Your browser doesn't support javascript.
loading
Show: 20 | 50 | 100
Results 1 - 20 de 150
Filter
Add more filters

Publication year range
1.
Cell ; 166(2): 328-342, 2016 Jul 14.
Article in English | MEDLINE | ID: mdl-27374332

ABSTRACT

Metastases are the main cause of cancer deaths, but the mechanisms underlying metastatic progression remain poorly understood. We isolated pure populations of cancer cells from primary tumors and metastases from a genetically engineered mouse model of human small cell lung cancer (SCLC) to investigate the mechanisms that drive the metastatic spread of this lethal cancer. Genome-wide characterization of chromatin accessibility revealed the opening of large numbers of distal regulatory elements across the genome during metastatic progression. These changes correlate with copy number amplification of the Nfib locus, and differentially accessible sites were highly enriched for Nfib transcription factor binding sites. Nfib is necessary and sufficient to increase chromatin accessibility at a large subset of the intergenic regions. Nfib promotes pro-metastatic neuronal gene expression programs and drives the metastatic ability of SCLC cells. The identification of widespread chromatin changes during SCLC progression reveals an unexpected global reprogramming during metastatic progression.


Subject(s)
Lung Neoplasms/pathology , NFI Transcription Factors/metabolism , Neoplasm Metastasis/pathology , Small Cell Lung Carcinoma/pathology , Amino Acid Motifs , Animals , Cell Line, Tumor , Cells, Cultured , Disease Models, Animal , Gene Expression Regulation, Neoplastic , Gene Knockdown Techniques , Humans , Lung Neoplasms/genetics , Lung Neoplasms/metabolism , Mice , NFI Transcription Factors/genetics , Promoter Regions, Genetic , Small Cell Lung Carcinoma/genetics , Small Cell Lung Carcinoma/metabolism , Up-Regulation
2.
Radiology ; 310(3): e222275, 2024 Mar.
Article in English | MEDLINE | ID: mdl-38530173

ABSTRACT

HISTORY: A 58-year-old man who was an active smoker was admitted twice to the intensive care unit (ICU) of a tertiary referral thoracic center for severe hypercapnic acute respiratory failure and persistent bilateral chest radiograph opacities that were unchanged over the course of the two ICU admissions within a 3-month period (Fig 1). He had obesity (body mass index, 36 kg/m2), stage 3 vascular chronic renal insufficiency, and hebephrenic schizophrenia treated with haloperidol, carbamazepine, and cyamemazine. He reported chronic dyspnea on exertion, which worsened for 6 months. At the second ICU admission, he was afebrile, with a blood pressure of 160/72 mm Hg and pulse oximetry of 93% on 6 L/min oxygen therapy through a nonrebreathing mask. Physical examination showed signs of respiratory failure with wheezing and active abdominal expiration, bilateral pulmonary crackles without chest pain, hemoptysis, clubbing, or signs of cardiac failure. He had no peripheral lymphadenopathy and no enlarged spleen. Blood gases (on 6 L/min oxygen) showed respiratory acidosis (pH, 7.15 [normal range, 7.38-7.42]; Pao2 level, 67 mm Hg [normal range, 80-100 mm Hg]; Paco2 level, 102 mm Hg [normal range, 38-42 mm Hg]; Hco3- level, 29 mmol/L [normal range, 22-27 mmol/L]). Noninvasive ventilation was initiated. Imaging performed during the second ICU hospitalization included noncontrast chest CT (Fig 2), MRI of the chest without contrast enhancement (Fig 3), and fluorine 18 fluorodeoxyglucose PET/CT (Fig 4).


Subject(s)
Chest Pain , Positron Emission Tomography Computed Tomography , Male , Humans , Middle Aged , Dyspnea , Blood Pressure , Oxygen
3.
Nature ; 545(7654): 360-364, 2017 05 18.
Article in English | MEDLINE | ID: mdl-28489825

ABSTRACT

The Notch signalling pathway mediates cell fate decisions and is tumour suppressive or oncogenic depending on the context. During lung development, Notch pathway activation inhibits the differentiation of precursor cells to a neuroendocrine fate. In small-cell lung cancer, an aggressive neuroendocrine lung cancer, loss-of-function mutations in NOTCH genes and the inhibitory effects of ectopic Notch activation indicate that Notch signalling is tumour suppressive. Here we show that Notch signalling can be both tumour suppressive and pro-tumorigenic in small-cell lung cancer. Endogenous activation of the Notch pathway results in a neuroendocrine to non-neuroendocrine fate switch in 10-50% of tumour cells in a mouse model of small-cell lung cancer and in human tumours. This switch is mediated in part by Rest (also known as Nrsf), a transcriptional repressor that inhibits neuroendocrine gene expression. Non-neuroendocrine Notch-active small-cell lung cancer cells are slow growing, consistent with a tumour-suppressive role for Notch, but these cells are also relatively chemoresistant and provide trophic support to neuroendocrine tumour cells, consistent with a pro-tumorigenic role. Importantly, Notch blockade in combination with chemotherapy suppresses tumour growth and delays relapse in pre-clinical models. Thus, small-cell lung cancer tumours generate their own microenvironment via activation of Notch signalling in a subset of tumour cells, and the presence of these cells may serve as a biomarker for the use of Notch pathway inhibitors in combination with chemotherapy in select patients with small-cell lung cancer.


