Cytoplasmic PAR-3 protein expression is associated with adverse prognostic factors in clear cell renal cell carcinoma and independently impacts survival.

International audienceClear cell renal cell carcinomas (ccRCCs) represent 70% of renal cancers, and several clinical and histolopathological factors are implicated in their prognosis. We recently demonstrated that the overexpression of PAR-3 protein encoded by the PARD3 gene could be implicated in renal oncogenesis. The object of this work was to study the association of intratumoral PAR-3 expression with known prognostic parameters and clinical outcome. In this aim, PAR-3 expression was assessed by immunohistochemistry in ccRCC tumors of 101 patients from 2003 to 2005. The immunostaining of PAR-3 was scored either as membranous (mPAR-3) or as both membranous and cytoplasmic (cPAR-3). Cytoplasmic PAR-3 was significantly associated with worse histopathological and clinical prognostic factors: Fuhrman grades 3 and 4, tumor necrosis, sarcomatoid component, adrenal invasion, renal and hilar fat invasion, eosinophilic component, a noninactivated VHL gene, higher tumor grade, lymph node involvement, metastasis, and worse clinical Eastern Cooperative Oncology Group and S classification scores. After multivariate analysis, 2 parameters were independently associated with cPAR-3: necrosis and eosinophilic components. In addition, cPAR-3 patients had shorter overall and progression-free survivals independently from strong prognostic validated factors like metastases. A cytoplasmic expression of PAR-3 is therefore implicated in worse clinical and pathological cancer features in ccRCC and could be useful to identify patients with high-risk tumors

Patient selection for laparoscopic excision of adrenal metastases: a multicenter cohort study

International audienceIntroduction The use of laparoscopy for the excision of adrenal metastasis remains controversial. We aimed to report oncological and perioperative outcomes of laparoscopic excision of adrenal metastases and to seek for predictive factors of unfavourable oncological outcomes. Methods A retrospective chart review was conducted and all consecutive patients who underwent laparoscopic adrenalectomy (LA) in the setting of metastatic cancer in two academic urology departments from November 2006 through January 2014 were included. Primary tumors were categorized as pulmonary, renal or “other primary” tumors to allow statistical comparison. Unfavourable surgical outcomes were defined as the occurrence of either postoperative complications and/or positive surgical margins. Results Forty-three patients who underwent a total of 45 LA were included for analysis. There were 8 complications (17.8%). Positive surgical margins were found in 12 specimens (26.7%). After a median follow-up of 37 months, estimated overall survival rates were 89.5% and 51.5% at 1 year and 5 years, respectively. In multivariable analysis the only predictor of unfavourable surgical outcomes was a tumor size > 5 cm (OR= 20.5; p=0.001). In multivariate analysis the pulmonary (OR=0.3; p=0.008) or “other” (OR= 0.1; p=0.0006) origin of the primary tumor was the only prognostic factor of shorter cancer specific survival. Conclusion Laparoscopic resection of adrenal metastasis can be safely performed in most patients but is associated with an increased risk of positive surgical margins and postoperative complications in larger tumors (>5 cm). Adrenalectomy provides better oncological outcomes in metastases from renal cell carcinoma compared to other primary tumors

Wild-type VHL Clear Cell Renal Cell Carcinomas Are a Distinct Clinical and Histologic Entity: A 10-Year Follow-up

International audienceBackground: Clear cell renal cell carcinoma (ccRCC) is an aggressive tumor with 50% risk of metastases at initial diagnosis or at follow-up. An inactivation of the tumor-suppressor gene von Hippel-Lindau (VHL) is present in >70% of sporadic cases by two of three different mechanisms: locus deletion, gene mutation, or promoter hypermethylation. Objective: To correlate the complete status of the VHL gene with clinical and pathologic criteria. Design, setting, and participants We retrospectively included 98 patients with ccRCC who underwent surgery between 2002 and 2005. VHL gene deletions (71 of 98; 72.4%), mutations (68 of 98; 69.4%), and promoter hypermethylations (13 of 98; 13.3%) were screened by gene copy analysis, gene sequencing, and methylation-specific multiplex ligation-dependent probe amplification, respectively. Outcome measurements and statistical analysis Relationships between VHL subgroups and the studied criteria were analyzed using chi-square and Student t tests. Survival was analyzed with the log-rank test and Kaplan-Meier curves. Results and limitations: Compared with ccRCCs with two events (66.3%), tumors with no or one genetic event (33.6%) were associated with a higher nuclear grade IV (p = 0.02), metastases (p = 0.04), sarcomatoid component (p = 0.01), dense lymphocyte infiltrate (p = 0.013), and vascular endothelial growth factor overexpression (>30%) (p = 0.003), which was also an independent factor after multivariate analysis. Furthermore, wild-type VHL tumors (no inactivating event, 11.2%) were associated with nodal involvement (p = 0.019), and patients with this type of tumor had a specific survival of 33 mo compared with patients with ccRCCs having one or two VHL inactivating events (107 mo; p = 0.016). The retrospective design with small number of wild-type tumors was a limitation of this work. Conclusions: This long-term study (10-yr clinical follow-up) confirms that ccRCCs with wild-type VHL are highly aggressive tumors that need to be formally identified. Patient summary Among activated VHL tumors, the wild-type subgroup defines an aggressive phenotype with worse survival rates, suggesting that these tumors must be more thoroughly screene

Reforming the Westminster Model of Agency Governance: Britain and Ireland after the Crisis

