PD-L1 Expression and Tumour Microenvironment Patterns in Resected Non-Small-Cell Lung Cancer.

Background and Objectives: Although perioperative immunotherapy is implemented as a standard of care for resected non-small cell lung cancer (NSCLC), there is unmet need for predictive biomarkers as programmed death-ligand 1 (PD-L1) is not the perfect one. The functionality of tumour-infiltrating immune cells in the tumour microenvironment (TME) and the involvement in immune system response is one of the crucial factors that lead to pro- or anti-tumourigenic role and could predict response to PD-1 and PD-L1 inhibitors. So, the investigation of PD-L1 expression in the context of TME in early stages of resected NSCLC is urgent required. Materials and Methods: PD-L1 expression by three scoring methods: tumour proportion score (TPS), immune cell score (IC), and combined proportion score (CPS) was assessed in 72 archival tumour tissue specimens from stage I-III surgically resected NSCLC patients and associations with immune cells in TME were explored. Results: PD-L1 expression ≥1% evaluated by TPS, IC, and CPS was detected in 28%, 36%, and 39% of cases and moderate, substantial, and strong agreement between TPS and IC, TPS and CPS, CPS and IC was detected (Cohen's κ coefficient 0.556, 0.63, and 0.941, respectively). PD-L1 TPS, IC, and CPS correlated with smoking intensity defined as pack-years (r = 0.0305, p = 0.012; r = 0.305, p = 0.013, and r = 0.378, p = 0.002, respectively). Only PD-L1 TPS was associated with squamous cell carcinoma (p = 0.028). PD-L1 IC ≥1% was more often seen in tumours with high CD4+ T cells infiltration (p = 0.02), while PD-L1 CPS ≥1%-in tumours with high CD4+ and CD8+ T cells infiltration (p = 0.021 and p = 0.048, respectively). PD-L1 IC and CPS ≥10% was more often detected in tumours with greater number of tumour-infiltrating CD4+Foxp3+ T cells (p = 0.01 and p = 0.025, respectively). PD-L1 TPS ≥50% was associated with higher probability to detect greater number of tumour-infiltrating M2 macrophages (p = 0.021). No association was found between PD-L1 alone or in combination with tumour-infiltrating lymphocytes, macrophages, and disease-free or overall survival. Conclusions: This study results revealed that rates of PD-L1 expression correlated among three scoring methods (TPS, IC, and CPS). Moreover, PD-L1 expression was significantly associated with smoking intensity, squamous histology, and tumour-infiltrating immune cells.

Detailed Characterization of the Lung-Gut Microbiome Axis Reveals the Link between PD-L1 and the Microbiome in Non-Small-Cell Lung Cancer Patients.

Next-generation sequencing technologies have started a new era of respiratory tract research in recent years. Alterations in the respiratory microbiome between healthy and malignant conditions have been revealed. However, the composition of the microbiome varies among studies, even in similar medical conditions. Also, there is a lack of complete knowledge about lung-gut microbiome interactions in lung cancer patients. The aim of this study was to explore the lung-gut axis in non-small-cell lung cancer (NSCLC) patients and the associations between lung-gut axis microbiota and clinical parameters (CRP, NLR, LPS, CD8, and PD-L1). Lung tissue and fecal samples were used for bacterial 16S rRNA sequencing. The results revealed, for the first time, that the bacterial richness in lung tumor tissue gradually decreased with an increase in the level of PD-L1 expression (p < 0.05). An analysis of ß-diversity indicated a significant positive correlation between the genera Romboutsia and Alistipes in both the lung tumor biopsies and stool samples from NSCLC patients (p < 0.05). Survival analysis showed that NSCLC patients with higher bacterial richness in their stool samples had prolonged overall survival (HR: 2.06, 95% CI: 1.025-4.17, p = 0.0426).

Effect of Short-Term Treatment with Continuous Positive Airway Pressure on Cardiopulmonary Exercise Tolerance, Pulmonary and Cardiac Function in Patients with Obstructive Sleep Apnea.

