Endoscopic follow-up of low-grade precancerous bronchial lesions in high-risk patients: long-term results of the SELEPREBB randomised multicentre trial.

BACKGROUND: 3-9% of low-grade preinvasive bronchial lesions progress to cancer. This study assessed the usefulness of an intensive bronchoscopy surveillance strategy in patients with bronchial lesions up to moderate squamous dysplasia. METHODS: SELEPREBB (ClinicalTrials.gov NCT00213603) was a randomised study conducted in 17 French centres. After baseline lung computed tomography (CT) and autofluorescence bronchoscopy (AFB) to exclude lung cancer and bronchial severe squamous dysplasia or carcinoma in situ (CIS), patients were assigned to standard surveillance (arm A) with CT and AFB at 36 months or to intensive surveillance (arm B) with AFB every 6 months. Further long-term data were obtained with a median follow-up of 4.7 years. RESULTS: 364 patients were randomised (A: 180, B: 184). 27 patients developed invasive lung cancer and two developed persistent CIS during the study, with no difference between arms (OR 0.63, 95% CI 0.20-1.96, p=0.42). Mild or moderate dysplasia at baseline bronchoscopy was a significant lung cancer risk factor both at 3 years (8 of 74 patients, OR 6.9, 95% CI 2.5-18.9, p<0.001) and at maximum follow-up (16 of 74 patients, OR 5.9, 95% CI 2.9-12.0, p<0.001). Smoking cessation was significantly associated with clearance of bronchial dysplasia on follow-up (OR 0.12, 95% CI 0.01-0.66, p=0.005) and with a reduced risk of lung cancer at 5 years (OR 0.15, 95% CI 0.003-0.99, p=0.04). CONCLUSION: Patients with mild or moderate dysplasia are at very high risk for lung cancer at 5 years, with smoking cessation significantly reducing the risk. Whereas intensive bronchoscopy surveillance does not improve patient outcomes, the identification of bronchial dysplasia using initial bronchoscopy maybe useful for risk stratification strategies in lung cancer screening programmes.

Survival Impact of Stations of Pathological Lymph Nodes in N2 Non-small Cell Lung Cancer in a French Hospital.

BACKGROUND: The prognosis of lung cancer remains poor; only 20% of patients can undergo surgery. N2 non-small cell lung cancer (NSCLC) is a heterogeneous disease. We conducted a retrospective study to analyze the impact of N2 location on survival. METHODS: This study included 342 NSCLC with N2 involvement between 1988 and 2014. Patient-related data were collected through the CRB biobank and included demographic, therapeutic, and survival data. Survival was analyzed according to Kaplan-Maier method. Cox's regression analysis and analysis of variance (ANOVA) were used to determine factors significantly associated with survival. RESULTS: The population average age was 61.6 years; 82.2% were men, a majority were former smokers (87.1%), and 45.3% had adenocarcinoma. The main prognostic factors were male gender (p = 0.01), number of nodes (p < 0.0001), and tumor size (p < 0.0001). N2 disease had a poor survival (16 months) compared with N0 (32 months) and N1 (21.1 months) disease (p < 0.0001). The patients with involvement of station 4 (survival = 17.8 months) seemed to have a prognosis between those with station 7 (survival = 10.5 months) and N1 (survival = 22.6 months), p = 0.0005. CONCLUSIONS: N2 location has a prognostic impact in surgically NSCLC, and station 4 involvement has a better prognostic than station 7.

Pharmaceutical cognitive doping in students: A chimeric way to get-a-head?

For students, the pressing demands for memorization, top-level performance, and peer competition create an environment favorable for pharmaceutical cognitive doping behavior. We aimed to describe recent practices and the benefit/risk ratio of such behavior and to discuss the issues at stake. The prevalence of pharmaceutical cognitive doping among students has been reported from 1.3% to 33% across studies, with variations depending on country and definition of pharmaceutical cognitive doping. The therapeutic classes most frequently cited as being diverted for doping purposes are psychostimulants and nootropics (methylphenidate, modafinil, piracetam), corticosteroids, sedative drugs and beta-blockers. Some illegal substances such as cannabis, amphetamines and cocaine are also consumed in order to boost mental function. Finally, over-the-counter products, such as caffeine-based tablets or energy drinks, or alcohol, are also widely used by students whose motivations involve enhanced performance, concentration, memory, and staying awake during the revision and exam period. However, the expected (often fantasized) effectiveness of these products does not correspond to the reality of a modest controversial impact on cognitive performance. There appears to be an emerging profile of the student more inclined to doping behavior. Cognitive doping thus raises the question of its regulation, opening a debate opposing, on one hand, individual freedom and supposed collective benefits and, on the other hand, health consequences, educational (in)equality, and the risk of tarnished academic success. Strengthening school and university medicine, through prevention campaigns and the identification of subjects at risk, is essential to limit the extent, risk, and damages associated with such practices.

