Cartron G.,Montpellier University |
De Guibert S.,Institut Universitaire de France |
Dilhuydy M.-S.,University of Bordeaux 1 |
Morschhauser F.,Lille University of Science and Technology |
And 7 more authors.
Blood | Year: 2014
GAUGUIN evaluated the safety and efficacy of obinutuzumab (GA101) monotherapy in patients with relapsed/refractory chronic lymphocytic leukemia (CLL). In phase 1 (dose escalation), 13 patients received obinutuzumab 400 to 1200 mg (days 1 and 8 of cycle 1; day 1 of cycles 2-8). In phase 2, 20 patients received a fixed dose of 1000 mg (days 1, 8, and 15 of cycle 1; day 1 of cycles 2-8). Infusion-related reactions occurred in nearly all patients, but fewwere grade 3/4. Grade 3/4 neutropenia occurred in 7 patients in phase 1 (but was not dose-related) and in 4 patients in phase 2. Overall end-of-treatment response (all partial responses) was 62% (phase 1) and 15% (phase 2); best overall response was 62% and 30%, respectively. Phase 2median progression-free survival was 10.7months and median duration of response was 8.9 months. In summary, obinutuzumab monotherapy is active in patients with heavily pretreated relapsed/refractory CLL. GAUGUIN was registered at www.clinicaltrials.gov as #NCT00517530. (Blood. 2014;124(14): 2196-2202). © 2014 by The American Society of Hematology.
Guichard C.,French Institute of Health and Medical Research |
Guichard C.,University of Paris Descartes |
Amaddeo G.,French Institute of Health and Medical Research |
Amaddeo G.,University of Paris Descartes |
And 27 more authors.
Nature Genetics | Year: 2012
Hepatocellular carcinoma (HCC) is the most common primary liver malignancy. Here, we performed high-resolution copy-number analysis on 125 HCC tumors and whole-exome sequencing on 24 of these tumors. We identified 135 homozygous deletions and 994 somatic mutations of genes with predicted functional consequences. We found new recurrent alterations in four genes (ARID1A, RPS6KA3, NFE2L2 and IRF2) not previously described in HCC. Functional analyses showed tumor suppressor properties for IRF2, whose inactivation, exclusively found in hepatitis B virus (HBV)-related tumors, led to impaired TP53 function. In contrast, inactivation of chromatin remodelers was frequent and predominant in alcohol-related tumors. Moreover, association of mutations in specific genes (RPS6KA3-AXIN1 and NFE2L2-CTNNB1) suggested that Wnt/β-catenin signaling might cooperate in liver carcinogenesis with both oxidative stress metabolism and Ras/mitogen-activated protein kinase (MAPK) pathways. This study provides insight into the somatic mutational landscape in HCC and identifies interactions between mutations in oncogene and tumor suppressor gene mutations related to specific risk factors. © 2012 Nature America, Inc. All rights reserved.
Bessede T.,Center Hospitalier University Henri Mondor |
Soulie M.,Toulouse University Hospital Center |
Mottet N.,Clinique Mutualiste Saint Etienne |
Rebillard X.,Clinique Beausoleil |
And 3 more authors.
Journal of Urology | Year: 2010
Purpose: We analyzed preoperative data, pathological results and followup of pT0 tumors after radical prostatectomy for prostate cancer diagnosed on previous positive biopsy. Materials and Methods: At 6 centers a total of 30 of 7,693 radical prostatectomy specimens were classified as pT0 despite prior biopsy proven prostate cancer. No patients were diagnosed after transurethral prostate resection or received neoadjuvant hormonal treatment. All biopsy cores and radical prostatectomy specimens were reanalyzed by a second pathologist. Followup comprised clinical examination and postoperative prostate specific antigen assay at 1 and 3 months, and every 6 months thereafter. Results: Median patient age was 63 years (range 46 to 73). Median preoperative prostate specific antigen was 7.4 ng/ml (range 1.3 to 23). Of the cases 24 were T1c and 6 were T2a. The median number of biopsy cores was 10 (range 6 to 21) with 1 positive (range 1 to 4). On biopsies median tumor length was 1 mm (range 0.3 to 18) and there was tumor in 11.1% (range 3.4% to 64%). In 25 cases (83.3%) there was only 1 positive biopsy. Gleason score was 3 + 3 in 23 cases and less than 6 in 5 with grade 4 in 2. Only 9 cases filled all nonsignificant tumor criteria. Median specimen weight was 61 gm (range 40 to 160). At a median 82-month followup (range 14 to 226) there was no biochemical progression. Conclusions: After biopsy proven cancer pT0 prostate cancer is an unpredictable pathological finding. Despite its excellent prognosis it has medicolegal repercussions that justify DNA based tissue analysis. There is no evidence that finding focal cancer after extensive prostate resection changes patient prognosis and postoperative treatment. © 2010 American Urological Association Education and Research, Inc.