Subject(s)
Lung Neoplasms/metabolism , Lung Neoplasms/pathology , Receptors, Notch/metabolism , Signal Transduction , Small Cell Lung Carcinoma/metabolism , Small Cell Lung Carcinoma/pathology , Tumor Microenvironment , Animals , Cell Differentiation , Cell Proliferation/drug effects , Disease Models, Animal , Female , Humans , Lung Neoplasms/drug therapy , Male , Mice , Neoplasm Recurrence, Local/prevention & control , Receptors, Notch/agonists , Receptors, Notch/antagonists & inhibitors , Receptors, Notch/deficiency , Repressor Proteins/metabolism , Small Cell Lung Carcinoma/drug therapy
4.
Int J Cancer ; 150(11): 1889-1904, 2022 06 01.
Article in English | MEDLINE | ID: mdl-35262190

ABSTRACT

The Hippo pathway effector YAP is dysregulated in malignant pleural mesothelioma (MPM). YAP's target genes include the secreted growth factor amphiregulin (AREG), which is overexpressed in a wide range of epithelial cancers and plays an elusive role in MPM. We assayed the expression of YAP and AREG in MPM pathology samples and that of AREG additionally in plasma samples of patients from the randomized phase 3 IFCT-0701 Mesothelioma Avastin Cisplatin Pemetrexed Study (MAPS) using immunohistochemistry and ELISA assays, respectively. MPM patients frequently presented high levels of tumor AREG (64.3%), a high cytosolic AREG expression being predictive of a better prognosis with longer median overall and progression-free survival. Surprisingly, tumor AREG cytosolic expression was not correlated with secreted plasma AREG. By investigating the AREG metabolism and function in MPM cell lines H2452, H2052, MSTO-211H and H28, in comparison with the T47D ER+ breast cancer cell line used as a positive control, we confirm that AREG is important for cell invasion, growth without anchorage, proliferation and apoptosis in mesothelioma cells. Yet, most of these MPM cell lines failed to correctly execute AREG posttranslational processing by metalloprotease ADAM17/tumor necrosis factor-alpha-converting enzyme (TACE) and extracell secretion. The favorable prognostic value of high cytosolic AREG expression in MPM patients could therefore be sustained by default AREG posttranslational processing and release. Thus, the determination of mesothelioma cell AREG content could be further investigated as a prognostic marker for MPM patients and used as a stratification factor in future clinical trials.


Subject(s)
Lung Neoplasms , Mesothelioma, Malignant , Mesothelioma , Pleural Neoplasms , Amphiregulin/genetics , Cell Line, Tumor , Humans , Lung Neoplasms/genetics , Mesothelioma/metabolism , Pleural Neoplasms/drug therapy , Pleural Neoplasms/pathology
5.
J Cardiothorac Vasc Anesth ; 36(6): 1694-1702, 2022 06.
Article in English | MEDLINE | ID: mdl-34330577

ABSTRACT

OBJECTIVES: To determine if venoarterial extracorporeal membrane oxygenation (VA ECMO) as a bridge to left ventricular assist device (LVAD) in heart transplant (HT) candidates (ie, double bridge to HT) was associated with increased morbidity and mortality when compared to LVAD bridging to HT (ie, single bridge to HT). DESIGN: A retrospective analysis of patients undergoing LVAD support from 2011 to 2020. A Kaplan-Meier survival curve and Cox-Mantel hazard ratios (HR) were calculated during LVAD support and after HT. Postoperative complications were collected. SETTING: University Hospital Erasme. PARTICIPANTS: HT candidates requiring LVAD. INTERVENTIONS: VA ECMO bridging to LVAD (ECMO-LVAD group [n = 24]) versus LVAD (LVAD group [n = 64]). MEASUREMENTS AND MAIN RESULTS: Eighty-eight patients underwent HeartWare LVAD (HVAD, Medtronic) placement. Survival to hospital discharge and during the entire study period were lower in the ECMO-LVAD group (66.7% v 92.2%; p = 0.0027, and 37.5% v 62.5%; p = 0.035, respectively). Overall HR of death was 2.46 (95% confidence interval [CI]: 1.13-5.37; p = 0.005) in the ECMO-LVAD group and remained elevated throughout their time on LVAD support (HR 3.24 [95% CI: 1.15-9.14]; p = 0.0036). However, in patients who underwent HT (n = 50), mortality was similar between groups (HR 1.33 [95% CI: 0.33-5.31]; p = 0.66). Postoperative complications were more frequent in the ECMO-LVAD group (infection = 83.3% v 51.6%, p = 0.007; renal replacement therapy = 45.8% v 9.4%, p = 0.0001; post-LVAD ECMO = 25.0% v 1.6%; p = 0.0003). CONCLUSIONS: VA ECMO as a bridge to LVAD support before HT was associated with increased morbidity and mortality during LVAD support. However, in patients who underwent HT, outcomes were similar regardless of VA ECMO bridging.


