[Prohibition of tobacco sales to minors in France and Quebec. Comparison of legislative frameworks, their enforcement, and underage smoking]. / Interdiction de vente de tabac aux mineurs en France et au Québec. Comparaison du cadre législatif, de son application, et du tabagisme des adolescents.

BACKGROUND: Prohibition of tobacco sales to minors is a provision of the World Health Organization Framework Convention on tobacco control. This measure is effective to reduce youth tobacco use, if the legislation adopted is properly implemented and enforced. Through the examples of France and Quebec, the objective of this study is to compare legislative frameworks prohibiting tobacco sales to minors, their enforcement, and possible impact on underage smoking. METHODS: Identification of legislative instruments, reports from public health authorities, and articles addressing the focused question was performed trough Medline and Google. RESULTS: Selling tobacco products to minors under 18 years of age has been banned by the law since 1998 in Quebec and 2009 in France. In 2011, in France for individuals aged 17, compliance with the law was 15%. In 2017 in France, 94% of 17-year-old daily smokers regularly bought their cigarettes in a tobacco store. Law enforcement controls and sanctions are non-existent. In 2013 in Quebec, 23% of underage smoking students usually bought their own cigarettes in a business. The compliance rate with the prohibition law rose from 37% in 2003 to 92.6% in 2017. An approach of underage "mystery shoppers" attempting to purchase tobacco products and dedicated inspectors has been implemented, and progressive sanctions are applied in case of non-compliance. In 2013, 12.2% of Quebec high school students and, in 2017, 34.1% of French 17 year olds reported using tobacco products in the last 30 days. CONCLUSION: Only an improved law enforcement, through the training of tobacco retailer's, inspections and effective deterrent penalties for non-compliance, leads to an effective legislative measure in terms of public health.

Occupational risk factors have to be considered in the definition of high-risk lung cancer populations.

BACKGROUND: The aim of this study was to compute attributable fractions (AF) to occupational factors in an area in North-Eastern France with high lung cancer rates and a past of mining and steel industry. METHODS: A population-based case-control study among males aged 40-79 was conducted, including confirmed primary lung cancer cases from all hospitals of the study region. Controls were stratified by broad age-classes, district and socioeconomic classes. Detailed occupational and personal risk factors were obtained in face-to-face interviews. Cumulative occupational exposure indices were obtained from the questionnaires. Attributable fractions were computed from multiple unconditional logistic regression models. RESULTS: A total of 246 cases and 531 controls were included. The odds ratios (ORs) adjusted on cumulative smoking and family history of lung cancer increased significantly with the cumulative exposure indices to asbestos, polycyclic aromatic hydrocarbons and crystalline silica, and with exposure to diesel motor exhaust. The AF for occupational factors exceeded 50%, the most important contributor being crystalline silica and asbestos. CONCLUSION: These AFs are higher than most published figures. This can be because of the highly industrialised area or methods for exposure assessments. Occupational factors are important risk factors and should not be forgotten when defining high-risk lung cancer populations.

[Tobacco use characteristics among apprentices in Vocational Centers]. / Caractéristiques du tabagisme chez les adolescents en Centre de formation des apprentis.

BACKGROUND: Most smokers start smoking during adolescence and become dependent before 20 years old. In France, vocational trainees are a population not much explored. The objective of our study is to present tobacco use characteristics among apprentices in Vocational Centers (VC). METHODS: This cross-sectional exhaustive study covered 1814 students (among whose 943 smokers) entering in a 1st year of the eight participating Vocational Centers in the Lorraine region (Eastern France, 2.3 million inhabitants, 16,500 vocational trainees), during the school years 2007-2008 and 2008-2009. Data collection concerned the sociocultural environment, tobacco use habits, degree of dependency to tobacco and co-addictions. RESULTS: Among the study population, 52.0% declared they were smokers among whom 89.4% daily smokers, and 5.7% were ex-smokers. The average age of tobacco use initiation was 12.1 years (standard deviation [SD]=2.1) and the average age at inception of regular cigarette smoking was 13.8 years (SD=1.6). Current consumption of the smokers was 12.8 cigarettes per day (SD=7.8). The average score of smoking addiction was 6.1 (SD=2.8), according to the Hooked On Nicotine checklist test (score from 0 to 10=strongly dependent). Finally, 37.1% of students (58.9% among smokers) smoked or have smoked cannabis. CONCLUSION: The high prevalence of smoking in Vocational Centers, the early start of tobacco use and the high tobacco consumption among apprentices show that they are overexposed compared to the general population of adolescents. In addition, these young people are already dependant to tobacco use. This underlines the need of specific measures dedicated to this population that amounts to 361,500 individuals in France.

