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Berney D.M.,Queen Mary, University of London | Algaba F.,Autonomous University of Barcelona | Comperat E.,Hopital La Pitie Salpetriere | Griffiths D.,University of Wales | And 5 more authors.
Histopathology | Year: 2014

Aims: The Gleason scoring system underwent revision at the International Society of Urological Pathology (ISUP) conference in 2005. It is not known how uropathologists have interpreted its recommendations. Method and results: A web-based survey to European Network of Uropathology members received replies from 266 pathologists in 22 countries. Eighty-nine per cent claimed to follow ISUP recommendations. Key areas of disagreement included the following. Smoothly rounded cribriform glands were assigned Gleason pattern (GP) 3 by 51% and GP 4 by 49%. Necrosis was diagnosed as GP 5 by 62%. Any amount of secondary pattern of higher grade in needle biopsies was included in the Gleason score by 58%. Tertiary GP of higher grade on needle biopsies was included in the Gleason score by only 58%. If biopsy cores were embedded separately, only 56% would give a Gleason score for each core/slide examined; 68% would give a concluding Gleason score and the most common method was a global Gleason score (77%). Among those who blocked multiple biopsy cores together, 46% would only give an overall Gleason score for the case. Conclusion: Misinterpretation of ISUP 2005 is widespread, and may explain the variation in Gleason scoring seen. Clarity and uniformity in teaching ISUP 2005 recommendations is necessary. © 2013 John Wiley & Sons Ltd.


Cognard C.,Hopital Purpan | Herbreteau D.,Hopital Bretonneau | Fransen H.,AZ Sint Lukas and Volkskliniek | Van Rooij W.J.,Elisabeth Ziekenhuis | And 8 more authors.
European Radiology | Year: 2013

Objectives: To evaluate the safety and efficacy of a new liquid embolic agent in brain arteriovenous malformation (bAVMs) embolisation. Methods: A prospective, multicentre series was conducted at 11 interventional centres in Europe to evaluate embolisation of bAVMs with the new liquid embolic agent. Technical conditions, complications, clinical outcome and anatomical results were independently analysed. Results: From December 2005 to December 2008, 117 patients (72 male; 45 female, aged 18-75 years) were included. Clinical presentation was mostly haemorrhage (34.2 %) and seizures (28.2 %). Most AVMs were located in the brain hemispheres (85.5 %). AVMs were <3 cm in 52.1 % of patients and ≥3 cm in 47.9 %. Morbidity was observed in 6/117 patients (5.1 %), related to haemorrhagic events in 2 cases and non-haemorrhagic complications in 4 cases. Five patients (4.3 %) died in relation to the treatment (bleeding in 4 patients and extensive venous thrombosis in 1). Complete occlusion of the AVM by embolisation alone was obtained in 23.5 % of patients. Complementary treatment was performed in 82.3 % of patients with partial AVM occlusion, mostly radiosurgery. Conclusions: In this prospective, multicentre, European, observational series, the new liquid embolic agent proved to be suitable for BAVM embolisation, with acceptable morbidity and mortality and good efficacy. Key Points: • Numerous interventional techniques have been used to embolise brain arteriovenous malformations (AVMs). • This prospective multicentre study demonstrates the suitability of a liquid embolic agent. • The safety of treatment using Onyx is acceptable. • Such embolisation leads to complete AVM occlusion in 23.5 % of patients. © 2013 European Society of Radiology.


De Gramont A.,Service dOncologie Medicale | De Gramont A.,French National Institute for Agricultural Research | De Gramont A.,University Pierre and Marie Curie | Chibaudel B.,Service dOncologie Medicale | And 8 more authors.
Seminars in Oncology | Year: 2011

Colorectal cancer represents a major public health problem due to its frequency and mortality rate. Adjuvant chemotherapy has improved the prognosis of colon cancer. Six months of oxaliplatin and fluoropyrimidine in combination is the standard adjuvant treatment in stage III patients. Ongoing trials are evaluating the optimal duration of chemotherapy. A critical issue, which needs to be specifically addressed, is the role of adjuvant therapy in elderly patients. Preliminary results of trials evaluating targeted therapies in combination with chemotherapy have shown disappointing results. The monoclonal antibodies bevacizumab, targeting vascular endothelial growth factor (VEGF) and cetuximab, targeting epidermal growth factor receptor (EGFR)/HER1, which improved survival in patients with metastatic colorectal cancer, could even induce chemotherapy resistance in a significant number of patients in the adjuvant setting. A major challenge is emerging to understand the mechanism leading to this effect and to multi-target the tumor cell proliferation and survival network. Clarity regarding the clinical signal needed before launching a phase III study and optimized designs adapted to multiple agents are urgently needed for new trials. © 2011 Elsevier Inc. All rights reserved.