Subject(s)
Extracorporeal Membrane Oxygenation , Heart Failure , Heart Transplantation , Heart-Assist Devices , Heart Failure/etiology , Heart Failure/surgery , Heart-Assist Devices/adverse effects , Humans , Postoperative Complications/epidemiology , Postoperative Complications/etiology , Postoperative Complications/therapy , Retrospective Studies , Treatment Outcome
6.
BMC Cancer ; 21(1): 711, 2021 Jun 16.
Article in English | MEDLINE | ID: mdl-34134640

ABSTRACT

BACKGROUND: This study aims to provide new insights on the role of smoking patterns and cigarette dependence in female lung cancer, and to examine differences by histological subtype. METHODS: We conducted a population-based case-control study in the great Paris area among women including 716 incident cases diagnosed between 2014 and 2017 and 757 age-matched controls. Detailed data on smoking history was collected during in-person interviews to assess intensity and duration of tobacco smoking, time since cessation, smoking habits (depth of smoke inhalation, use of filter, type of tobacco, and type of cigarettes) and Fagerström test for cigarette dependence. The comprehensive smoking index (CSI), a score modelling the combined effects of intensity, duration and time since quitting smoking was determined for each subject. Multivariable logistic regression models were fitted to calculate odds ratios (ORs) and their confidence intervals (95%CI) of lung cancer associated with smoking variables. RESULTS: Lung cancer risk increased linearly with intensity and duration of tobacco smoking while it decreased with time since cessation, to reach the risk in never-smokers after 20 years of abstinence. The combined effect of intensity and duration of tobacco smoking was more than multiplicative (p-interaction 0.012). The OR in the highest vs the lowest quartile of CSI was 12.64 (95%CI 8.50; 18.80) (p-trend < 0.001). The risk of small cell or squamous cell carcinomas increased with the CSI more sharply than the risk of adenocarcinomas. Deep smoke inhalation, dark vs blond tobacco, conventional vs light cigarettes, and unfiltered vs filtered cigarettes, as well as having mixed smoking habits, were found to be independent risk factors. Having high cigarette addiction behaviours also increased the risk after adjusting for CSI. CONCLUSION: This study provides additional insights on the effects of tobacco smoking patterns on lung cancer risk among women.


Subject(s)
Lung Neoplasms/chemically induced , Smoking/adverse effects , Aged , Case-Control Studies , Female , France , Humans , Middle Aged , Risk Factors , Time Factors
7.
Ann Pathol ; 41(6): 507-520, 2021 Nov.
Article in French | MEDLINE | ID: mdl-34393014

ABSTRACT

The last international guidelines on HER2 determination in breast cancer have been updated in 2018 by the American Society of Clinical Oncology and College of American Pathologists, on the basis of a twenty-year practice and results of numerous clinical trials. Moreover, the emerging HER2-low concept for 1+ and 2+ non amplified breast cancers lead to refine French practices for HER2 status assessment. The GEFPICS group, composed of expert pathologists, herein presents the latest French recommendations for HER2 status evaluation in breast cancer, taking into account the ASCO/CAP guidelines and introducing the HER2-low concept. In the era of personalized medicine, HER2 status assessment remains one of the most important biomarkers in breast cancer and its quality guaranties the optimal patients' care. French pathologists' commitment in theranostic biomarker quality is more than ever required to provide the most efficient cares in oncology.


Subject(s)
Breast Neoplasms , Biomarkers, Tumor , Breast Neoplasms/diagnosis , Breast Neoplasms/genetics , Female , Humans , Immunohistochemistry , In Situ Hybridization, Fluorescence , Receptor, ErbB-2/genetics
8.
Gastroenterology ; 154(4): 1061-1065, 2018 03.
Article in English | MEDLINE | ID: mdl-29158190