[Predictive factors for skeletal-related events in lung cancer]. / Facteurs prédictifs de survenue d'évènements osseux dans le cancer bronchique.

INTRODUCTION: Skeletal-related events (SRE) are common in patients with bone metastatic lung cancer and have a negative impact on quality of life and survival. The objective of this study is to identify predictive factors for SRE occurrence among this population. METHODS: We conducted a 3-year retrospective study including 100 lung cancer patients with bone metastasis. RESULTS: Eighty-two patients presented at least one SRE (69.5% at baseline). The median occurrence for SRE was 4.5 months and severe bone pain was the most common SRE (56%). The alkaline phosphatase serum level>120IU/L (hazard ratio [sHR]=2.8; 95% confidence interval (CI) [1.5-5.4]; P=0.002) and calcemia>2.6mmol/L ([sHR]=9.7; 95% CI [5.1-18.4]; P<0.001) were identified as risk factors for SRE occurrence while the presence of an initial SRE was associated with a decrease of this risk ([sHR]=0.2; 95% CI [0.1-0.4]; P<0.001). CONCLUSION: The elevated alkaline phosphatase serum level and hypercalcemia are risk factors for SRE occurrence in bone metastatic lung cancer patients and should be used as biomarkers to adapt current medical practice for these patients.

EUELC project: a multi-centre, multipurpose study to investigate early stage NSCLC, and to establish a biobank for ongoing collaboration.

The European Early Lung Cancer (EUELC) project aims to determine if specific genetic alterations occurring in lung carcinogenesis are detectable in the respiratory epithelium. In order to pursue this objective, nonsmall cell lung cancer (NSCLC) patients with a very high risk of developing progressive lung cancer were recruited from 12 centres in eight European countries: France, Germany, southern Ireland, Italy, the Netherlands, Poland, Spain and the UK. In addition, NSCLC patients were followed up every 6 months for 36 months. A European Bronchial Tissue Bank was set up at the University of Liverpool (Liverpool, UK) to optimise the use of biological specimens. The molecular-pathological investigations were subdivided into specific work packages that were delivered by EUELC Partners. The work packages encompassed mutational analysis, genetic instability, methylation profiling, expression profiling utilising immunohistochemistry and chip-based technologies, as well as in-depth analysis of FHIT and RARbeta genes, the telomerase catalytic subunit hTERT and genotyping of susceptibility genes in specific pathways. The EUELC project engendered a tremendous collaborative effort, and it enabled the EUELC Partners to establish protocols for assessing molecular biomarkers in early lung cancer with the view to using such biomarkers for early diagnosis and as intermediate end-points in future chemopreventive programmes.

[Respiratory diseases related to passive smoking]. / Les pathologies respiratoires liées au tabagisme passif.

Passive smoking, measured in practice by using specific biomarkers, is a well known factor of morbidity and mortality. The main victims are children, often starting from conception, but adults are not spared. Many respiratory diseases are caused and/or worsened by passive smoking and environmental tobacco smoke (ETS) exposure can have serious health consequences that reduce life expectancy (sudden infant death, respiratory infections, asthma, chronic obstructive pulmonary diseases and lung cancer). Better knowledge of these risks has favourably influenced the legislation banning smoking in enclosed public places in France and in other countries. If one of the main objectives of this measure is to protect non-smokers as well as smokers, its rigorous application fits directly within the goals of prevention and treatment of tobacco dependency.

Modulation of fibronectin gene expression in human mononuclear phagocytes.