Mazzucotelli J.-P.,Service de chirurgie cardiaque | P. Pascal,Hopital La Pitie Salpetriere | Litzler P.-Y.,Hopital Charles Nicolle | Vincentelli A.,Hopital Cardiologique | And 4 more authors.
European Journal of Cardio-thoracic Surgery | Year: 2011

Objective: To present the analyzed results on mechanical circulatory support (MCS) collected over a 7-year period, from 2000 to 2006, in France. Methods: A cohort of 520 patients was analyzed. Mean age was 43.7 ± 13.6 years. The main causes of cardiac failure were ischemic cardiomyopathy (39%), idiopathic dilated cardiomyopathy (41.3%), or myocarditis (6.4%). Bridge to transplantation was indicated in 87.8% of patients, bridge to recovery in 9%, while destination therapy was proposed in 3.2% of patients. Results: For patients in cardiogenic shock or advanced heart failure undergoing device implantation as bridge to transplantation or recovery (n = 458), overall mortality was 39% (n = 179). The main causes of mortality under MCS were multi-organ failure (MOF) (57.4%), neurological events (14.1%), or infections (11.9%). Heart transplantation was performed in 249 (54.3%) patients. The main causes of death following heart transplantation were primary graft failure (22.4%), MOF (14.3%), neurological event (14.3%), or infection (10.2%). Long-term survival in transplanted patients was 75 ± 2.8% at 1 year and 66 ± 3.4% at 5 years. Conclusions: MCS is an essential therapeutic tool to save the life of young patients with cardiogenic shock or advanced cardiac failure. Early MCS implantation and the availability of a device that is adapted to the patient's clinical status are prerequisites for reducing overall mortality rates. © 2011 European Association for Cardio-Thoracic Surgery.


Do-Pham G.,Hopital Henri Mondor | Do-Pham G.,University Paris Est Creteil | Monsel G.,Hopital La Pitie Salpetriere | Chosidow O.,Hopital Henri Mondor | Chosidow O.,University Paris Est Creteil
Seminars in Cutaneous Medicine and Surgery | Year: 2014

Pediculosis (capitis, corporis, and pubis) share well-known features: worldwide prevalence (involving millions of people annually); parasites inducing skin lesions directly, and indirectly as a result of itching and hypersensitivity to parasites; and treatment based on good entomological knowledge of the parasite and practical considerations (ie, most available treatments do not act on eggs and should be repeated, depending on the life cycle of the parasites). Infestations are spread most commonly by close contacts. Social stigma and persistent misconceptions complicate the implementation of appropriate management strategies. Head and pubic lice infestations are diagnosed by the visualization of insects or viable nits (eggs). Primary treatments are topical pediculicides (permethrin or malathion), used twice, but emergence of resistance against pediculicides has created the need of alternative treatments including topical or oral ivermectin. Pubic lice are treated the same as head lice, but this finding should prompt evaluation for other sexually transmitted diseases. Body lice infestation should be suspected when symptoms of generalized itching occur in persons who do not change or wash their clothing or bedding regularly; lice may be found in the seams of their clothing. Topically administered permethrin may help to eradicate body lice, but personal hygiene measures are essential for successful treatment. Environmental treatment is also necessary for the eradication of the infestation. Health care personnel who come into contact with this population need to be well informed of the facts in order to disseminate accurate information for diagnosis and management. © 2014 Frontline Medical Communications.