Conventional understandings of what the Westminster model implies anticipate reliance on a top-down, hierarchical approach to budgetary accountability, reinforced by a post-New Public Management emphasis on re-centralizing administrative capacity. This paper, based on a comparative analysis of the experiences of Britain and Ireland, argues that the Westminster model of bureaucratic control and oversight itself has been evolving, hastened in large part due to the global financial crisis. Governments have gained stronger controls over the structures and practices of agencies, but agencies are also key players in securing better governance outcomes. The implication is that the crisis has not seen a return to the archetypal command-and-control model, nor a wholly new implementation of negotiated European-type practices, but rather a new accountability balance between elements of the Westminster system itself that have not previously been well understood

Noninvasive Urine-Based Tests to Diagnose or Detect Recurrence of Bladder Cancer

International audienceLiquid biopsies are increasingly used for the diagnosis and follow-up of cancer patients. Urine is a body fluid that can be used to detect cancers and others diseases. It is noninvasive and easy to collect. To detect Bladder Cancer (BC), cytology is the first assay used. It is an effective way to detect high grade BC but has a high rate of equivocal results, especially for low grade BC. Furthermore, cystoscopy is used to confirm cytology results and to determine cancer status. Cystoscopy is also effective but highly invasive, and not well accepted by patients, especially for BC follow-up. In this review we survey the numerous assays recently developed in order to diagnose BC at an early stage, and to facilitate the follow-up of patients. We discuss their effectiveness, ease of use, and applications. Finally, we discuss assays that, in the future, could improve the diagnosis and management of BC patients

La néphrectomie laparoscopique par accès ombilical unique : évolution ou révolution chirurgicale ? [Renal LESS surgery: Slight modification or surgical revolution?].

International audienceOBJECTIVE: to present our initial experience of laparoendoscopic single site (LESS) renal surgery. METHODS: between May 2009 and March 2010, nine nephrectomies and one cyst decortication were performed in nine patients. Eight of the procedures were done with three 5mm trocars inserted through a unique peri-umbilical incision. In two cases, a specific single-port device was used. All operations were achieved with a 5-mm 30° lens and conventional laparoscopic instruments. The specimens were entrapped in a 10mm endoscopic bag and extracted through the umbilical incision. RESULTS: mean age was 56 years old. Mean BMI was 23.5 [19-34]. Mean operative time was 149min [80-240], and estimated blood loss was 90ml [20-250]. None of the patients required blood transfusion. Mean length of stay was 4.1 days [3-5]. Only one major complication occurred (functional occlusion). One conversion to conventional laparoscopy was necessary in a case of inflammatory kidney. Histologic exam showed benign lesions (cyst and non functional kidney) in seven cases, and papillary carcinoma in three cases. CONCLUSION: LESS surgery is feasible. Its advantages over conventional laparoscopy are not clear. LESS is a new procedure that should benefit from the improvement of technical instrumentation

Role of quantitative computed tomography texture analysis in the prediction of adherent perinephric fat

International audienceObjective - To assess the performance of computed tomography (CT) texture analysis to predict the presence of adherent perinephric fat (APF). Materials and methods - Seventy patients with small renal tumors treated with robot-assisted partial nephrectomy were included. Patients were divided into two groups according to the presence of APF. We extracted 15 image features from unenhanced CT and contrast-enhanced CT corresponding to first-order and second-order Haralick textural features. Predictors of APF were evaluated by univariable and multivariable analysis. Receiver operating characteristic (ROC) analysis was performed and the area under the ROC curve (AUC) to predict APF was calculated for the independent predictors. Results - APF was observed in 26 patients (37%). We identified entropy (p = 0.01), sum entropy (p = 0.02) and difference entropy (p = 0.05) as significant independent predictors of APF. In the portal phase, we identified correlation (p = 0.03), inverse difference moment (p = 0.01), sum entropy (p = 0.02), entropy (p = 0.01), difference variance (p = 0.04) and difference entropy (p = 0.02) as significant independent predictors of APF. Combining these parameters yielded to an ROC-AUC of 0.82 (95% CI 0.65-0.86). Conclusion - Results from this preliminary study suggest that CT texture analysis might be a promising quantitative imaging tool that helps urologist to identify APF

Impact of routine imaging in the diagnosis of recurrence for patients with localized and locally advanced renal tumor treated with nephrectomy

International audienceObjective - Modalities of surveillance to detect recurrence after nephrectomy for localized or locally advanced renal tumor are not standardized. The aim was to assess the impact of surveillance scheme on oncological outcomes. Methods - Patients treated for localized or locally advanced renal tumor with total or partial nephrectomy between 2006 and 2010 in an academic institution were included retrospectively. According to the University of California Los Angeles Integrated Staging System (UISS) protocol, follow-up was considered adequate or not. Symptoms, location and number of lesions at recurrence diagnosis were collected. Recurrence-free, cancer-specific and overall survivals were estimated using the Kaplan-Meier method and compared with the log-rank test. Cox proportional hazards regression models were calculated to identify prognostic factors. Results - A total of 267 patients were included. Median follow-up was 72 months. Recurrence rate was 23.2% (62/267 patients). Recurrences were local (16%), single metastatic (23%), oligo-metastatic (15%) or multi-metastatic (46%). 72.6% of the recurrences occurred within the 3 years after surgery. No recurrence was diagnosed by chest X-ray or abdominal ultrasound. One hundred and twenty-one patients had inadequate follow-up. They had similar recurrence-free survival, cancer-specific survival and overall survival as patients with adequate follow-up. In multivariable analysis, the presence of multi-metastatic lesions was an independent prognostic factor of worse cancer-specific mortality after recurrence diagnosis (HR = 10.15, 95% CI: 2.29-44.82, p = 0.002). Conclusion - Role of chest X-ray and abdominal ultrasound for the detection of recurrences is limited. Rigorous follow-up according to the UISS protocol does not improve oncological outcomes. Follow-up schedules with less frequent imaging should be discussed