Perioperative Blood Transfusion Is a Predictor of Acute and Chronic Renal Function Deterioration after Partial and Radical Nephrectomy for Renal Cell Carcinoma.

INTRODUCTION: The aim was to evaluate the impact of perioperative blood transfusions (PBTs) on renal function after surgery for renal cell carcinoma (RCC). METHODS: Consecutive patients with RCC who underwent partial nephrectomy or radical nephrectomy between 2005 and 2015 at a tertiary care center were included. Minimum follow-up period was 6 months. A PBT was defined as the transfusion of packed erythrocyte concentrate (EC) within 7 days before until 30 days after surgery. The multivariable analyses were carried out by Cox regression. RESULTS: The overall cohort included 851 patients, of whom 93 (10.9%) received a PBT. The median follow-up was 46 months (range 28-72). In case of a PBT, a median of 2 EC was transfused. PBT patients were older and had a poorer performance status and more comorbidities as well as locally more advanced or metastatic tumors. In the multivariable analyses, PBT was an independent prognostic factor for acute as well as chronic renal impairment (hazard ratio (HR) 2.72, 95% confidence interval (95% CI) 1.45-5.10, p = 0.002 and HR 2.23, 95% CI 1.26-3.70, p = 0.007). CONCLUSION: PBT is associated with acute and chronic deterioration of kidney function after surgery for RCC. Thus, it may be used to identify patients requiring close nephrological monitoring.

Partial nephrectomy preserves renal function without increasing the risk of complications compared with radical nephrectomy for renal cell carcinomas of stages pT2-3a.

OBJECTIVES: To compare the operative and functional result of partial and radical nephrectomy in renal cell carcinomas of stages pT2-3a. METHODS: Consecutive patients with renal cell carcinoma of stages pT2-3a, cN0 and cM0, who underwent partial or radical nephrectomy between January 2005 and October 2019 at a tertiary care center were included. Data were collected retrospectively. End-points included severe postoperative complications (Clavien-Dindo classification ≥3), acute and chronic renal function impairment, and overall survival. Uni- and multivariable outcome analyses were based on logistic regression. RESULTS: A total of 158 patients were included (110 radical nephrectomy and 48 partial nephrectomy). Over time, partial nephrectomy was increasingly used. A RENAL score ≥10 was the only independent predictor influencing the surgical approach (radical nephrectomy vs partial nephrectomy, odds ratio 8.62, 95% confidence interval 3.32-22.37, P < 0.001). No significant differences in complications for radical nephrectomy versus partial nephrectomy were found (12.7% vs 8.3%, P = 0.424). Renal function was better preserved in the partial nephrectomy group (the latest chronic kidney disease stage ≥3: radical nephrectomy 73% vs partial nephrectomy 41%, P = 0.005). The surgical approach was a significant factor for chronic kidney disease (odds ratio 51.07, 95% confidence interval 3.57-730.59, P = 0.004). Overall survival did not significantly differ between radical nephrectomy and partial nephrectomy (mean overall survival 85.86 months, 95% confidence interval 3.83-78.36 vs 81.28 months, 95% confidence interval 4.59-72.29, P = 0.702). CONCLUSIONS: In selected patients, partial nephrectomy can be used in large or locally advanced renal cell carcinoma. Compared with radical nephrectomy, it allows better preservation of renal function without harboring an increased risk of severe postoperative complications.

Are there limits of robotic partial nephrectomy? TRIFECTA outcomes of open and robotic partial nephrectomy for completely endophytic renal tumors.

