Online teaching of inflammatory skin pathology by a French-speaking International University Network.

INTRODUCTION: Developments in technology, web-based teaching and whole slide imaging have broadened the teaching horizon in anatomic pathology. Creating online learning material including many types of media such as radiologic images, whole slides, videos, clinical and macroscopic photographs, is now accessible to most universities. Unfortunately, a major limiting factor to maintain and update the learning material is the amount of resources needed. In this perspective, a French-national university network was initiated in 2011 to build joint online teaching modules consisting of clinical cases and tests. The network has since expanded internationally to Québec, Switzerland and Ivory Coast. METHOD: One of the first steps of the project was to build a learning module on inflammatory skin pathology for interns and residents in pathology and dermatology. A pathology resident from Québec spent 6 weeks in France and Switzerland to develop the contents and build the module on an e-learning Moodle platform under the supervision of two dermatopathologists. The learning module contains text, interactive clinical cases, tests with feedback, virtual slides, images and clinical photographs. For that module, the virtual slides are decentralized in 2 universities (Bordeaux and Paris 7). Each university is responsible of its own slide scanning, image storage and online display with virtual slide viewers. RESULTS: The module on inflammatory skin pathology includes more than 50 web pages with French original content, tests and clinical cases, links to over 45 virtual images and more than 50 microscopic and clinical photographs. The whole learning module is being revised by four dermatopathologists and two senior pathologists. It will be accessible to interns and residents in the spring of 2014. The experience and knowledge gained from that work will be transferred to the next international resident whose work will be aimed at creating lung and breast pathology learning modules. CONCLUSION: The challenges of sustaining a project of this scope are numerous. The technical aspect of whole-slide imaging and storage needs to be developed by each university or group. The content needs to be regularly updated and its accuracy reviewed by experts in each individual domain. The learning modules also need to be promoted within the academic community to ensure maximal benefit for trainees. A collateral benefit of the project was the establishment of international partnerships between French-speaking universities and pathologists with the common goal of promoting pathology education through the use of multi-media technology including whole slide imaging

Stack or trash? Quality assessment of virtual slides

International audienc

A multicenter randomized phase II study of sequential epirubicin/cyclophosphamide followed by docetaxel with or without celecoxib or trastuzumab according to HER2 status, as primary chemotherapy for localized invasive breast cancer patients

International audienceTo assess anti-tumor activity of sequential epirubicin/cyclophosphamide followed by docetaxel with the randomized addition of celecoxib in HER2 negative patients or trastuzumab in HER2 positive patients. From May 2004 till October 2007, 340 patients with stage II and III breast adenocarcinoma, ineligible for breast conserving surgery, received eight sequential three weekly cycles of EC-D [epirubicin (75 mg/m)–cyclophosphamide (750 mg/m) for four cycles followed by docetaxel (100 mg/m) for four cycles]. HER2-negative patients ( = 220) were randomized to receive concomitantly with docetaxel celecoxib 800 mg/day during cycles 5–8 or no additional treatment, while HER2-positive patients confirmed by FISH ( = 120) were randomized to trastuzumab concomitant to docetaxel (8 mg/kg then 6 mg/kg IV every 3 weeks) or no additional preoperative treatment. In the HER2 negative group, pCR (grade 1 and 2 of Chevallier's classification) was observed in 11.5 and 13% of patients treated without and with neoadjuvant Celecoxib, respectively. In the HER2 positive group, pCR rate reached 26% in those who received neoadjuvant trastuzumab versus 19% in the others. There was no unexpected toxicity, no cardiac toxicity, and no toxic death. Triple negative breast cancers experience the highest pCR rate of 30%. Celecoxib is not likely to improve pCR rates in addition to EC-D in patients with HER2-negative tumor. In HER2-positive tumor patients, trastuzumab added to ECD leads to increased pCR rates. It was the only combination to deserve further study according to the two-stage Fleming's design used in this trial

Exquisite Sensitivity of TP53 Mutant and Basal Breast Cancers to a Dose-Dense Epirubicin−Cyclophosphamide Regimen

