Françoise Le Pimpec-Barthes

Université René Descartes - Paris 5, Lutetia Parisorum, Île-de-France, France

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Publications (158)323.53 Total impact

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    ABSTRACT: STK11 is commonly mutated in lung cancer. In light of recent experimental data showing that specific STK11 mutants could acquire oncogenic activities due to the synthesis of a short STK11 isoform, we investigated whether this new classification of STK11 mutants could help refine its role as a prognostic marker. We conducted a retrospective high-throughput genotyping study in 567 resected non-squamous non-small-cell lung cancer (NSCLC) patients. STK11 exons 1 or 2 mutations (STK11ex1-2) with potential oncogenic activity were analyzed separately from exons 3 to 9 (STK11ex3-9). STK11ex1-2 and STK11ex3-9 mutations occurred in 5% and 14% of NSCLC. STK11 mutated patients were younger (P = .01) and smokers (P< .0001). STK11 mutations were significantly associated with KRAS and inversely with EGFR mutations. After a median follow-up of 7.2 years (95%CI 6.8-.4), patients with STK11ex1-2 mutation had a median OS of 24 months (95%CI 15-57) as compared to 69 months (95%CI 56-93) for wild-type (log-rank, P = .005) and to 91 months (95%CI 57-unreached) for STK11ex3-9 mutations (P = .003). In multivariate analysis, STK11ex1-2 mutations remained associated with a poor prognosis (P = .002). Results were validated in two public datasets. Western blots showed that STK11ex1-2 mutatedtumors expressed short STK11 isoforms. Finally using mRNAseq data from the TCGA cohort, we showed that a stroma-derived poor prognosis signature was enriched in STK11ex1-2 mutated tumors. All together our results show that STK11ex1-2 mutations delineate an aggressive subtype of lung cancer for which a targeted treatment through STK11 inhibition might offer new opportunities.
    Full-text · Article · Dec 2015 · Oncotarget

  • No preview · Conference Paper · Sep 2015
  • M Riquet · C Rivera · C Pricopi · A Badia · A Arame · A Dujon · C Foucault · F Le Pimpec-Barthes · E Fabre
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    ABSTRACT: Lung cancer prognosis is mainly based on the TNM, histology and molecular biology. Our aim was to analyze the prognostic value of certain clinical and paraclinical variables. We studied among 6105 patients operated on, divided during 3 time-periods (1979 to 2010), the following prognostic factors: type of surgery, pTNM, histology, age, sex, smoking history, clinical presentation, and paraclinical variables. Postoperative mortality was 4% (243/6105), rate of complications was 23.3% (1424/6105). The 5-year overall survival was 43.2% and 10-year was 27%. Best survival was observed after complete resection (R0) (P<10(-6)), lobectomy (P<10(-6)), lymph node dissection (P=0.0006), early pTNM stages (P<10(-6)), absence of a solid component in adenocarcinoma. Other pejorative factors were: male gender (P=10(-5)), age (P=0.0000002), comorbidity (P=0.016), history of cancer (P<10(-5)), postoperative complications (P=0.0018), FEV lower than 80% (P=0.0000025), time-periods (P<10(-6)). All these factors were confirmed by multivariate analysis, except gender. Smoking was not poor prognostic factor in univariate analysis (P=0.09) but became significant in the multivariate one (P=0.013). Medical and human factors, and the general physiological state, play an important role in prognosis after surgery. We do not know their exact meaning and, like studies on chemotherapy, they justify special research. Copyright © 2015 Elsevier Masson SAS. All rights reserved.
    No preview · Article · Aug 2015 · Revue de Pneumologie Clinique
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    Françoise Le Pimpec-Barthes · C. Pricopi · B. Chevalier · J.C. Boucherie · B. Grand · P. Bagan · J. Das Neves Pereira · A. Badia · A. Arame · C. Rivera

    Preview · Article · Aug 2015
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    ABSTRACT: OBJECTIVES To determine contemporary early outcomes associated with bilobectomy for lung cancer and to identify their predictors using a nationally representative general thoracic surgery database.
    Full-text · Article · Aug 2015 · European Journal of Cardio-Thoracic Surgery
  • Françoise Le Pimpec-Barthes · Marc Riquet