Zbinden M.,University of Geneva | Duquet A.,University of Geneva | Lorente-Trigos A.,University of Geneva | Ngwabyt S.-N.,Hopital la Pitie Salpetriere | And 2 more authors.
EMBO Journal | Year: 2010

A cohort of genes associated with embryonic stem (ES) cell behaviour, including NANOG, are expressed in a number of human cancers. They form an ES-like signature we first described in glioblastoma multiforme (GBM), a highly invasive and incurable brain tumour. We have also shown that HEDGEHOG-GLI (HH-GLI) signalling is required for GBM growth, stem cell expansion and the expression of this (ES)-like stemness signature. Here, we address the function of NANOG in human GBMs and its relationship with HH-GLI activity. We find that NANOG modulates gliomasphere clonogenicity, CD133+ stem cell cell behavior and proliferation, and is regulated by HH-GLI signalling. However, GLI1 also requires NANOG activity forming a positive loop, which is negatively controlled by p53 and vice versa. NANOG is essential for GBM tumourigenicity in orthotopic xenografts and it is epistatic to HH-GLI activity. Our data establish NANOG as a novel HH-GLI mediator essential for GBMs. We propose that this function is conserved and that tumour growth and stem cell behaviour rely on the status of a functional GLI1-NANOG-p53 network. © 2010 European Molecular Biology Organization | All Rights Reserved.


Gauler T.C.,University of Duisburg - Essen | Besse B.,Institute Gustave Roussy | Mauguen A.,Institute Gustave Roussy | Meric J.B.,Hopital La Pitie Salpetriere | And 8 more authors.
Annals of Oncology | Year: 2012

Background: The objective of this multicenter, prospective uncontrolled phase II trial was to determine efficacy, safety and tolerability of vatalanib, an oral angiogenesis inhibitor targeting all known vascular endothelial growth factor receptors, in the second-line treatment of non-small-cell lung cancer (NSCLC). Patients and methods: Patients with stage IIIB/IV NSCLC-proven tumor progression during or after one platinum-based chemotherapy regimen received a fixed dose of 1250 mg vatalanib either once-daily dosing (QD) or two divided daily dosing (TDD: 500 mg a.m. + 750 mg p.m.) until disease progression or unacceptable toxicity. Primary end point was the disease control rate (DCR) at 12 weeks. Results: Fifty-four and 58 patients were enrolled to the QD and TDD arms. DCR at 12 weeks was 35% in the QD and 37% in the TDD arm. The best overall response included one (2%) patient with confirmed partial response with QD and three (5%) with TDD. Median progression-free survival and overall survival were 2.1/7.3 months in the QD arm and 2.8/9.0 months with TDD arm. This therapy showed a moderate toxicity profile for the majority of patients. Conclusions: In the chosen patient population, vatalanib QD and TDD dosing demonstrated potential benefits in tumor size reduction, DCR, and survival. © The Author 2011. Published by Oxford University Press on behalf of the European Society for Medical Oncology. All rights reserved.


Soubrier M.,Hopital G Montpied | Lukas C.,Hopital Lapeyronie | Sibilia J.,Hopital Hautepierre | Fautrel B.,Hopital la Pitie Salpetriere | And 4 more authors.
Annals of the Rheumatic Diseases | Year: 2011

Objectives: To compare the efficacy of disease activity score in 28 joints (DAS28ESR)-driven therapy with antitumour necrosis factor (patients from the GUEPARD trial) and routine care in patients with recent-onset rheumatoid arthritis (patients of the ESPOIR cohort). Results: After matching GUEPARD and ESPOIR patients on the basis of a propensity score and a 1:2 ratio, at baseline all patients had comparable demographic characteristics, rheumatoid factor, anticyclic citrullinated peptide antibody positivity and clinical disease activity parameters: erythrocyte sedimentation rate, C-reactive protein, mean DAS (6.26±0.87), Sharp/van der Heijde radiographic score (SHS), health assessment questionnaire (HAQ). Disease duration was longer in GUEPARD patients (5.6±4.6 vs 3.5±2.0 months, p<0.001). After 1 year, the percentage of patients in remission with an HAQ (<0.5) and an absence of radiological progression was higher in the tight control group (32.3% vs 10.2%, p=0.011) as well as the percentage of patients in low DAS with an HAQ (<0.5) and an absence of radiological progression (36.1% vs 18.9%, p=0.045). However, there was no difference in the decrease in DAS, nor in the percentage of EULAR (good and moderate), ACR20, ACR50 and ACR70 responses. More patients in the tight control group had an HAQ below 0.5 (70.2% vs 45.2%, p=0.005). Overall, pain, patient and physician assessment and fatigue decreased more in the tight control group. The mean SHS progression was similar in the two groups as was the percentage of patients without progression. Conclusions: In patients with recent onset active rheumatoid arthritis, a tight control of disease activity allows more patients to achieve remission without disability and radiographic progression.