ABSTRACT

Microsatellite instability (MSI) caused by mismatch repair deficiency (dMMR) is detected in a small proportion of pancreatic ductal adenocarcinomas (PDACs). dMMR and MSI have been associated with responses of metastatic tumors, including PDACs, to immune checkpoint inhibitor therapy. We performed immunohistochemical analyses of a 445 PDAC specimens, collected from consecutive patients at multiple centers, to identify those with dMMR, based on loss of mismatch repair proteins MLH1, MSH2, MSH6, and/or PMS2. We detected dMMR in 1.6% of tumor samples; we found dMMR in a larger proportion of intraductal papillary mucinous neoplasms-related tumors (4/58, 6.9%) than non- intraductal papillary mucinous neoplasms PDAC (5/385, 1.3%) (P = .02). PDACs with dMMR contained potentially immunogenic mutations because of MSI in coding repeat sequences. PDACs with dMMR or MSI had a higher density of CD8+ T cells at the invasive front than PDACs without dMMR or MSI (P = .08; Fisher exact test). A higher proportion of PDACs with dMMR or MSI expressed the CD274 molecule (PD-L1, 8/9) than PDACs without dMMR or MSI (4/10) (P = .05). Times of disease-free survival and overall survival did not differ significantly between patients with PDACs with dMMR or MSI vs without dMMR or MSI. Studies are needed to determine whether these features of PDACs with dMMR or MSI might serve as prognostic factors.


Subject(s)
Carcinoma, Pancreatic Ductal/genetics , Microsatellite Instability , Neoplasms, Cystic, Mucinous, and Serous/genetics , Pancreatic Neoplasms/genetics , Adult , Aged , Aged, 80 and over , Biomarkers, Tumor/analysis , CD8-Positive T-Lymphocytes/immunology , Carcinoma, Pancreatic Ductal/chemistry , Carcinoma, Pancreatic Ductal/immunology , Carcinoma, Pancreatic Ductal/pathology , DNA-Binding Proteins/analysis , Disease-Free Survival , Female , Genetic Predisposition to Disease , Humans , Lymphocytes, Tumor-Infiltrating/immunology , Male , Middle Aged , Mismatch Repair Endonuclease PMS2/analysis , MutL Protein Homolog 1/analysis , MutS Homolog 2 Protein/analysis , Neoplasms, Cystic, Mucinous, and Serous/chemistry , Neoplasms, Cystic, Mucinous, and Serous/immunology , Neoplasms, Cystic, Mucinous, and Serous/pathology , Pancreatic Neoplasms/chemistry , Pancreatic Neoplasms/immunology , Pancreatic Neoplasms/pathology , Phenotype , Time Factors
9.
Ann Pathol ; 39(6): 425-432, 2019 Dec.
Article in French | MEDLINE | ID: mdl-31604575

ABSTRACT

Gross examination is an essential step for pathological report of a surgical sample. It includes the description of the surgical specimen and their disease(s), the precise and exhaustive sampling of tumoral and adjacent tumoral tissue areas. This examination requires a good knowledge of the updated pTNM classification. Pathologists from the PATTERN group have collaborated with thoracic surgeons, under the auspices of the Sociéte française de pathologie, to propose guidelines for resected specimen management. This approach fits into the context of the elaboration of structured pathological report proposed by the société française de pathologie, which is necessary for a standardized management of patients.


Subject(s)
Carcinoma/pathology , Carcinoma/surgery , Lung Neoplasms/pathology , Lung Neoplasms/surgery , Specimen Handling/standards , Carcinoma/classification , France , Humans , Lung Neoplasms/classification , Medical Illustration , Neoplasm Staging , Pathology, Clinical/standards , Societies, Medical
10.
Ann Pathol ; 39(6): 383-398, 2019 Dec.
Article in French | MEDLINE | ID: mdl-31257035

ABSTRACT

Neoadjuvant therapy is an increasing treatment option in the management of breast cancer. The tumor response to neoadjuvant therapy, especially the pathological complete response, is a validated endpoint frequently used in clinical trials. However, there is still a lack of standardization for the surgical specimen management in the neoadjuvant setting. This leads to heterogeneity in the specimen handling and might lead to significant bias for the prognostic assessment of patients or in clinical trials. The GEFPICS group, composed of expert breast cancer pathologists, herein presents guidelines for the management of breast and axillary specimen before treatment (management of biopsy, items of the pathological report) and after neoadjuvant therapy (specimen handling, histological assessment of response, items of the pathological report and response grading systems).


Subject(s)
Breast Neoplasms/pathology , Breast/pathology , Lymph Nodes/pathology , Neoadjuvant Therapy , Specimen Handling/standards , Biomarkers, Tumor , Biopsy/methods , Biopsy/standards , Breast Neoplasms/chemistry , Breast Neoplasms/mortality , Breast Neoplasms/therapy , Chemotherapy, Adjuvant/standards , Drug Screening Assays, Antitumor , Female , France , Humans , Lymph Nodes/drug effects , Lymph Nodes/surgery , Medical Records/standards , Microscopy , Neoplasm, Residual/pathology , Prognosis , Sentinel Lymph Node Biopsy/methods , Specimen Handling/methods , Treatment Outcome , Tumor Burden/drug effects
11.
Eur Respir J ; 51(3)2018 03.
Article in English | MEDLINE | ID: mdl-29545318