BACKGROUND: To compare the outcomes of robot-assisted (RAPN) and open partial nephrectomy (OPN) for completely endophytic renal tumors. METHODS: Consecutive patients undergoing OPN or RAPN for entirely endophytic tumors in four high-volume centers between 2008 and 2016 were identified. Endophytic masses were identified based on sectional imaging. Patient characteristics and surgical outcome were compared using Mann-Whitney-U-test and chi-squared-tests. Uni- and multivariate analyses were performed to identify predictors of TRIFECTA achievement and excisional volume loss. RESULTS: Out of 1128 patients, 10.9% (64) of RAPN and 13.9% (76) of OPN underwent surgery for entirely endophytic tumors. Operative time was longer for RAPN (169 vs 140 min, P = 0.03) while ischemia time was shorter (13 vs 18 min, P = 0.001). Complication rates were comparable (21% OPN vs 22% RAPN, P = 0.91) and TRIFECTA achievement was not different between the groups (68% OPN vs 75% RAPN, P = 0.39). In multivariate analyses type of surgery was not associated with TRIFECTA achievement or excisional volume loss. Here, only tumor complexity (OR 0.48, P = 0.001) and size (OR 1.01, P = 0.002) were independent predictors. CONCLUSION: For entirely endophytic tumors, both RAPN and OPN offer good TRIFECTA achievement. This encourages the use of NSS even for these highly complex tumors using the surgeon's preferred approach.

Tumor size and invasiveness matters for partial nephrectomy: External validation and modification of the arterial based complexity score.

BACKGROUND: Outcome of partial nephrectomy (PN) depends on anatomic features of the renal tumor, which can be assessed by nephrometry scores. The aim was to externally validate and refine the Arterial Based Complexity (ABC) score and to compare it to established systems. METHODS: Tumors of 300 patients undergoing PN were categorized according to the ABC, RENAL, and PADUA score. Size and tumor invasiveness were combined to form the ABCD score. Correlation analysis and multivariate logistic regression was performed to validate and compare the respective scores as predictors of surgical outcome. RESULTS: The ABC score shows significant correlation with ischemia time (IT) (P < 0.01), opening of the collecting system (CS) (P < 0.01), and conversion to nephrectomy (P = 0.01). In the multivariate analysis, the ABC score was predictive for on-clamp excision (P < 0.01) and opening of the CS (P < 0.01) only. The RENAL and ABCD scores were independent predictors for complications (P = 0.02, P = 0.05), IT (P < 0.01, P = 0.03), on clamp excision (P < 0.01, P < 0.01), and opening of the CS (P < 0.01, P < 0.01). CONCLUSIONS: The ABC score correlates well with surgical parameters. Expanding the score by tumor diameter gives the ABCD system. It has similar predictive effectiveness to the well-established RENAL score, but features simplicity by only assessing invasiveness and tumor size.

The soluble Decoy Receptor 3 is regulated by a PI3K-dependent mechanism and promotes migration and invasion in renal cell carcinoma.

BACKGROUND: Overexpression of Decoy Receptor 3 (DcR3), a soluble member of the tumor necrosis factor receptor superfamily, is a common event in several types of cancer. In renal cell carcinoma (RCC), DcR3 overexpression is associated with lymph node and distant metastasis as well as a poor prognosis. However, the functional role and regulation of DcR3 expression in RCC is so far unknown. METHODS: Modulation of DcR3 expression by siRNA and ectopic gene expression, respectively, was performed in ACHN and 769-P RCC cell lines. Functional effects of a modulated DcR3 expression were analyzed with regard to migration, invasion, adhesion, clonogenicity, and proliferation. Furthermore, quantitative RT-PCR and immunoblot analyses were performed to evaluate the expression of downstream mediators of DcR3. In further experiments, luciferase assays, quantitative RT-PCR and immunoblot analyses were applied to study the regulation of DcR3 expression in RCC. Additionally, an ex vivo tissue slice culture technique combined with immunohistochemistry was used to study the regulation of DcR3 expression in human RCC specimens. RESULTS: Here, we show that DcR3 promotes adhesion, migration and invasiveness of RCC cells. The DcR3-dependent increase in cellular invasiveness is accompanied with an up-regulation of integrin alpha 4, matrixmetalloproteinase 7 and urokinase plasminogen activator (uPA). Further, we identified a signaling pathway regulating DcR3 expression in RCC. Using in vitro experiments as well as an ex vivo RCC tissue slice culture model, we demonstrate that expression of DcR3 is regulated in a PI3K/AKT-dependent manner involving the transcription factor nuclear factor of activated T-cells (NFAT). CONCLUSIONS: Taken together, our results identify DcR3 as a key driver of tumor cell dissemination and suggest DcR3 as a promising target for rational therapy of RCC.