    No preview · Article · Aug 2015 · The Annals of thoracic surgery
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    Preview · Article · Aug 2015

  • No preview · Article · Jul 2015 · Intensive Care Medicine
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    ABSTRACT: Cyclin B1 (CCNB1) is considered as a potential target for a cancer vaccine, as it is overexpressed in many malignant cells, while being transiently expressed in normal cells. To evaluate the CD4 T cell response to CCNB1, we derived T cell lines by multiple weekly rounds of stimulation with recombinant CCNB1 of T cells collected in healthy donors (long-term T cell assays). T cell lines were specific for 15 immunodominant peptides and derived preferentially from naive T cells. From 74 overlapping peptides, 20 peptides were selected for their broad specificity of binding to HLA class II molecules and included most of the immunodominant epitopes. They primed in vitro a large number of specific CD4 T cell lines in all the donors. Immunodominant epitopes were the most efficacious in long-term T cell assays, both in terms of number of specific T cell lines and number of responding donors. The 20 peptides were also submitted to short-term T cell assays using cells collected in healthy and cancer patients with the aim to evaluate the memory response. The recognized peptides differed from the immunodominant peptides and were part of the best promiscuous peptides. We also observed pre-existing CCNB1-specifc IgG Abs in both healthy and cancer donors. Long- and short-term T cell assays revealed that CCNB1 contained many CD4 T cell epitopes, which are differentially recognized by pre-existing naive and memory CD4 T cells. These observations are of value for the design of cancer vaccines. Copyright © 2015 by The American Association of Immunologists, Inc.
    No preview · Article · Jul 2015 · The Journal of Immunology
  • A. Buero · C. Rivera · L. Gibault · F. Le Pimpec-Barthes
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    ABSTRACT: Background Osseous metaplasia is an extremely rare histological variation of thymus tumors. Despite intratumoral calcifications are described ossification is exceptional. Case report A 27-year-old woman with no relevant medical history was referred to our department for the treatment of a full-calcified anterior mediastinal tumor. It was detected on a spinal X-ray performed for chronic back pain and confirmed by a chest X-ray. On the computed tomography, a bulky anterior mediastinal tumor containing heterogeneous calcification was confirmed. The patient underwent a posterolateral thoracotomy. Intraoperatively there was a large hard stony mass in the anterior mediastinum extending to the right hemi thorax. Complete excision of the mass including thymectomy was done. The patient underwent uneventful recovery. Histopathology reported a thymoma type B1 with osseous metaplasia according to the World Health Organization classification and Masaoka I stage according to intraoperative findings. Results To our knowledge it is the third case published in all literature of a thymus tumor with complete osseous metaplasia in an adult and the first case that tumor is almost entirely ossified. Conclusion The mechanism of osseous metaplasia is unknown. Several theories have been given. Certain cell mediators would stimulate and influence connective tissue to be replaced by heterotopic bone. Further cases of osseous metaplasia will be necessary to figure out pathogenesis, prognosis and treatments outcomes of these particular types of thymomas.
    No preview · Article · Jun 2015 · European Surgery
