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Background Treatment of patients with stage pT1 urothelial bladder cancer (UBC) continues to be a challenge due to its unpredictable clinical course. Reliable molecular markers that help to determine appropriate individual treatment are still lacking. Loss of aquaporin (AQP) 3 protein expression has previously been shown in muscle-invasive UBC. The aim of the present study was to investigate the prognostic value of AQP3 protein expression with regard to the prognosis of stage pT1 UBC. Method AQP 3 protein expression was investigated by immunohistochemistry in specimens of 87 stage T1 UBC patients, who were diagnosed by transurethral resection of the bladder (TURB) and subsequent second resection at a high-volume urological centre between 2002 and 2009. Patients underwent adjuvant instillation therapy with Bacillus Calmette-Guérin (BCG). Loss of AQP3 protein expression was defined as complete absence of the protein within the whole tumour. Expression status was correlated retrospectively with clinicopathological and follow-up data (median: 31 months). Multivariate Cox regression analysis was used to assess the value of AQP3 tumour expression with regard to recurrence-free (RFS), progression-free (PFS) and cancer-specific survival (CSS). RFS, PFS and CSS were calculated by Kaplan-Meier analysis and Log rank test. Results 59% of patients were shown to exhibit AQP3-positive tumours, whereas 41% of tumours did not express the marker. Loss of AQP3 protein expression was associated with a statistically significantly worse PFS (20% vs. 72%, p=0.020). This finding was confirmed by multivariate Cox regression analysis (HR 7.58, CI 1.29 – 44.68; p=0.025). Conclusions Loss of AQP3 protein expression in pT1 UBC appears to play a key role in disease progression and is associated with worse PFS. Considering its potential prognostic value, assessment of AQP3 protein expression could be used to help stratify the behavior of patients with pT1 UBC.

Objective To assess the impact of detailed clinical and histopathological criteria on gender-dependent cancer-specific survival (CSS) in a large consecutive series of patients following radical cystectomy (RCE) for muscle-invasive bladder cancer (MIBC). Patients and methods Between 1992 and 2007, 388 men and 133 women (25.5%) underwent RCE for MIBC. A prospectively maintained database was analysed retrospectively. Uni- and multivariable Cox-regression analyses calculated the impact of detailed clinical and histopathological criteria on CSS. Median follow-up was 59 months (2–162). Results Among clinical and histopathological parameters, only type of urinary diversion differed between men and women. In univariable analysis, CSS did not differ between genders. In multivariable Cox-regression analysis, advanced pT-stage (HR = 2.12; P  < 0.001), lymphovascular invasion (LVI) (HR = 3.47; P  < 0.001), time interval between diagnosis of MIBC and RCE exceeding 90 days (HR = 2.07; P  < 0.001) and female gender (HR = 1.35; P  = 0.048) were related to reduced CSS. In separate multivariable Cox-models for time period of surgery between 1992 an 1999 (HR = 1.52; P  = 0.050), age ≤55 years (HR = 3.00; P  = 0.022), presence of LVI (HR = 1.45; P  = 0.031) and female gender were associated with independent reduced CSS. Conclusion Established clinical and histopathological parameters do not differ significantly between both genders in the present series. Reduced CSS in women is present in historic cohorts possibly suggesting improvement in management over the last years. In particular, female gender has a significant negative impact on CSS in patients younger of age and with positive LVI status possibly suggesting different clinical phenotypes.

Purpose To evaluate the still controversially discussed prognostic role of preoperative platelet level (PPL) and thrombocytosis (TC) in patients who undergo surgery for renal cell carcinoma (RCC) based on the largest patient series reported to date. Methods A total of 3,139 patients, who underwent radical or nephron-sparing nephrectomy at four centres, were subdivided based on a threshold for preoperative platelets of 400 × 10 9 cells/L. Univariate and multivariable Cox regression analyses were applied to determine the prognostic influence of PPL and TC on cancer-specific survival (CSS) for patients with localized and metastatic disease at presentation. Results Group 1 (PPL ≤ 400/nl) and Group 2 (PPL > 400/nl) included 2,862 (91 %) and 277 patients (9 %), respectively. With a median follow-up (FU) of 69.5 months (IQR: 35–105), CSS of all patients after 5 years was 84.6 % in Group 1 versus 53.4 % in Group 2 ( p  < 0.001). At multivariable analysis, TC (HR:1.337; p  = 0.007) and continuous PPL (HR:1.001; p  = 0.002) independently predicted a decreased survival. However, integration of these parameters into multivariable models for the entire study group and for patients with localized tumours did only result in marginal improvement of the model quality (0.66 and 1.04 %, respectively). Interestingly, neither TC ( p  = 0.257) nor PPL ( p  = 0.132) significantly influenced survival in M1 patients. Conclusions Preoperative TC turned out an independent predictor for decreased CSS in patients undergoing surgery for localized RCC. However, significant improvement of multivariable models comprising standard clinical and pathological parameters by the inclusion of TC is not achieved. In metastatic disease, TC did not reveal an independent influence on CSS.

