Clinicopathological characteristics of incidental prostate cancer discovered from radical cystoprostatectomy specimen: a multicenter French study.

PURPOSE: The present study assessed the incidence and histopathological features of incidentally diagnosed prostate cancer (PCa) in specimens from radical cystoprostatectomy (RCP) for bladder cancer. The patient outcomes also were evaluated. METHODS: We retrospectively reviewed the histopathological features and survival data of 4,299 male patients who underwent a RCP for bladder cancer at 25 French centers between January 1996 and June 2012. No patients had preoperative clinical or biological suspicion of PCa. RESULTS: Among the 4,299 RCP specimens, PCa was diagnosed in 931 patients (21.7%). Most tumors (90.1%) were organ-confined (pT2), whereas 9.9% of them were diagnosed at a locally advanced stage (≥pT3). Gleason score was <6 in 129 cases (13.9%), 6 in 575 cases (61.7%), 7 (3 + 4) in 149 cases (16.0%), 7 (4 + 3) in 38 cases (4.1%), and >7 in 40 cases (4.3%). After a median follow-up of 25.5 months (interquartile range 14.2-47.4), 35.4% of patients had bladder cancer recurrence and 23.8% died of bladder cancer. Only 16 patients (1.9%) experienced PCa biochemical recurrence during follow-up, and no preoperative predictive factor was identified. No patients died from PCa. CONCLUSIONS: The rate of incidentally diagnosed PCa in RCP specimens was 21.7%. The majority of these PCas were organ-confined. PCa recurrence occurred in only 1.9% of cases during follow-up.

National prospective study on the use of local haemostatic agents during partial nephrectomy.

OBJECTIVE: To assess the use of local haemostatic agents (HAs) in a prospective multicentre large series of partial nephrectomies (PNs). PATIENTS AND METHODS: Prospective National Observational Registry on the Practices of Haemostasis in Partial Nephrectomy (NEPHRON): the study was conducted in 54 French urological centres from 1 June to 31 December 2010. In all, 570 consecutive patients undergoing a PN were enrolled in this study in a prospective manner. The data was collected prospectively via an electronic case-report form: five different sheets were included for preoperative, perioperative, postoperative and follow-up data respectively. Information related to haemostasis was analysed. RESULTS: The median patient age was 60 years and the mean (range) tumour size was 3.68 (0.19-15) cm. An HA was primarily used in 71.4% of patients, with a statistically significant difference among surgical approaches (P = 0.024). In 91.8% of cases, a single use of a HA was sufficient for achieving haemostasis. The HA was used either alone (13.9%) or in association with sutures (80.3%). One or more additional haemostatic action(s) was needed in 12.3% of the cases. When comparing patients who received a HA with those who did not receive a HA, there was no statistical difference between the groups for tumour size (P = 0.542), collecting system drainage (P = 0.538), hospital stay (P = 0.508), operation time (P = 0.169), blood loss (P = 0.387) or transfusion rate (P = 0.713). CONCLUSION: HAs are widely used by urologists during PN. Progress is needed for standardising HA application, especially for the timing of application. For the time being, the role of the HA in nephron-sparing surgery is still to be evaluated.

Neoadjuvant targeted molecular therapies in patients undergoing nephrectomy and inferior vena cava thrombectomy: is it useful?

OBJECTIVE: To assess the effect of neoadjuvant targeted molecular therapies (TMTs) on size and level of inferior vena cava tumor thrombi and to evaluate their impact on surgical management. METHODS: We retrospectively analyzed the data of 14 patients treated for a clear cell renal cell carcinoma with inferior vena cava thrombi by neoadjuvant TMT before nephrectomy. Clinical, pathological and perioperative data were gathered retrospectively at each institution. The primitive tumor size and the thrombus size were defined by computed tomography before TMT. The tumor thrombus level was defined according to the Novick's classification. RESULTS: Before TMT, thrombus level was staged I for 1 (7%), II for 10 (72%) and III (21%) for 3 patients. First-line therapy was sunitinib in 11 cases and sorafenib in 3 cases. Median therapy duration was two cycles (1-5). Three patients experienced major adverse effects (grade III) during TMT. Following TMT, 6 (43%) patients had a measurable decrease, 6 (43%) had no change, and 2 (14%) had an increase in the thrombus. One patient (7%) had a downstage of thrombus level, 12 (85%) had stable thrombi, and 1 (7%) had an upstage. Regarding primary tumor, 7 (50%), 5 (36%) and 2 (14%) patients had a decrease, stabilization and an increase in tumor size, respectively. CONCLUSION: Neoadjuvant TMT appears to have limited effects on renal tumor thrombi. This retrospective study failed to demonstrate a significant impact of neoadjuvant TMT on surgical management of clear cell renal cell carcinoma with inferior vena cava tumor thrombi.

