B. Debré

microRNA expression profile in a large series of bladder tumors: Identification of a 3-miRNA signature associated with aggressiveness of muscle-invasive bladder cancer†

The aim of this study was to evaluate the expression levels of microRNAs (miRNAs) in bladder tumors in order to identify miRNAs involved in bladder carcinogenesis with potential prognostic implications. Expression levels of miRNAs were assessed by quantitative real‐time RT‐PCR in 11 human normal bladder and 166 bladder tumor samples (86 non‐muscle‐invasive bladder cancer (NMIBC) and 80 muscle‐invasive bladder cancer (MIBC)). The expression level of 804 miRNAs was initially measured in a well‐defined series of seven NMIBC, MIBC and normal bladder samples (screening set). The most strongly deregulated miRNAs in tumor samples compared to normal bladder tissue were then selected for RT‐PCR validation in a well‐characterized independent series of 152 bladder tumors (validation set), and in six bladder cancer cell lines. Expression levels of these miRNAs were tested for their association with clinical outcome. A robust group of 15 miRNAs was found to be significantly deregulated in bladder cancer. Except for two miRNAs, miR‐146b and miR‐9, which were specifically upregulated in MIBC, the majority of miRNAs (n = 13) were deregulated in the same way in the two types of bladder tumors, irrespective of pathological stage : three miRNAs were upregulated (miR‐200b, miR‐182 and miR‐138) and the other 10 miRNAs were downregulated (miR‐1, miR‐133a, miR‐133b, miR‐145, miR‐143, miR‐204, miR‐921, miR‐1281, miR‐199a and miR‐199b). A 3‐miRNA signature (miR‐9, miR‐182 and miR‐200b) was found to be related to MIBC tumor aggressiveness and was associated with both recurrence‐free and overall survival in univariate analysis with a trend to significance in the multivariate analysis (p = 0.05). Our results suggested a promising individual prognostic value of these new markers.

Large-scale Real-time Reverse Transcription-PCR Approach of Angiogenic Pathways in Human Transitional Cell Carcinoma of the Bladder: Identification of VEGFA as a Major Independent Prognostic Marker

BACKGROUND Actors of the angiogenesis pathways are targets for the new promising targeted therapies already used in several malignancies. In bladder cancer, antiangiogenic molecules could also add to already existing treatment options. OBJECTIVE To evaluate the involvement of angiogenesis pathways in bladder carcinogenesis and identify new molecular markers having a clinical implication. DESIGN, SETTING, AND PARTICIPANTS Expression levels of 40 genes involved in angiogenesis were assessed by quantitative real time RT-PCR in 157 urothelial tumour bladder samples obtained from patients who underwent transurethral bladder resection or radical cystectomy between 2001 and 2005. Pathologic tumour staging showed: 73 non-muscle-invasive bladder tumours (30 low-grade pTa, 14 high-grade pTa, and 29 high-grade pT1), and 84 muscle-invasive tumours (> or = pT2), all of high grade. RT-PCR results were associated with a survival analysis. RESULTS AND LIMITATIONS VEGFA, MET, CXCR4, and IL8 were significantly overexpressed in tumour samples as compared to normal bladder tissue. VEGFA overexpressions were found in 89% of non-muscle-invasive and 66% of muscle-invasive tumour samples. In univariate analysis, for invasive tumours, VEGFA overexpression was associated with a poorer outcome in both overall and disease-free survival (p=0.011 and 0.026 respectively) at a 13-mo median follow-up. Multivariate analysis retained T stage, N status, and VEGFA overexpression as independent prognostic factors in both overall and disease-free survival (p=0.02 and p=0.04, respectively, for VEGFA). CONCLUSIONS This study shows that, in bladder cancer, VEGFA status could be used as a prognostic factor at the individual level. VEGFA overexpression could guide a rationalized use of the costly antiangiogenic therapies which could therefore become part of the treatment options in bladder cancer.

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 partners satisfaction.