Molecular heterogeneity of TFE3 activation in renal cell carcinomas.

Renal cell carcinomas associated with Xp11.2 translocations have recently been identified as a distinct biological entity. The translocation results in the fusion of the transcription factor TFE3 to one of several different fusion partners including PRCC, PSF, NONO, ASPL or CTLC with consecutive overexpression of the chimeric protein. As the true frequency of these neoplasms as well as the biological properties of TFE3 activation in renal cell carcinomas are largely unknown, we have examined TFE3 expression as well as the underlying genetic alterations in a large, hospital-based series of renal cell carcinomas with long-term follow-up information. Out of a total of 876 tumours, TFE3 translocations were detected in five cases (0.6%). Three additional cases were identified in a second series of cases comprising of renal cell carcinomas developing in patients before the age of 50. However, using immunohistochemistry, 9% of all renal cell carcinomas showed some degree of TFE3 reactivity. Interestingly, these cases were associated with high nuclear grade, greater tumour extent and metastatic disease as well as an unfavourable patient outcome on uni- and multivariate analysis. Fluorescence in situ hybridisation (FISH) revealed TFE3 amplifications as an additional, novel mechanism leading to increased TFE3 expression levels. In conclusion, our data show that Xp11 translocation renal cell carcinomas are uncommon tumours accounting for <1% of adult renal cell carcinomas and that the diagnosis of Xp11 translocation renal cell carcinomas needs to be verified using molecular techniques. In turn, TFE3 overexpressing tumours show an aggressive behaviour and Xp11 translocation is only one of several possible underlying genomic alterations.

PSA density lower cutoff value as a tool to exclude pathologic upstaging in initially diagnosed unilateral prostate cancer: impact on hemiablative focal therapy.

PURPOSE: To investigate prostate-specific antigen density as a predictor for pathologic upstaging in patients initially thought to have unilateral prostate cancer. METHODS: We analyzed 438 patients with unilateral prostate cancer in prostate biopsy samples that were treated with radical prostatectomy. Bilateral or extracapsular growth in the final surgical specimens was defined as upstaging. Using Kaplan-Meier curves and a multivariate Cox proportional hazard model, we evaluated the oncologic effect of pathologic upstaging on biochemical recurrence-free survival. Prostate-specific antigen density was evaluated as a diagnostic tool to predict upstaging using ROC-curve analysis. RESULTS: Of the patients, 30.8% had bilateral prostate cancer or extracapsular extension in the surgical specimen. Prostate-specific antigen density was a diagnostic predictor for pathologic upstaging in patients initially thought to have unilateral prostate cancer (AUC 0.62, P < 0.001). Using a lower cutoff value of PSA density <0.056 ng/ml/cm3, upstaging could be excluded in patients with a sensitivity of >98%. CONCLUSIONS: A considerable amount of patients that are initially diagnosed with unilateral prostate cancer on biopsy are underdiagnosed and are upstaged in the radical prostatectomy specimen. In general, AUC of PSA density is too low to use PSA density as diagnostic tool to predict pathologic upstaging in all patients. Nonetheless, PSA density could be used for hemiablative focal therapy decision making using a lower cutoff value of <0.056 ng/ml/cm3.

[Impact of the experience of urological senior physicians in Germany on professional and personal aspects]. / Welchen Einfluss hat die Dauer der Oberarzttätigkeit auf die Berufsausübung und Zufriedenheit urologischer OberärztInnen in Deutschland?

