The influence of occupational stress factors on the nicotine dependence: a cross sectional study

Objective This study analyses the association between occupational stress factors and nicotine dependence. Our hypothesis is that occupational stress factors increase nicotine dependence. Methods Data were taken from the Cologne Smoking Study, a case-control study that examines which genetic/psychosocial factors lead to a higher risk for smokers to suffer from cardiac infarction, lung cancer and/or to become addicted to nicotine. Our sample consisted of N = 197 currently smoking and employed participants. Nicotine dependence was measured using the Fagerström Test for Nicotine Dependence (FTND). The extent of the stress factors experienced at work was assessed using the Effort-Reward Imbalance scale (ERI). Logistic regression was used for the statistical analysis. Results Contrary to our hypothesis, the results show that occupational stress factors are actually associated with lower levels of nicotine dependence (N = 197; adjusted OR = 0.439; p = .059). Conclusions One possible explanation for the study's findings is that the participants have a heavy workload and can only smoke in their spare time. Another reason may be workplace smoking bans. Furthermore, the Fagerström Test for Nicotine Dependence is unable to examine nicotine dependence during working hours

Osteoblastic Response in Patients with Non-small Cell Lung Cancer with Activating EGFR Mutations and Bone Metastases during Treatment with EGFR Kinase Inhibitors

© 2010International Association for the Study of Lung Cance

Stereotactic, single-dose irradiation of stage I non-small cell lung cancer and lung metastases

BACKGROUND: We prospectively reviewed response rates, local control, and side effects after non-fractionated stereotactic high single-dose body radiation therapy for lung tumors. METHODS: Fifty-eight patients underwent radiosurgery involving single-dose irradiation. With 25 patients, 31 metastases in the lungs were irradiated; with each of 33 patients, stage I non-small cell lung cancer (NSCLC) was subject to irradiation. The standard dose prescribed to the isocenter was 30 Gy with an axial safety margin of 10 mm and a longitudinal safety margin of 15 mm. The planning target volume (PTV) was defined using three CT scans with reference to the phases of respiration so that the movement span of the clinical target volume (CTV) was enclosed. RESULTS: The volume of the metastases (CTV) varied from 2.8 to 55.8 cm(3 )(median: 6.0 cm(3)) and the PTV varied from 12.2 to 184.0 cm(3 )(median: 45.0 cm(3)). The metastases ranged from 0.7 to 4.5 cm in largest diameter. The volume of the bronchial carcinomas varied from 4.2 to 125.4 cm(3)(median: 17.5 cm(3)) and the PTV from 15.6 to 387.3 cm(3 )(median: 99.8 cm(3)). The bronchial carcinomas ranged from 1.7 to 10 cm in largest diameter. Follow-up periods varied from 6.8 to 63 months (median: 22 months for metastases and 18 months for NSCLC). Local control was achieved with 94% of NSCLC and 87% of metastases. No serious symptomatic side effects were observed. According to the Kaplan-Meier method the overall survival probability rates of patients with lung metastases were as follows: 1 year: 97%, 2 years: 73%, 3 years: 42%, 4 years: 42%, 5 years: 42% (median survival: 26 months); of those with NSCLC: 1 year: 83%, 2 years: 63%, 3 years: 53%, 4 years: 39%: (median survival: 20.4 months). CONCLUSION: Non-fractionated single-dose irradiation of metastases in the lungs or of small, peripheral bronchial carcinomas is an effective and safe form of local treatment and might become a viable alternative to invasive techniques

Replication of Lung Cancer Susceptibility Loci at Chromosomes 15q25, 5p15, and 6p21: A Pooled Analysis From the International Lung Cancer Consortium

Background Genome-wide association studies have identified three chromosomal regions at 15q25, 5p15, and 6p21 as being associated with the risk of lung cancer. To confirm these associations in independent studies and investigate heterogeneity of these associations within specific subgroups, we conducted a coordinated genotyping study within the International Lung Cancer Consortium based on independent studies that were not included in previous genome-wide association studies. Methods Genotype data for single-nucleotide polymorphisms at chromosomes 15q25 (rs16969968, rs8034191), 5p15 (rs2736100, rs402710), and 6p21 (rs2256543, rs4324798) from 21 case-control studies for 11 645 lung cancer case patients and 14 954 control subjects, of whom 85% were white and 15% were Asian, were pooled. Associations between the variants and the risk of lung cancer were estimated by logistic regression models. All statistical tests were two-sided. Results Associations between 15q25 and the risk of lung cancer were replicated in white ever-smokers (rs16969968: odds ratio [OR] = 1.26, 95% confidence interval [CI] = 1.21 to 1.32, Ptrend = 2 × 10−26), and this association was stronger for those diagnosed at younger ages. There was no association in never-smokers or in Asians between either of the 15q25 variants and the risk of lung cancer. For the chromosome 5p15 region, we confirmed statistically significant associations in whites for both rs2736100 (OR = 1.15, 95% CI = 1.10 to 1.20, Ptrend = 1 × 10−10) and rs402710 (OR = 1.14, 95% CI = 1.09 to 1.19, Ptrend = 5 × 10−8) and identified similar associations in Asians (rs2736100: OR = 1.23, 95% CI = 1.12 to 1.35, Ptrend = 2 × 10−5; rs402710: OR = 1.15, 95% CI = 1.04 to 1.27, Ptrend = .007). The associations between the 5p15 variants and lung cancer differed by histology; odds ratios for rs2736100 were highest in adenocarcinoma and for rs402710 were highest in adenocarcinoma and squamous cell carcinomas. This pattern was observed in both ethnic groups. Neither of the two variants on chromosome 6p21 was associated with the risk of lung cancer. Conclusions In this international genetic association study of lung cancer, previous associations found in white populations were replicated and new associations were identified in Asian populations. Future genetic studies of lung cancer should include detailed stratification by histolog