ABSTRACT

ALK rearrangement and EGFR/KRAS mutations constitute the primary biomarkers tested to provide targeted or nontargeted therapies in advanced nonsmall cell lung cancer (NSCLC) patients. Our objective was to assess the cost-effectiveness of biomarker testing for NSCLC.Between 2013 and 2014, 843 treatment-naive patients were prospectively recruited at 19 French hospitals into a longitudinal observational cohort study. Two testing strategies were compared, i.e. with "at least one biomarker status known" and "at least KRAS status known", in addition to "no biomarker testing" as the reference strategy. The Kaplan-Meier approach was employed to assess restricted mean survival time. Direct medical costs incurred by hospitals were estimated with regard to treatment, inpatient care and biomarker testing.Compared with "no biomarker testing", the "at least one biomarker status known" strategy yielded an incremental cost-effectiveness ratio of EUR13 230 per life-year saved, which decreased to EUR7444 per life-year saved with the "at least KRAS status known" testing strategy. In sensitivity analyses, biomarker testing strategies were less costly and more effective in 41% of iterations.In summary, molecular testing prior to treatment initiation proves to be cost-effective in advanced NSCLC management and may assist decision makers in defining conditions for further implementation of these innovations in general practice.


Subject(s)
Carcinoma, Non-Small-Cell Lung/economics , Carcinoma, Non-Small-Cell Lung/genetics , DNA Mutational Analysis/economics , Genetic Testing/economics , Lung Neoplasms/economics , Lung Neoplasms/genetics , Adult , Aged , Aged, 80 and over , Anaplastic Lymphoma Kinase/genetics , Biomarkers , Cost-Benefit Analysis , Decision Making , ErbB Receptors/genetics , Female , France , Humans , Longitudinal Studies , Male , Middle Aged , Mutation , Proto-Oncogene Proteins p21(ras)/genetics , Pulmonary Medicine/economics , Pulmonary Medicine/methods
12.
Lung ; 196(1): 33-42, 2018 02.
Article in English | MEDLINE | ID: mdl-29026982

ABSTRACT

PURPOSE: Severe hemoptysis (SH) associated with non-tuberculosis bacterial lower respiratory tract infection (LRTI) is poorly described, and the efficacy of the usual decision-making process is unknown. This study aimed at describing the clinical, radiological patterns, mechanism, and microbiological spectrum of SH related to bacterial LRTI, and assessing whether the severity of hemoptysis and the results of usual therapeutic strategy are influenced by the presence of parenchymal necrosis. METHODS: A single-center analysis of patients with SH related to bacterial LRTI from a prospective registry of consecutive patients with SH admitted to the intensive care unit of a tertiary referral center between November 1996 and May 2013. RESULTS: Of 1504 patients with SH during the study period, 65 (4.3%) had SH related to bacterial LRTI, including non-necrotizing infections (n = 31), necrotizing pneumonia (n = 23), pulmonary abscess (n = 10), and excavated nodule (n = 1). The presence of parenchymal necrosis (n = 34, 52%) was associated with a more abundant bleeding (volume: 200 ml [70-300] vs. 80 ml [30-170]; p = 0.01) and a more frequent need for endovascular procedure (26/34; 76% vs. 9/31; 29%; p < 0.001). Additionally, in case of parenchymal necrosis, the pulmonary artery vasculature was involved in 16 patients (47%), and the failure rate of endovascular treatment was up to 25% despite multiple procedures. CONCLUSIONS: Bacterial LRTI is a rare cause of SH. The presence of parenchymal necrosis is more likely associated with bleeding severity, pulmonary vasculature involvement, and endovascular treatment failure.


Subject(s)
Bacterial Infections/complications , Hemoptysis/microbiology , Lung Abscess/complications , Lung/pathology , Pneumonia/complications , Pulmonary Artery/pathology , Vascular Diseases/complications , Adult , Aged , Bronchoscopy , Computed Tomography Angiography , Endovascular Procedures , Female , Hemoptysis/therapy , Humans , Lung Abscess/diagnostic imaging , Lung Abscess/microbiology , Male , Middle Aged , Necrosis/complications , Necrosis/diagnostic imaging , Necrosis/microbiology , Pneumonia/diagnostic imaging , Pneumonia/microbiology , Radiography, Thoracic , Retrospective Studies , Severity of Illness Index , Treatment Outcome , Vascular Diseases/microbiology , Vascular Diseases/surgery
14.
Acta Cardiol ; 73(3): 248-255, 2018 Jun.
Article in English | MEDLINE | ID: mdl-28847218

ABSTRACT

BACKGROUND: With more than 15,000 implanted patients worldwide and a survival rate of 80% at 1-year and 59% at 5-years, left ventricular assist device (LVAD) implantation has become an interesting strategy in the management of heart failure patients who are resistant to other kinds of treatment. There are limited data in the literature on the change over time of exercise capacity in LVAD patients, as well as limited knowledge about the beneficial effects that rehabilitation might have on these patients. Therefore, the aim of our study was to evaluate the evolution of exercise capacity on a cohort of patients implanted with the same device (HeartWare©) and to analyse the potential impact of rehabilitation. METHODS: Sixty-two patients implanted with a LVAD between June 2011 and June 2015 were screened. Exercise capacity was evaluated by cardiopulmonary exercise testing at 6 weeks, 6 and 12 months after implantation. RESULTS: We have observed significant differences in the exercise capacity and evolution between the trained and non-trained patients. Some of the trained patients nearly normalised their exercise capacity at the end of the rehabilitation programme. CONCLUSIONS: Exercise capacity of patient implanted with a HeartWare© LVAD increased in the early period after implantation. Rehabilitation allowed implanted patients to have a significantly better evolution compared to non-rehabilitated patients.


