Lung cancer registries in Denmark, Finland, Norway and Sweden: a comparison and proposal for harmonization.

BACKGROUND: Lung cancer is the leading cause of cancer-related death in all Nordic countries which, though similar in demographics and healthcare systems, have noticeable differences in lung cancer survival. Historically, Denmark and Finland have had higher lung cancer incidences and lower survival than Norway and Sweden. All four countries have national cancer registries. Data in these registries are often compared, but their full potential as a source of learning across the Nordic countries is impeded by differences between the registries. In this paper, we describe and compare the Nordic registries on lung cancer-specific data and discuss how a more harmonized registration practice could increase their usefulness as a source for mutual learning and quality improvements. METHODS: We describe and compare the characteristics of data on lung cancer cases from registries in Denmark, Finland, Norway and Sweden. Moreover, we compare the results from the latest annual reports and specify how data may be acquired from the registries for research. RESULTS: Denmark has a separate clinical lung cancer registry with more detailed data than the other Nordic countries. Finland and Norway report lung cancer survival as relative survival, whereas Denmark and Sweden report overall survival. The Danish Lung Cancer Registry and the Swedish Cancer Registry do not receive data from the Cause of Death registries in contrast to the Finnish Cancer Registry and the Cancer Registry of Norway. CONCLUSION: The lung cancer registries in Denmark, Finland, Norway and Sweden have high level of completeness. However, several important differences between the registries may bias comparative analyses.

Increased use of computed tomography in Denmark: stage shift toward early stage lung cancer through incidental findings.

BACKGROUND: Computed tomography (CT) examinations are increasingly used worldwide and incidental findings are growing likewise. Lung cancer stage at diagnosis is pivotal to survival. The earliest stage of lung cancer, stage IA is in most cases asymptomatic. Potentially, increased use of clinical CTs could induce a stage shift toward earlier lung cancer diagnosis. MATERIALS AND METHODS: Data on the number of CT thorax in Denmark and the stage distribution of Danish lung cancer patients 2013-2020 were acquired from, respectively, the Danish Health Data Authority and the Danish Lung Cancer Registry. Clinical auditing of stage IA lung cancer patients was performed in the period 2019-2021 in a Danish region to assess the reasons for referral. Auditing of stage IV lung cancer patients was done to see whether a CT thorax was performed in a two-year period before diagnosis. RESULTS: All regions showed an increase in CTs per 1000 inhabitants. However, the number of CTs performed in 2013 differed by more than 50% among regions, and the increase per year also differed, from an increase of 1.9 to 3.4 more examinations per year. A significant correlation between CTs and fraction of stage IA lung cancers was seen in four out of the five regions. The audit of stage IA lung cancer cases revealed that 86.8% were incidental findings. Audit of stage IV lung cancer found that 4.3% had a nodule/infiltrate on a previous CT within a 2-year period prior to the diagnosis of lung cancer that was the probable origin of stage IV lung cancer. CONCLUSION: The study found that the vast majority of early-stage lung cancers were incidental findings. It highlights that follow-up algorithms of incidental findings should be used in accordance with guidelines and it should be unequivocally how the CT follow-up of pulmonary infiltrates is managed.

Exosomal proteins as prognostic biomarkers in non-small cell lung cancer.

BACKGROUND: Use of exosomes as biomarkers in non-small cell lung cancer (NSCLC) is an intriguing approach in the liquid-biopsy era. Exosomes are nano-sized vesicles with membrane-bound proteins that reflect their originating cell. Prognostic biomarkers are needed to improve patient selection for optimal treatment. We here evaluate exosomes by protein phenotyping as a prognostic biomarker in NSCLC. METHODS: Exosomes from plasma of 276 NSCLC patients were phenotyped using the Extracellular Vesicle Array; 49 antibodies captured the proteins on the exosomes, and a cocktail of biotin-conjugated antibodies binding the general exosome markers CD9, CD81 and CD63 was used to visualise the captured exosomes. For each individual membrane-bound protein, results were analysed based on presence, in a concentration-dependent manner, and correlated to overall survival (OS). RESULTS: The 49 proteins attached to the exosomal membrane were evaluated. NY-ESO-1, EGFR, PLAP, EpCam and Alix had a significant concentration-dependent impact on inferior OS. Due to multiple testing, NY-ESO-1 was the only marker that maintained a significant impact on inferior survival (hazard rate (HR) 1.78 95% (1.78-2.44); p = 0.0001) after Bonferroni correction. Results were adjusted for clinico-pathological characteristics, stage, histology, age, sex and performance status. CONCLUSION: We illustrate the promising aspects associated with the use of exosomal membrane-bound proteins as a biomarker and demonstrate that they are a strong prognostic biomarker in NSCLC.