Creange A.,Center Hospitalier University Henri Mondor |
Creange A.,University Paris Est Creteil |
Careyron A.,Center Hospitalier University Henri Mondor
Journal of Neurology | Year: 2013
The diagnosis of chronic inflammatory demyelinating polyneuropathy (CIDP) is based on a set of clinical and neurophysiological parameters. However, in clinical practice, CIDP remains difficult to diagnose in atypical cases. In the present study, 32 experts from 22 centers (the French CIDP study group) were asked individually to score four typical, and seven atypical, CIDP observations (TOs and AOs, respectively) reported by other physicians, according to the Delphi method. The diagnoses of CIDP were confirmed by the group in 96.9 % of the TO and 60.1 % of the AO (p < 0.0001). There was a positive correlation between the consensus of CIDP diagnosis and the demyelinating features (r = 0.82, p < 0.004). The European CIDP classification was used in 28.3 % of the TOs and 18.2 % of the AOs (p < 0.002). The French CIDP study group diagnostic strategy was used in 90 % of the TOs and 61 % of the AOs (p < 0.0001). In 3 % of the TOs and 21.6 % of the AOs, the experts had difficulty determining a final diagnosis due to a lack of information. This study shows that a set of criteria and a diagnostic strategy are not sufficient to reach a consensus for the diagnosis of atypical CIDP in clinical practice. © 2013 Springer-Verlag Berlin Heidelberg.
Long A.,Center Hospitalier University Of Reims |
Rouet L.,Philips |
Lindholt J.S.,Viborg Hospital |
Allaire E.,Center Hospitalier University Henri Mondor |
Allaire E.,University Paris Est Creteil
European Journal of Vascular and Endovascular Surgery | Year: 2012
Objectives: Maximum diameter is a determinant parameter for the clinical management of asymptomatic abdominal aortic aneurysm (AAA). However, its measurement is not standardised. We review the different methods used to measure AAA maximum diameter, with ultrasound (US) or computed tomography (CT). Methods: A review of maximum diameter measurement methods with US and CT was performed, focussing on screening, surveillance before repair and decision for intervention. Diameter measurement methodology was described according to four parameters: plane of acquisition, axis of measurement, position of callipers and selected diameter. A quality score to evaluate methodology descriptions was defined (plane, axis, callipers placement and selected diameter), ranging from 0 (worst) to 4 (best). Results: Review showed a wide range of definitions and practices. The mean value of the quality score was 2.52 in screening studies, 1.66 in guidelines for screening, 2.81 in follow-up studies and 1.63 in studies describing decision for intervention. Conclusion: To improve the efficiency of AAA management (in screening programmes, follow-up and decision for intervention), and enable comparison between future studies, a standardised methodology for AAA maximum diameter measurement is necessary. Until such a consensus is reached, publications should at least clearly report the method of measurement. © 2012 European Society for Vascular Surgery. Published by Elsevier Ltd. All rights reserved.
Dessap A.M.,Center Hospitalier University Henri Mondor |
Dessap A.M.,University Paris Est Creteil |
Dessap A.M.,French Institute of Health and Medical Research |
Roche-Campo F.,Center Hospitalier University Henri Mondor |
And 16 more authors.
American Journal of Respiratory and Critical Care Medicine | Year: 2012
Rationale: Difficult weaning from mechanical ventilation is often associated with fluid overload. B-type natriuretic peptide (BNP) has been proposed as a tool for predicting and detecting weaning failure of cardiovascular origin. Objectives: To investigate whether fluid management guided by daily BNP plasma concentrations improves weaning outcomes compared with empirical therapy dictated by clinical acumen. Methods: In a randomized controlled multicenter study, we allocated 304 patients to either a BNP-driven or physician-driven strategy of fluid management during ventilator weaning. To standardize the weaning process, patients in both groups were ventilated with an automatic computer-driven weaning system. The primary end point was time to successful extubation. Measurements and Main Results: In the BNP-driven group, furosemide and acetazolamide were given more often and in higher doses than in the control group, resulting in a more negative median (interquartile range) fluid balance during weaning (-2,320 [-4,735, 738] vs. -180 [-2,556, 2,832] ml; P < 0.0001). Time to successful extubation was significantly shorter with the BNP-driven strategy (58.6 [23.3, 139.8] vs. 42.4 [20.8, 107.5] h; P = 0.034). The BNP-driven strategy increased the number of ventilator-free days but did not change length of stay or mortality. The effect on weaning time was strongest in patients with left ventricular systolic dysfunction. The two strategies did not differ significantly regarding electrolyte imbalance, renal failure, or shock. Copyright © 2012 by the American Thoracic Society.
