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Abstract: Background: Outcome of patients with urothelial carcinoma of the bladder (UCB) varies between sexes. Although overall incidence is higher in men, cancer-specific survival (CSS) has been suggested to be lower in women. Although the former effect is attributed to greater exposure to carcinogens in men, the latter has not been elucidated. Objectives: The aim of the study was to identify sex-specific outcomes based on one of the largest databases of patients with UCB who underwent radical cystectomy (RC). Methods: This retrospective multicenter series comprised 2483 patients in Stage M0 who underwent RC for UCB from 1989 to 2008; 20.4% of patients were women. The impact of sex on CSS in the entire study group and in specific subgroups was analyzed. The median follow-up time was 42 months (interquartile range, 21–79). Results: Histopathologic criteria of pathologic tumor (pT), pathologic nodal (pN), grade, lymphovascular invasion (LVI), and associated carcinoma in situ (CIS) of the study did not differ between sexes. The percentage of female patients increased over time. Five-year CSS in female patients was significantly lower than in male patients (60% vs 66%; P = 0.005). In multivariate analysis adjusted to other covariates, tumor stage ≥pT3 (hazard ratio [HR] = 2.44; P < 0.001), positive pN status (HR = 1.91; P < 0.001), LVI (HR = 1.48; P < 0.001), lower count of lymph nodes removed (HR = 0.98; P = 0.002), older age (HR = 1.01; P < 0.001), and female gender (HR = 1.26; P = 0.011) had an independent impact on CSS. Deterioration of CSS in female patients was pronounced when LVI was present (HR = 1.57; P < 0.001) and when RC was performed in the earlier time period (HR = 2.44; P < 0.001). However, women showed significantly lower perioperative mortality (within 90 days after RC) compared with men. Conclusions: After RC for UCB, cancer-specific mortality was higher in female patients; this disadvantage was more pronounced in earlier time periods. In addition, worse outcome of women with verified LVI was shown to be comparable with men. These findings were suggestive of different tumor biology and potentially unequal access to timely RC in earlier time periods because of reduced awareness of UCB in women. Further studies are required to improve UCB outcome in both sexes, notably in female patients. [Copyright &y& Elsevier]

Docetaxel had been the only treatment of castration-resistant prostate cancer (CRPC) that demonstrated a survival benefit for the patients. After its approval, no considerable progress has been made for several years until cabazitaxel and abiraterone acetate demonstrated a significant survival benefit in phase III clinical trials. Apart from that several other new drugs appeared including inhibitors of the androgen receptor (MDV3100), endothelin receptor antagonists (atrasentan, zibotentan), bone-targeted drugs (denosumab, Alpharadin) and immunotherapies (sipuleucel-T) capable of improving the prognosis of patients with CRPC. Here, we review the most recent advances in the treatment of CRPC and highlight the most promising new agents currently being investigated in clinical trials. [ABSTRACT FROM AUTHOR]

Purpose: Patients with stage pT3N0 urothelial bladder cancer vary in outcome after radical cystectomy. To improve prognosis estimation a model was recently developed that defines 3 risk groups for recurrence-free survival based on pT substaging, lymphovascular invasion and positive surgical margin. We present what is to our knowledge the first external validation of this risk model. Materials and Methods: Analogous to the risk model derivation cohort our study group comprised 472 patients with stage pT3, pN0, cM0 disease without perioperative chemotherapy and with a median followup of 42 months (IQR 20–75). The primary end point was recurrence-free survival. The effect of variables was determined by univariate and multivariate Cox regression analysis, and predictive accuracy was determined by ROC analysis. Results: Stage pT3aN0 and pT3bN0 cases showed significantly different recurrence-free survival after 5 years (51% vs 29%, p <0.001). In the multivariate Cox model pT3 substage (HR 1.86, p <0.001), lymphovascular invasion (HR 1.48, p = 0.002), positive surgical margins (HR 1.90, p = 0.030) and patient age with a dichotomy at 70 years (HR 1.51, p = 0.001) had an independent effect on recurrence-free survival. In the low (221 patients or 47%), intermediate (184 or 39%) and high (67 or 14%) risk groups the 5-year recurrence-free survival rate was 55%, 45% and 13%, respectively (p <0.001). The concordance index of the risk model to predict recurrence-free survival was 0.64 (95% CI 0.59–0.69). Conclusions: This user friendly risk model can be recommended to estimate prognosis in patients with stage pT3N0 after radical cystectomy. Patients at high risk showed clearly compromised recurrence-free survival and should be included in adjuvant therapy studies. [ABSTRACT FROM AUTHOR]

Background: A larger number of dissected lymph nodes (LN) during pelvic lymphadenectomy in patients with muscle-invasive transitional-cell carcinoma of the bladder treated by radical cystectomy (RC) is crucial for exact tumor staging and is associated with a positive oncological outcome. Methods: Clinical and pathological records of 1291 patients undergoing RC due to LN-negative transitional-cell carcinoma of the bladder were summarized and evaluated in a multi-institutional database. The number of removed LNs and the presence or absence of lymphovascular invasion were assessed. On the basis of multivariate Cox regression analyses, a threshold number of removed LNs was defined that exerted an independent influence on cancer-specific survival (CSS). Results: In multivariate Cox regression models for different numbers of removed LNs, a statistically significant enhancement of CSS could be demonstrated for a LN count of 16. Furthermore, the integration of the dichotomized LN count of 16 resulted in a statistically significantly enhanced predictive ability of the model for CSS. Patients with <16 and ≥16 removed LNs showed CSS rates after 5 years of 72% and 83%, respectively ( P = 0.01). In addition, age, sex, pT stage, and lymphovascular invasion had independent influences on CSS in every Cox regression model. Conclusions: In patients undergoing RC, removal of a higher LN count is associated with an improved oncological outcome. The information resulting from an assessment of lymphovascular invasion and an extended lymphadenectomy is critical for stratification of risk groups and identification of patients who might benefit from adjuvant treatment. [ABSTRACT FROM AUTHOR]

