Evaluation d'une procédure standardisée pour le diagnostic endoscopique de cancer bronchique primitif (impact sur la sensibilité diagnostique)

Introduction : actuellement, le diagnostic de cancer bronchique primitif nécessite l'obtention de matériel cytologique ou histologique. Plusieurs types de prélèvement peuvent être associés au cours d'une fibroscopie bronchique. Le but était de rechercher un bénéfice en sensibilité diagnostique à la mise en place d'une procédure standardisée. Matériels et méthodes : l'étude portait rétrospectivement sur les patients porteurs de cancer bronchique primitif diagnostiqués dans le service sur la période de janvier 1998 à décembre 2001. A partir de février 2000, un protocole standardisé à été mis en place, comprenant, en cas de fibroscopie normale 1) une aspiration bronchique, 2) un LBA ; un cas de fibroscopie anormale : 1) quatre biopsies sur site tumoral, 2) deux biopsies pour congélation, 3) une brosse bronchique, 4) une aspiration bronchique. Le critère principal était la sensibilité globale de la première fibroscopie dans la période avant (Période) et la période après (Période 2) la procédure. Les autres critères portaient sur la sensibilité individuelle de chaque prélèvement et le respect de la procédure par les examinateurs. Résultats : 307 patients ont été étudiés (Période 1 : 143 patients ; Période 2 : 164 patients). Il n'y avait pas de différence significative de sexe, âge, VEMS, histologie ou stade de tumeur entre les deux groupes. La procédure était respectée dans 28% des cas. Les prélèvements les moins souvent réalisés ont été le LBA (37%), la brosse bronchique (39%), et la biopsie pour congélation (43%). La sensibilité globale était de 61,6%. Il n'y avait pas de différence significative entre les deux périodes. Les biopsies bronchiques étaient le prélèvement le plus sensible, les autres prélèvements apportaient peu de diagnostics supplémentaires. Conclusions : la procédure a peu modifié les comportements des fibroscopistes et n'a pas eu d'impact significatif sur la sensibilité de la fibroscopie bronchique. La réalisation à titre systématique de prélèvements comme le lavage broncho alvéolaire ou la brosse bronchique est susceptible d'allonger la durée d'examen, la charge de travail et le coût de la fibroscopie sans bénéfice substantiel.PARIS7-Xavier Bichat (751182101) / SudocPARIS-BIUM (751062103) / SudocSudocFranceF

Trouble ventilatoire obstructif et sarcoidose

Le trouble ventilatoire obstructif (TVO) au cours de la sarcoïdose est rare et mal connu. But de l étude 11 étudier les caractéristiques épidémiologiques, cliniques, fonctionnelles et radiologiques du TVO en fonction de son mécanisme, 2/ évaluer la réponse thérapeutique du TVO en fonction de son mécanisme. Patients et méthodes étude rétrospective mono-centrique de 68 patients atteints de sarcoïdose avec TVO (VEMS/CV < 70%). Le mécanisme du TVO était défini à partir du scanner thoracique et de la fibroscopie bronchique. La réponse au traitement d attaque était évaluée entre le 3eme et 12eme mois par des EFR. Résultats : 4 groupes ont été déterminés en fonction du mécanisme de TVO: groupe I (n=24), distorsion bronchique ; groupe II (n=8), compression ganglionnaire ; groupe III (n=16), granulomatose bronchique ; groupe IV (n=20), miscellané . Certains paramètres étaient corrélés à un type de mécanisme de TVO: sexe (p=0,006), ethnie (p=0,002), ancienneté de la sarcoïdose, stade radiographique (p=0,00 1), VEMS (p=0,007). L amélioration du rapport VEMS/CV après traitement d attaque était indéniable dans les groupe II (62 à 82,5%) et III (60 à 68%). Le VEMS/CV restait stable chez les patients du groupe I. Conclusion : Il y a une corrélation entre certains paramètres et le mécanisme du TVO. La TDM et la fibroscopie définissent le mécanisme du TVO dans 75% des cas. Cependant, la relation de cause à effet entre anomalies radiologiques et/ou endoscopiques et TVO n était pas toujours simple à affirmer. L identification précise du mécanisme du TVO est importante pour prévoir la réponse thérapeutique : disparition de l obstruction en cas de compression ganglionnaire , amélioration en cas de granulomatose bronchique , stabilisation en cas de distorsion bronchique .PARIS13-BU Serge Lebovici (930082101) / SudocSudocFranceF

Pulmonary complications of immune checkpoint inhibitors in patients with nonsmall cell lung cancer