Dynamic contrast-enhanced CT in suspected lung cancer: quantitative results.

OBJECTIVES: To examine whether dynamic contrast-enhanced CT (DCE-CT) could be used to characterise and safely distinguish between malignant and benign lung tumours in patients with suspected lung cancer. METHODS: Using a quantitative approach to DCE-CT, two separate sets of regions of interest (ROIs) in tissues were placed in each tumour: large ROIs over the entire tumour and small ROIs over the maximally perfused parts of the tumour. Using mathematical modelling techniques and dedicated perfusion software, this yielded a plethora of results. RESULTS: First, because of their non-normal distribution, DCE-CT measurements must be analysed using log scale data transformation. Second, there were highly significant differences between large ROI and small ROI measurements (p<0.001). Thus, the ROI method used in a given study should always be specified in advance. Third, neither quantitative parameters (blood flow and blood volume) nor semi-quantitative parameters (peak enhancement) could be used to distinguish between malignant and benign tumours. This was irrespective of the method of quantification used for large ROIs (0.13

Limited value of 99mTc depreotide single photon emission CT compared with CT for the evaluation of pulmonary lesions.

OBJECTIVES: A contrast-enhanced multidetector CT (MDCT) scan is the first choice examination when evaluating patients with suspected lung cancer. However, while the clinical focus is on CT, research focus is on molecular biological methods whereby radiolabelled pharmaceuticals are injected into participants and target malignant lung tumours. We examined whether a contrast-enhanced MDCT scan supplied with an additional non-contrast enhanced high-resolution CT scan, or a newer but more expensive (99m)Tc depreotide single photon emission CT (SPECT) scan, was the better first-choice examination for the work-up of pulmonary lesions. Furthermore, we examined whether a (99m)Tc depreotide SPECT scan was an appropriate second-choice examination for patients with indeterminate lesions. METHODS: 140 participants were included in the analysis. CT images were given a malignancy potential rating of 1, 2 or 3 with higher rating being indicative of disease. (99m)Tc depreotide SPECT images were graded either positive or negative. Histopathology and CT follow-up were used as reference standard. Sensitivity, specificity and diagnostic accuracy were calculated. RESULTS: Overall sensitivity, specificity and diagnostic accuracy of CT were 97%, 30% and 84%, respectively. Overall sensitivity, specificity and diagnostic accuracy of (99m)Tc depreotide SPECT were 94%, 58% and 76%, respectively. For indeterminate lesions sensitivity, specificity and diagnostic accuracy of (99m)Tc depreotide SPECT were 71%, 68% and 69%, respectively. CONCLUSION: Both CT and (99m)Tc depreotide SPECT made valuable contributions to the evaluation of pulmonary lesions. (99m)Tc depreotide SPECT results were not superior to CT results and did not contribute further to the diagnostic work-up. Regarding indeterminate lesions,( 99m)Tc depreotide SPECT sensitivity was too low.

Intensified microbiological investigations in adult patients admitted to hospital with lower respiratory tract infections.

