Thymoma with pleural metastases. / Tymom med pleurametastaser.

Metastatic thymoma is a rare and serious condition that is treated with cytostatics according to the guidelines. Cytostatics have limited efficacy and are toxic. This case report illustrates how glucocorticoid treatment can have a significant effect.

Levels and prognostic impact of circulating markers of inflammation, endothelial activation and extracellular matrix remodelling in patients with lung cancer and chronic obstructive pulmonary disease.

BACKGROUND: The development of both chronic obstructive pulmonary disease (COPD) and lung cancer (LC) is influenced by smoking related chronic pulmonary inflammation caused by an excessive innate immune response to smoke exposure. In addition, the smoking induced formation of covalent bonds between the carcinogens and DNA and the accumulation of permanent somatic mutations in critical genes are important in the carcinogenic processes, and can also induce inflammatory responses. How chronic inflammation is mirrored by serum markers in COPD and LC and if these markers reflect prognosis in patients with LC is, however, largely unknown. METHODS: Serum levels of 18 markers reflecting inflammation, endothelial activation and extracellular matrix remodelling were analysed in 207 patients with non-small lung carcinoma (NSCLC) before surgery and 42 COPD patients. 56% of the LC patients also suffered from COPD. The serum samples were analysed by enzyme immunoassays. RESULTS: Serum levels of OPG, PTX3, AXL, ALCAM, sCD163, CD147, CatS and DLL1 were significantly higher in patients with COPD as compared to patients with LC. High sTNFR1 levels were associated with improved progression free survival (PFS) and overall survival (OS) in LC patients with (PFS hazard ratio (HR) 0.49, OS HR 0.33) and without COPD (OS HR 0.30). High levels of OPG were associated with improved PFS (HR 0.17) and OS (HR 0.14) for LC with COPD. CRP was significantly associated with overall survival regardless of COPD status. CONCLUSION: Several markers reflecting inflammation, endothelial activation and extracellular matrix remodelling are elevated in serum from patients with COPD compared to LC patients. Presence of COPD might influence the levels of circulating biomarkers. Some of these markers are also associated with prognosis.

EGFR mutation testing of lung cancer patients - Experiences from Vestfold Hospital Trust.

BACKGROUND: Patients with advanced stage lung cancer and somatic mutations in the epithelial growth factor receptor (EGFR) gene are currently treated with tyrosine-kinase inhibitors. The Norwegian Lung Cancer Group (NLCG) recommended EGFR testing of all patients with non-small cell lung carcinoma (NSCLC) from June 2010. From March 2013, testing of squamous cell carcinomas was terminated. We have analysed how these recommendation were followed at a medium-sized Norwegian hospital and we present data on mutation frequency, retesting and possible explanations for missing test results. MATERIAL AND METHODS: All pathology reports for patients diagnosed with NSCLC at Vestfold Hospital Trust were examined for the period June 2010 to December 2013. Mutation analyses were done at the Department of Pathology, Oslo University Hospital. RESULTS: Material was sent for EGFR analysis for 256 of the 304 eligible patients diagnosed in the period. Material from 48 patients was never sent for EGFR testing, of which five samples consisted of too few tumour cells. For the rest, no obvious reason for omitting EGFR mutation analyses was identified. During the first six months of our study period, material from 25 of 66 NSCLC patients (38%) was not tested, whereas only six of the 118 patients (5%) in 2013 were not tested. For 34 patients, the first tissue specimen contained too few tumour cells and a new sample was sent for EGFR analyses for 11 of these. EGFR mutation was detected in 7.1% of the analysed NSCLC and in 9.4% of adenocarcinomas. DISCUSSION: Especially for patients with advanced stages of NSCLC, EGFR mutation status is necessary for treatment stratification. Our results show that the guidelines were followed increasingly over time for patients diagnosed with NSCLC at the Vestfold Hospital Trust. The establishment of interdisciplinary meetings has improved the diagnostic routines.