International audienceImmune checkpoint inhibitor-related pneumonitis (ICI-P) during cancer treatment is rarely observed (<5%). ICI-P is more often observed in patients with nonsmall cell lung cancer (NSCLC) than in those with other cancers. Likewise, it is more common in those receiving programmed cell death (PD)-1/PD-1 ligand inhibitors rather than cytotoxic T-lymphocyte antigen (CTLA)-4 inhibitors alone. The frequency of ICI-P is higher when anti-PD-1 and anti-CTLA-4 are administered concomitantly. Despite the low fatality rate (≈13%), ICI-P is the leading cause of ICI-related deaths. This narrative review focuses on the epidemiology, clinical and radiological presentation and prognosis of ICI-P occurring in patients, especially those with advanced NSCLC. Emphasis is placed on the differences in terms of frequency or clinical picture observed depending on whether the ICI is used as monotherapy or in combination with another ICI or chemotherapy. Other pulmonary complications observed in cancer patients, yet not necessarily immune-related, are reviewed, such as sarcoid-like granulomatosis, tuberculosis or other infections. A proposal for pragmatic management, including differential diagnosis and therapeutic strategies, is presented, based on the ICI-P series reported in the literature and published guidelines

Cancer et VIH : actualités 2017

International audienceSince the era of combined antiretroviral therapy, life expectancy of people living with HIV has been improved and is associated with a change in causes of death. Cancer, both AIDS-defining or non-AIDS-defining cancers, has become the leading cause of death in people living with HIV associated with an increase in the incidence of some cancers compared to the general population. Epidemiology and the identification of risk factors is a crucial issue, particularly to determine the most appropriate prevention and screening strategies in this population. In the absence of dedicated clinical trials, the cancer management in these patients is based on general recommendations, with specific attention to comorbidities and drug interactions. In addition, the development of new innovative therapies such as immunotherapy with inhibitory antibodies of immune checkpoints receptor represents a hope for the patient care, both infected or not with HIV. In this context, the establishment of the national network CancerVIH makes sense, allowing the establishment of multi-disciplinary consultation meetings involving all the practitioners involved in the care of these patients with cancer, as well as the constitution of a national cohort and the promotion of dedicated trials, to improve and optimize the management for these patients

Pulmonary arteriovenous malformations in hereditary hemorrhagic telangiectasia - A Series of 126 patients

Hereditary hemorrhagic telangiectasia (HHT) is a genetic disorder characterized by epistaxis, telangiectasia, and visceral vascular manifestations. Infectious and ischemic central nervous system (CNS) manifestations due to embolism through pulmonary arteriovenous malformations (PAVMs) represent the main causes of morbidity. To improve the phenotypic characterization of HHT with PAVM, we conducted a retrospective multicenter study of patients with HHT and at least 1 PAVM detected by chest computed tomography (CT) and/or pulmonary angiography, with particular attention to CNS and infectious manifestations. The study included 126 patients (47 men, 79 women), with a mean age of 43.1 +/- 17.4 years; 45 patients had a mutation of the ENG gene and 16 had a Mutation of ACVRL1. PAVMs were diagnosed as a result of systematic screening procedures (29%), incidental imaging findings (15%), dyspnea (22%), or CNS symptoms (13%). The PAVMs were diagnosed at a mean age of 43 17 years, with a linear distribution of diagnosis between 20 and 75 years. Dyspnea on exertion was present in 56% of patients. Four patients had a hemothorax, including 1 during pregnancy. Fifty-three CNS events directly related to HHT (excluding migraine) were observed in 35% of patients: cerebral abscess (19.0%), ischemic cerebral stroke (9.5%), transient cerebral ischemic attack (6.3%), and cerebral hemorrhage (2.4%). The median age of onset was 33 years for cerebral abscesses (range, 11-66 yr), and 53.5 years for ischemic cerebral events (range, 2-72 yr). Migraine was reported in 16% of patients. The diagnoses of PAVM and HHT were made at the time of the cerebral abscess in 13 cases (54%). Forty-three percent of patients were hypoxemic at rest. Contrast ecliocardiography showed intrapulmonary right-to-left shunting ill 87% of tested patients. PAVMs were seen oil chest radiograph in 54% of patients, and on the CT scan in all patients. One hundred five patients (83%) underwent treatment of the PAVM, by percutaneous embolization (71%) and/or by surgical resection (23%). A high frequency of CNS and infectious complications was observed in this large series of patients with HHT-related PAVM. Physicians may not lie sufficiently aware of the clinical manifestations of this orphan disorder. Patients diagnosed with HHT should be informed by physicians and patient associations of the risk of PAVM-related complications, and systematic screening for PAVM should be proposed, regardless of a patient's symptoms, familial history, or genetic considerations

Sonic Hedgehog pathway activation is associated with resistance to platinum-based chemotherapy in advanced non-small cell lung carcinoma