Efflux pump ABCB1 single nucleotide polymorphisms and dose reductions in patients with metastatic renal cell carcinoma treated with sunitinib.

UNLABELLED: There is growing evidence that sunitinib plasma levels have an impact on treatment outcome in patients with metastatic renal cell carcinoma (mRCC). We studied the impact of single nucleotide polymorphisms (SNPs) in genes involved in sunitinib pharmacokinetics, and additionally, sunitinib pharmacodynamics on dose reductions of the tyrosine kinase inhibitor. METHODS: We retrospectively analyzed germ-line DNA retrieved from mRCC patients receiving sunitinib as first-line therapy. We genotyped 11 key SNPs, respectively, in ABCB1, NR1/2, NR1/3 and CYP3A5, involved in sunitinib pharmacokinetics as well as VEGFR1 and VEGFR3, which have been suggested as regulators of sunitinib pharmacodynamics. Association between these SNPs and time-to-dose-reduction (TTDR) was studied by Cox regression. RESULTS: We identified 96 patients who were treated with sunitinib and from whom germ-line DNA and data on dose reductions were available. We observed an increased TTDR in patients carrying the TT-genotype in ABCB1 rs1125803 compared to patients with CC- or CT-genotypes (19 vs. 7 cycles; p = 0.031 on univariate analysis and p = 0.012 on multivariate analysis) and an increased TTDR in patients carrying the TT/TA-variant in ABCB1 rs2032582 compared to patients with the GG- or GT/GA-variant (19 vs. 7 cycles; p = 0.046 on univariate analysis and p = 0.024 on multivariate analysis). CONCLUSION: mRCC patients carrying the rs1128503 TT-variant or the TT/TA-variant in rs2032582 in ABCB1, which encodes for an efflux pump, do require less dose reductions due to adverse events compared to patients with the wild type or heterozygote variants in these genes.

Detailed analysis of morbidity following nephrectomy for renal cell carcinoma in octogenarians.

PURPOSE: We evaluated the morbidity of nephrectomy in patients older than age 80 years. MATERIALS AND METHODS: Between June 2002 and March 2011, 2,530 patients underwent surgery for renal tumor at 5 French academic centers. Of these patients 180 (7.1%) were age 80 years or older, including 22 (12%) and 158 (88%) who underwent partial and radical nephrectomy, respectively, and 47 (26.1%) who were treated with a laparoscopic approach. RESULTS: Mean patient age was 82.3 years. Median Charlson score was 4. Mean preoperative glomerular filtration rate was 47 ml/minute. A total of 136 complications were recorded in 70 patients (38.8% of all patients). Of the patients 28 (15.5%), 25 (13.9%) and 17 (9.4%) experienced 1, 2 and 3 or more complications, respectively. According to the modified Clavien classification grade I, II, III, IV and V complications were observed in 7, 81, 19, 23 and 6 patients, respectively. The transfusion rate was 31.1% (56). On logistic regression analysis the parameters of Eastern Cooperative Oncology Group Performance Status 2 to 4 (p = 0.035) and preoperative glomerular filtration rate less than 30 ml/minute (p = 0.03) were independent predictive factors of morbidity. CONCLUSIONS: Morbidity and mortality are significant in the octogenarian population. The risk of complications should be considered in decision making for patients with renal cell carcinoma older than age 80 years.

Overall mortality after radical nephrectomy in patients aged over 80 years with renal cancer: a retrospective study on preoperative prognostic factors.

OBJECTIVES: To evaluate the overall survival postnephrectomy for renal cancer for patients aged over 80 years, and to identify preoperative prognostic factors that might influence therapeutic strategies. METHODS: In a retrospective study in five French departments of urology, 179 patients aged over 80 years with renal cell carcinoma underwent radical nephrectomy between 1990 and 2011. The following data were collected: age, sex, body mass index, Charlson Comorbidity Index, American Society of Anesthesiology class, Eastern Cooperative Oncology Group Performance Status, type of surgery, period of follow-up, survival, death etiology, symptoms, Fuhrman grade and tumor-nodes-metastasis stage. RESULTS: After a 29.6-month follow up, 89 patients (49.7%) died. Death etiologies were: cancer for 46 (52%) patients, immediate or distant perioperative complications for five patients (6%) and three patients (3%) respectively, cardiovascular disease for 16 patients (18%), other cancers for three patients (3%) and unknown for 16 patients (18%). In a multivariate analysis, T-stage, M-stage and Charlson Comorbidity Index were identified as independent prognostic factors. Patients were divided into three groups (good, intermediate and bad prognosis) with significantly different survivals of 91, 36 and 22 months (P < 0.0001), respectively. CONCLUSIONS: Preoperative data, including T-stage, M-stage and Charlson Comorbidity Index represent significant independent prognostic factors for survival for patients aged over 80 years. These data might help the clinician in selecting the most suitable candidates for radical nephrectomy among elderly patients with renal cancer.

