Norbert Pauk

Adenocarcinoma of the lung among women: risk associated with smoking, prior lung disease, diet and menstrual and pregnancy history

To investigate the role of tobacco and some other known or suspected factors responsible for the risk of developing adenocarcinoma of the lung, and to compare with other cell types (squamous-, small- and large-cell cancers) in Czech women, we conducted a case-control study. Data collected by personal interviews from 145 cases of adenocarcinoma of the lung, 221 lung cancer cases of other cell types, and 1624 controls were analyzed using unconditional logistic regression. Cigarette smoking was the main determinant of all major cell types of lung cancer among Czech women, its effect was weaker on adenocarcinoma than on squamous-, small- and large-cell cancers. Among never smokers, passive smoking in childhood (before age 16) did not significantly increase the risk of adenocarcinoma (OR=1.35, 95%CI 0.75-2.45), contrasting with an elevation in the risk of squamous-, small- and large-cell cancers combined (OR=2.10, 95%CI 1.02-4.33). Excess risk associated with consumption of red meat daily or several times per week (OR=1.81, 95%CI 1.04-3.18) was restricted to squamous-, small- and large-cell cancers combined. Wine drinking, at higher frequency than once per month, was inversely associated with the risk of adenocarcinoma (OR=0.46, 95%CI 0.23-0.92), however, not with squamous-, small- and large-cell cancers combined (OR=0.77, 95%CI 0.47-1.28). Inverse associations with the risk of squamous-, small- and large-cell cancers combined emerged for the quantity of menstrual flow (OR=0.63, 95%CI 0.40-0.99), and pains or mental tension related to menses (OR=0.61, 95%CI 0.42-0.89).

Differential sensitivity to apoptosome apparatus activation in non-small cell lung carcinoma and the lung

The intrinsic apoptosis pathway represents an important mechanism of stress-induced death of cancer cells. To gain insight into the functional status of the apoptosome apparatus in non-small cell lung carcinoma (NSCLC), we studied its sensitivity to activation, the assembly of apoptosome complexes and stability of their precursors, and the importance of X-linked inhibitor of apoptosis (XIAP) in the regulation of apoptosome activity, using cell-free cytosols from NSCLC cell lines and NSCLC tumours and lungs from 62 surgically treated patients. Treatment of cytosol samples with cytochrome c (cyt-c) and dATP induced proteolytic processing of procaspase-9 to caspase-9, which was followed by procaspase-3 processing to caspase-3, and by generation of caspase-3-like activity in 5 of 7 studied NSCLC cell lines. Further analysis demonstrated formation of high-Mr Apaf-1 complexes associated with cleaved caspase-9 in the (cyt-c + dATP)-responsive COLO-699 and CALU-1 cells. By contrast, in A549 cells, Apaf-1 and procaspase-9 co-eluted in the high-Mr fractions, indicating formation of an apoptosome complex unable of procaspase-9 processing. Thermal pre-treatment of cell-free cytosols in the absence of exogenous cyt-c and dATP lead to formation of Apaf-1 aggregates, unable to recruit and activate procaspase-9 in the presence of cyt-c and dATP, and to generate caspase-3-like activity. Further studies showed that the treatment with cyt-c and dATP induced a substantially higher increase of caspase-3-like activity in cytosol samples from NSCLC tumours compared to matched lungs. Tumour histology, grade and stage had no significant impact on the endogenous and the (cyt-c + dATP)-induced caspase-3-like activity. Upon addition into the cytosol, the XIAP-neutralizing peptides AVPIAQK and ATPFQEG only moderately heightened the (cyt-c + dATP)-induced caspase-3-like activity in some NSCLC tumours. Taken together, the present study provides evidence that the apoptosome apparatus is functional in the majority of NSCLCs and that its sensitivity to the (cyt-c + dATP)-mediated activation is often enhanced in NSCLCs compared to lungs. They also indicate that XIAP does not frequently and effectively suppress the activity of apoptosome apparatus in NSCLCs.

Neumomediastino y neumopericardio en un paciente con cáncer de pulmón espinocelular

Documented cases of lung cancer complicated by pneumomediastinum and pneumopericardium are extremely rare. We report the case of a 55-year-old man with lung cancer complicated by pneumomediastinum and pneumopericardium. The patient was admitted with a 3-month history of dyspnea (Day 1). Computed tomography (CT) was performed and disease staging was established as cT4N3M0, although the tumor was not confirmed by histopathology. Pericardial and tracheal invasion were observed, causing tracheomediastinal fistula, pneumomediastinum (Fig. 1), and pneumopericardium. No distant metastases were observed. Bronchoscopy showed significant tumor stenosis on the trachea, approximately 6 cm below the glottis. Samples could not be obtained and the procedure had to be terminated prematurely due to dyspnea. The invasive bronchology team was consulted, but the conclusion was that bronchological intervention was impossible – at that time Y stents were not yet available in the hospital. The patient’s condition deteriorated rapidly and he died on Day 10. Autopsy revealed squamous cell lung cancer with direct invasion of the pericardium and trachea, forming a tracheomediastinal fistula, pneumohydropericardium, left lung pneumonia (not present at the time of performing the CT). No distant metastases were observed, so stage pT4 and pM0 was confirmed (no information on N3 lymph node invasion was provided). Only 4 cases of spontaneous pneumomediastinum in patients with primary lung cancer have been described.1–4 In 2 of them, the clinical situation deteriorated rapidly until death,1,2 1 patient recovered,3 and clinical progress was not reported in the fourth case.4 Histological types were large cell carcinoma,1 small cell carcinoma2,3 and undifferentiated carcinoma.4 There are 2 explanations for poor clinical progress in the cases discussed. Tracheomediastinal fistula carries a high risk for acute mediastinitis and possible development of tension pneumomediastinum. This, like tension pneumothorax, can rapidly be fatal. We have identified 2 risk factors for the development of pneumomediastinum, both of which were presented by our case: direct