Study Type – Therapy (case series) Level of Evidence 4 What's known on the subject? and What does the study add? The reported discordance between staging on transurethral bladder resection and on radical cystectomy pathology in the literature ranges from 20 to 80%.Correct staging in bladder cancer has direct implications for its management. The upstaging from organ‐confined (OC) to non‐organ‐confined (nOC) disease has been reported in 40% of cases. Lymphovascular invasion (LVI) is a factor known to be associated with poor clinical outcome. Pathological upstaging was observed in our cohort in 40% of cases and most cases (80%) were upstaged from OC to nOC disease. During the study period the frequency of upstaging observed increased. We found LVI (hazard ratio [HR]= 5.07, 95% CI = 3.0–8.3, P < 0.001) and any histological variant variant (HR = 2.77, 95% CI = 1.6–4.8, P < 0.001) to be strong independent predictors of upstaging. Patients with clinical T2 bladder cancer found with upstaging at the time of radical cystectomy had a poorer outcome than patients with no upstaging. Identification of patients at high risk of upstaging at radical cystectomy is key to improving their management and outcome. OBJECTIVES To analyse the details of bladder cancer (BC) staging in a large combined radical cystectomy (RC) database from two academic centres. To study rate and time trends, as well as risk factors for upstaging, especially clinical factors associated with staging errors after RC. PATIENTS AND METHODS Characteristics of patients undergoing RC at University Health Network, Toronto, Canada (1992–2010) and University of Turku, Turku, Finland (1986–2005) were analysed. RESULTS Among 602 patients undergoing RC, 306 (51%) had a discordance in clinical and pathological stages. Upstaging occurred in 240 (40%) patients and 192 (32%) patients were upstaged from organ‐confined (OC) to non‐organ‐confined (nOC) disease. During the study period, upstaging became more common in both centres. In multivariate analyses, T2 disease at initial presentation ( P = 0.001, odds ratio [OR]= 2.62, 95% confidence interval [CI]: 1.44–4.77), high grade disease ( P = 0.01, OR = 2.85, 95% CI: 1.21–6.7), lymphovascular invasion (LVI) ( P < 0.001, OR = 5.17, 95% CI: 3.48–7.68), female gender ( P = 0.038, OR = 0.6, 95% CI: 0.38–0.97, and histological variants ( P < 0.001, OR = 2.77, 95% CI: 1.6–4.8) were associated with a risk of upstaging from OC to nOC disease. Upstaged patients had worse survival rates than patients with correct staging. This was especially significant among patients with carcinoma invading bladder muscle before undergoing RC (16% vs 46% 10‐year disease‐specific mortality, P < 0.001). CONCLUSIONS Upstaging is a common problem and unfortunately no improvements have been observed during the last two decades. LVI and the presence of histological variants are strong predictors of upstaging at the time of RC. Pathologists should be encouraged to report LVI and any histological variant at the time of TURBT.

BACKGROUND. Many critical events in prostatic carcinogenesis appear to relate to the emergence of genomic instability. Characteristic genomic abnormalities such as 8p loss, 8q gain, trisomy 7, and PTEN microdeletions may provide selective advantages to increase neoplastic transformation. Evidence suggests that telomere dysfunction is a plausible mechanism for some of these abnormalities on the basis of the break-fusion-bridge cycle that can lead to manifestations of genomic instability.METHODS. In this study, we correlate telomere length measured by quantitative FISH in various prostatic histologies with markers of genomic instability and immunohistochemical measures of proliferation and oxidative stress.RESULTS. We find that telomere shortening is correlated with abnormalities on chromosome 8, but not with trisomy 7 or abnormalities of the PTEN locus. There are associations with C-MYC aberrations in stroma with greater proximity to cancer and a correlation between telomere length in a number of prostatic histologies and the adjacent stroma, suggesting the importance of microenvironmental effects on telomere maintenance in the prostate. This finding was also supported by the finding of the correlation between telomere attrition and the levels of oxidative stress as measured by malondialdehyde staining in HPIN lesions close to cancer.CONCLUSIONS. Telomere attrition in the prostate gland is associated with particular genomic aberrations that contribute to the genomic instability characteristic of prostatic carcinogenesis. Correlations between various histologies and adjacent stroma telomere length suggest it is also may reveal microenvironmental effects within the prostate gland. Oxidative stress may contribute to telomere attrition in HPIN close to cancer. Prostate 71: 778-790, 2011. (C) 2010 Wiley-Liss, Inc.

Atrazine (ATZ) is probably the most widely used herbicide in the world. However there are still many controversies regarding its impacts on human health. Our investigations on the role of pesticides in liver dysfunctions have led us to detect an inhibition of FSP1 expression of 70% at 50 μm and around 95% at 500 μM of ATZ (p < 0.01). This gene encodes the protein S100a4 and is a clinical biomarker of epithelial–mesenchymal transition (EMT), a key step in the metastatic process. Here we investigated the possible effect of ATZ on cell migration and noticed that it prevents the EMT and motility of the HepG2 cells induced by the phorbol ester TPA. ATZ decreases Fak pathway activation but has no effect on the Erk1/2 pathway known to be involved in metastasis in this cell line. These results suggest that ATZ could be involved in cell homeostasis perturbation, potentially through a S100a4-dependant mechanism.