Mathieu R.,University of Rennes 2 – Upper Brittany | Verhoest G.,University of Rennes 2 – Upper Brittany | Droupy S.,University of Nimes | De La Taille A.,Hopital Henri Mondor | And 6 more authors.
BJU International | Year: 2013

Objective To analyse the predictive factors of complications after robot-assisted laparoscopic partial nephrectomy (RALPN). Materials and Methods Data from six French institutions on 240 patients who underwent RALPN between 2009 and 2011 were retrospectively reviewed. Clinical (age, body mass index, American Society of Anesthesiologists and Charlson comorbidity index scores, anticoagulant treatment), tumoral (size, R.E.N.A.L nephrometry score) and operative (surgeon experience, blood loss, opening of the collecting system, operating time) variables were considered. Univariate and multivariate regression models were used to assess the impact of these variables on the occurrence of global and major postoperative complications, classified according to the Clavien system. Results The median (range) patient age was 61 (26-83) years. Tumours were of low complexity in 62% of cases. Median (range) operating time, blood loss and warm ischaemia time were 161 (45-425) min, 100 (0-2500) mL and 20 (0-59) min, respectively. Postoperative complications occurred in 79 (33%) patients. Complications were ≥grade III in 25 (10%) patients and were mostly haemorrhagic. In multivariate analysis, surgeon's experience (hazard ratio [HR]: 2.14 [1.07-4.27], P = 0.03) and blood loss (HR: 1.002 [1.001-1.003], P < 0.001) were independent predictors of overall complications. When considering major complications, opening of the collecting system was the only factor that was significant (OR: 2.99 [1.2-7.26], P = 0.02). Nephrometry R.E.N.A.L. score was not associated with postoperative complications. Conclusion In our experience, RALPN is associated with a 30% risk of postoperative complications; surgeon's experience, blood loss and opening of the collecting system were the three predictors of postoperative complications. © 2013 The Authors. BJU International © 2013 BJU International.


Aissaoui N.,University of Paris Descartes | Aissaoui N.,French Institute of Health and Medical Research | Guerot E.,University of Paris Descartes | Combes A.,Hopital la Pitie Salpetriere | And 8 more authors.
Journal of the American Society of Echocardiography | Year: 2012

Background: To evaluate hemodynamic and functional changes of the failed left ventricle by Velocity Vector Imaging (VVI) and tissue Doppler, 22 patients with cardiogenic shock supported by extracorporeal life support (ECLS) were imaged during ECLS output variations inducing severe load manipulations. Methods: The following data were acquired: (1) mean arterial pressure, aortic Doppler velocity-time integral, left ventricular end-diastolic volume, and mitral Doppler E wave; (2) tissue Doppler systolic (Sa) and early diastolic (Ea) velocities; and (3) systolic peak velocity (Sv), strain, and strain rate using VVI. Results: Load variations were documented by a significant decrease in afterload (mean arterial pressure, -21%), an increase in preload (left ventricular end-diastolic volume, +12%; E, +46%; E/Ea ratio, +22%), and an increase in the velocity-time integral (+45%). VVI parameters increased (Sv, +36%; strain, +81%; and strain rate, +67%; P <.05), unlike tissue Doppler systolic velocities (+2%; P = NS). Whatever the ECLS flow, Sa was higher in patients who survived. Conclusions: VVI parameters are not useful in characterizing the failed left ventricle with rapidly varying load conditions. Tissue Doppler systolic velocities appear to be load independent and thus could help in the management of ECLS patients. Copyright © 2012 by the American Society of Echocardiography.

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