Benchmarking of Mutation Diagnostics in Clinical Lung Cancer Specimens

Treatment of EGFR-mutant non-small cell lung cancer patients with the tyrosine kinase inhibitors erlotinib or gefitinib results in high response rates and prolonged progression-free survival. Despite the development of sensitive mutation detection approaches, a thorough validation of these in a clinical setting has so far been lacking. We performed, in a clinical setting, a systematic validation of dideoxy ‘Sanger’ sequencing and pyrosequencing against massively parallel sequencing as one of the most sensitive mutation detection technologies available. Mutational annotation of clinical lung tumor samples revealed that of all patients with a confirmed response to EGFR inhibition, only massively parallel sequencing detected all relevant mutations. By contrast, dideoxy sequencing missed four responders and pyrosequencing missed two responders, indicating a dramatic lack of sensitivity of dideoxy sequencing, which is widely applied for this purpose. Furthermore, precise quantification of mutant alleles revealed a low correlation (r2 = 0.27) of histopathological estimates of tumor content and frequency of mutant alleles, thereby questioning the use of histopathology for stratification of specimens for individual analytical procedures. Our results suggest that enhanced analytical sensitivity is critically required to correctly identify patients responding to EGFR inhibition. More broadly, our results emphasize the need for thorough evaluation of all mutation detection approaches against massively parallel sequencing as a prerequisite for any clinical implementation

Die Bedeutung des Immunsystems in der Pathogenese makrozytärer Anämien bei myelodysplastischen und aplastischen Erkrankungen des Knochenmarks : eine immunhistologische Untersuchung der myeloiden Expression des Alarmins S100A8

The purpose of this study was to analyse the hypothesis, that a dysregulation of the immune system including an elevated expression of the alarmin S100A8, an increased pro-inflammatory activity of macrophages and an induced expression of PD-L1 leads to a macrocytic anaemia in myelodysplastic syndrome (MDS) and aplastic anaemia (AA) via disturbing the erythropoiesis. To answer this question bone marrow biopsies from 62 patients (x=62) were immunohistochemically stained and the myeloid expression of S100A8, CD68 and PD-L1 was quantified and compared to common haematological parameters. Consistent with the hypothesis of a common S100A8-induced pathogenesis of macrocytic anaemia, there was an increased expression of S100A8 in the bone marrow of patients with non-hypocellular myelodysplastic syndrome and in the myeloid Hot spots of patients with AA and hypoplastic MDS (hMDS). The number of monocytes and macrophages was significantly increased in the bone marrow of patients with MDS with deletion of chromosome 5q (del(5q)). These macrophages appeared to be of a pro-inflammatory phenotype and they were also similar to macrophages which are located in an environment with impaired erythropoiesis. However, this phenotype could not be found in the bone marrow of patients with non-hypocellular MDS without del(5q). The bone marrow of these patients and of patients with AA/hMDS showed a significantly reduced number of monocytes and macrophages. These results support the hypothesis, that monocytes and macrophages are involved in the pathogenesis of 5q- syndrome, yet this appears not to be the case in the development of neither MDS without del(5q) nor AA. PD-L1 was not increased in any of the patient groups, nor was there a correlation with parameters of anaemia. Thus an increased expression of PD-L1 does not seem to be a part of the pathogenesis of macrocytic anaemia. On the contrary, the bone marrow of patients with AA and hMDS showed a significantly reduced expression of PD-L1, suggesting that PD-L1 may play a role in the development of AA. All results considered, the primary hypothesis of a dysregulated immunological signal pathway as the reason of the macrocytic anaemia in both MDS and AA, could not be confirmed, although new important knowledge was gained

A new classification of bronchial anastomosis after sleeve lobectomy

ObjectiveIschemia and infection of the distal part of the tracheobronchial anastomosis are the leading causes of bronchial anastomotic leakage with a high morbidity and mortality. To improve interpretation of healing of the anastomosis and the consequences, we have developed a classification scheme that allows quality control and defines early and standardized treatment of complications.Patients and MethodWe conducted a retrospective analysis of the records of 202 patients treated in our institution between January 1, 2006 and December 31, 2010 after sleeve lobectomy. All patients received prophylactic inhalation with tobramycin 80 mg twice a day. Neoadjuvant treatment was given in 21% of the patients. Routine bronchoscopy on day 7 was performed with classification of the anastomosis as follows: X, unknown; 1, healing well with no fibrin deposits; 2, focal fibrin deposits and superficial (mucosal) necrosis; 3, circular fibrin deposits, superficial (mucosal) necrosis, and/or ischemia of the distal mucosa; 4, transmural necrosis with instability of the anastomosis; and 5, perforation, necrosis of the anastomosis, and insufficiency.ResultsThe anastomosis was graded as satisfactory (1 and 2) in 86% of the patients. In 14%, it was regarded as critical (≥3-5) leading to systemic antibiotic treatment and control bronchoscopy. The overall 30-day mortality was 1%.ConclusionsQuality control of the tracheobronchial anastomosis comprised bronchoscopy performed before patients were dismissed. Inasmuch As postoperative bronchoscopy is not always performed by the operating surgeon, this classification is an aid to improve the description of endobronchial healing and to commence treatment of critical bronchial healing