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The 2009 International Society of Urological Pathology Consensus Conference in Boston made recommendations regarding the standardization of pathology reporting of radical prostatectomy specimens. Issues relating to the handling and processing of radical prostatectomy specimens were coordinated by working group 1. Most uropathologists followed similar procedures for fixation of radical prostatectomy specimens, with 51% of respondents transporting tissue in formalin. There was also consensus that the prostate weight without the seminal vesicles should be recorded. There was consensus that the surface of the prostate should be painted. It was agreed that both the prostate apex and base should be examined by the cone method with sagittal sectioning of the tissue sample. There was consensus that the gland should be fully fixed before sectioning. Both partial and complete embedding of prostates was considered to be acceptable as long as the method of partial embedding is stated. No consensus was determined regarding the necessity of weighing and measuring the length of the seminal vesicles, the preparation of whole mounts rather than standardized blocks and the methodology for sampling of fresh tissue for research purposes, and it was agreed that these should be left to the discretion of the working pathologist.

The International Society of Urological Pathology Consensus Conference on Handling and Staging of Radical Prostatectomy Specimens in Boston made recommendations regarding the standardization of pathology reporting of radical prostatectomy specimens. Issues relating to extraprostatic extension (pT3a disease), bladder neck invasion, lymphovascular invasion and the definition of pT4 were coordinated by working group 3. It was agreed that prostate cancer can be categorized as pT3a in the absence of adipose tissue involvement when cancer bulges beyond the contour of the gland or beyond the condensed smooth muscle of the prostate at posterior and posterolateral sites. Extraprostatic extension can also be identified anteriorly. It was agreed that the location of extraprostatic extension should be reported. Although there was consensus that the amount of extraprostatic extension should be quantitated, there was no agreement as to which method of quantitation should be employed. There was overwhelming consensus that microscopic urinary bladder neck invasion by carcinoma should be reported as stage pT3a and that lymphovascular invasion by carcinoma should be reported. It is recommended that these elements are considered in the development of practice guidelines and in the daily practice of urological surgical pathology.

Background Up to 40% of patients initially diagnosed with clinically-confined renal cell carcinoma (RCC) and who undergo curative surgery will nevertheless relapse with metastatic disease (mRCC) associated with poor long term survival. The discovery of novel prognostic/predictive biomarkers and drug targets is needed and in this context the aim of the current study was to investigate a putative caveolin-1/ERK signalling axis in clinically confined RCC, and to examine in a panel of RCC cell lines the effects of caveolin-1 (Cav-1) on pathological processes (invasion and growth) and select signalling pathways. Methods Using immunohistochemistry we assessed the expression of both Cav-1 and phosphorylated-ERK (pERK) in 176 patients with clinically confined RCC, their correlation with histological parameters and their impact upon disease-free survival. Using a panel of RCC cell lines we explored the functional effects of Cav-1 knockdown upon cell growth, cell invasion and VEGF-A secretion, as well Cav-1 regulation by cognate cell signalling pathways. Results We found a significant correlation ( P  = 0.03) between Cav-1 and pERK in a cohort of patients with clinically confined disease which represented a prognostic biomarker combination (HR = 4.2) that effectively stratified patients into low, intermediate and high risk groups with respect to relapse, even if the patients’ tumours displayed low grade and/or low stage disease. In RCC cell lines Cav-1 knockdown unequivocally reduced cell invasive capacity while also displaying both pro-and anti-proliferative effects; targeted knockdown of Cav-1 also partially suppressed VEGF-A secretion in VHL-negative RCC cells. The actions of Cav-1 in the RCC cell lines appeared independent of both ERK and AKT/mTOR signalling pathways. Conclusion The combined expression of Cav-1 and pERK serves as an independent biomarker signature with potential merit in RCC surveillance strategies able to predict those patients with clinically confined disease who will eventually relapse. In a panel of in-vitro RCC cells Cav-1 promotes cell invasion with variable effects on cell growth and VEGF-A secretion. Cav-1 has potential as a therapeutic target for the prevention and treatment of mRCC.

Deregulation of Wnt signalling has recently been implicated in human renal cancer. Here, we directly test this association by using a Cre-LoxP strategy to inactivate the Adenomatous Polyposis Coli (Apc) gene in the murine renal epithelium. Mice homozygous for a conditional Apc allele were intercrossed with mice transgenic for Cre recombinase under control of the Cyp1A promoter, which delivers constitutive recombination within a proportion of cells in the renal epithelium. Inactivation of Apc leads to the accumulation of nuclear β -catenin and the rapid development of multiple dysplastic foci. Renal carcinoma was observed with an earliest onset of 4 months. This predisposition was accelerated by p53 deficiency, reducing the earliest onset to 2 months. Compared to other murine models of kidney neoplasia, this represents particularly rapid onset of disease, and so implicates an important role for Apc in suppressing renal carcinoma.

