Tumoral CD105 is a novel independent prognostic marker for prognosis in clear-cell renal cell carcinoma

International audienceBackground: Angiogenesis is essential for tumour growth and metastasis. There are conflicting reports as to whether microvessel density (MVD) using the endothelial marker CD105 (cluster of differentiation molecule 105) in clear-cell renal cell carcinomas (ccRCC) is associated with prognosis. Recently, CD105 has been described as a RCC cancer stem cell marker.Methods: A total of 102 ccRCC were analysed. Representative tumour sections were stained for CD105. Vascularity (endothelial CD105) was quantified by MVD. The immunohistochemistry analysis detected positive (if present) or negative (if absent) CD105 tumoral staining. This retrospective population-based study was evaluated using Kaplan–Meier method, t-test and Cox proportional hazard model.Results: We found that the expression of endothelial CD105 (MVD) negatively correlated with nuclear grade (P<0.001), tumour stage (P<0.001) and Leibovitch score (P<0.001), whereas the expression of tumoral CD105 positively correlated with these three clinicopathological factors (P<0.001). In multivariate analysis, tumoral CD105 was found to be an independent predictor of poor overall survival (P=0.002).Conclusions: We have shown for the first time that tumoral CD105 is an independent predictive marker for death risk and unfavourable prognosis in patients with ccRCC after curative resection

Driving down Poisson error can offset classification error in clinical tasks

Medical machine learning algorithms are typically evaluated based on accuracy vs. a clinician-defined ground truth, a reasonable initial choice since trained clinicians are usually better classifiers than ML models. However, this metric does not fully capture the actual clinical task: it neglects the fact that humans, even with perfect accuracy, are subject to non-trivial error from the Poisson statistics of rare events, because clinical protocols often specify a relatively small sample size. For example, to quantitate malaria on a thin blood film a clinician examines only 2000 red blood cells (0.0004 uL), which can yield large Poisson variation in the actual number of parasites present, so that a perfect human's count can differ substantially from the true average load. In contrast, an ML system may be less accurate on an object level, but it may also have the option to examine more blood (e.g. 0.1 uL, or 250x). Then while its parasite identification error is higher, the Poisson variability of its estimate is lower due to larger sample size. To qualify for clinical deployment, an ML system's performance must match current standard of care, typically a very demanding target. To achieve this, it may be possible to offset the ML system's lower accuracy by increasing its sample size to reduce Poisson error, and thus attain the same net clinical performance as a perfectly accurate human limited by smaller sample size. In this paper, we analyse the mathematics of the relationship between Poisson error, classification error, and total error. This mathematical toolkit enables teams optimizing ML systems to leverage a relative strength (larger sample sizes) to offset a relative weakness (classification accuracy). We illustrate the methods with two concrete examples: diagnosis and quantitation of malaria on blood films.Comment: 8 pages + appendix, 4 figure

Gleason Grade 4 Prostate Adenocarcinoma Patterns: An Inter-observer Agreement Study among Genitourinary Pathologists

Aims To assess the interobserver reproducibility of individual Gleason grade 4 growth patterns. Methods and results Twenty-three genitourinary pathologists participated in the evaluation of 60 selected high-magnification photographs. The selection included 10 cases of Gleason grade 3, 40 of Gleason grade 4 (10 per growth pattern), and 10 of Gleason grade 5. Participants were asked to select a single predominant Gleason grade per case (3, 4, or 5), and to indicate the predominant Gleason grade 4 growth pattern, if present. ‘Consensus’ was defined as at least 80% agreement, and ‘favoured’ as 60–80% agreement. Consensus on Gleason grading was reached in 47 of 60 (78%) cases, 35 of which were assigned to grade 4. In the 13 non-consensus cases, ill-formed (6/13, 46%) and fused (7/13, 54%) patterns were involved in the disagreement. Among the 20 cases where at least one pathologist assigned the ill-formed growth pattern, none (0%, 0/20) reached consensus. Consensus for fused, cribriform and glomeruloid glands was reached in 2%, 23% and 38% of cases, respectively. In nine of 35 (26%) consensus Gleason grade 4 cases, participants disagreed on the growth pattern. Six of these were characterized by large epithelial proliferations with delicate intervening fibrovascular cores, which were alternatively given the designation fused or cribriform growth pattern (‘complex fused’). Conclusions Consensus on Gleason grade 4 growth pattern was predominantly reached on cribriform and glomeruloid patterns, but rarely on ill-formed and fused glands. The complex fused glands seem to constitute a borderline pattern of unknown prognostic significance on which a consensus could not be reached

ACUTE EFFECTS OF WHOLE-BODY VIBRATION ON KNEE JOINT DROP LANDING KINEMATICS AND DYNAMIC POSTURAL STABILITY

Whole-body vibration (WBV) is being increasingly utilized in addition to other training modalities in order to prevent and rehabilitate athletic injuries. Excessive knee joint movement has been reported to be a contributing factor to many traumatic and overuse knee joint injuries (Sigward et al., 2008). However the effects of WBV on sensorimotor function and consequent knee joint kinematics is unknown. Thus, the aim of the present study was to examine the effects of an acute WBV exposure on knee joint drop landing kinematics and dynamic postural stability in healthy participants. The null hypothesis was that acute WBV exposure would not influence lower limb drop landing kinematics or dynamic postural stability

Update for the practicing pathologist: The International Consultation On Urologic Disease-European association of urology consultation on bladder cancer

The International Consultations on Urological Diseases are international consensus meetings, supported by the World Health Organization and the Union Internationale Contre le Cancer, which have occurred since 1981. Each consultation has the goal of convening experts to review data and provide evidence-based recommendations to improve practice. In 2012, the selected subject was bladder cancer, a disease which remains a major public health problem with little improvement in many years. The proceedings of the 2nd International Consultation on Bladder Cancer, which included a 'Pathology of Bladder Cancer Work Group,' have recently been published; herein, we provide a summary of developments and consensus relevant to the practicing pathologist. Although the published proceedings have tackled a comprehensive set of issues regarding the pathology of bladder cancer, this update summarizes the recommendations regarding selected issues for the practicing pathologist. These include guidelines for classification and grading of urothelial neoplasia, with particular emphasis on the approach to inverted lesions, the handling of incipient papillary lesions frequently seen during surveillance of bladder cancer patients, descriptions of newer variants, and terminology for urine cytology reporting