Complex statistical models utilizing multiple inputs to derive a risk assessment may benefit prostate cancer (PC) detection where focus has been on prostate-specific antigen (PSA). This study develops a polychotomous logistic regression (PR) model and an artificial neural network (ANN) for predicting biopsy results, particularly for clinically significant PC.

Histological heterogeneity in renal cell carcinoma (RCC) has the potential to lead to misleading biopsy results that may impact on patient management. The purpose of this study was to assess concordance of histology after percutaneous renal mass biopsy performed on 2 separate occasions, as well as concordance between biopsy results and subsequent nephrectomy specimens. Ethics board approval was obtained for this retrospective review of all patients at 2 hospitals who had percutaneous biopsy of a renal mass from Jan. 2004 to Sept. 2009. There were 325 biopsies of 281 renal masses in 271 patients. Maximum tumor diameter was 0.6-17.9 cm (mean 3.1). Patient age range was 19-88 years (mean 63). 27 masses had two diagnostic quality biopsies (with the 2nd biopsy performed just prior to ablation): tumor diameter was 0.8-4.2 cm (mean 2.6), with 9-855 days between biopsies (mean 156). 64 patients treated with nephrectomy had a diagnostic quality biopsy prior to surgery. Full histology for RCC, defined as having Fuhrman grading reported, was available for 17 of the 27 pairs of repeated biopsies, and for 50 of the 64 patients who had a single biopsy followed by nephrectomy. Low grade vs. high grade RCC was defined as Fuhrman grade 1 or 2 vs. 3 or 4, respectively. Diagnostic repeat biopsies revealed a concordance for tumor type of 26/27 (96%) and for histopathological subtype (e.g. clear clear) of 21/27 (78%). Exact histological concordance for repeat biopsies was 12/17 (71%), with low vs. high grade concordance of 16/17 (94%). In patients who had one diagnostic biopsy prior to nephrectomy, concordance of tumor type was 64/64 (100%), of histopathologic subtype 58/64 (891%), and exact histological concordance was 29/50 (58%), with low vs. high grade concordance of 44/50 (88%). There is only moderate exact histological concordance between two separate renal mass biopsy results (71%), or between biopsy result and nephrectomy specimen (58%). When considering low vs. high Fuhrman grading, however, which may be more relevant to decision-making regarding patient management, concordance between 2 separate biopsies and between biopsy and nephrectomy is high (94% and 88%, respectively).

Prostate cancer is a leading cause of cancer death for men in the United States. There is currently no widely adopted accurate noninvasive method for localizing prostate cancer using imaging. If such as technique were available it could be used to guide biopsy, radiotheraphy and surgery. However, current imaging techniques are limited due to inability to detect cancers, intensity changes related to non-malignant pathologies and interobserver variability. Recently, multispectral magnetic resonance imaging (MRI) has emerged as a promising noninvasive method for the localization of prostate cancer alternative to transrectal ultrasound (TRUS). This paper develops automated methods for prostate cancer localization with conditional random fields using multispectral MRI. We propose to combine cost-sensitive Support Vector Machines with Conditional Random Fields and show that this method results in higher accuracy of localization compared to other common methods. Our results also show that multispectral modality images helps to increase the accuracy of prostate cancer localization. Using multispectral MR images, we demonstrate the effectiveness of each algorithm by testing them on real data sets and compare them to recently proposed SVMstruct and Conditional Random Fields.

Prostate cancer is one of the leading causes of cancer death for men. However, early detection before cancer spreads beyond the prostate can reduce the mortality. Therefore, in vivo imaging techniques play an important role to localize the prostate cancer for treatment. Although magnetic resonance imaging (MRI) has been proposed to localize prostate cancer, the studies on automated localization with multispectral MRI have been limited. In this study we propose combining the pharmacokinetic parameters derived from DCE MRI with T2 MRI and DWI. We also propose to use relevance vector machines (RVM) for automatic prostate cancer localization, compare its performance to support vector machines (SVM) and show that RVM can produce more accurate and more efficient segmentation results than SVM for automated prostate cancer localization with multispectral MRI.

Prostate cancer is the second leading cause of cancer death in American men. Current prostate MRI can benefit from automated tumor localization to help guide biopsy, radiotherapy and surgical planning. An important step of automated prostate cancer localization is the segmentation of the prostate. In this paper, we propose a fully automatic method for the segmentation of the prostate. We firstly apply a deformable ellipse model to find an ellipse that best fits the prostate shape. Then, this ellipse is used to initiate the level set and constrain the level set evolution with a shape penalty term. Finally, certain post processing methods are applied to refine the prostate boundaries. We apply the proposed method to real diffusion-weighted (DWI) MRI images data to test the performance. Our results show that accurate segmentation can be obtained with the proposed method compared to human readers.