BACKGROUND: In breast cancers, only a minority of patients fully benefit from the different chemotherapy regimens currently in use. Identification of markers that could predict the response to a particular regimen would thus be critically important for patient care. In cell lines or animal models, tumor protein p53 (TP53) plays a critical role in modulating the response to genotoxic drugs. TP53 is activated in response to DNA damage and triggers either apoptosis or cell-cycle arrest, which have opposite effects on cell fate. Yet, studies linking TP53 status and chemotherapy response have so far failed to unambiguously establish this paradigm in patients. Breast cancers with a TP53 mutation were repeatedly shown to have a poor outcome, but whether this reflects poor response to treatment or greater intrinsic aggressiveness of the tumor is unknown. METHODS AND FINDINGS: In this study we analyzed 80 noninflammatory breast cancers treated by frontline (neoadjuvant) chemotherapy. Tumor diagnoses were performed on pretreatment biopsies, and the patients then received six cycles of a dose-dense regimen of 75 mg/m(2) epirubicin and 1,200 mg/m(2) cyclophosphamide, given every 14 days. After completion of chemotherapy, all patients underwent mastectomies, thus allowing for a reliable assessment of chemotherapy response. The pretreatment biopsy samples were used to determine the TP53 status through a highly efficient yeast functional assay and to perform RNA profiling. All 15 complete responses occurred among the 28 TP53-mutant tumors. Furthermore, among the TP53-mutant tumors, nine out of ten of the highly aggressive basal subtypes (defined by basal cytokeratin [KRT] immunohistochemical staining) experienced complete pathological responses, and only TP53 status and basal subtype were independent predictors of a complete response. Expression analysis identified many mutant TP53-associated genes, including CDC20, TTK, CDKN2A, and the stem cell gene PROM1, but failed to identify a transcriptional profile associated with complete responses among TP53 mutant tumors. In patients with unresponsive tumors, mutant TP53 status predicted significantly shorter overall survival. The 15 patients with responsive TP53-mutant tumors, however, had a favorable outcome, suggesting that this chemotherapy regimen can overcome the poor prognosis generally associated with mutant TP53 status. CONCLUSIONS: This study demonstrates that, in noninflammatory breast cancers, TP53 status is a key predictive factor for response to this dose-dense epirubicin–cyclophosphamide regimen and further suggests that the basal subtype is exquisitely sensitive to this association. Given the well-established predictive value of complete responses for long-term survival and the poor prognosis of basal and TP53-mutant tumors treated with other regimens, this chemotherapy could be particularly suited for breast cancer patients with a mutant TP53, particularly those with basal features

Importance of pre-analytical steps for transcriptome and RT-qPCR analyses in the context of the phase II randomised multicentre trial REMAGUS02 of neoadjuvant chemotherapy in breast cancer patients

<p>Abstract</p> <p>Background</p> <p>Identification of predictive markers of response to treatment is a major objective in breast cancer. A major problem in clinical sampling is the variability of RNA templates, requiring accurate management of tumour material and subsequent analyses for future translation in clinical practice. Our aim was to establish the feasibility and reliability of high throughput RNA analysis in a prospective trial.</p> <p>Methods</p> <p>This study was conducted on RNA from initial biopsies, in a prospective trial of neoadjuvant chemotherapy in 327 patients with inoperable breast cancer. Four independent centres included patients and samples. Human U133 GeneChips plus 2.0 arrays for transcriptome analysis and quantitative RT-qPCR of 45 target genes and 6 reference genes were analysed on total RNA.</p> <p>Results</p> <p>Thirty seven samples were excluded because <it>i) </it>they contained less than 30% malignant cells, or <it>ii) </it>they provided RNA Integrity Number (RIN) of poor quality. Among the 290 remaining cases, taking into account strict quality control criteria initially defined to ensure good quality of sampling, 78% and 82% samples were eligible for transcriptome and RT-qPCR analyses, respectively. For RT-qPCR, efficiency was corrected by using standard curves for each gene and each plate. It was greater than 90% for all genes. Clustering analysis highlighted relevant breast cancer phenotypes for both techniques (ER+, PR+, HER2+, triple negative). Interestingly, clustering on trancriptome data also demonstrated a "centre effect", probably due to the sampling or extraction methods used in on of the centres. Conversely, the calibration of RT-qPCR analysis led to the centre effect withdrawing, allowing multicentre analysis of gene transcripts with high accuracy.</p> <p>Conclusions</p> <p>Our data showed that strict quality criteria for RNA integrity assessment and well calibrated and standardized RT-qPCR allows multicentre analysis of genes transcripts with high accuracy in the clinical context. More stringent criteria are needed for transcriptome analysis for clinical applications.</p