Subject(s)
Cardiac Rehabilitation/methods , Exercise Therapy/methods , Heart Failure/rehabilitation , Heart-Assist Devices , Exercise Test , Exercise Tolerance/physiology , Female , Follow-Up Studies , Heart Failure/physiopathology , Humans , Male , Middle Aged , Retrospective Studies , Time Factors
15.
Ann Pathol ; 38(2): 110-125, 2018 Apr.
Article in French | MEDLINE | ID: mdl-29571563

ABSTRACT

Lung cancer is the leading cause of cancer death in France with low response rates to conventional chemotherapy. Nevertheless, new therapies have emerged recently, among which PD1 immune checkpoint inhibitors (ICI), such as nivolumab (OPDIVO®, Bristol-Myers Squibb) and pembrolizumab (KEYTRUDA®, Merck & Co), or PD-L1 ICI, such as atezolizumab (TECENTRIQ®, Genentech), durvalumab (IMFINZI®, Astra-Zeneca), and avelumab (BAVENCIO®, EMD Serono). The prescription of pembrolizumab for advanced stage non-small cell lung carcinoma (NSCLC) patients requires the demonstration of PD-L1 expression by tumor cells by immunohistochemistry (IHC) (minimum of 50% of positive tumor cells is required for first-line setting, and of 1% for second-line and beyond) and PD-L1 assay is now considered as a companion diagnostic tool for this drug. Numerous standardized PD-L1 assays performed on dedicated platforms have been validated in clinical trials, each antibody being associated to one specific PD1 or PD-L1 inhibitor. However, not all pathologists have access to the dedicated platforms and the high cost of these assays is still a limitation to their implementation; in addition, the small size of the NSCLC tumor samples does not allow to perform at the same time multiple assays for multiple drugs. The use of laboratory-developed tests seems feasible but their validation must guarantee the same sensitivities and specificities as standardized tests. In this context, the French group of thoracic pathologists PATTERN has teamed up with thoracic oncologists to provide recommendations on the indication, the critical technical steps and the interpretation of the PD-L1 IHC test to help pathologists to implement quickly and in the best conditions this new theranostic test.


Subject(s)
B7-H1 Antigen/analysis , Biomarkers, Tumor/analysis , Carcinoma, Non-Small-Cell Lung/chemistry , Immunohistochemistry/methods , Lung Neoplasms/chemistry , Neoplasm Proteins/analysis , Specimen Handling/methods , Algorithms , Antineoplastic Agents, Immunological/pharmacology , Antineoplastic Agents, Immunological/therapeutic use , Antineoplastic Combined Chemotherapy Protocols/therapeutic use , B7-H1 Antigen/antagonists & inhibitors , Carcinoma, Non-Small-Cell Lung/drug therapy , Carcinoma, Non-Small-Cell Lung/pathology , Clinical Trials, Phase III as Topic , Humans , Immunohistochemistry/standards , Lung Neoplasms/drug therapy , Lung Neoplasms/pathology , Molecular Targeted Therapy , Neoplasm Proteins/antagonists & inhibitors , Organoplatinum Compounds/therapeutic use , Patient Selection , Quality Assurance, Health Care , Randomized Controlled Trials as Topic , Reagent Kits, Diagnostic , Specimen Handling/standards
16.
Respiration ; 94(2): 157-175, 2017.
Article in English | MEDLINE | ID: mdl-28609772

ABSTRACT

This review aims to describe some of the most frequent lymphoproliferative disorders arising from the lung: pulmonary mucosa-associated lymphoid tissue (MALT) lymphoma, lymphomatoid granulomatosis (LG), multicentric Castleman disease (MCD), primary effusion lymphoma (PEL), and nodular lymphoid hyperplasia (NLH). Primary pulmonary lymphoma is defined as a clonal lymphoproliferative disorder affecting one or both lungs, without extrapulmonary involvement 3 months after diagnosis, and includes pulmonary MALT lymphoma and LG. MALT lymphoma is the most common pulmonary lymphoma. The disease is slow growing, most often asymptomatic, and revealed by chronic alveolar opacity on radiography. The diagnosis should involve minimally invasive techniques, and the prognosis is typically excellent. LG is a rare B-cell lymphoma driven by Epstein-Barr virus infection. The disease may mimic pulmonary vasculitis, often revealed by systemic signs. The diagnosis usually requires surgical lung biopsy. Its evolution is unpredictable, but median survival is poor and chemotherapy is usually proposed. MCD and PEL are both driven by Human herpesvirus 8 infection. Patients with MCD present with fever and lymphadenopathy associated with interstitial lung disease. PEL provokes a febrile, lymphocytic-exudative pleural effusion, without any pleural mass on CT. Specific chemotherapy is urgent for both MCD and PEL. NLH is a benign lymphoproliferative disorder of the lung that is usually asymptomatic and revealed by a single nodular opacity. The prognosis is good, without recurrence after surgical resection.