Circulating T Cell Activation and Exhaustion Markers Are Associated With Radiation Pneumonitis and Poor Survival in Non-Small-Cell Lung Cancer.

Introduction: Persistent inflammation and immune activation in the lungs are associated with adverse outcomes such as radiation pneumonitis (RP) and poor survival in non-small-cell lung cancer (NSCLC) patients. However, it is unknown how this is reflected by leukocyte activation markers in serum. Objective: The aim was to evaluate the serum levels of activation of different leukocyte subsets and to examine those in relation to the pathogenesis of RP and survival in NSCLC. Methods: We analyzed the serum levels of MPO, sCD25, sTIM-3, sPD-L1, sCD14, sCD163, CCL19 and CCL21 in 66 inoperable NSCLC patients with stage IA-IIIA disease. The patients were treated with stereotactic body radiation therapy (SBRT) or concurrent chemoradiation therapy (CCRT), followed by regular blood sampling for 12 months after treatment and for 5 years for survival. Results: Nineteen (29%) patients developed RP, which occurred more frequently and earlier in patients receiving CCRT than in those receiving SBRT. Increases in sCD25, sTIM-3 and CCL21 levels were observed at the last 6 months of follow-up in patients who had RP after SBRT. Patients who had RP after CCRT had higher sTIM-3 levels during the first 3 months of follow-up. Baseline sCD25 was independently associated with both 2- and 5-year mortality outcomes, while baseline sTIM-3 was independently associated with 2-year mortality. Conclusion: We showed that T cell activation and exhaustion markers such as sCD25 and sTIM-3 are enhanced in patients developing RP and are associated with poor survival in NSCLC.

Corrigendum: Circulating T cell activation and exhaustion markers are associated with radiation pneumonitis and poor survival in non-small-cell lung cancer.

[This corrects the article DOI: 10.3389/fimmu.2022.875152.].

Lung Function After Stereotactic Body Radiation Therapy for Early-Stage Non-Small Cell Lung Cancer, Changes and Predictive Markers.

INTRODUCTION: The present study explores changes in pulmonary function, symptoms and radiological signs of pneumonitis after curatively intended stereotactic body radiation therapy (SBRT). METHODS: All inoperable, early-stage non-small cell lung cancer patients treated with stereotactic body radiation therapy (SBRT) from 2014-2017 were included in this single-centre study. They were followed regularly for 12 months after treatment. The patients were classified into three groups based on radiology and symptomatology: no radiation pneumonitis, asymptomatic and symptomatic radiation pneumonitis. RESULTS: Forty-four patients with stage IA-IIB disease were treated with 45-56 Gy in 3-8 fractions. The median age was 75 years, 43% of the patients were female; 60% of the patients had a COPD in GOLD grade of 2-4, and 95.5% were active or former smokers. Symptomatic radiation pneumonitis occurred in 18% of the patients and asymptomatic pneumonitis as defined by radiology, in 39%. The mean of forced expiratory volume in 1 second (FEV1) and diffusion capacity for carbon monoxide (DLCO) decreases for all patients during the first years were higher than one would expect from physiologic ageing. FEV1 and DLCO in percent decrease 7-8% at 1-1.5 months in the symptomatic radiation pneumonitis group. CT scan findings consistent with radiation pneumonitis occurred after a median of 2.9 months in the symptomatic and 5.4 months in the asymptomatic radiation pneumonitis groups. In the group with symptomatic radiation pneumonitis, symptoms, as measured by the Clinical COPD questionnaire score, significantly increased at 3 and 6 months. Significant higher maximum doses to the critical lung volumes DC1000cm3 (1000 cm3 of lung receiving a given dose or less) and DC 1500cm3 (1500 cm3 of lung receiving a given dose or less) were observed in patients who developed radiation pneumonitis. CONCLUSION: Early decrease in measured FEV1 and DLCO occurred before imaging changes and symptoms and might indicate the development of symptomatic radiation pneumonitis. The dose to critical lung volumes of DC1000 cm3 and DC1500 cm3 may predict the risk for the development of symptomatic radiation pneumonitis.