Under some conditions, mononuclear phagocytes spontaneously synthesize and release fibronectin, an extracellular matrix glycoprotein with versatile effects on cell-matrix interactions. To gain insight into the processes that modulate the level of fibronectin secretion by these cells, we used monocytes, in vitro matured monocytes and alveolar macrophages as models to compare fibronectin mRNA levels and fibronectin secretion in a variety of circumstances. Using Northern analysis and dot-blot analysis with a 32P-labeled human fibronectin cDNA probe, we evaluated steady-state mRNA levels and a human fibronectin-specific ELISA was used to evaluate fibronectin secretion. In all cases the amounts of fibronectin secreted paralleled fibronectin mRNA levels. Specifically (a) when fibronectin mRNA was undetectable, as in the case of normal blood monocytes, no fibronectin was secreted, but whenever fibronectin mRNA was present, as in normal alveolar macrophages, fibronectin was secreted by the cells; (b) as monocytes matured into macrophages in vitro, the cells began to express fibronectin mRNA and the cells secreted fibronectin; (c) when alveolar macrophages were activated with surface stimuli such as lipopolysaccharide (LPS) or immune complexes, fibronectin mRNA levels decreased and in parallel, the cells secreted less fibronectin; (d) in idiopathic pulmonary fibrosis (IPF), alveolar macrophages contained severalfold more fibronectin mRNA transcripts that normal and the cells spontaneously secreted severalfold more fibronectin than normal; and (e) when IPF alveolar macrophages were placed in culture the fibronectin mRNA levels in the cells decreased with time, and concurrently the amounts of fibronectin produced per unit time continually decreased. The observation of a strict concordance of fibronectin mRNA levels and fibronectin release by mononuclear phagocytes suggests that, at least in many circumstances, fibronectin secretion by mononuclear phagocytes is controlled by steady-state levels of fibronectin mRNA.

Expression of the alpha-1-antitrypsin gene in mononuclear phagocytes of normal and alpha-1-antitrypsin-deficient individuals.

To evaluate the contribution of mononuclear phagocytes, and particularly alveolar macrophages, to alpha-1-antitrypsin (alpha 1AT) production in normal and alpha 1AT-deficient individuals, Northern analysis with a human alpha 1AT complementary DNA was used to demonstrate that alpha 1AT messenger RNA (mRNA) can be detected in liver, blood monocytes, and alveolar macrophages. Quantification of alpha 1AT mRNA expression demonstrated that: (a) type PiMM monocytes and alveolar macrophages expressed, respectively, 200-fold and 70-fold less alpha 1AT mRNA per cell than the liver; (b) the level of expression of the alpha 1AT gene was increased during the in vitro maturation of blood monocytes; and (c) blood monocyte and alveolar macrophage levels of expression of the alpha 1AT gene were the same in PiMM and PiZZ individuals. However, the amount of newly synthesized alpha 1AT secreted by ZZ alveolar macrophages was 10 times lower than that secreted by MM alveolar macrophages. Thus, mononuclear phagocytes of PiZZ individuals express a secretory defect in alpha 1AT in a fashion similar to hepatocytes. Not only do mononuclear phagocytes provide a readily accessible cell to evaluate the regulation of alpha 1AT gene expression, but these cells may contribute to the levels of alpha 1AT present in the lower respiratory tract in the normal and ZZ states.

Spontaneous expression of the c-sis gene and release of a platelet-derived growth factorlike molecule by human alveolar macrophages.

Alveolar macrophages from normal individuals and patients with interstitial lung diseases spontaneously expressed a 4.2-kilobase mRNA complementary to the c-sis gene, a proto-oncogene coding for one of the chains of platelet-derived growth factor (PDGF). Concomitantly, these cells released a mediator with the properties of PDGF, including: chemotactic factor for smooth muscle cells whose activity was resistant to heat and acid, but sensitive to reduction; mitogenic (competence) activity for fibroblasts; ability to compete with PDGF for its receptor; and precipitated by an anti-PDGF antibody. While blood monocytes did not contain c-sis mRNA transcripts, monocytes matured in vitro expressed c-sis, consistent with the concept that expression of c-sis occurs during the differentiation of monocytes into alveolar macrophages. Together with the known actions of PDGF, these observations suggest that the c-sis proto-oncogene and its PDGF product are part of the armamentarium available to the alveolar macrophages for normal lung defense and participation in lung inflammation.