International audienceIntroduction : Chemoresistance is a major challenge in the treatment of advanced non-small cell lung cancer (NSCLC). As the Sonic Hedgehog (Shh) pathway is reactivated in NSCLC, we investigated an association between chemoresistance and Shh activation.Materials and Methods : From a cohort of 178 patients with advanced NSCLC treated with platinum-based chemotherapy as first-line treatment, we selected all surgical tumor samples at diagnosis (n=36). Shh activation was evaluated through Gli1 and Gli2 expression by immunohistochemistry (IHC) (quantitative score). In vitro treatment studies with cisplatin, vismodegib (Shh-pathway inhibitor) or both were performed on NSCLC cell lines (H322 and A549) and on primary cultures from patients with sarcomatoid carcinoma (n=4).Results : Twelve patients were refractory to chemotherapy (r-patients, 33.3%) and 24 had controlled disease (c-patients). Gli1 expression did not differ between the r- and c-patients (p=0.35). Gli2 expression was more often positive in the r-patients (41.7% versus 8.3%, p=0.02). Progression-free survival (PFS) and overall survival (OS) in patients with Gli2-positive score were 2.1 and 8.0 months, respectively, versus 6.7 and 18.0 months in patients with Gli2-negative score (p=0.03; p=0.002). In multivariate analysis, Gli2 score was independently correlated with PFS (hazard ratio [HR]=2.64; 95% confidence interval [CI]: 1.05-6.63; p=0.04) and OS (HR=4.36; 95% CI: 1.67-11.36; p=0.003). The sarcomatoid carcinoma cell lines were more resistant to cisplatin than the H838 and A549 cell lines. The cisplatin - vismodegib combination displayed a synergistic cytotoxic effect in the most chemoresistant cells in vitro.Conclusion : The Shh pathway is associated with resistance to platinum-based chemotherapy in NSCLC

Factors associated with early progression of non-small-cell lung cancer treated by epidermal growth factor receptor tyrosine-kinase inhibitors

International audienceEpidermal growth factor receptor tyrosine-kinase inhibitors (EGFR-TKI) are a therapeutic option as second-line therapy in non-small-cell lung carcinoma (NSCLC), regardless of the EGFR gene status. Identifying patients with early progression during EGFR-TKI treatment will help clinicians to choose the best regimen, TKI or chemotherapy. From a prospective database, all patients treated with gefitinib or erlotinib between 2001 and 2010 were retrospectively reviewed. Patients were classified into two groups according to their tumor response by RECIST after 45 days of treatment, progressive disease (PD) or controlled disease (CD). Two hundred and sixty-eight patients were treated with EGFR-TKI, among whom 239 were classified as PD (n = 75) and CD (n = 164). Median overall survival was 77 days (95% CI 61–109) for PD and 385 days (95% CI 267–481) for CD. Patients with PD were of younger age (P = 0.004) and more frequently current smokers (P = 0.001) had more frequently a performance status ≥2 (P = 0.012), a weight loss ≥10% (P = 0.025), a shorter time since diagnosis (P < 0.0001), a pathological classification as non-otherwise-specified NSCLC (P = 0.01), and the presence of abdominal metasta-ses (P = 0.008). In multivariate analysis, abdominal metastases were the only factor associated with early progression (odds ratio (OR) 2.17, 95% CI [1.12– 4.19]; P = 0.021). Wild-type EGFR versus mutated EGFR was associated with early progression. The presence of abdominal metastasis was independently associated with early progression in metastatic NSCLC receiving EGFR-TKI

Protease inhibitors exposure is not related to lung cancer risk in HIV smoker patients: a nested case-control study

International audienceOBJECTIVE: We aimed at assessing in persons living with HIV with a smoking history an association between lung cancer risk and protease inhibitors exposure, especially ritonavir. DESIGN: A nested case-control study was conducted within the ANRS CO4 FHDH, CO3 Aquitaine and Tenon's Hospital Cohorts. METHODS: Cases and controls were eligible if they were ex-smokers or current smokers at the index date, and had a CD4 cell count reported in the year preceding the index date. Cases were incident cases of lung cancer diagnosed between 1 January 2000 and 31 December 2011. All cancer cases were validated and histological types identified when available. Three controls were randomly selected by incidence density sampling using calendar time as the time axis, with individual matching on cohort, age (± 5 years), route of HIV acquisition, sex and hospital. Analyses were performed using conditional logistic regression adjusted for nadir CD4 cell count and smoking status. Ritonavir and protease inhibitors exposures were represented in separate models using categorical variables (never exposed, ever exposed). Several sensitivity analyses were performed. RESULTS: This study performed in 1447 persons living with HIV with a smoking history (383 lung cancer cases and 1064 control patients) did not evidence any association between lung cancer risk and protease inhibitors exposure including ritonavir. CONCLUSION: These results suggest that the risk of lung cancer is not influenced by pharmacologically induced P450 cytochrome protease inhibitors inhibition among smokers or ex-smoker