Non-small cell lung cancer is characterised by a distinct inflammatory signature in serum compared with chronic obstructive pulmonary disease.

Development of lung cancer is closely related to smoking in a majority of patients. Most smokers, however, do not develop lung cancer in spite of a high mutational load accumulating in the lung tissue. Here we investigate whether a cancer-specific footprint can be revealed by investigating circulating inflammatory markers in patients with non-small cell lung cancer (NSCLC) compared with patients with chronic obstructive pulmonary disease (COPD), both cohorts characterised by similar smoking history. Serum concentrations of 57 cytokines and matrix metalloproteinases (MMPs) from 43 patients with advanced NSCLC were evaluated by multiplex immunoassays and compared with serum samples from 35 patients with COPD. Unsupervised hierarchical clustering and non-parametric analyses were performed. False discovery rate was used to adjust for multiple testing. Clustering of cytokine and MMP concentrations in the serum revealed a distinct separation of the NSCLC patients from the COPD group. Individual concentrations of thymus and activation-regulated cytokine (C-C motif chemokine ligand 17), Gro-b (C-X-C motif chemokine ligand 2 (CXCL2)), CXCL13, interleukin (IL)-1ra, IL-6, IL-8 (CXCL8), IL-16, IL-17A, macrophage migration inhibitory factor (MIF), granulocyte colony-stimulating factor, platelet-derived growth factor subunit B, MMP-2, MMP-8 and MMP-12 were significantly different in serum from NSCLC and COPD patients. Moreover, the interferon-γ/IL-10 ratio was lower in cancer patients compared with COPD patients, consistent with a cytokine milieu favouring tumour tolerance. Our results suggest that NSCLC is characterised by a distinct inflammatory signature in serum. The different cytokine profiles in NSCLC and COPD patients may represent tumour-promoting and tumour-suppressing immune responses developing in response to mucosal inflammation and mutations induced by smoking.

The value of cytology in the diagnostics of lung cancer.

In order to elucidate the relative contributions made by cytology and histology in the diagnosis of lung cancer, we studied the cytology and histology reports of all patients who received a microscopic diagnosis of lung cancer in our hospital during the 7 years 1996-2002. This gave a total of 407 patients. The most frequent diagnoses were squamous cell carcinoma (34.9%), adenocarcinoma (24.8%), and small cell carcinoma (17.8%). One hundred and fifteen patients (28.3%) received their microscopic diagnosis based only on cytology, which therefore proved to be of great diagnostic value. The most useful type of cytology specimen was taken by bronchial lavage or bronchial brushing. These types of specimens provided the diagnosis in 71 patients (17.4%). Cytology was especially capable of finding squamous cell carcinomas. Small cell carcinomas were underrepresented (9.6% versus 17.8%) and unspecified carcinomas greatly overrepresented (9.6% versus 2.9%) among the diagnoses obtained by cytology alone. We conclude that cytology is of considerable diagnostic value, although not as specific as histology for the subtyping of carcinomas. Clinicians should be more aware of the usefulness of cytology, especially in cases where it is difficult to obtain bronchoscopic biopsy samples for histological examination.

[Ingested lead cartridges cause trouble]. / Blyhagl til besvaer.

BACKGROUND: Lead poisoning is rare. Intake of lead shots may cause damage of the bone marrow, the nervous system, the liver, the kidneys and the endocrine organs. MATERIALS AND METHODS: We present two patients who had taken approximately 120 grams of lead shots. They developed asthenia, nausea and abdominal pain. We tried to remove the lead shots with fluids, laxatives and colonoscopy, but ultimately surgical intervention had to be performed. The patients were also treated with dimercaptosuccinic acid (DMSA). RESULTS AND INTERPRETATION: Although DMSA treatment is associated with a significant decrease in blood lead concentration and an increase of lead urinary excretion, surgical intervention is the most efficient way of treating oral intake of lead. Treatment with DMSA will probably have to go on for months in order to give an additional effect.