Laser treatment of benign prostatic hyperplasia in patients on oral anticoagulant therapy.

Because the number of patients requiring oral anticoagulation (OA) is steadily growing, more and more patients requiring surgical treatment of benign prostatic hyperplasia (BPH) are on OA. Laser treatment of BPH was said to offer a higher quality of hemostasis than transurethral resection of the prostate (TURP). Thus, laser was considered an interesting tool for BPH surgery in patients on OA therapy. To date, no randomized studies focusing on laser treatment in patients on OA are available. Compared to TURP, laser seems to decrease the risk of hemorrhage in patients on OA. Therefore, the laser could be considered a useful tool for managing patients on OA, and could be proposed as a first-line therapy for those patients requiring surgery. Continuing platelet aggregation inhibitors during the procedure is feasible. A switch to low molecular weight heparine medication prior to surgery is preferable to the continued use of OA during TURP. No conclusion can be reached regarding the preferred laser technique to treat these patients.

Weather-based indicators for analysis of moisture risks in buildings.

Moisture is one of the main issues in building disorders. It can lead to microorganism's growth, material deterioration and impact on energy consumption. A comprehensive overview on the scale of the country considering climatic conditions may be an important starting point for potential moisture risks in building analyses. In this paper, we present a method in which weather-based indicators are developed for a first outline of the potential moisture risk in buildings considering the main climatic sources of moisture. The proposed method is related to weather parameters, comprising two new indicators - in a total of three - that are plotted in the country map using Geographic Information System to spatially represent the risk across the country territory. The method is applied for Brazil, and results indicate high weather-based moisture risks in highly densely populated areas. The case study highlights the importance of the presented methodology as a first analysis of potential moisture risk on a country scale.

Metastatic chromophobe renal cell carcinoma treated with targeted therapies: A Renal Cross Channel Group study.

BACKGROUND: Treatment of non-clear cell renal cell carcinoma (RCC) remains controversial despite several recent prospective studies of targeted therapies (TT). Often Vascular Endothelial growth Factor (VEGF) and Mammalian Target of Rapamycin (mTOR) inhibitors are used, extrapolating the data from use of these agents in clear cell RCC. METHODS: We performed a retrospective data analysis within the Renal Cross Channel Group to determine metastatic chromophobe RCC (mChRCC) outcomes in the TT era. The end-points were overall response, overall survival (OS) and time to treatment failure (TTF). The two latter were estimated using the Kaplan-Meier method. RESULTS: 91 mChRCC patients from 26 centres were included. Median follow-up from the date of first metastasis was 6.1 years (range: 0-13.9). Median OS was 37.9 months (95% confidence interval [CI]: 21.4-46.8) from the diagnosis of metastatic disease. Among the 61 patients who received TT, 50 (82%) were treated with anti-angiogenic (AA) and 11 with mTOR inhibitors. Median TTF and OS in patients receiving a first line of AA was 8.7 months (95% CI: 5.2-10.9) and 22.9 months (95% CI: 17.8-49.2) versus 1.9 months (95% CI: 1.0-6.0) and 3.2 months (95% CI: 2.3-not evaluable) with mTOR inhibitors, respectively. A stratified log-rank test was used to compare AA and mTOR inhibitors TT, while controlling the effect of the International Metastatic RCC Database Consortium risk group and no significant difference between AA and mTOR inhibitors was observed for TTF (p = 0.26) or for OS (p = 0.55). CONCLUSION: We report the largest retrospective cohort of patients with mChRCC treated with TT and no significant difference between AA and mTOR inhibitors was observed for TTF and OS.

p75 neurotrophin receptor and pro-BDNF promote cell survival and migration in clear cell renal cell carcinoma.

p75NTR, a member of TNF receptor family, is the low affinity receptor common to several mature neurotrophins and the high affinity receptor for pro-neurotrophins. Brain-Derived Neurotrophic Factor (BDNF), a member of neurotrophin family has been described to play an important role in development and progression of several cancers, through its binding to a high affinity tyrosine kinase receptor B (TrkB) and/or p75NTR. However, the functions of these two receptors in renal cell carcinoma (RCC) have never been investigated. An overexpression of p75NTR, pro-BDNF, and to a lesser extent for TrkB and sortilin, was detected by immunohistochemistry in a cohort of 83 clear cell RCC tumors. p75NTR, mainly expressed in tumor tissues, was significantly associated with higher Fuhrman grade in multivariate analysis. In two derived-RCC lines, 786-O and ACHN cells, we demonstrated that pro-BDNF induced cell survival and migration, through p75NTR as provided by p75NTR RNA silencing or blocking anti-p75NTR antibody. This mechanism is independent of TrkB activation as demonstrated by k252a, a tyrosine kinase inhibitor for Trk neurotrophin receptors. Taken together, these data highlight for the first time an important role for p75NTR in renal cancer and indicate a putative novel target therapy in RCC.