[Pharmaceutical cognitive doping in students: a chimeric way to get-a-head?] / Dopage cognitif chez les étudiants : un moyen chim(ér)ique de s'en mettre plein la tête ?

For students, the pressing demands for memorization, top-level performance, and peer competition create an environment favorable for pharmaceutical cognitive doping behavior. We aimed to describe recent practices and the benefit / risk ratio of such behavior and to discuss the issues at stake. The prevalence of pharmaceutical cognitive doping among students has been reported from 1.3% to 33% across studies, with variations depending on country and definition of pharmaceutical cognitive doping. The therapeutic classes most frequently cited as being diverted for doping purposes are psychostimulants and nootropics (methylphenidate, modafinil, piracetam), corticosteroids, sedative drugs and beta-blockers. Some illegal substances such as cannabis, amphetamines and cocaine are also consumed in order to boost mental function. Finally, over-the-counter products, such as caffeine-based tablets or energy drinks, or alcohol, are also widely used by students whose motivations involve enhanced performance, concentration, memory, and staying awake during the revision and exam period. However, the expected (often fantasized) effectiveness of these products does not correspond to the reality of a modest controversial impact on cognitive performance. There appears to be an emerging profile of the student more inclined to doping behavior. Cognitive doping thus raises the question of its regulation, opening a debate opposing, on one hand, individual freedom and supposed collective benefits and, on the other hand, health consequences, educational (in)equality, and the risk of tarnished academic success. Strengthening school and university medicine, through prevention campaigns and the identification of subjects at risk, is essential to limit the extent, risk, and damages associated with such practices.

Efficacy of Whole-Lung Lavage in Pulmonary Alveolar Proteinosis: A Multicenter International Study of GELF.

BACKGROUND: New therapies have emerged in the treatment of pulmonary alveolar proteinosis (PAP) and, therefore, there is a real need to evaluate the efficacy of whole-lung lavage (WLL) in this rare disease. OBJECTIVES: The aim of this study was to assess the efficacy of WLL in patients with PAP. METHODS: We included 33 patients from 12 centers, which are members of the French-Speaking Thoracic Endoscopy Group, for analysis. Data collection concerned patients and disease characteristics, pulmonary function tests (PFTs) and technical information on the procedure. RESULTS: The median age of the patients was 44 years (range 13-77). There were 23 (71.9%) patients with respiratory insufficiency at presentation. All patients underwent WLL by general anesthesia and selective lung ventilation, except 1 who underwent awake flexible bronchoscopy. We noted differences in the technique, as 12 (36.36%) patients had percussion during the procedure and only 4 (12.1%) patients underwent 2-lung lavage during 1 anesthesia. A median of 12 L was used to perform WLL (1.0-40 L). Complications occurred in 11 (33.3%) patients, and 18 (56.25%) of them relapsed in a median period of 16.9 months. No significant changes were found in any PFT parameters studied, except for PaO2, which was significantly improved by 6.375 mm Hg (p = 0.0213) after the procedure compared to before. CONCLUSIONS: Although the application of the WLL technique was variable, overall, it significantly improved patients' short-term respiratory condition by improving PaO2. However, a long-term effect needs to be confirmed, as many of our patients relapsed.

[Diagnostic accuracy of endobronchial ultrasound-guided transbronchial needle aspiration in mediastinal lymph nodes]. / Performances diagnostiques de la ponction ganglionnaire médiastinale transbronchique guidée par vidéo écho-endoscopie.