BACKGROUND: Urological senior physicians in Germany are a heterogeneous group with various clinical priorities and career objectives. To date, there are no reliable data concerning the impact of the time span for which senior physicians have been holding their position on professional, personal and position-linked aspects. MATERIAL AND METHODS: The objective of this study was a comparative analysis of perspectives, private and professional settings, specific job-related activities and individual professional goals of urological senior physicians in Germany based on their experience in this position assessed as number of years (dichotomised at 8 years as senior physician). As part of a cross-sectional study, a 55-item web-based questionnaire was designed, which was sent via a link to members of a mailing list of the German Society of Urology. The survey was available for urological senior physicians between February and April 2019. Group differences were evaluated using multivariate regression models. RESULTS: 107 of 192 evaluable questionnaires were completed by senior physicians holding this position for less than 8 years (< 8y senior physicians), 85 were completed by senior physicians holding this position for at least 8 years (≥ 8y senior physicians). < 8y senior physicians worked significantly more often at university hospitals (42.1 % vs. 18.8 %, p = 0.002). Overall, 82.4 % of ≥ 8y senior physicians assessed themselves autonomously safe in performing open surgery, compared to 39.3 % among < 8y senior physicians (p < 0.001). No significant differences concerning the self-assessment were found for endourological procedures (94.1 % vs. 87.9 %) and for the overall lower-rated self-assessment concerning laparoscopy (29.4 % vs. 20.6 %) and robotic surgery (14.1 % vs. 10.3 %). Despite the high management responsibility associated with their position, only about one third of participants (34.8 %) had received specific postgraduate education preparing them for managing and executive tasks. CONCLUSION: This study shows significant differences among senior physicians regarding surgical skills depending on the time span they hold their position. Moreover, there is considerable dissatisfaction regarding the development of leadership skills and the preparation for managing tasks. In order to ensure availability of senior staff members for the field of urology in the future, it is important to consider their professional needs and to overcome existing shortcomings by education programs within well-orchestrated human resources development strategies.

Selective transarterial embolization for posttraumatic renal hemorrhage: a second try is worthwhile.

PURPOSE: Selective percutaneous transarterial embolization has proved to be effective, safe treatment for posttraumatic renal hemorrhage but inefficacious procedures often lead to nephrectomy. Thus, the success rate of transarterial embolization should be maximized. MATERIAL AND METHODS: We retrospectively investigated the clinical success rate of transarterial embolization for posttraumatic bleeding. Study inclusion criteria were imaging evidence and clinical signs of hemorrhage or a hemoglobin decrease of more than 2 gm/dl in urological cases. We excluded spontaneous bleeding from analysis. RESULTS: A total of 21 patients with a median age of 66 years (range 12 to 78) met study inclusion criteria. Etiology was blunt trauma in 3 cases (14%), stab wound in 1 (5%) and an iatrogenic cause in 17 (81%). In 2 patients an active bleeding site could not be detected during selective angiography. Transarterial embolization was done in 19 patients and led to primary clinical success in 12 (63%), including 2 with grade V parenchymal injury. In 6 of 7 cases (86%) in which primary treatment failed transarterial embolization was repeated. It resulted in clinical success in 4 of 6 patients (67%) with equal efficiency (p =1). Three patients (16%) who could not be sufficiently treated with transarterial embolization underwent nephrectomy. CONCLUSIONS: When conservative measures fail and clinical symptoms or a relevant hemoglobin decrease occur, transarterial embolization should be considered. Since the success rate is equally high for initial and repeat interventions, re-intervention is justified when the clinical course allows.

Initial experience with temsirolimus in 2nd-, 3rd- and 4th-line therapy for metastatic renal cell cancer: good clinical response.