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    ABSTRACT: There are no guidelines regarding the surgical approach for spontaneous pneumothorax. It has been reported, however, that the risk of recurrence following video-assisted thoracic surgery is higher than that following open thoracotomy (OT). The objective of this study was to determine whether this higher risk of recurrence following video-assisted thoracic surgery could be attributable to differences in intraoperative parenchymal resection and the pleurodesis technique. Data for 7647 patients operated on for primary or secondary spontaneous pneumothorax between 1 January 2005 and 31 December 2012 were extracted from Epithor®, the French national database. The type of pleurodesis and parenchymal resection was collected. Outcomes were (i) bleeding, defined as postoperative pleural bleeding; (ii) pulmonary and pleural complications, defined as atelectasis, pneumonia, empyema, prolonged ventilation, acute respiratory distress syndrome and prolonged air leaks; (iii) in-hospital length of stay and (iv) recurrence, defined as chest drainage or surgery for a second pneumothorax. Of note, 6643 patients underwent videothoracoscopy and 1004 patients underwent OT. When compared with the thoracotomy group, the videothoracoscopy group was associated with more parenchymal resections (62.4 vs 80%, P = 0.01), fewer mechanical pleurodesis procedures (93 vs 77.5%, P < 10(-3)), fewer postoperative respiratory complications (12 vs 8.2%, P = 0.01), fewer cases of postoperative pleural bleeding (2.3 vs 1.4%, P = 0.04) and shorter hospital lengths of stay (16 vs 9 days, P = 0.01). The recurrence rate was 1.8% (n = 18) in the thoracotomy group versus 3.8% (n = 254) in the videothoracoscopy group (P = 0.01). The median time between surgery and recurrence was 3 months (range: 1-76 months). In the surgical management of spontaneous pneumothorax, videothoracoscopy is associated with a higher rate of recurrence than OT. This difference might be attributable to differences in the pleurodesis technique rather than differences in the parenchymal resection. © The Author 2015. Published by Oxford University Press on behalf of the European Association for Cardio-Thoracic Surgery. All rights reserved.
    Full-text · Article · Jun 2015 · European journal of cardio-thoracic surgery: official journal of the European Association for Cardio-thoracic Surgery
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    P. Mordant · C. Pricopi · A. Legras · A. Arame · C. Foucault · A. Dujon · F. Le Pimpec-Barthes · M. Riquet
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    ABSTRACT: Objectives: Non-small cell lung carcinoma (NSCLC) with N1 involvement is associated with 5-year survival rates ranging from 7% to 55%. Numerous factors have been independently reported to explain this heterogeneous prognosis, but their relative weight on long-term survival is unknown. Methods: Patients who underwent surgical resection for NSCLC in two French centers from 1993 to 2010 were prospectively recorded and retrospectively reviewed. The overall survival (OS) of patients undergoing first-line surgery for pN1 disease was analyzed according to the type of extension, number of metastatic LN, number and anatomic location of metastatic stations. Results: The study group included 450 patients (male 80.2%, mean age 63.3 ± 9.9 years, 5-year overall survival 46%). The number of metastatic station was 1 in 340 (75.6%, single-station disease) and ≥2 in 110 patients (24.4%, multi-station disease). The number of metastatic stations was correlated with the number of metastatic LN ( p < .001), and associated with adverse OS ( p = .0014). The presence of intralobar metastatic LN (station 12-13-14) was associated with a mechanism of direct extension ( p < .001), but did not impact OS ( p = .71). The location of metastatic stations was of prognostic significance only in case of multi-station disease, with hilar (station 10) involvement being associated with adverse OS ( p = .005). The 110 patients with multi-station pN1 disease and the 134 patients operated on for single-station pN0N2 (skip-N2) disease during the study period yield comparable outcome ( p = .52). Conclusions: In patients with resected pN1 NSCLC, the number of metastatic stations and their location in case of multi-station disease have a prognostic value.
    Full-text · Article · May 2015 · European Journal of Surgical Oncology