Subject(s)
Lung Diseases/diagnostic imaging , Lymphoproliferative Disorders/diagnostic imaging , Castleman Disease/diagnostic imaging , Castleman Disease/pathology , Castleman Disease/therapy , Castleman Disease/virology , Epstein-Barr Virus Infections , Herpesviridae Infections , Herpesvirus 8, Human , Humans , Lung Diseases/pathology , Lung Diseases/therapy , Lung Diseases/virology , Lung Neoplasms/diagnostic imaging , Lung Neoplasms/pathology , Lung Neoplasms/therapy , Lymphoma/diagnostic imaging , Lymphoma/pathology , Lymphoma/therapy , Lymphoma, B-Cell, Marginal Zone/diagnostic imaging , Lymphoma, B-Cell, Marginal Zone/pathology , Lymphoma, B-Cell, Marginal Zone/therapy , Lymphoma, Primary Effusion/diagnostic imaging , Lymphoma, Primary Effusion/pathology , Lymphoma, Primary Effusion/therapy , Lymphoma, Primary Effusion/virology , Lymphomatoid Granulomatosis/diagnostic imaging , Lymphomatoid Granulomatosis/pathology , Lymphomatoid Granulomatosis/therapy , Lymphomatoid Granulomatosis/virology , Lymphoproliferative Disorders/pathology , Lymphoproliferative Disorders/therapy , Lymphoproliferative Disorders/virology
17.
BMC Public Health ; 17(1): 324, 2017 Apr 17.
Article in English | MEDLINE | ID: mdl-28415992

ABSTRACT

BACKGROUND: Lung cancer aetiology and clinical aspects have been mainly studied in men, although specific risk factors probably exist in women. Here we present the rationale, design and organization of the WELCA study (Women Epidemiology Lung CAncer) that has been launched to investigate lung cancer in women, focusing particularly on hormonal and occupational factors. METHODS/DESIGN: WELCA is a population based case-control study and planned to recruit 1000 cases and 1000 controls in three years, based on study power calculation. Eligible cases are female patients newly diagnosed with lung cancer, living in Paris and the Ile de France area and aged up to 75 years. Almost all Parisian pneumology and oncology clinical departments are involved. The control group is a random sample of the population living in the same area, frequency-matched on age and additionally stratified on the distribution of socio-professional categories of women residing there. After acquisition of written consent, research nurses administer standardized computer assisted questionnaires to all the subjects in face-to-face interviews and acquire anthropometric measures. Besides usual socio-demographic characteristics, information is gathered about menstrual and reproductive factors, hormonal treatments, lifestyle and leisure characteristics, occupational history, personal and familial medical history. Biological samples are also collected, in order to establish a biobank for molecular epidemiology studies. Molecular characteristics of the tumours will be obtained and patients will be followed up for five years. DISCUSSION: The WELCA study aims to answer key questions in lung cancer aetiology and clinical characteristics specifically in women. The role of hormonal impregnation is investigated, and the interactions with cigarette smoking or body mass index (BMI) will be analyzed in detail. The occupational history of the subjects is carefully reconstructed, focusing in particular on the service sector. The creation of a biobank for collection of serum, plasma, DNA and tumour tissue will allow the genetic and biochemical characterization of both the subjets and the tumours. The follow-up of the patients will help in disentangling the role of hormonal factors and tumour molecular characteristics in survival.


Subject(s)
Biological Specimen Banks , Hormone Replacement Therapy/adverse effects , Lung Neoplasms/epidemiology , Lung Neoplasms/etiology , Occupational Exposure/adverse effects , Reproductive History , Women's Health , Adult , Aged , Body Mass Index , Case-Control Studies , Female , Follow-Up Studies , France/epidemiology , Humans , Middle Aged , Occupational Diseases/epidemiology , Occupational Diseases/etiology , Paris/epidemiology , Risk Factors , Smoking/epidemiology , Surveys and Questionnaires
18.
Eur Respir J ; 47(4): 1244-60, 2016 Apr.
Article in English | MEDLINE | ID: mdl-26797028

ABSTRACT

This general review sought to clarify the pathophysiological, diagnostic, prognostic, and therapeutic features of pulmonary mucosa-associated lymphoid tissue (MALT) lymphoma.MALT lymphoma is the most common pulmonary B-cell lymphoma, which usually occurs in the context of acquired MALT. The disease is slow-growing with an asymptomatic chronic alveolar opacity visible on radiography. Diagnosis requires tissue samples that should be retrieved using minimally invasive techniques, such as bronchoscopy or computed tomography-guided biopsies. The pathophysiology includes cytogenetic abnormalities and autoimmune diseases, whereas an association with a chronic pulmonary infection is still suspected but not yet demonstrated. Disease prognosis is typically excellent and the current available treatments are discussed in this review, including the decision not to treat, surgery, and single- or double-agent chemotherapy.