PURPOSE: To report our experience with temsirolimus in 2nd-, 3rd- and 4th-line therapy for patients with metastatic renal cell carcinoma (mRCC). PATIENTS AND METHODS: In our prospectively maintained tumor registry, we identified 6 mRCC patients with temsirolimus in >1st-line systemic therapy. Patients were followed by weekly clinical and laboratory examination during admission of temsirolimus. Re-staging with chest CT and abdominal MRI was performed every 3 months. RESULTS: We observed excellent response rates. Progression-free survival (PFS) ranged from 6 to 40 months with a median of 15 months. Treatment was generally well tolerated. However, pneumonitis was observed in 4 of 6 patients. Drug-related pneumonitis led to severe dyspnea, with the result that treatment with temsirolimus had to be interrupted for a short period of time in 2 patients and discontinued in 1 patient. CONCLUSIONS: Temsirolimus proved to be a very good treatment option in 2nd- to 4th-line therapy with excellent response rates and manageable side effects. The incidence of pneumonitis must not be underestimated.

Preoperative hydronephrosis predicts advanced bladder cancer but is not an independent factor for cancer-specific survival after radical cystectomy.

INTRODUCTION: Hydronephrosis and BMI are analyzed together with established factors such as TNM stage and surgical margins in a multivariate modality to investigate their status as independent prognostic factors for bladder cancer-specific survival in patients undergoing radical cystectomy. PATIENTS AND METHODS: We studied a prospective cohort of 328 patients who underwent radical cystectomy for bladder cancer at our institution. Statistical analyses were performed using the Kaplan-Meier method, Kendall-tau rank correlation and multivariate Cox proportional hazard model. RESULTS: Hydronephrosis was positively correlated with advanced tumor stage, positive lymph node involvement and positive surgical margins. Adjusted for all other investigated parameters, BMI and hydronephrosis did not affect cancer-specific survival. In multivariate analysis only non-organ-confined disease (HR: 1.40, 95% CI: 1.04-1.87, p = 0.024), positive lymph node stage (HR 1.71: 95% CI: 1.12-2.61, p = 0.013) and positive surgical margins (HR 3.00, 95% CI: 1.74-5.15, p < 0.001) were prognostic factors. CONCLUSIONS: Hydronephrosis at the time of radical cystectomy is significantly correlated with the presence of more advanced bladder cancer and positive surgical margins. However, the long-established parameters pT stage, pN stage and surgical margins predominantly influence cancer-specific survival for patients undergoing radical cystectomy irrespective of hydronephrosis and BMI status.

Prognostic factors influencing long-term survival of patients undergoing nephron-sparing surgery for nonmetastatic renal-cell carcinoma (RCC) with imperative indications.

BACKGROUND: We assessed the effect of T stage, Fuhrman's grade, multifocality, bilaterality, positive surgical margins, and synchronism of bilateral tumors on cancer-specific survival of patients with nonmetastatic renal-cell carcinoma (RCC) undergoing nephron-sparing surgery for imperative indications. METHODS: We retrospectively analyzed 168 patients who underwent nephron-sparing surgery for imperative RCC indications between 1974 and 2002. A total of 85 patients had bilateral RCCs; in 27 patients, the tumors were multifocal. Multivariate Cox proportional hazards models were fitted to assess the features associated with cancer-specific survival. RESULTS: The median follow-up was 99 months (range, 2-326 months). Patients were followed until January 2008. A total of 52 patients died of their cancer during follow-up. Multivariate analyses of the total group only revealed Fuhrman's grade 3 (hazard ratio [HR] 2.94) and bilateral occurrence of RCC (HR 1.82) as independent prognostic factors. In a subgroup analysis of patients with bilateral occurrence of RCC, we observed a tendency toward positive surgical margins (HR 2.89, P = 0.08) being another negative prognostic factor. There was no difference in cancer-specific survival between patients with synchronous and metachronous bilateral RCC presence (HR 1.08). CONCLUSIONS: Fuhrman's grade 3 and bilateral occurrence of RCC were the only statistically significant prognostic factors for cancer-specific survival in patients undergoing nephron-sparing surgery for imperative indications for nonmetastatic RCC. The presence of sporadic multifocal tumors and the synchronous occurrence of bilateral tumors have no influence on cancer-specific survival, while positive surgical margins may have an impact in the subset of patients with bilateral RCC.