The 2009 International Society of Urological Pathology Consensus Conference in Boston made recommendations regarding the standardization of pathology reporting of radical prostatectomy specimens. Issues relating to the infiltration of tumor into the seminal vesicles and regional lymph nodes were coordinated by working group 4. There was a consensus that complete blocking of the seminal vesicles was not necessary, although sampling of the junction of the seminal vesicles and prostate was mandatory. There was consensus that sampling of the vas deferens margins was not obligatory. There was also consensus that muscular wall invasion of the extraprostatic seminal vesicle only should be regarded as seminal vesicle invasion. Categorization into types of seminal vesicle spread was agreed by consensus to be not necessary. For examination of lymph nodes, there was consensus that special techniques such as frozen sectioning were of use only in high-risk cases. There was no consensus on the optimal sampling method for pelvic lymph node dissection specimens, although there was consensus that all lymph nodes should be completely blocked as a minimum. There was also a consensus that a count of the number of lymph nodes harvested should be attempted. In view of recent evidence, there was consensus that the diameter of the largest lymph node metastasis should be measured. These consensus decisions will hopefully clarify the difficult areas of pathological assessment in radical prostatectomy evaluation and improve the concordance of research series to allow more accurate assessment of patient prognosis.

We outline a new class of robust and efficient methods for solving the Navier -- Stokes equations. We describe a general solution strategy that has two basic building blocks: an implicit time integrator using a stabilized trapezoid rule with an explicit Adam -- Bashforth method for error control, and a robust Krylov subspace solver for the spatially discretized system. We present numerical experiments illustrating the potential of our approach.

Aim To determine the degree of variation in the handling of prostate needle biopsies (PBNx) in laboratories across Europe. Methods A web based survey was emailed to members of the European Network of Uropathology and the British Association of Urological Pathologists. Results Responses were received from 241 laboratories in 15 countries. PNBx were generally taken by urologists (93.8%) or radiologists (23.7%) but in 8.7% were also taken by non-medical personnel such as radiographers, nurses or biomedical assistants. Of the responding laboratories, 40.8% received cores in separate containers, 42.3% processed one core/block, 54.2% examined three levels/block, 49.4% examined one H&E section/level and 56.1% retained spare sections for potential immunohistochemistry. Of the laboratories, 40.9% retained unstained spares for over a year while 36.2% discarded spares within 1 month of reporting. Only two (0.8%) respondents routinely performed immunohistochemistry on all PNBx. There were differences in laboratory practice between the UK and the rest of Europe (RE). Procurement of PNBx by non-medical personnel was more common in the UK. RE laboratories more commonly received each core in a separate container, processed one core/block, examined fewer levels/block and examined more H&E sections/level. RE laboratories also retained spares for potential immunohistochemistry less often and for shorter periods. Use of p63 as the sole basal cell marker was more common in RE. Conclusions There are marked differences in procurement, handling and processing of PNBx in laboratories across Europe. This data can help the development of best practice guidelines.

Even the simplest advection-diffusion problems can exhibit multiple time scales. This means that robust variable step time integrators are a prerequisite if such problems are to be efficiently solved computationally. The performance of the second order trapezoid rule using an explicit Adams-Bashforth method for error control is assessed in this work. This combination is particularly well suited to long time integration of advection-dominated problems. Herein it is shown that a stabilized implementation of the trapezoid rule leads to a very effective integrator in other situations: specifically diffusion problems with rough initial data; and general advection-diffusion problems with different physical time scales governing the system evolution.

Spurious long-term solutions of a finite-difference method for a hyperbolic conservation law with a general nonlinear source term are studied. Results are contrasted with those that have been established for nonlinear ordinary differential equations. Various types of spurious behavior are examined, including spatially uniform equilibria that exist for arbitrarily small time-steps, nonsmooth steady states with profiles that jump between fixed levels, and solutions with oscillations that arise from nonnormality and exist only in finite precision arithmetic. It appears that spurious behavior is associated in general with insufficient spatial resolution. The potential for curbing spuriosity by using adaptivity in space or time is also considered.

In the numerical solution of initial value ordinary differential equations, to what extent does local error control confer global properties? This work concentrates on global steady states or fixed points. It is shown that, for systems of equations, spurious fixed points generally cease to exist when local error control is used. For scalar problems, on the other hand, locally adaptive algorithms generally avoid spurious fixed points by an indirect method--the stepsize selection process causes spurious fixed points to be unstable. However, problem classes exist where, for arbitrarily small tolerances, stable spurious fixed points persist with significant basins of attraction. A technique is derived for generating such examples.