Objectives: We studied the role of minor mismatch repair proteins (MMR) human MutL homologue 1 (hMLH1) and human MutS homologue 2 (hMSH2) in the main subtypes of renal cell carcinoma (RCC). Methods: Expression of MMR proteins hMLH1 and hMSH2 were investigated in 166 RCC tumors, containing the main subtypes by immunohistochemistry. Furthermore, each tumor was screened for microsatellite instability (MSI) using the National Cancer Institute consensus panel for hereditary non-polyposis colon carcinoma as well as for elevated microsatellite alterations at selected tetranucleotide repeats (EMAST) by 10 additional markers. Results: MSI was found only in 2.0% of analyzable cases and EMAST was detected only in 1 patient. hMLH1 and hMSH2 expression was reduced in 83.7 (118/141) and 51.2% (65/127) of cases, respectively, in a subtype-specific manner. None of the clear cell RCC tumors retained a high hMLH1 expression and 92.0% lost hMLH1 completely, while papillary and chromophobe RCC preserved the expression in 25.0 and 33.3% of cases (p < 0.001). Subtype specificity was also present in hMSH2 staining, where chromophobe RCC retained a high expression in 41.7% of cases, while clear cell and papillary tumors did not (29.9 and 23.1%; p = 0.01). Conclusion: MSI and EMAST are rare events in sporadic RCC, whereas diminished MMR protein expression is linked to tumor entity and might contribute to the different biological behavior of the RCC subtypes.

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.

Objective To determine which pretreatment clinical parameters were predictive of a low prostate-specific antigen (PSA) nadir following high-intensity focused ultrasound (HIFU) treatment. Patients and methods Retrospective study of patients with clinically localised prostate cancer undergoing HIFU at a single centre between December 1997 and September 2009. Whole-gland treatment was applied. Patients also included if they had previously undergone transurethral resection of the prostate (TURP). TURP was also conducted simultaneously to HIFU. Biochemical failure based on Phoenix definition (PSA nadir + 2). Univariate and multivariate analysis of pretreatment clinical parameters conducted to assess those factors predictive of a PSA nadir ≤0.2 and >0.2 ng/ml. Results Mean (SD) follow-up was 6.2 (2.8) years; median (range) was 6.3 (1.1–12.2) years. Kaplan–Meier estimate of biochemical disease-free survival rate at 8 years was 83 and 48 % for patients achieving a PSA nadir of ≤0.2 and >0.2 ng/ml, respectively. Prostate volume and incidental finding of cancer were significant predictors of low PSA nadir (≤0.2 ng/ml). Conclusions Prostate volume and incidental finding of cancer could be predictors for oncologic success of HIFU based on post-treatment PSA nadir.

A 61-year-old man presented with hematuria and intermittent right pelvic pain. Intravenous urography showed a tubular filling defect and ureteroscopy a tumor in the right mid ureter. Urine cytology and tumor biopsy showed nonmalignant results. Open surgery was performed, and an intraoperative frozen section revealed a fibroepithelial polyp of the right mid ureter. A fibroepithelial polyp is a rare benign lesion that can occur in childhood but is an important differential diagnosis of an upper urinary tract urothelial cell carcinoma in adults.

NAD(P)H:quinone oxidoreductase 1 (NQO1) catalyses the reduction of quinoid compounds to hydroquinones, preventing the generation of free radicals and reactive oxygen. A “C” to “T” transversion at position 609 of NQO1, leading to a nonsynonymous amino acid change (Pro187Ser, P187S), results in an altered enzyme activity. No NQO1 protein activity was detected in NQO1 609TT genotype, and low to intermediate activity was detected in NQO1 609CT genotype compared with 609CC genotype. Thus, this polymorphism may result in altered cancer predisposition. For prostate cancer, only sparse data are available. We therefore analyzed the distribution of the NQO1 P187S SNP (single nucleotide polymorphism) in prostate cancer patients and a healthy control group. Allelic variants were determined using RFLP analysis. Overall, 232 patients without any malignancy and 119 consecutive prostate cancer patients were investigated. The genotype distribution in our cohorts followed the Hardy–Weinberg equilibrium in cases and controls. The distribution of the NQO1 codon 187 SNP did not differ significantly between prostate cancer patients and the control group (p = 0.242). There was also no association between the allelic variants and stage or Gleason score of the tumors. The NQO1 P187S SNP was not significantly associated with an increased prostate cancer risk in our cohorts. The SNP has also no influence on histopathological characteristics of the tumors. A combined analysis of all available data from published European studies also showed no significant differences in the genotype distribution between controls and prostate cancer patients. Our data suggest a minor role of the NQO1 nucleotide 609 polymorphism in prostate carcinogenesis.

Purpose To investigate cancer detection rates and percentage of tumour per core between real-time sonoelastography (RTE) targeted biopsy and lateralised tenfold random biopsy of the prostate in the primary and re-biopsy setting. Methods Patients undergoing primary or re-biopsy of the prostate were included. Systematic RTE (EUB 7500, Hitachi Medical Systems, Tokio, Japan) was performed with the patient in the left lateral position. A maximum of four RTE targeted biopsies of the peripheral zone were taken following by a lateralised tenfold biopsy done by a second investigator blinded to the RTE findings. RTE targeted and random biopsy cylinders from corresponding areas were compared for percentage of tumour per core. Chi-square test and Wilcoxon signed rank test were used to compare differences between different groups. Results One hundred and thirty-nine patients were included (52 with primary biopsy, 87 with re-biopsy). Prostate cancer was found in 73 (52.5%) patients. Cancer detection rates per core were 23.2% versus 9.2% and 21.9% versus 12.7% for RTE targeted and random biopsies in the primary and re-biopsy setting, which was statistically significant ( P  < 0.05). The mean percentage of prostate cancer per core from corresponding areas was significantly higher in RTE targeted compared to random biopsy cores with 21.5% versus 16.4% ( P  < 0.05). Conclusions RTE targeted biopsy significantly increases cancer detection rates per core in comparison with random biopsy. The difference is more pronounced in the primary biopsy setting. RTE targeted biopsy cores are of improved diagnostic value due significantly higher percentages of cancer compared to random biopsy cores.