  • No preview · Article · Apr 2015 · European Respiratory Journal
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    ABSTRACT: Background Tobacco-induced pulmonary vascular disease is partly driven by endothelial dysfunction. The bioavailability of the potent vasodilator nitric oxide (NO) depends on competition between NO synthase-3 (NOS3) and arginases for their common substrate (L-arginine). We tested the hypothesis whereby tobacco smoking impairs pulmonary endothelial function via upregulation of the arginase pathway. Methods Endothelium-dependent vasodilation in response to acetylcholine (Ach) was compared ex vivo for pulmonary vascular rings from 29 smokers and 10 never-smokers. The results were expressed as a percentage of the contraction with phenylephrine. We tested the effects of L-arginine supplementation, arginase inhibition (by N(omega)-hydroxy-nor-l-arginine, NorNOHA) and NOS3 induction (by genistein) on vasodilation. Protein levels of NOS3 and arginases I and II in the pulmonary arteries were quantified by Western blotting. Results Overall, vasodilation was impaired in smokers (relative to controls; p < 0.01). Eleven of the 29 smokers (the ED+ subgroup) displayed endothelial dysfunction (defined as the absence of a relaxant response to Ach), whereas 18 (the ED− subgroup) had normal vasodilation. The mean responses to 10−4 M Ach were −23 ± 10% and 31 ± 4% in the ED+ and ED− subgroups, respectively (p < 0.01). Supplementation with L- arginine improved endothelial function in the ED+ subgroup (−4 ± 10% vs. -32 ± 10% in the presence and absence of L- arginine, respectively; p = 0.006), as did arginase inhibition (18 ± 9% vs. -1 ± 9%, respectively; p = 0.0002). Arginase I protein was overexpressed in ED+ samples, whereas ED+ and ED− samples did not differ significantly in terms of NOS3 expression. Treatment with genistein did not significantly improve endothelial function in ED+ samples. Conclusion Overexpression and elevated activity of arginase I are involved in tobacco-induced pulmonary endothelial dysfunction.
    Full-text · Article · Mar 2015 · Respiratory Research
  • C Rivera · S Rivera · E Fabre · C Pricopi · F Le Pimpec-Barthes · M Riquet
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    ABSTRACT: In France, in 2010, tobacco induced 81% of deaths by lung cancer corresponding to about 28,000 deaths. Continued smoking after diagnosis has a significant impact on treatment. In patients with lung cancer, the benefits of smoking cessation are present at any stage of disease. For early stages, smoking cessation decreases postoperative morbidity, reduces the risk of second cancer and improves survival. Previous to surgery, smoking cessation of at least six to eight weeks or as soon as possible is recommended in order to reduce the risk of infectious complications. Tobacco could alter the metabolism of certain chemotherapies and targeted therapies, such as tyrosine kinase inhibitors of the EGF receptor, through an interaction with P450 cytochrome. Toxicity of radiations could be lower in patients with lung cancer who did not quit smoking before treatment. For patients treated by radio-chemotherapy, overall survival seems to be better in former smokers but no difference is observed in terms of recurrence-free survival. For advanced stages, smoking cessation enhances patients' quality of life. Smoking cessation should be considered as full part of lung cancer treatment whatever the stage of disease. Copyright © 2015 Elsevier Masson SAS. All rights reserved.
    No preview · Article · Feb 2015 · Revue de Pneumologie Clinique
  • C Rivera · N Pecuchet · D Wermert · C Pricopi · F Le Pimpec-Barthes · M Riquet · E Fabre
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    ABSTRACT: Obesity and lung cancer are major public health problems. The purpose of this work is to review the data concerning this association. We report clinical and epidemiological data on obesity and discuss the impact on the incidence of lung cancer, as well as the safety and efficiency of anti-tumor treatments. Obesity does not contribute to the occurrence of lung cancer, unlike other malignancies. Patients may be more likely to undergo treatment at lower risk. Regarding surgery, obesity makes anaesthesia more difficult, increases the operative duration but does not increase postoperative morbidity and mortality. Chemotherapy and radiotherapy seem to be administered according to the same criteria as patients with normal weight. Paradoxically, survival rates of lung cancer are better in obese patients as well after surgery than after non-surgical treatment. Obesity is related to many neoplasms but not to lung cancer. Regarding long-term survival all treatments combined, it has a favorable effect: this is the "obesity paradox". Copyright © 2014 Elsevier Masson SAS. All rights reserved.
    No preview · Article · Feb 2015 · Revue de Pneumologie Clinique