[Paraneoplastic hypoglycemia: The hopes of pathophysiological documentation]. / Hypoglycémie paranéoplasique : les espoirs d'une documentation physiopathologique.

Doege-Potter syndrome is a paraneoplastic syndrome characterized by non-islet cell tumor hypoglycemia secondary to a solitary fibrous tumor. These tumors are rare and usually asymptomatic. The syndrome of hypoglycemia is seen in less than 5% of the cases, and the associated tumors are large with a high mitotic rate. The cause of hypoglycemia is related to insulin-like growth factors produced by these tumors called "big" IGF-2. Several biological tests can demonstrate the increase of "big" IGF-2 plasma levels confirming the diagnosis of non-islet cell tumor induced hypoglycemia. The diagnosis is suggested by imaging but diagnostic confirmation is provided by the surgery, which remains the treatment of choice. Resection in many cases is the cure leading to hypoglycemia resolution. Recurrences and malignant transformations are possible which imposes a long-term monitoring. We report a case with relapsed malignant pleural fibrous tumor for which the pathophysiological mechanism of hypoglycemia could be documented as a paraneoplastic syndrome.

[Complementary and alternative medicine use by lung cancer patients]. / Le recours aux médecines « complémentaires et alternatives ¼ par les patients atteints d'un cancer bronchique.

INTRODUCTION: Complementary and alternative medicine (CMA) use is frequent among cancer patients. Only few results are available about lung cancer patients. The aim of this study was to evaluate how often the CMA were used by lung cancer patients and to define the type of CMA used. METHODS: Every lung cancer patients with an ongoing chemotherapy in the respiratory department of the University Hospital of Nancy were approached between November 2014 to July 2015. A detailed and anonymous survey was conducted and the socioeconomic characteristics were collected from medical records. RESULTS: Ninety-one patients were questioned. On 82 patients having answered, 19.5 % had used at least a CMA. The main CMA used was the physical exercise in 50 % of the patients. CMA users were significantly younger with a mean age of 56.4 years versus 65.4 years (P=0.0007). More than half patients did not indicate to their specialist that they used a CMA. The main information source was the circle of acquaintances. CONCLUSIONS: CMA use is frequent among lung cancer patients. The physical exercise is quoted most of the time among the various CMA. There is a real lack of communication on the subject between the physician and the patient. It is thus imperative that the pulmonologists give much interest to these practices in order to give better advices and to reinforce the patient-physician relationship.

Expression of retinoid receptor genes and proteins in non-small-cell lung cancer.

BACKGROUND: Retinoids can suppress carcinogenesis in high-risk non-neoplastic bronchial lesions and can reduce the risk of second primary non-small-cell lung cancer (NSCLC). The effects of retinoids are mediated by nuclear receptors, i.e., the retinoic acid receptors (RARalpha, RARbeta, and RARgamma) and the retinoid X receptors (RXRalpha, RXRbeta, and RXRgamma). We investigated whether abnormalities in the in vivo expression of retinoid receptors are observed in NSCLC. METHODS: Expression of retinoid receptors in paired specimens of normal and cancerous tissues from the lungs of 76 patients with NSCLC was studied by use of antiretinoid receptor antibodies (except those against RXRgamma) and immunohistochemistry. RAR messenger RNAs were analyzed by use of in situ hybridization and by reverse transcription-polymerase chain reaction (RT-PCR). Samples were also studied for loss of heterozygosity (LOH) at chromosome 3p24. All P values are two-sided. RESULTS: All studied receptors were expressed in normal lung cells and in high- risk non-neoplastic lesions. In tumor cells, overexpression of RXRalpha and RARalpha was frequently observed. In contrast, RXRbeta expression decreased in 18% of the tumor specimens. Furthermore, there was a marked decrease in the expression of RARbeta in 63% of the tumors (P<.0001). Decreased expression of RARgamma was observed by RT-PCR in 41% of the tumors (P<.0001). LOH at 3p24 was observed in 41% of the tumor specimens from informative patients and in 20% of the non-neoplastic lesions. CONCLUSIONS: Expression of RARalpha and RXRalpha is either normal or elevated in NSCLC. In contrast, a large percentage of tumors show a marked decrease in the expression of RARbeta, RARgamma, and RXRbeta as well as a high frequency of LOH at 3p24, which was also observed in non-neoplastic lesions. These data suggest that altered retinoid receptor expression may play a role in lung carcinogenesis.