Enhancer of zeste homolog 2 (EZH2) expression is an independent prognostic factor in renal cell carcinoma.

BACKGROUND: The enhancer of zeste homolog 2 (EZH2) gene exerts oncogene-like activities and its (over)expression has been linked to several human malignancies. Here, we studied a possible association between EZH2 expression and prognosis in patients with renal cell carcinoma (RCC). METHODS: EZH2 protein expression in RCC specimens was analyzed by immunohistochemistry using a tissue microarray (TMA) containing RCC tumor tissue and corresponding normal tissue samples of 520 patients. For immunohistochemical assessment of EZH2 expression, nuclear staining quantity was evaluated using a semiquantitative score. The effect of EZH2 expression on cancer specific survival (CSS) was assessed by univariate and multivariate Cox regression analyses. RESULTS: During follow-up, 147 patients (28%) had died of their disease, median follow-up of patients still alive was 6.0 years (range 0-16.1 years). EZH2 nuclear staining was present in tumor cores of 411 (79%) patients. A multivariate Cox regression analysis revealed that high nuclear EZH2 expression was an independent predictor of poor CSS (> 25-50% vs. 0%: HR 2.72, p = 0.025) in patients suffering from non-metastatic RCC. Apart from high nuclear EZH2 expression, tumor stage and Fuhrman's grading emerged as significant prognostic markers. In metastatic disease, nuclear EZH2 expression and histopathological subtype were independent predictive parameters of poor CSS (EZH2: 1-5%: HR 2.63, p = 0.043, >5-25%: HR 3.35, p = 0.013, >25%-50%: HR 4.92, p = 0.003, all compared to 0%: HR 0.36, p = 0.025, respectively). CONCLUSIONS: This study defines EZH2 as a powerful independent unfavourable prognostic marker of CSS in patients with metastatic and non-metastatic RCC.

Prognostic value of tumor necrosis factor-related apoptosis-inducing ligand (TRAIL) and TRAIL receptors in renal cell cancer.

PURPOSE: The death ligand tumor necrosis factor-related apoptosis-inducing ligand (TRAIL) and its receptors (TRAIL-R) are involved in immune surveillance and tumor development. Here, we studied a possible association between the expression of TRAIL/TRAIL-Rs and the prognosis in patients with renal cell carcinomas (RCC). EXPERIMENTAL DESIGN: A tissue microarray containing RCC tumor tissue samples and corresponding normal tissue samples from 838 patients was generated. Expression of TRAIL and TRAIL-Rs was examined by immunohistochemistry and the effect of TRAIL and TRAIL-R expression on disease-specific survival was assessed. RESULTS: High TRAIL-R2 expression levels were associated with high-grade RCCs (P < 0.001) and correlated negatively with disease-specific survival (P = 0.01). Similarly, high TRAIL expression was associated with a shorter disease-specific survival (P = 0.01). In contrast, low TRAIL-R4 expression was associated with high-stage RCCs (P < 0.001) as well as with the incidence of distant metastasis (P = 0.03) and correlated negatively with disease-specific survival (P = 0.02). In patients without distant metastasis, multivariate Cox regression analyses revealed that TRAIL-R2 and TRAIL are independent prognostic factors for cancer-specific survival (in addition to tumor extent, regional lymph node metastasis, grade of malignancy, and type of surgery). CONCLUSION: High TRAIL-R2, high TRAIL, and low TRAIL-R4 expression levels are associated with a worse disease-specific survival in patients with RCCs. Therefore, the assessment of TRAIL/TRAIL-R expression offers valuable prognostic information that could be used to select patients for adjuvant therapy studies. Moreover, our findings are of relevance for a potential experimental therapeutic administration of TRAIL-R agonists in patients with RCCs.

Intestinal reconstruction of the lower urinary tract as a prerequisite for renal transplantation.