Cancer de la prostate: aspects médicoéconomiques

Prostate cancer is the first cancer in men. Its incidence is constantly increasing. The significant evolution of diagnostic and therapeutic means during the two last decades contrasts with the scarcity of medicoeconomic studies. The aim of this review is to present a synthesis of the different studies published and to respond to questions about the economic aspects of this disease, with the evaluation of its direct and indirect costs. The cost-effectiveness and the benefits of the prevention and the screening are still being studied. The costs of the surgery and the radiotherapy are roughly similar. The new surgical techniques, especially the laparoscopic and the robotic surgeries, are not necessarily associated with higher costs, in condition of a high-volume laparoscopic surgery program and a faster discharge. The indirect costs of prostate cancer concern the loss of economic production associated with the disease and death and are more difficult to determine.

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.

Tumeurs rénales hybrides : à propos de deux patients

PURPOSE Renal hybrid tumors (HT) are characterized by the association of both oncocytes- and chromophobe-cells within the same tumor. They have been reported in patients with Birt-Hogg-Dube (BHD) syndrome. The aim of this report was to describe two cases of HT and summarize recent literature. PATIENT AND METHOD Case study was summarized from the patients medical chart. Review of literature was performed using the National Center for Biotechnology Information (NCBI) database. RESULTS Two patients were diagnosed with multiple but small tumors of the kidney, and were treated with partial nephrectomy. Pathological analysis of these tumors showed oncocytoma-like and chromophobe-like cells intermixed in the same stroma. CONCLUSIONS HT may constitute a spectrum of tumors between renal oncocytoma and chromophobe renal cell carcinoma. From a pragmatic management perspective, it would be appropriate to consider such tumors as chromophobe carcinoma. In case of HT, a genetic study for BHD syndrome can be proposed to family relatives.

Impact of sarcopenia (Sp) on early dose-limiting toxicity (DLT) and acute vascular toxicity in patients (pts) with metastatic renal cell carcinoma (mRCC) receiving sunitinib (SUT).

e15094 Background: mRCC pts with severe muscle wasting (Sp) are at increased risk of DLT during anti-VEGF therapy with sorafenib (Antoun et al., Ann Oncol 2010). We hypothesized that Sp could also predict SUT-induced toxicity. METHODS mRCC outpatients received SUT 50 mg OD (4/6 weeks) or 37.5 mg OD, from June 2006 to December 2010. From July 2008, SUT plasma levels were routinely monitored every 15 days. Skeletal muscle cross-sectional area at the third lumbar vertebra was measured by CT-scan, and Sp was defined using standardized thresholds. Blood pressure was monitored twice daily at home, and other toxicities were assessed every 15 days. The primary evaluation criterion was DLT during the first month. Secondary criteria were SUT AUC on day 28, acute vascular toxicities (thrombotic microangiopathy, TMA and reversible posterior leukoencephalopathy syndrome, RPLS) during treatment, and progression-free survival (PFS). RESULTS 45 pts (71.1% males, median age: 60.3 years, range 29-83) were eligible for CT-scan, toxicity and PFS analyses. Pharmacokinetic data were available for 16 pts. A total of 287 cycles (median/pt: 6, range 1-22) were given, for a median follow-up of 14.4 months (range: 1.5-51.3). During the first month, grade 3 hypertension (not dose-limiting) occurred in 11 pts (24.4%), and DLT occurred in 8 pts (17.8%), including grade 3 fatigue (3 pts, 6.7%), TMA and RPLS (2 pts each, 4.4%), grade 3 hand-foot syndrome and pulmonary embolism (1 pt each, 2.2%). 22 pts (48.9%) had Sp at baseline. Pts with Sp experienced significantly more DLTs during the first month of treatment (7/22 vs. 1/23, p = 0.02). SUT AUC on day 28 (median: 1599 vs. 1228 ng.h/ml, p = 0.12) and PFS (median: 8.0 vs. 8.5 months, p = 0.29) did not differ between pts with or without Sp. Of 7 pts who experienced TMA or RPLS during the whole treatment period, 6 (86%) had Sp at baseline. CONCLUSIONS mRCC pts with Sp receiving SUT are at higher risk of early DLT, and experience more frequently acute vascular toxicities (TMA and RPLS). Sp appears to be a marker of tissular vulnerability that deserves further validation on larger cohorts of pts receiving anti-VEGF agents.