Purpose: Enhanced surgical techniques and standardised selection criteria have led to a higher rate of nerve-sparing (NS) radical prostatectomy (RP) procedures. The aim of this study was to evaluate the clinical value of intraoperative frozen sections (IFS) during nerve-sparing radical prostatectomy (NSRP). Materials and methods: Thousand and eighty-three patients with localised prostatic carcinoma were treated using retropubic RP (from 2004 to 2006). Two hundred and eighty-seven of the 1083 documented cases received NS. One hundred and thirty procedures were carried out with IFS from the area of the neurovascular bundles and 157 without IFS. The decision to use IFS was made intraoperatively and based on clinical suspicion of possible positive resection margins in the area of the bundles. Results: In the NS group with IFS, the results revealed positive margins in nine (6.9%) out of 130 cases, resulting in subsequent resection of the ipsilateral neurovascular bundle. The final histological report on this group revealed four additional patients (3.1%) with positive margins, but only one (0.7%) in the area of the previous neurovascular bundle. The final histopathologic reports on the 157 NS cases without IFS showed that the positive margin was in the area of the previous neurovascular bundle in only one (0.6%) of the nine cases with positive margins (5.7%). Conclusion: According to our data, there is no need for routine IFS during NSRP. The negative predictive value for infiltration of the NVB is high, and IFS can be dispensed with. Intraoperative biopsies should be taken in those cases where the surgeon is in doubt about the resection margins in the area of bundles. [ABSTRACT FROM AUTHOR]

Purpose: We examined papillary renal cell carcinoma prognostic variables and validated the 2002 UICC TNM staging system in a multicenter analysis. Materials and Methods: From 10 urological institutions in Germany followup data were collected on a total of 675 patients with papillary renal cell carcinoma. Central pathological review was done to validate external histopathological diagnoses. The Kaplan-Meier method was used to derive cumulative cancer specific and overall survival, and the log rank test was used to compare the curves of 2 or more groups. For multivariate analysis of prognostic factors Cox regression analysis was done. All proportional hazard assumptions were systemically verified using the Grambsch-Therneau test. Results: Cancer specific survival was significantly related to TNM stage and histological grading on univariate and multivariate analyses. Five-year cancer specific survival in pT1b cases was significantly shorter than in pT1a cases (90.0% vs 98.3%, p = 0.017). No significant difference was found between pT1b and pT2 tumors. Patients with pT3 or greater disease were at high risk for metastasis (50.6%) while metastatic disease associated with pT2 or less tumors occurred in 7.8% (p <0.0001). After metastatic disease was present the prognosis was poor with 7.2% 5-year cancer specific survival. Age was associated with poor prognosis in the subgroup with pT3 or greater tumors on univariate analysis (p = 0.026) but not on multivariate analysis. Conclusions: In its current form the 2002 UICC TNM staging system is not applicable to papillary renal cell carcinoma. Clinical and radiological followup should be offered at frequent intervals to patients with venous thrombus and/or locally advanced disease. The role of age remains unclear but should not be underestimated in risk stratification after surgery. [Copyright &y& Elsevier]

To evaluate intravesical paclitaxel monotherapy and combined treatment with antiapoptotic bcl-xL antisense oligodeoxynucleotides (AS-ODNs) on urothelial carcinoma (UC). Forty-eight FoxNrnu athymic nude rats with orthotopic human bladder UC were randomized to four treatment groups [1, paclitaxel; 2, paclitaxel/bcl-xL AS-ODNs; 3, bcl-xL AS-ODNs (control); 4, medium (control)]. Three consecutive instillations were applied and weekly endoscopic tumor size measurements were performed. Significant tumor size reduction was achieved in groups 1 and 2 (each P < 0.0001), whereas continuous UC growth was observed in control animals (groups 3 and 4; P < 0.0001 and P < 0.0020). Complete tumor eradication was achieved in four treated animals (groups 1 and 2). No significant difference in chemoresection effects was found between groups 1 and 2 ( P = 0.2251). We present an in vivo evaluation of intravesical treatment with paclitaxel and combined bcl-xL AS-ODNs. Despite efficient tumor size reduction, no gain was observed when adding bcl-xL AS-ODNs in this experimental setting. [ABSTRACT FROM AUTHOR]

Despite the large number of surgical techniques for continent cutaneous diversion described in literature, the creation of a reliable, continent and easily catheterizable continence mechanism remains a complex surgical procedure. Aim of this study was the evaluation of a new method for a catheterizable continence mechanism using stapled pig intestine. Small and large pig intestines were used for construction. A 3 or 6 cm double row stapling system was used. Three variations using small and large intestine segments were constructed. A 3 or 6 cm long stapler line was placed alongside a 12 Fr catheter positioned at the antimesenterial side creating a partially two-luminal segment. Construction time for the tube was measured. The created tube was then embedded into the pouch. Pressure evaluation of the continence mechanism was performed for each variation. Intermittent external manual compression was used to simulate sudden pressure exposure. All variations were 100% continent under filling volumes of up to 700 ml and pressure levels of 58 ± 6 cm H2O for large intestine and 266 ml and 87 ± 18 cm H2O for small intestine, respectively. With further filling above the mentioned capacity suture insufficiency occurred but no tube insufficiency. Construction time for all variations was less than 12 min. The described technique is an easy and fast method to construct a continence mechanism using small or large intestine. Our ex vivo experiments have shown sufficient continence situation in an ex-vivo model. Further investigations in an in-vivo model are needed to confirm these results. [ABSTRACT FROM AUTHOR]