OBJECTIVE To report a two-stage protocol for children in whom bladder reconstruction was followed by kidney transplantation, as about a quarter of children requiring a kidney transplantation show significant lower urinary tract dysfunction, and consequently their bladder is unsuitable for a kidney transplant. PATIENTS AND METHODS Twelve children (median age 9.5 years, range 4.2-16.8) with end-stage renal disease had a lower urinary tract reconstruction before kidney transplantation. The cause of bladder dysfunction and renal failure included posterior urethral valves in five, neuropathic bladder in two, prune-belly syndrome in two, anal-rectum and urethral atresia syndrome in one, primary obstructive uropathy in one and caudal regression syndrome in one. Two children were diverted with an ileal conduit; four had a bladder augmentation, and four had a bladder augmentation with additional continent cutaneous stoma. A continent urinary reservoir was constructed in one boy, and one boy had a Mitrofanoff-only procedure. Subsequently, 11 children were transplanted. RESULTS The graft survival rate was 11 of 12 at 1 year and eight of 12 at 5 years. No patient lost the graft related to the reconstructed lower urinary tract. During the median (range) follow-up of 5.4 (1.6-12.5) years all but one child had free drainage of the upper urinary tract. All 10 children who did not have an ileal conduit are continent. CONCLUSION Reconstruction of the lower urinary tract followed by renal transplantation is a safe and efficient approach. It has the advantage of restoring the lower urinary tract before immunosuppressive therapy, and supplies the best possible reservoir for a transplanted kidney.

The enhancer of zeste homolog 2 gene contributes to cell proliferation and apoptosis resistance in renal cell carcinoma cells.

The enhancer of zeste homolog 2 (EZH2) gene has been recently linked to human malignancies where it may serve as a new target for cancer therapy. Here, we analyzed EZH2 expression in primary renal cell carcinoma (RCC) specimens and in nontumorous tissue samples from adult kidney. EZH2 transcripts were detectable in all RCC specimens examined. Expression levels were significantly higher in tumor tissue (p < or = 0.0001) than in samples from normal adult kidney. Moreover, inhibition of endogenous EZH2 expression in RCC cell lines by RNA interference (RNAi) led to reduced proliferation and increased apoptosis in RCC cells. These data show that EZH2 is overexpressed in RCC. Furthermore, they indicate that the EZH2 gene plays a role for both the proliferation and the apoptosis resistance of RCC cells. Targeted inhibition of EZH2 could therefore represent a novel strategy to improve the therapeutic response of RCC.

The influence of body mass index on the long-term survival of patients with renal cell carcinoma after tumour nephrectomy.

OBJECTIVE: To assess whether under- or overweight at the time of surgery has any effect on the survival of the patients with renal cell carcinoma (RCC), as obesity increases the risk of developing RCC. PATIENTS AND METHODS: We prospectively evaluated 780 patients who had nephrectomy for RCC between 1990 and 2005. We used uni- and multivariate Cox proportional hazards models to assess the effect of body mass index (BMI), tumour stage, Fuhrman grade, age, sex, histological type and performance status on cancer-specific survival (CSS). Patients were grouped according to BMI (in kg/m(2)), as underweight (<18.5), normal (18.5-<25), overweight (25-<30) and obese (>or=30). RESULTS: The median (range) follow-up was 5.3 (0.5-15.4) years, the patients being followed until June 2006; 254 patients died during the follow-up. Multivariate analyses of all patients showed that tumour stage, Fuhrman grade, Karnofsky performance status, age, sex and BMI were independent prognostic factors for CSS. While underweight patients had a significantly worse prognosis than those of normal weight, overweight or obese patients had a similar outcome to that of patients of normal weight. In a subgroup analyses including patients with localized RCC only, there was a strong tendency to less aggressive disease in the overweight group (P = 0.081). CONCLUSIONS: Being underweight is an unfavourable and new risk factor for CSS in patients with RCC treated by nephrectomy. Although not significant, there seems to be a limited favourable prognostic effect of overweight on CSS in patients with localized RCC.