INTRODUCTION: Endobronchial ultrasound-guided transbronchial needle aspiration in mediastinal lymph nodes is a safe method that can be performed for mediastinal and hilar lymph nodes sampling. Because it allows collecting only a small amount of materiel, an optimal processing of the samples is needed. MATERIAL AND METHODS: Based on 150 consecutive procedures, we evaluate the overall diagnostic performances and of each technical methods used for the exploitation of the samples. RESULTS: The global diagnostic yield is 64.0% for the 50 first exams (learning phase), 88.0% for the next 100 exams. The maximal sensitivity and negative predictive value (NPV) are 79.3%, 96.3% and 92.7%, respectively. The yield, sensitivity and NPV of smears are 68.0%, 75.0% and 66.0%, of monolayer preparation 77.8%, 62.1% and 50.0%, of sections from tissue cores of 65.8%, 94.4% and 86.7%. The combination of the different methods increases the yield comparing to tissue cores and smears when taken alone (P < 0.05), and the sensibility and the NPV comparing to smears (P < 0.0005 and P < 0.01, respectively) and monolayer preparation (P < 0.0001 and P < 0.0005, respectively). The sensitivity of tissue cores is greater than smears (P < 0.005) and monolayer preparations (P < 0.0001). This increase in sensitivity is significant for granuloma (sarcoidosis), but not for carcinoma. CONCLUSION: Endobronchial ultrasound-guided transbronchial needle aspiration is an accurate and sensitive technique. Liquid based conditioning of samples and paraffin embedded tissue cores increases the diagnostic performances comparing to smears, notably for the diagnosis of sarcoidosis.

[The impact of the patient's age on the delay of the lung cancer treatment]. / Influence de l'âge des patients sur le délai de prise en charge du cancer bronchique.

INTRODUCTION: The results from the medical literature regarding the influence of patient's age on the delay of treatment in lung cancer are controversial in the absence of a consensual definition. The aim of this study was to determine the impact of the patient's age on the delay of the lung cancer treatment. METHODS: A retrospective monocentric study was performed including patients treated for a lung cancer in our department between November 1, 2014 and October 31, 2015. The delay of treatment was defined by the delay between the first abnormal imaging and the first treatment. The patients were divided into three groups depending on their age: group 1 with≤60 years old, group 2 between 60 and 70 years old, and group 3 with>70 years old. The statistical analysis was realized with Pearson's chi-squared and the Anova tests. RESULTS: Two-hundred and forty-six patients were included with a mean age at 65±10 years. The mean delay of the treatment was 97±41 days. The mean delay of the treatment in patients with>70 years old was statically longer than the delay of treatment in patients with≤60 years old (116±98 days vs. 76±65 days, P=0.04), secondary to an extended time for the lung cancer surgery (129±75 days vs. 88±54 days, P=0.03). CONCLUSION: In patients with>70 years old, the delay of treatment is longer than in other groups, secondary to an extended time for the preoperative assessment. An improvement in therapeutic management is necessary in our care system to shorten this delay.

[Phosphatidylethanol blood analysis]. / Dosage sanguin du phosphatidyléthanol.

This article aims to place the phosphatidylethanol (PEth) blood test in the detection area of ethanol consumption causing alcohol-related disorders, to present the current methods of analysis, data on interpretation, some practical applications and the prospects of use of this biomarker. PEth is a minor metabolite of ethanol. Among nearly 50 PEth counterparts, PEth 16:0/18:1 is the most abundant. The interest that PEth brings compared to other biomarkers is the extended window of detection of ethanol consumptions. Indeed, it has a blood elimination half-life of approximately 5 days, which offers estimated alcohol consumption for a 21 to 28 days period. Thus, the detection of alcohol use disorders and withdrawal monitoring (systematically combined with urinary ethylglucuronide) in addictology and in liver pre- and post-transplantation are today its main routine applications. Nevertheless, additional data are still necessary to improve the interpretation of measured concentrations and to reach a consensus on interpretation cut-offs of blood PEth concentrations.

Psychiatric comorbidities associated with a positive screening using the Montreal Cognitive Assessment (MoCA) test in subjects with severe alcohol use disorder.