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    ABSTRACT: The aim of this study was to evaluate the clinical characteristics and factors that influence the long-term outcomes of solitary fibrous tumors of the pleura. We conducted a retrospective study in 2 centers and reviewed 80 patients who underwent surgery between May 1984 and April 2011. Of the 80 patients (29 male; median age, 60 years [33 to 85 years]), 47 were symptomatic (59%). The tumors originated from the visceral pleura in 62 cases (79%) and from the parietal pleura in 18 cases (22%). The tumors were pedunculated in 66 cases (83%) and sessile in 20 cases (17%). Surgical resection with histologically free margins was accomplished in 76 of 79 patients (93%). The tumors were classified as benign in 51 cases (65%) and as malignant in 28 (35%). The factors that were significantly associated with malignant tumors were the presence of symptoms (p = 0.03), a mean diameter 10 cm or greater (p = 0.0004), fibrous adherences (p = 0.003), pleural effusion (p = 0.003), and a Ki67 10% or greater (p = 0.003). The median follow-up was 69 months (range, 1 to 315). Local recurrence occurred in 3 cases. The overall 5- and 10-year survival rates were 90% and 86%, respectively, and the mean survival time was 255 ± 15 months. There were no differences between the benign and malignant tumors. The recurrence rates are low after surgeries for both benign and malignant solitary fibrous tumors of the pleura. However, the factors that are predictive of recurrence have yet to be specified and require additional immunohistochemical and genetic investigations. Copyright © 2015 The Society of Thoracic Surgeons. Published by Elsevier Inc. All rights reserved.
    No preview · Article · Jan 2015 · The Annals of Thoracic Surgery
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    P-B Pagès · R Grima · P Mordant · B Grand · A Badia · F Le Pimpec-Barthes · A Bernard · M Riquet
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    ABSTRACT: Surgical resection of pulmonary aspergilloma is associated with symptoms control, complications prevention, and improved survival, given that the disease is localized and the patient fit enough to undergo surgery. In these operable forms, the impact of perioperative antifungal therapy remains controversial. The purpose of this study was to analyze the impact of antifungal therapy on postoperative morbidity and overall survival in patients with operable pulmonary aspergilloma. The clinical records of 113 patients who underwent thoracic surgery for aspergilloma in our institution from January 1989 to December 2010 were retrospectively reviewed. Of these, 64 patients received antifungal therapy in the perioperative period and were included in group 1, and 49 patients did not receive antifungal therapy and were included in group 2. Postoperative complication rates were 31.2% in group 1 and 20.4% in group 2 (P=0.30). Univariable analysis showed that immunocompromised status (P<0.001), past history of cancer (P=0.50), preoperative purulent sputum (P=0.024), and pneumonectomy (P<0.001) were significantly associated with postoperative complications, but that antifungal therapy was not. Five- and 10-year overall survival rates were respectively 78.3% and 57.8% in group 1 vs. 85.9% and 65.7% in group 2 (P=0.23). Multivariate analysis revealed that age higher than 50, immunocompromised status and pneumonectomy were significantly associated with adverse long-term survival (χ(2)=6.59, df=5, P<0.001), but that antifungal therapy was not. Antifungal therapy has no significant impact on postoperative morbidity or long-term survival following surgical resection of pulmonary aspergilloma. Such procedure is associated with acceptable postoperative morbidity and long-term survival. Copyright © 2014 Elsevier Masson SAS. All rights reserved.
    Full-text · Article · Nov 2014 · Revue de Pneumologie Clinique
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    P.-B. Pagès · R. Grima · P. Mordant · B. Grand · A. Badia · F. Le Pimpec-Barthes · A. Bernard · M. Riquet
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    ABSTRACT: Le traitement chirurgical des aspergillomes pulmonaires permet de contrôler les symptômes, de prévenir les complications et d’améliorer la survie. Dans les formes accessibles à la chirurgie, l’impact d’un traitement antifongique demeure controversé. L’objectif de cette étude est d’analyser l’impact d’un traitement antifongique sur la morbidité postopératoire et la survie globale des patients opérés pour un aspergillome pulmonaire.
    Full-text · Article · Nov 2014 · Revue de Pneumologie Clinique
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    P. Mordant · P.-B. Pagès · B. Grand · F. Le Pimpec-Barthes · M. Riquet

    Full-text · Article · Nov 2014

Publication Stats

1k Citations
323.53 Total Impact Points

Institutions

  • 2009-2015
    • Université René Descartes - Paris 5
      • Faculté de Médecine
      Lutetia Parisorum, Île-de-France, France
    • Fondation Jean Dausset (CEPH)
      Lutetia Parisorum, Île-de-France, France
  • 2001-2015
    • Hôpital Européen Georges-Pompidou (Hôpitaux Universitaires Paris-Ouest)
      • Service d’Anatomie-Pathologie
      Lutetia Parisorum, Île-de-France, France
  • 2014
    • Paris Diderot University
      Lutetia Parisorum, Île-de-France, France