The objective of this study was to investigate the diagnostic yield of a programme with intensified microbiological investigations in immunocompetent adult patients with lower respiratory tract infections (LRTI). Patients in the study group were included prospectively and consecutively from September 1st 1997 to May 31st 1998 and were compared with a control group from the preceding year. A total of 67 adult patients were included in the study group and they were compared with 122 adult patients in the control group. The study group underwent fibre-optic bronchoscopy (FOB) with bronchoalveolar lavage (BAL). Only 7% in the historic control group were discharged with an aetiological diagnosis of their infections; while the diagnostic yield in the study group increased to 51% of patients. In the study group the presence of new infiltrates on chest X-ray increased the detection of a microbiological aetiology from 37% with no infiltrates to 62% with infiltrates and recent antibiotic therapy reduced the detection of a microbiological cause of infection from 61% in 36 patients who had not received antibiotic therapy to 39% in 31 patients who had received recent antibiotic therapy prior to microbiological sampling. Patients in the study group with known aetiology had higher values of inflammatory markers than patients with unknown aetiology. For Streptococcus pneumoniae infection culture and urine antigen detection were complimentary depending on recent antibiotic therapy since seven of eight culture-positive patients had not received antibiotic therapy within 72 h prior to investigation, while all four patients positive for urine antigens from S. pneumoniae had received antibiotic therapy within 72 h of urine sampling. In conclusion intensified microbiologic investigations increase the diagnostic yield from 7% to 51% of patients in the study group with an aetiologic diagnosis. Routine FOB with BAL had no apparent effect on clinical outcome and seems only justified in selected patients with severe LRTI with infiltrates on chest X-ray and signs of severe inflammation where a high diagnostic yield is achieved.

Quantitative culture of bronchoalveolar lavage fluid in community-acquired lower respiratory tract infections.

To evaluate the diagnostic value of quantitative bacterial culture of bronchoalveolar lavage (BAL) fluid obtained by fibreoptic bronchoscopy, 67 consecutive immunocompetent adult patients admitted to hospital with community-acquired lower respiratory tract infections from September 1997 to May 1998 were investigated. Results were compared to the findings in eight healthy control persons investigated in February 1998. There was no difference between study patients and control persons when quantitative culture of total cumulative bacterial findings or bacteria categorized as members of the oropharyngeal normal flora were compared. The culture of normal flora in bronchial washings probably reflects contamination of the lower airways with secretions from upper arways by the fibreoptic procedure itself, as fractionated sampling showed a 10-fold reduct on in quantitative culture results when a primary bronchial washing was compared to a secondary sampling from the same bronchus in the control group. Twenty-four (36%) of 67 patients were cultured as positive in the study group while all control persons were cultured as negative for bacteria categorized as potential pathogens. With a threshold value for positive culture of 10(4) cfu ml(-1) the specificity of lavage culture of potential pathogenic bacteria in relation to actual lower airway infection was 100%. Therefore, quantitative bacterial culture of potential pathogenic bacteria in BAL fluid is very specific but only positive in about one-third of unselected immunocompetent adult patients with a lower respiratory tract infection.

[Effects of low concentrations of NO2 on alveolar permeability and glutathione peroxidase in healthy subjects]. / Virkninger af mindre NO2-koncentrationer på alveolaer permeabilitet og glutationperoxidase blandt raske mennesker.

Potential toxic effects of prolonged NO2 exposure below the current threshold limit value (TLV) were examined in 14 healthy, non-smoking adults. The subjects were exposed to 2,3 ppm NO2 and to clean air for five hours with a one week interval between exposures. Physiological and biochemical measurements were obtained during exposure and the following 24 hours after. A 14% decrease in serum glutathione peroxidase activity (GSH-Px) was observed 24 hours after the start of the NO2 exposure while indications of a 22% decrease in alveolar permeability were found 11 hours after the start. There were no indications of mucous membrane irritation or of decreased lung function during or after NO2 exposures. The results support the assumption that a delayed response is a feature of the human reaction to NO2 even below the current TLV of three ppm, and they stress the importance of an extended period of observation in future NO2 exposure studies.

Delayed effects of NO2 exposure on alveolar permeability and glutathione peroxidase in healthy humans.

Potential toxic effects of prolonged NO2 exposure below the current threshold limit value (TLV) were examined in 14 healthy, nonsmoking adults. The subjects were exposed to 2.3 ppm NO2 and to clean air for 5 h with a 1-wk interval between exposures. Physiologic and biochemical measurements were obtained during the exposures and until 24 h after. A 14% decrease in serum glutathione peroxidase activity (GSH-Px) was observed 24 h after the start of the NO2 exposure, while indications of a 22% decrease in alveolar permeability were found 11 h after the start. There were no indications of mucous membrane irritation or of decreased lung function during or after NO2 exposures. The results support the assumption that a delayed response is a feature of the human reaction to NO2 even below the current TLV of 3 ppm, and they stress the importance of an extended period of observation in future NO2 exposure studies.