BACKGROUND: Patients with severe alcohol use disorder (SAUD) frequently show cognitive deficits that can be efficiently identified using screening tools such as the Montreal Cognitive Assessment (MoCA) test. These cognitive deficits, which reduce the efficacy of therapeutic interventions and may contribute to dropout and relapse, could be, however, partly due to a treatable other cause. Accordingly, this exploratory study examined whether psychiatric comorbid disorders can induce a positive MoCA screening among recently detoxified SAUD subjects. METHODS: One hundred recently detoxified patients with SAUD were divided into two groups according to whether they presented cognitive deficits using the MoCA. Groups were compared for demographic data, SAUD severity, impulsivity, and psychiatric comorbidities. The significant parameters were then introduced in a logistic regression model to establish their relative contributions in a positive MoCA status in SAUD subjects. RESULTS: Among the significant parameters revealed by the bivariable analyses, agoraphobia and current depressive episode were found to be significant predictors of the MoCA status in the multivariable comparisons. CONCLUSIONS: A positive MoCA screening for cognitive impairments among post-detoxification SAUD patients could also be related to comorbid agoraphobia and depressive episode rather than to SAUD itself. A comprehensive psychiatric assessment must be performed in SAUD patients so that other potential causes of cognitive deficits, in particular with regard to mood and anxiety disorders, can be identified and treated.

Model of multi-modal cortical processing: coherent learning in self-organizing modules.

In this paper (An abbreviated version of some portions of this article appeared in reference Menard and Frezza-Buet (Menard, O., & Frezza-Buet, H. (2004). Rewarded multi-modal neuronal self-organization: Example of the arm reaching movement. In: Proceedings of international conference on advances in intelligent systems theory and application.), as part of the IJCNN 2005 conference proceedings, published under the IEEE copyright.), an original self-organizing model is presented, with experiments highlighting its ability to be used in different frameworks, as phonetic coding dependent on semantics and arm-reaching. The model relies on the coupling of the learning processes that stand at different self-organizing modules, and exhibits dynamics that can be discussed in terms of the binding of different modalities, scattered over the different modules. Such a binding property is based on an emerging constraint of keeping consistency between the modules. This process is induced by partial connectivity and appropriate neural field competition mechanisms.

Intrapleural infusion of activated macrophages and gamma-interferon in malignant pleural mesothelioma: a phase II study.

STUDY OBJECTIVES: Intrapleural immunotherapy has shown some activity in patients with malignant mesothelioma. We conducted a multicentric pilot phase II study to evaluate the tolerance and the activity of intrapleurally infused autologous human activated macrophages (AM Phi) in patients with stage IA, IB, and IIA malignant pleural mesothelioma (MPM). DESIGN: AM Phi derived from in vitro monocyte culture were infused into the pleura of patients every week for 8 consecutive weeks. Each infusion was followed 3 days later by an intrapleural injection of 9 millions units of gamma-interferon (gamma-IFN) in an attempt to prolong the in vivo activation of infused AM Phi. Response was assessed by CT scan and thoracoscopy when possible. If the patient's disease progressed after AM Phi treatment, an additional treatment was left to the choice of the investigator. PATIENTS: Nineteen patients with histologically proven stage IA, IB, or IIA MPM were enrolled. Two patients were excluded before any AM Phi infusion because of complications impeding infusion. Seventeen patients were actually treated. After completion of the AM Phi cellular therapy, 10 patients were treated with chemotherapy as their diseases progressed. RESULTS: The overall response rate of patients actually treated was 14%. When including the two patients enrolled but not treated, the overall response "in intention to treat" was 11%; two patients had a partial response, with a duration of response of 30 months and 3 months, respectively. One patient, who could not be evaluated by thoracoscopy because of pleural symphysis, is still alive without any clinical or radiologic sign of disease 69 months after treatment. No major adverse effects were observed during the infusion of either AM Phi or gamma-IFN, and there was no interruption of treatment because of toxicity. However, symphysis was observed in 7 of 14 patients who received the complete treatment. The median survival of patients actually treated, including those who received chemotherapy after AM Phi, was 29.2 months. CONCLUSION: Combined infusion of AM Phi and gamma-IFN was well tolerated in patients with MPM; however, it had limited antitumor activity.

Is there a relationship between the presence of lung mucosa preinvasive lesions and lung cancer incidence? Influence of tobacco consumption.