[Risk reduction strategies in smoking]. / La réduction de risque en tabacologie.

INTRODUCTION: Around the world, due to its high efficiency in delivering nicotine, cigarette is, by far, the first device used to consume tobacco. But, as far as health is concerned, cigarette is the worst nicotine delivery system and cleaner delivery systems would be welcome. In respect to tobacco smoking, up to now, most doctors have supported the "quit smoking or die" dogma. However, some smokers cannot or do not want to completely give up the consumption of nicotine. BACKGROUND: Indeed, while some smokers can stop smoking and, for some of them, simply switch to a nicotine replacement therapy (NRT), other smokers crave the acute effects associated with the rapid massive surge of nicotine delivered to the brain by tobacco smoke. Currently, this rapid nicotine "high" is mainly experienced by smoking cigarettes, thus explaining the high rate of smoking relapse. VIEWPOINT: Thus, for smokers who cannot totally give up nicotine, it is sound to evaluate the rationale for the use of tobacco products with possible lower toxicity than cigarette smoke. CONCLUSIONS: Unfortunately, this important question triggers off passionate statements, while scientific and experimental observations are still very tenuous. Furthermore, the tobacco companies, by producing new tobacco products and promoting the use of smokeless tobacco such as snus, put a constant pressure on the Public Health community.

The role of platelet-derived growth factor production by tumor-associated macrophages in tumor stroma formation in lung cancer.

Lung cancer is the most common cause of death by cancer in developed countries. Since a tumor cannot develop without the parallel expansion of a tumor stroma, a better understanding of its formation could lead to new therapeutical approaches. In this respect, since platelet-derived growth-factor (PDGF) is a chemotactic and growth factor for mesenchymal and endothelial cells, lung tumors of patients undergoing surgery for non-small cell lung cancer were evaluated for their replication rate using iododeoxyuridine incorporation, and for the expression of PDGF genes and the presence of PDGF A and B chains and of PDGF receptor alpha and beta subunits. This observation demonstrates that: (a) tumor cells and stroma mesenchymal cells, but not tumor-associated macrophages, display a high replication rate; (b) 1 of 3 tumors are characterized by cancer cells expressing the genes for PDGF A and/or B chains, while 1 of 2 tumors are composed of tumor cells presenting PDGF receptors alpha and beta subunits on their surface, and in only 1 of 6 tumors, tumor cells coexpress PDGF and its receptor; (c) in almost all tumors, tumor-associated macrophages express PDGF A and/or B chain genes; (d) mesenchymal cells, as well as endothelial cells, do not express PDGF A and B chain genes but do express PDGF receptor alpha and beta subunits; and (e) an ongoing active process was suggested in the periphery of the tumor by the simultaneous strong expression of PDGF A and B chain genes by tumor-associated macrophages and the high replication rate of mesenchymal and endothelial cells in the same area. Thus, PDGF is likely to have a limited autocrine role in tumor cell replication but is a potential player, in a paracrine fashion, in tumor stroma development.

Retinoic acid receptor and retinoid X receptor alterations in lung cancer precursor lesions.

