[Pharmaceutical involvement in academic clinical trials: Quality assessment of pharmaceutical manufacturing operations]. / Implication pharmaceutique dans le cadre d'essais cliniques institutionnels : évaluation de la qualité des opérations de mise sous forme pharmaceutique.

INTRODUCTION: For academic clinical trials, the hospital pharmacy may be required to perform the specific activity of preparing investigational drugs. MATERIAL AND METHODS: With regards to such activity, and in light of the recent changes in the regulatory environment, the main objective of this study was to evaluate whether quality levels and traceability were in compliance with the applicable regulatory standards. In order to do so, two internal audits have been conducted, the first on the compliance of operations with existing regulatory standards and the second on the quality of traceability of the operations. RESULTS: The proportion of academic clinical trials is constantly growing and currently represents 41% of the total clinical trials in the establishment. An average of 29,000 therapeutic units of investigational drugs are prepared each year (84% under the form of capsules). An overall conformity level of 75% and 88% has been identified in the aforementioned audits, respectively. Such audits have also allowed for the identification of weaknesses in current practices as well as potential improvement areas to achieve better compliance. DISCUSSION: The hospital pharmacy can provide expertise for the preparation of specific dosage or drugs that are not available on the market. It also can be involved for the conception of appropriated packaging function of the study design. CONCLUSION: Results of audits encourage us to continue this activity with a satisfactory level of quality in accordance with the necessary requirements to ensure the safety of patients and the quality of clinical trials conducted.

CT-texture analysis of subsolid nodules for differentiating invasive from in-situ and minimally invasive lung adenocarcinoma subtypes.

PURPOSE: The purpose of this study was to evaluate the usefulness of computed tomography-texture analysis (CTTA) in differentiating between in-situ and minimally-invasive from invasive adenocarcinomas in subsolid lung nodules (SSLNs). MATERIAL AND METHODS: Two radiologists retrospectively reviewed 49 SSLNs in 44 patients. There were 27 men and 17 women with a mean age of 63±7 (SD) years (range: 47-78years). For each SSLN, type (pure ground-glass or part-solid) was assessed by consensus and CTTA was conducted independently by each observer using a filtration-histogram technique. Different filters were used before histogram quantification: no filtration, fine, medium and coarse, followed by histogram quantification using mean intensity, standard deviation (SD), entropy, mean positive pixels (MPP), skewness and kurtosis. RESULTS: We analyzed 13 pure ground-glass and 36 part-solid nodules corresponding to 16 adenocarcinomas in-situ (AIS), 5 minimally invasive adenocarcinomas (MIA) and 28 invasive adenocarcinomas (IVA). At uni- and multivariate analysis CTTA allowed discriminating between IVAs and AIS/MIA (P<0.05 and P=0.025, respectively) with the following histogram parameters: skewness using fine textures and kurtosis using coarse filtration for pure ground-glass nodules, and SD without filtration for part-solid nodules. CONCLUSION: CTTA has the potential to differentiate AIS and MIA from IVA among SSLNs. However, our results require further validation on a larger cohort.

[Prediction of the efficiency of endoscopic lung volume reduction by valves in severe emphysema]. / Prédiction de l'efficacité de la réduction endoscopique d'emphysème pulmonaire par valve.

INTRODUCTION: In severe emphysema, endoscopic lung volume reduction with valves is an alternative to surgery with less morbidity and mortality. In 2015, selection of patients who will respond to this technique is based on emphysema heterogeneity, a complete fissure visible on the CT-scan and absence of collateral ventilation between lobes. Our case report highlights that individualized prediction is possible. CASE REPORT: A 58-year-old woman had severe, disabling pulmonary emphysema. A high resolution thoracic computed tomography scan showed that the emphysema was heterogeneous, predominantly in the upper lobes, integrity of the left greater fissure and no collateral ventilation with the left lower lobe. A valve was inserted in the left upper lobe bronchus. At one year, clinical and functional benefits were significant with complete atelectasis of the treated lobe. CONCLUSION: The success of endoscopic lung volume reduction with a valve can be predicted, an example of personalized medicine.

Lung adenocarcinomas: correlation of computed tomography and pathology findings.