UNLABELLED: Although studied for years, the nature of the relationships between tobacco consumption, bronchial preinvasive lesions and lung cancer are still not completely elucidated. Objectives were to determine the relationship between tobacco consumption and lung mucosa preinvasive and invasive lesions and to describe patients' evolution according to baseline characteristics. METHODS: Bronchial biopsy specimens were taken at six predetermined sites in 156 males, current smokers, aged above 18 years. Relationships between smoking characteristics and preinvasive lesions indexes and between baseline characteristics and lung cancer occurrence during a prospective follow-up were examined. RESULTS: Maximum grade was hyperplasia for 16.7% of patients, metaplasia 33.3%, dysplasia 25.0%, and carcinoma in situ 1.3%. For 23.7% of patients, all biopsies were considered normal. Preinvasive lesion indexes were related to smoking intensity (cigarettes/day). Lung cancer incidence during the follow-up was 19.9%. No association between severity of mucosa lesions at baseline and incidence of cancer during the follow-up period was observed. CONCLUSION: The majority of smokers had mucosa lesions, but a relatively small number of them would have a cancer, and there was a poor correlation between severity of mucosalesions and incidence of cancer. Even if an evolution from preinvasive lesions to an invasive cancer is plausible and coherent with current concepts, this link does not appear strong enough to recommend the use of systematic classic endoscopy for targeting of a sub-group of higher risk smokers who would require a closer follow up.

A combination of smears and cell block preparations provides high diagnostic accuracy for endobronchial ultrasound-guided transbronchial needle aspiration.

Endobronchial ultrasound-guided transbronchial needle aspiration has demonstrated its accuracy in the diagnostic workup of enlarged mediastinal lymph nodes. In addition to conventional smears, the use of liquid-based cytology (LBC) and cell block preparations (CBP) has been introduced more recently. The aim of our study was to determine the performance of each of the different techniques, separately and combined, in terms of diagnostic yield and sensitivity. A total of 290 consecutive patients were included. The pathological examination was based on smear cytology, LBC, and CBP. Adequate sampling was defined by the presence of pathological material or lymphocytes. The global diagnostic yield was 82.7 % and the sensitivity was 89.1 %. The diagnostic yield was 72.8 % for smears, 78.8 % for LBC, and 69.9 % for CBP. The combination of smears with CBP significantly increased diagnostic yield (p = 0.01) and sensitivity (p = 0.006), but not the combination of smears with LBC (yield: p = 0.07; sensitivity: p = 0.13). The combination of the three techniques further increased yield (p = 0.007) and sensitivity (p = 0.006), compared with smears alone. CBP were more sensitive than smears for both diagnoses of carcinoma (p = 0.01) and granulomatous inflammation (p = 0.048). Conversely, LBC was less sensitive than smears for granulomatous inflammation (p = 0.004), but the difference was not significant for carcinoma (p = 0.42). CBP, as a complement to smears, increases diagnostic yield and sensitivity for both diagnoses of carcinoma and granulomatous inflammation. LBC, if used alone, increases the risk of a false-negative result.

Evaluation of the spatial diffusion of methylene blue injected in vivo by bronchoscopy into non-small cell lung carcinoma.

BACKGROUND: Due to smoking prevalence and the poor efficiency of current therapy, lung cancer is the leading cause of cancer death in developed countries, and its worldwide incidence is steadily increasing. Gene therapy by direct intratumoral injection of different types of gene constructs through a fiberscope has been suggested and evaluated in a few patients. OBJECTIVE: It was the aim of this study to observe the actual volume of diffusion within a lung tumor using a color marker. METHODS: Using bronchoscopy, just after anesthesia, methylene blue was injected into patient tumors. These patients subsequently underwent surgery for treatment of a non-small cell lung cancer. RESULTS: We observed a diffusion of methylene blue in resected lung tumors with a mean infiltrated versus noninfiltrated tumor volume ratio of 29 +/- 15%. Interestingly, some large tumor areas were not stained. At the cellular level, a preferential diffusion of the dye was observed in the tumor stroma compartment versus the tumor cellular compartment, where basal cells were more frequently and strongly labeled than the other tumor cells. CONCLUSIONS: Since a cancer is cured when most, if not all, cancer cells are killed, the preliminary evaluation of the spatial diffusion of any injected gene construct should be carried out as a first step in any cancer type.