Smoking prevention will decrease lung cancer incidence in time. However, early detection would improve lung cancer prognosis in subjects at risk provided that specific markers could be identified. We previously reported that retinoic acid receptor (RAR) and retinoid X receptor (RXR) expression was altered in lung tumors. RAR-beta gene status could be derived from corresponding allelotyping and immunohistochemistry data. We now report the continued study on lung cancer precursor lesions. Fluorescence PCR-based assays were used for allelotyping at the RAR/RXR loci of: (a) 66 lung precursor lesions found at the free resection margins of 41 patients undergoing surgery for lung cancer (+ 31 paired tumors); and (b) bronchial cells also found at the free resection margins from 16 current and 8 never smokers operated on for noncancerous diseases. Three microsatellites located at 3p14-21 and 9p21 were also used for interwork comparison. Immunohistochemistry was additionally performed to evaluate P53 and RAR-beta expression in precursor lesions. Chi2 tests showed significant differences (P < 0.05) when comparing the results obtained from never smokers, smokers, squamous metaplasia, dysplasia + in situ carcinoma, and tumors. Microsatellite changes occurred frequently in all samples, but without specificity for any group (P < 0.08-0.52). They were globally correlated with tobacco exposure (P < 0.04), for which the RAR-gamma marker appeared as a preferential target (P < 0.004). Few reparation error phenotypes were observed, mostly at the RXR-alpha and RXR-gamma markers for which combined changes were also linearly increasing from never smokers to dysplasia + in situ carcinoma (P < 0.05 and P < 0.03). RAR-beta marker losses also increased from the first to the last group studied (P < 0.01), with a concomitant decrease in RAR-beta protein expression and correlated p53 increased immunoreactivity (P < 0.02). Losses at 3p14, 3p21, and P16 were frequent, but no significant differences between groups could be found. Unexpectedly, high constitutive homozygosity was observed near the RAR-alpha locus in squamous cell lung cancer cases. RARs/RXRs form homodimers or heterodimers involved in ligand binding. Their added alterations could result in a state of functional vitamin A deficiency in the affected bronchial cells. Further deletion events drawn from a limited repertoire of specific regions such as 3p14-21 and 9p21 could subsequently drive the deficient cells to invasive carcinoma.

[Malignant rhabdoid tumor of the lung]. / Tumeur pulmonaire maligne de type rhabdoïde.

INTRODUCTION: Rhabdoid tumours usually develop in brain and spinal cord or kidney; they are highly malignant neoplasms that typically arise in infancy and early childhood. However, rare cases of pulmonary localization have been described, particularly among young adults. CASE REPORT: A 26-year-old man, smoker, had a right apical lung mass associated with a Pancoast syndrome leading to haemoptysis. There was also a tumour of the left thigh and scalp. Histological samples taken at these three locations were in favour of an undifferentiated carcinoma. The lack of nuclear integrase interactor 1 expression, and immunohistochemical appearance supported the diagnosis of rhabdoid tumour. Despite treatment, unfavourable progression confirmed this hypothesis, doubling time was less than six weeks with development of multiple metastases resulted in death within only three months after diagnosis. CONCLUSION: The lack of expression of integrase interactor 1 should suggest the diagnosis of rhabdoid tumour, especially when there is quick progression. The prognosis of these tumours remains poor and therapeutic options are limited.

Predictive survival markers in patients with surgically resected non-small cell lung carcinoma.

Among patients with resected non-small cell lung carcinoma, about 50% will present a tumor recurrence. Thus, it would be of major importance to be able to predict and try to prevent these relapses by an active chemotherapy and/or radiotherapy. In an attempt to answer this question, the tumors of 227 patients with a surgically resected non-small cell lung carcinoma were evaluated as follows: tumors were classified as squamous cell carcinoma (n = 132) or adenocarcinoma (n = 95), and tumor differentiation was evaluated for each type. Then, all tumors were classified in respect to their pathological TNM staging (WHO) and screened by immunohistochemistry for the detection of the expression of the following antigens: Bcl-2, A+B+H blood group antigens, c-erb-b2, p53, and Pan-Ras antigens. Furthermore, adenocarcinomas were screened for the presence of point mutations in Ki-Ras codons 1-31. Finally, the patient blood group was defined, and patient survival was analyzed using nonparametric tests and proportional hazard Cox models. Using Kaplan-Meier survival curves, disease pathological TNM staging was shown to be a strong predictive factor of survival for both squamous cell carcinoma and adenocarcinoma. Patients with squamous cell carcinoma experienced fewer relapses than those with adenocarcinoma (42% versus 63%; P = 0.0002) and had a significantly better survival. All evaluated antigens were more often present in squamous cell carcinoma than in adenocarcinoma except for Pan-Ras (three times more frequent in adenocarcinoma). In patients with squamous cell carcinoma, only tumor staging had a significant prognosis value (P = 0.01). In patients with lung adenocarcinoma, a well-differentiated tumor (P = 0.009) as well as a positive Bcl-2 staining (P = 0.009) and an A+B+H antigen tumor staining (P = 0.024) were associated with a better survival. In contrast, patients with a stage I or II disease and a p53-positive tumor staining and patients with the O blood group (P = 0.01) had a shorter survival. Interestingly, no relation with patient survival was related to c-erb-b2 and Pan-Ras staining. Finally, 12 point mutations were found out of 81 tumors (15%) evaluated for Ki-Ras codons 1-31; they involved codon 12 but also 8, 14, and 15 without any relationship to survival. In respect to lung adenocarcinoma, using Cox proportional hazard models stratified on tumor staging, the following markers were shown to be related to survival: (a) Independent markers of longer survival (ie., high histological degree of tumor differentiation and positive Bcl-2 and A+B+H blood group antigen expression by tumor cells); and (b) Independent markers of shorter survival (i.e., O blood group for all patients and p53 tumor staining in patients with stage I and II diseases). This study suggests that, in patients who undergo surgery for lung adenocarcinoma, the presence or absence of these criteria could be used to define a subset of patients who may benefit from a more specific follow-up.