Plante-Bordeneuve V.,Center Hospitalier University Henri Mondor |
Said G.,Center Hospitalier University Pitie Salpetriere
The Lancet Neurology | Year: 2011
Familial amyloid polyneuropathies (FAPs) are a group of life-threatening multisystem disorders transmitted as an autosomal dominant trait. Nerve lesions are induced by deposits of amyloid fibrils, most commonly due to mutated transthyretin (TTR). Less often the precursor of amyloidosis is mutant apolipoprotein A-1 or gelsolin. The first identified cause of FAP-the TTR Val30Met mutation-is still the most common of more than 100 amyloidogenic point mutations identified worldwide. The penetrance and age at onset of FAP among people carrying the same mutation vary between countries. The symptomatology and clinical course of FAP can be highly variable. TTR FAP typically causes a nerve length-dependent polyneuropathy that starts in the feet with loss of temperature and pain sensations, along with life-threatening autonomic dysfunction leading to cachexia and death within 10 years on average. TTR is synthesised mainly in the liver, and liver transplantation seems to have a favourable effect on the course of neuropathy, but not on cardiac or eye lesions. Oral administration of tafamidis meglumine, which prevents misfolding and deposition of mutated TTR, is under evaluation in patients with TTR FAP. In future, patients with FAP might benefit from gene therapy; however, genetic counselling is recommended for the prevention of all types of FAP. © 2011 Elsevier Ltd.
Romano H.,Center hospitalier University Henri Mondor |
Annales Medico-Psychologiques | Year: 2010
The media relieve daily the traumatic events, which take place worldwide as in closer of the everyday life of the spectators. This overbid of images joins in a context where political, judiciary, media and medical logic are forced to coexist. The spectacularisation of the distress and the suffering invades all the space and leads to the stigmatization of the persons involved in this type of event in a specific human category, that of the victims so fast sanctuarised that sacrificed on the scene of the ratings. Our comment aims at understanding better the stakes bound to the evolution of the media culture and its repercussions both with the subjects directly involved in the traumatic event and towards the spectators. © 2010 Elsevier Masson SAS.
Plonquet A.,Center Hospitalier University Henri Mondor
Revue Francophone des Laboratoires | Year: 2013
B lymphocytes transform into antibody-producing cells in response to a specific antigenic stimulus. However, it has been shown that production of antibodies can alternatively be triggered by other stimuli, explaining at least in part the efficacy of Rituximab in auto-immune diseases. B lymphocytes rearrange the genes coding for the chains of immunoglobulins in the bone marrow, during B-lymphopoiesis. Epigenetic phenomenon regulating this process are increasingly recognized. B lymphocytes exit the bone marrow as transitional B lymphocytes which turn rapidly in naïve B-cells. Part of those cells recirculate in blood and peripheral lymphoid organs until they encounter the antigen of which their BCR is specific. From there on, they can mount a specific response against the antigen, transform into antibody-producing cells, either directly, or by undergoing the process of germinal centre differenciation which will lead to Immunoglobulin-class switch and somatic hypermutation. Some of them will remain in the long term as memory B-cell or plasma cells. Other B-lymphocytes spontaneously secrete natural IgM, others can be stimulated by Toll-like-receptors, as innate immune cells do, and will respond by proliferation and/or transforming into cells able to produce high levels of antibodies. Finally, some naïve B-cells join the marginal zones of secondary lymphoid organs and will lead to a quick production of IgM in response to encapsulated bacteria. © 2013 - Elsevier Masson SAS - Tous droits réservés.
For the practice: Place of the clinical pathologist in taking care acute leukemias: From the complete blood count to the WHO classification [Place du biologiste dans la prise en charge des leucémies aiguës: de lhémogramme à la classification OMS]
Imbert M.,Center Hospitalier University Henri Mondor |
Wagner-Ballon O.,Center Hospitalier University Henri Mondor
Revue Francophone des Laboratoires | Year: 2015
The clinical pathologist is in first line for the diagnosis and follow-up of acute leukemia. In private practice, the complete blood count and the peripheral blood smear examination remain the major tests for the detection and the follow-up of acute leukemia. In specialized institution, bone marrow aspirates, flow cytometry analysis, cytogenetic and molecular studies allow a specific sub-classification according to the WHO 2008, which will lead to an adapted treatment and an appropriate follow-up of residual disease. © 2015 Elsevier Masson SAS.