Innovation et intelligence collective

National audienceResearch states that the success of a specific innovation cannot be predicted. As a consequence, the value of such an innovation can only be stated very late in the development process, or even in retrospect. Our empirical research shows that professionals directly engaged in the design process are able to perform an early and complete valuation, and that similar patterns emerge during this valuation process.La recherche en gestion a établi l'imprévisibilité du succès d'une innovation. Un corollaire largement accepté veut que la détermination de la valeur de cette innovation ne puisse être que tardive, voire rétrospective. Nous observons dans cette recherche que les acteurs directs de l'innovation sont à même de procéder à une " valuation " précoce, complète et révisable, et que des patterns similaires sont observables lors de ces processus de valuation

Innovation et intelligence collective

National audienceResearch states that the success of a specific innovation cannot be predicted. As a consequence, the value of such an innovation can only be stated very late in the development process, or even in retrospect. Our empirical research shows that professionals directly engaged in the design process are able to perform an early and complete valuation, and that similar patterns emerge during this valuation process.La recherche en gestion a établi l'imprévisibilité du succès d'une innovation. Un corollaire largement accepté veut que la détermination de la valeur de cette innovation ne puisse être que tardive, voire rétrospective. Nous observons dans cette recherche que les acteurs directs de l'innovation sont à même de procéder à une " valuation " précoce, complète et révisable, et que des patterns similaires sont observables lors de ces processus de valuation

Une introduction d'espèces exotiques n'est jamais anodine

Tribune du 14 mai 2014National audienc

Management de l'innovation et erreurs de représentation

International audienceThis chapter is a first effort, mainly descriptive, to explore possible cross-fertilization between two active fields of research - management of innovation and cognitive psychology. Both approaches question some important aspects of the dominant vision of the firm, especially those related to the existence of rational choice in organizations. Our reasonning is based on two pillars: First, specific situations of innovation are a privileged field for the observation of cognitive bias and representation errors. Why? Because the innovation, which always includes some transgression, often questions the practices and management systems. In doing so, it illuminates representation errors (ie the " inappropriate application of antecedent interpretative models").Second, there is a striking convergence between the results of research on cognitive bias and some strong assumptions of the management of innovation . The two streams , in particular, emphasize the inadequacy of the classical theories of decision.L"innovation n'a, jusqu"ici et à notre connaissance, jamais été le terrain d"études portant explicitement sur les erreurs de représentation. Ce chapitre constitue donc un premier effort, essentiellement descriptif, pour explorer les fertilisations croisées possibles entre deux courants de recherche – le management de l"innovation et la psychologie cognitive. Les deux approches ont en commun de remettre en cause certains aspects importants de la vision dominante de la firme, en particulier les mythes rationnels liés aux processus de choix dans les organisations. Notre réflexion est ici fondée sur deux piliers : 1. Les situations concrètes de l"innovation en train de se faire forment un terrain privilégié pour l"observation des erreurs de représentation. Pourquoi ? Parce que l"innovation, qui comporte toujours une part de transgression, interroge en profondeur les pratiques et les dispositifs de gestion. Ce faisant, elle éclaire les erreurs de représentation (autrement dit l"application inappropriée de grilles de lectures antécédentes) d"un jour souvent cru. L"analyse des cas d"innovation, qu"elle soit technologique, organisationnelle ou sociale, est donc un remarquable révélateur de la banalité des erreurs de représentation dans le fonctionnement des organisations et, peut-être, l"occasion de nouveaux développements théoriques. 2. Il y a une convergence de résultats entre les recherches menées depuis une quarantaine d’années sur les erreurs de représentation et certaines hypothèses fortes du management de l’innovation. Les deux courants, en particulier, insistent sur le caractère insuffisant des théories classiques de la décision