Nicotine inhaler and nicotine patch as a combination therapy for smoking cessation: a randomized, double-blind, placebo-controlled trial.

BACKGROUND: Nicotine replacement therapy is an effective treatment for nicotine-dependent smokers. However, cessation rates are modest, and preliminary studies suggest that combination therapy may be superior. We compared the efficacy of the nicotine inhaler plus nicotine patch vs nicotine inhaler plus placebo patch for smoking cessation. METHODS: A double-blind, randomized, placebo-controlled trial was conducted in 400 subjects who had smoked 10 or more cigarettes per day for 3 years or longer. Group 1 (n = 200) received the nicotine inhaler plus nicotine patch (delivering 15 mg of nicotine per 16 hours) for 6 weeks, then inhaler plus placebo patch for 6 weeks, then inhaler alone for 14 weeks. Group 2 (n = 200) received the nicotine inhaler plus placebo patch for 12 weeks, then inhaler for 14 weeks. Inhaler was used at a rate of 6 to 12 cartridges per day ad libitum for 3 months and then tapered off. Main outcome measures were complete abstinence (self-reported) and expired carbon dioxide concentration less than 10 ppm. RESULTS: Group 1 vs group 2 complete abstinence rates were 60.5% and 47.5% at 6 weeks (P =.009), 42.0% and 31.0% at 12 weeks (P =.02), 25.0% and 22.5% at 6 months (P =.56), and 19.5% and 14.0% at 12 months (P =. 14). One-year survival analysis showed a significant association between abstinence and treatment with nicotine inhaler plus nicotine patch (P =.04). Mean nicotine substitution at week 6 was 60.1% (group 1) and 24.6% (group 2) (P<.001). At 12 months, the frequency of respiratory symptoms in abstinent subjects fell significantly and lung function showed a trend toward improvement. The most common adverse events were throat irritation (inhaler) and itching (patch). CONCLUSIONS: Treatment with the nicotine inhaler plus nicotine patch resulted in significantly higher cessation rates than inhaler plus placebo patch.

[Passive smoking]. / Le tabagisme passif.

INTRODUCTION: Environmental tobacco smoke is a recognized factor of morbidity and mortality. The first victims are children, sometimes starting from conception, but adults are not spared. In practice, evaluation of exposure to tobacco smoke can be achieved with more or less specific markers of tobacco smoke. CURRENT KNOWLEDGE: Exposure of the fetus to maternal smoking and of the infant to environmental smoke can have a serious sometimes life-threatening impact. Such exposure increases the risk of spontaneous abortion, ectopic pregnancy, intrauterine growth retardation, premature membrane rupture, preterm birth, retroplacental hematoma, placenta praevia, and sudden infant death. Adult respiratory and cardiovascular disease are also influenced by environmental smoke. In France passive smoking causes premature death of 3000 persons per year. PERSPECTIVES: Better knowledge of the risks of exposure to passive smoking can facilitate application of legislation with the objective of protecting non-smokers. CONCLUSIONS: Rigorous application of current legislation is important to achieve the stated goals of prevention of smoking as well as assistance to cease smoking.