Subject(s)
Lymphoid Tissue/pathology , Lymphoma, B-Cell, Marginal Zone/immunology , Respiratory Mucosa/metabolism , Animals , Bronchi/pathology , Bronchoalveolar Lavage , Bronchoscopy , Diagnosis, Differential , Humans , Lung/metabolism , Lymphoma, B-Cell, Marginal Zone/genetics , Lymphoma, B-Cell, Marginal Zone/pathology , Prognosis , Tomography, X-Ray Computed
19.
Eur Radiol ; 26(8): 2510-9, 2016 Aug.
Article in English | MEDLINE | ID: mdl-26511630

ABSTRACT

PURPOSE: To identify pathological features for sample analysis of magnetic resonance imaging-guided vaccum-assisted breast biopsy (MRIgVaBB) to optimize radio pathological correlation and identify discordant benign result. MATERIAL AND METHODS: Databases of two centres were queried to identify MRIgVaBB performed between January 2009 and February 2013. A cohort of 197 women (mean age: 54.5 years (24-77)) with 208 lesions was identified. We retrospectively analyzed all prebiopsy MRI examinations according to the new BI-RADS lexicon, and all biopsy samples to describe the lesion of interest, its interface with the surrounding breast tissue and other associated features. RESULTS: The malignancy rate was 26.0 % (54/208) with an underestimation rate of 15.67 % (5/32). A visible interface at pathology between a biopsied lesion and the surrounding breast tissue was more frequently identified in mass enhancement compared to NME or focus (p = 0.0003). Regional NME was correlated with a high degree of fibrosis (p = 0.001) and the presence of PASH (p = 0.0007). Linear or segmental NME was correlated with the presence of periductal mastitis (p = 0.0003). CONCLUSION: The description of a visible interface between the target lesion and the surrounding tissue is crucial to confirm the correct targeting of an MR mass or a NME. KEY POINTS: • Pathological interface correlated with magnetic resonance mass and focal non-mass enhancement (NME). • Linear or segmental NME correlated with mastitis or ductal carcinoma in situ. • Fibrosis and pseudoangiomatous stromal hyperplasia (PASH) are correlated with regional NME.


Subject(s)
Biopsy, Needle/methods , Breast Neoplasms/diagnosis , Breast/diagnostic imaging , Carcinoma, Intraductal, Noninfiltrating/diagnosis , Image-Guided Biopsy/methods , Adult , Aged , Female , Humans , Magnetic Resonance Imaging , Middle Aged , Retrospective Studies , Young Adult
20.
Ann Pathol ; 36(1): 44-54, 2016 Jan.
Article in French | MEDLINE | ID: mdl-26778815

ABSTRACT

Pulmonary sarcomatoid carcinomas are a rare group of tumors accounting for about one percent of non-small cell lung carcinoma (NSCLC). In 2015, the World Health Organization classification united under this name all the carcinomas with sarcomatous-like component with spindle cell or giant cell appearance, or associated with a sarcomatous component sometimes heterologous. There are five subtypes: pleomorphic carcinoma, spindle cell carcinoma, giant cell carcinoma, carcinosarcoma and pulmonary blastoma. Clinical characteristics are not specific from the other subtypes of NSCLC. Epithelial to mesenchymal transition pathway may play a key role. Patients, usually tobacco smokers, are frequently symptomatic. Tumors are voluminous more often peripherical than central, with strong fixation on FDG TEP CT. Distant metastases are frequent with atypical visceral locations. These tumors have poorer prognosis than the other NSCLC subtypes because of great aggressivity, and frequent chemoresistance. Here we present pathological description and a review of literature with molecular features in order to better describe these tumors and perhaps introduce new therapeutics.


Subject(s)
Carcinoma/classification , Lung Neoplasms/classification , Biomarkers, Tumor , Carcinoma/chemistry , Carcinoma/diagnostic imaging , Carcinoma/epidemiology , Carcinoma/pathology , Cell Differentiation , Diagnosis, Differential , Epithelial-Mesenchymal Transition , Humans , Lung Neoplasms/chemistry , Lung Neoplasms/diagnostic imaging , Lung Neoplasms/epidemiology , Lung Neoplasms/pathology , Prognosis
SELECTION OF CITATIONS
SEARCH DETAIL