High nuclear Livin expression is a favourable prognostic indicator in renal cell carcinoma.

OBJECTIVES: To assess the protein expression of Livin, an apoptosis inhibitor, in renal cell carcinoma (RCC) and to determine its prognostic relevance. PATIENTS AND METHODS: Immunohistochemical staining for Livin was performed in tissue microarrays (TMAs), including tumour tissue cores, from patients with RCC who had undergone renal surgery. In 682 TMAs cytoplasmatic staining intensity and nuclear staining quantity were evaluated, and the association of Livin expression with progression-free survival (PFS) and cancer-specific survival (CSS) was analysed with a multivariate Cox regression model. RESULTS: Over a median (range) follow-up of 5.2 (0-16.1) years, 204 patients (28%) had died from their disease. The CSS rates at 1 and 5 years for the entire cohort was 88% and 71%. Cytoplasmatic Livin staining was absent in 516 (76%) specimens; staining was positive in 166 (24%) specimens. Weak nuclear Livin staining (25%) nuclear Livin expression was a favourable independent predictor of PFS and CSS even after adjusting for tumour stage, Fuhrman grade, age, sex and Karnofsky severity rating. Cytoplasmatic Livin expression did not offer additional prognostic information. CONCLUSION: High nuclear Livin expression is a favourable independent predictor of PFS and CSS in patients with RCC.

Nephrometry Scores: The Effect of Imaging on Routine Read-out and Prediction of Outcome of Nephron-sparing Surgery.

BACKGROUND/AIM: This study investigated the impact of available preoperative imaging on the reliability and predictive accuracy of RENAL and PADUA nephrometry-scoring systems for renal tumors. PATIENTS AND METHODS: Five urologists determined RENAL and PADUA scores using preoperative imaging data (computed tomography and magnetic resonance imaging) of 100 patients admitted for partial nephrectomy with the following combinations: T0: transverse planes without excretory phase (EP), TC0: transverse and coronal planes without EP, TC1: transverse and coronal planes with EP. Reference standard was obtained by a uro-radiologist. Ischemia time was used as surrogate for surgical complexity. RESULTS: Assignment of EP significantly reduced interobserver-variability among urologists (p<0.0001). Predictive accuracy for surgical complexity or correct assignment to nephrometry risk groups did not depend on image planes or EP. CONCLUSION: Interobserver variability, but not predictive accuracy of nephrometric systems, is affected by additional usage of EP.

Bladder Neck Contracture After Radical Prostatectomy: What Is the Reality of Care?

OBJECTIVES: To evaluate the therapeutic methods and algorithms currently used in the treatment of bladder neck contracture (BNC) after radical prostatectomy (RP). MATERIALS AND METHODS: Heads of 170 urologic departments in Germany, listed at the German Society of Urology (DGU), were invited to participate in an Internet-based customized survey. The questions consisted of an epidemiologic part (kind of hospital, state of practice) and questions inquiring used surgical techniques with their respective incidence and given algorithms for therapy. RESULTS: Of 170 contacted heads of urologic departments in Germany, 84 responded to the questionnaire (return rate 49.41%). The most common treatment modalities are transurethral resection, cold knife incision, hot knife incision, and dilation in descending order. For those institutions using several treatment modalities, 56 (66.67%) follow a therapeutic algorithm, while 28 (33.33%) follow no set order of treatment. However, among the 56 institutions with a set algorithm, 33 different approaches were identified. Of 84 institutions, 29 (34.52%) perform open reanastomosis in case of recurrent BNC, the remaining 55 (65.48%) do not. CONCLUSION: Despite several published guidelines on urethral strictures, numerous self-employed treatment algorithms are used to treat BNC. Although treatment results of these algorithms and the underlying treatment modalities cannot be determined with this work, it highlights the necessity for further studies comparing the different surgeries to allow for a more evidence-based approach.