group A) and open-ended ureteral stent were used in 36 patients (group B). Mean hospital stay, early and late complications were also observed. RESULTS: Seventeen anastomotic strictures have been documented during the follow-up: 5.2% in group A versus 18.3% in group B (p=0.012). Mean catheterization period was six weeks in group A and 12 days in group B. No significant differences were found in mean hospital stay, early and late complications. CONCLUSION: The use of internal double J ureteral stent is now a feasible option and can decrease the rate of anastomotic stricture. The fact that the double J stent is removed after the anastomosis healing period may be a possible explanation.

[Testicular implants, patient's and partner's satisfaction: a questionnaire-based study of men after orchidectomy]. / Prothèses testiculaires après orchidectomie: enquête de satisfaction auprès des patients et de leurs partenaires.

OBJECTIVE: To assess the satisfaction of men and of their partner towards their testicular implants after undergoing orchidectomy. MATERIALS AND METHODS: Hundred and twenty-four consecutive patients, who had undergone orchidectomy, and their partner were sent an anonymous questionnaire. The follow-up after the implantation was at least one year. The testicular implants used were all Perthèse. RESULTS: Seventy-two patients answered to the questionnaire, among whom 63 had a testicular implant. Fifty-eight partners answered. From the patients with implant, 5% thought their body image was worse than before the operation and 80% thought their sexual activity was unchanged. Ninety-six percent thought the implantation was worthwhile and would do it again if they had to do the choice again. The reasons for dissatisfaction were: for the shape (n=8), for the size (n=3), for the position (n=2) and one patient thought the implant was too cold. Forty percent of the partners did not care about the implants and 58% thought the implant was essential. The dissatisfaction rate for the partners was 26% and reasons for were: for the shape (n=5), for the size (n=2), and one partner thought the implant was too cold. From the patients without implant, only one is thinking about having one. CONCLUSION: Testicular implants are well accepted, but some reasons of dissatisfaction appeared in our study. It was the first evaluation of the partner's satisfaction.

Structural organization and expression of human MTUS1, a candidate 8p22 tumor suppressor gene encoding a family of angiotensin II AT2 receptor-interacting proteins, ATIP.

The Mitochondrial Tumor suppressor 1 (MTUS1) gene is a newly identified candidate tumor suppressor gene at chromosomal position 8p22. We report here that MTUS1 encodes a family of proteins whose leader member (ATIP1) was previously isolated in our laboratory as a novel interacting partner of the angiotensin II AT2 receptor involved in growth inhibition (Nouet, JBC 279: 28989-97, 2004). The MTUS1 gene contains 17 coding exons distributed over 112 kb of genomic DNA. Alternative exon usage generates three major transcripts (ATIP1, ATIP3 and ATIP4), each showing different tissue distribution. ATIP polypeptides are identical in their carboxy-terminal region carrying four coiled-coil domains. In their amino-terminal portion, ATIP polypeptides exhibit distinct motifs for localisation in the cytosol, nucleus or cell membrane, suggesting that MTUS1 gene products may be involved in a variety of intracellular functions in an AT2-dependent and independent manner. ATIP1 is ubiquitous and highly expressed in the brain. ATIP3 is the major transcript in tissues (prostate, bladder, breast, ovary, colon) corresponding to cancer types with frequent loss of heterozygosity at 8p22. Interestingly, ATIP4 is a brain-specific transcript highly abundant in the cerebellum and fetal brain. High evolutionary conservation of ATIP amino-acid sequences suggests important biological roles for this new family of proteins in tumor suppression and/or brain function.

Intermittent androgen suppression in patients with prostate cancer.

OBJECTIVES: To evaluate intermittent androgen suppression (IAS) in patients with prostate cancer and to try to define predictive factors for biochemical progression. PATIENTS AND METHODS: From 1989 to 2001, 146 patients received IAS as a primary treatment for localized, advanced or metastatic prostate cancer (72 men) or as a treatment for prostate-specific antigen (PSA) recurrence after radical prostatectomy (RP) and/or radiation therapy (74 men). Androgen-deprivation treatment (ADT) was continued up to 6 months after PSA became undetectable or a nadir PSA level was reached. ADT was then re-instituted when the PSA level was> 4 ng/mL for patients who had RP or> 10 ng/mL for the others. RESULTS: After a mean (range) follow-up of 45.6 (12-196.9) months, 24 patients had biochemical progression. These patients were younger than those with no biochemical progression (67 vs 72 years, P = 0.004) and had a statistically higher Gleason score (7.21 vs 6.52, P = 0.01) and PSA level (111.1 vs 32.1 ng/mL, P = 0.05), and a shorter first phase without treatment (7.6 vs 11.2 months, P = 0.05). Overall 5-year metastatic disease free survival of 91.3%. The overall 5-year biochemical recurrence-free survival was 68%. Using multivariate analysis, a Gleason score of >or= 8 (P = 0.021), first-phase duration with no treatment of < 1 year (P = 0.044), positive lymph nodes or metastatic disease at the time of starting IAS (P = 0.023) and age < 70 years (P = 0.037) were the strongest predictors of biochemical progression. CONCLUSION: IAS appeared to be a feasible treatment; the best candidates being those aged> 70 years with localized prostate cancer and a Gleason score of

[Stage T1a prostatic cancer: long-term retrospective study of 27 patients]. / Cancer de prostate de stade T1a: étude rétrospective à long terme de 27 patients.

OBJECTIVE: The natural history of stage T1a prostate cancer is generally favourable, but is nevertheless associated with a considerable progression rate of 7% to 27% depending on the study. The objective of this study was to identify possible predictive criteria of tumour progression to improve patient surveillance and early treatment. MATERIAL AND METHODS: 27 patients with stage T1a prostate cancer according to the TNM 97 classification, were followed for a mean duration of 79 months (range: 24-132, median: 68). A complementary assessment was performed in patients under the age of 70 years, and a strict clinical (DRE) and laboratory (PSA) surveillance protocol was performed in all patients. The initial mean PSA was 7 ng/ml and the mean Gleason score was 4.8. RESULTS: 20 patients (75%) did not present any clinical and/or laboratory signs of progression and were therefore not treated. Seven patients (25%) received treatment with a mean follow-up of 63 months (radical prostatectomy in 2 cases, external beam radiotherapy in 1 case, endocrine therapy in 4 cases). All patients are alive and in complete remission at last follow-up. CONCLUSION: Based on our results and a review of the literature, conservative management based on strict, long-term surveillance, is a frequent approach to stage T1a prostate cancer confirmed by negative biopsies of the residual capsule. The PSA velocity is the key to surveillance, and the only factor of predictive of tumour progression that can be really used in routine clinical practice. However, our study showed tumour progression in 25% of cases, raising the question of curative treatment, especially in young patients.