Adenocarcinoma is the most common histologic type of lung cancer. Recent lung adenocarcinoma classifications from the International Association for the Study of Lung cancer, the American Thoracic Society and the European Respiratory Society (IASLC/ETS/ERS, 2011) and World Health Organization (WHO, 2015) define a wide range of adenocarcinoma types and subtypes featuring different prognosis and management. This spectrum of lesions translates into various CT presentations and features, which generally show good correlation with histopathology, stressing the key role of the radiologist in the diagnosis and management of those patients. This review aims at helping radiologists to understand the basics of the up-to-date adenocarcinoma pathological classifications, radio-pathological correlations and how to use them in the clinical setting, as well as other imaging-related correlations (radiogenomics, quantitative analysis, PET-CT).

Personalized chemotherapy of lung cancer: What the radiologist should know.

Lung cancer is the leading cause of deaths due to cancer in France. More than half of lung cancers are discovered at an advanced-stage. New anticancer treatment strategies (i.e., the so-called personalized or targeted therapy) have recently been introduced and validated for non-small-cell lung cancer (NSCLC), in addition to or in association with standard chemotherapy. Personalized therapy includes tyrosine kinase inhibitors (TKIs), antiangiogenic treatments and immunotherapy. Because these treatments may be responsible for atypical thoracic adverse effects and responses as compared to standard chemotherapy, RECIST 1.1 criteria may be inadequate to evaluate the responses to these agents. The goal of this article was to review personalized treatment strategies for NSCLC, to consider the therapy-specific responses and thoracic complications induced by these new therapeutic agents and finally to discuss future directions for the personalized assessment of tumor response.

[Phenotypes of essential arterial hypertension in Caribbean women]. / Phénotypes de l'hypertension artérielle essentielle chez les femmes antillaises.

UNLABELLED: The characterisation of phenotypes of patients with essential hypertension (EH) is an important pre-requisite for genetic research. The present study compares clinical and renal function parameters in 2 groups of patients from different origins. METHOD: Out of a cohort of essential hypertensives disclosed on routine work medical examinations, 21 caucasian (CC) women were paired with 21 Caribbean (CB) women. In the 2 groups we recorded family history of hypertension (FHH), duration of hypertension, BMI, salt intake based on 24 h urinary sodium excretion, microalbuminuria, and blood pressure (BP). Glomerular filtration rate (GFR) and renal plasma flow (RPF) were measured with inulin and para-amino-hippuric acid clearances. Plasma active renin (AR) and aldosterone (Aldo) levels were measured by immuno-assays. White coat (WC) effect was assessed on the difference between BP values measured on medical visits and by the nurses on clearance measurements. Anova and t-test were used for analysis, statistical significance was assumed for p < 0.05. RESULTS: Casual BP values were 150/94 mmHg in CB and 153/95 mmHg in CC. There were no significant differences on BMI (CB 30.6 kg/m2 vs CC 27.1 kg/m2). AR (CB 6.6 pg/mL vs CC 8.7 pg/mL) and Aldo (CB 195.1 pmol/L vs CC 202.8 pmol/L) provided an equivalent dietary salt intake (CB 11.2 g/d vs CC 10.7 g/d). Mother FHH was found predominantly in CB women (60% vs 30% in CC, p < 0.05), whereas paternal FHH was more frequent in CC women (21% vs 8% in CB, p < 0.05). At the same age, duration of hypertension was longer by 1 year in CB. White coat effect was more marked in CC (BP > 30 mmHg: 40% in CC vs 5% in CB, p < 0.05). GFR values were normal and similar in CB and CC women. But a significantly lower RPF was measured in CB (489 vs 542 mL/min/1.73 m2 in CC, p < 0.05). Higher filtration fraction and microalbuminuria were also observed in CB women. CONCLUSION: Essential hypertension occurs at younger ages in Caribbean women. The decrease in RPF could be genetically determined and is likely to participate in early onset of hypertension, as previously described in young normotensive subjects. In paired women, we did not found significant differences in active renin and aldosterone levels. The ongoing longitudinal study should contribute to assess the consequences of these findings on renal prognosis and the effects of antihypertensive therapy.

The new classification of lung adenocarcinomas: implications for pathologists and radiologists.

The present manuscript is a summary of two lectures which were given respectively by B. Weynand and G.R. Ferretti. The new classification of lung adenocarcinomas has changed the view of the radiologists and the pathologists especially regarding the former bronchiolo-alveolar carcinoma (BAC). The aim of this paper is to correlate radiological and histopathological images according to the 2011 classification for lung adenocarcinoma proposed by the International Association for the Study of Lung cancer, the American Thoracic Society and the European Respiratory Society and to draw attention to the way these lesions can be approached preoperatively.