Background: Obstructive sleep apnea (OSA) is a condition with a high prevalence, linked to an increased risk of cardiovascular disease as well as increased morbidity and death. CPAP is currently considered the "gold standard" treatment for OSA, but more thorough research and testing are required to assess its efficacy on cardiopulmonary function. Objectives: To evaluate pulmonary function of OSA patients, cardiopulmonary exercise tolerance test (CPET) performance, cardiac magnetic resonance imaging (MRI) parameters, and polysomnographic changes before and after 3 months of CPAP therapy. Materials and methods: A total of 34 patients diagnosed with moderate or severe OSA, as well as 17 patients as a control group for the evaluation of the cardiac MRI, were included in this study. All the subjects were obese (body mass index (BMI) > 30 kg/m2). Lung function tests, CPETs, cardiac MRIs, and polysomnography were performed at the time of the study's enrolment before the initiation of the CPAP therapy and after 3 months of the CPAP treatment. Results: The patients' VO2max during the CPAP treatment tended to increase, but no statistical significance was found (before treatment it was 17.52 ± 3.79 mL/kg/min and after 3 months of treatment, it was 18.6 ± 3,4 mL/kg/min; p = 0.255). The CPAP treatment had positive effects on pulmonary ventilation at the anaerobic threshold (VEAT): 44.51 L/min (43.21%) during the baseline visit and 38.60 L/min (37.86%) after the 3-month treatment period (p = 0.028). The ventilator equivalent for the carbon dioxide slope (VE/VCO2) at peak exercise decreased from 23.47 to 20.63 (p = 0.042). The patients' pulmonary function tests were without abnormalities and did not change after treatment. When assessing cardiac the MRIs, the RV ejection fraction was lower in the OSA group compared to that of the control subjects (53.69 ± 8.91 and 61.35 ± 9.08, p = 0.016). Both LA and RA global longitudinal strains (GLS) improved after 3 months of treatment with CPAP (20.45 ± 7.25 and 26.05 ± 14.00, p = 0.043; 21.04 ± 7.14 and 26.18 ± 7.17, p = 0.049, respectively). Additionally, it was found that CPAP therapy led to statistical improvements in RV end-diastolic volume (164.82 ± 32.57 and 180.16 ± 39.09, p = 0.042). The AHI and oxygen desaturation index (ODI) significantly changed after 3 months of the initiation of the CPAP treatment (p = 0.049 and p = 0.001, respectively). The REM sleep duration decreased, while the duration of non-REM sleep increased after treatment initiation with CPAP (p = 0.016 and p = 0.017, respectively). Conclusions: Short-term CPAP treatment improves pulmonary ventilation, sleep efficiency, and sleep architecture. Significant alterations in both atrias' GLS and RV end-diastolic volume were observed after 3 months of treatment. Longer-term follow-up and a larger patient sample are needed to confirm the reproducibility of our results.

Changes in Left Heart Geometry, Function, and Blood Serum Biomarkers in Patients with Obstructive Sleep Apnea after Treatment with Continuous Positive Airway Pressure.

Background: Cardiovascular remodeling is essential in patients with obstructive sleep apnea (OSA), and continuous positive airway pressure (CPAP) therapy could improve these processes. Two-dimensional (2D) speckle-tracking (ST) echocardiography is a useful method for subclinical biventricular dysfunction diagnosis and thus might help as an earlier treatment for OSA patients. It is still not clear which blood serum biomarkers could be used to assess CPAP treatment efficacy. Objectives: To evaluate left heart geometry, function, deformation parameters, and blood serum biomarker (galectin-3, sST2, endothelin-1) levels in patients with OSA, as well as to assess changes after short-term CPAP treatment. Materials and Methods: Thirty-four patients diagnosed with moderate or severe OSA, as well as thirteen patients as a control group, were included in the study. All the subjects were obese (body mass index (BMI) > 30 kg/m2). Transthoracic 2D ST echocardiography was performed before and after 3 months of treatment with CPAP; for the control group, at baseline only. Peripheral blood samples for the testing of biomarkers were collected at the time of study enrolment before the initiation of CPAP therapy and after 3 months of CPAP treatment (blood samples were taken just for OSA group patients). Results: The left ventricle (LV) end-diastolic diameter and volume, as well as LV ejection fraction (EF), did not differ between groups, but an increased LV end-systolic volume and a reduced LV global longitudinal strain (GLS) were found in the OSA group patients (p = 0.015 and p = 0.035, respectively). Indexed by height, higher LV MMi in OSA patients (p = 0.007) and a higher prevalence of LV diastolic dysfunction (p = 0.023) were found in this group of patients. Although left atrium (LA) volume did not differ between groups, OSA group patients had significantly lower LA reservoir strain (p < 0.001). Conventional RV longitudinal and global function parameters (S', fractional area change (FAC)) did not differ between groups; however, RV GLS was reduced in OSA patients (p = 0.026). OSA patients had a significantly higher right atrium (RA) diameter and mean pulmonary artery pressure (PAP) (p < 0.05). Galectin-3 and sST2 concentrations significantly decreased after 3 months of CPAP treatment. Conclusions: OSA is associated with the left heart remodeling process­increased LV myocardial mass index, LV diastolic dysfunction, reduced LV and RV longitudinal strain, and reduced LA reservoir function. A short-term, 3-months CPAP treatment improves LV global longitudinal strain and LA reservoir function and positively affects blood serum biomarkers. This new indexing system for LV myocardial mass by height helps to identify myocardial structural changes in obese patients with OSA.

Diagnostic Yield of Transbronchial Cryobiopsy Guided by Radial Endobronchial Ultrasound and Fluoroscopy in the Radiologically Suspected Lung Cancer: A Single Institution Prospective Study.

Transbronchial cryobiopsy (TBCB) is being studied in the diagnosis of peripheral lung lesions; however, there are only a few clinical studies around the world. The aim of our study was to evaluate the diagnostic values and safety of transbronchial cryobiopsy for radiologically suspected peripheral lung cancer. The prospective clinical study was executed from September 2019 to September 2021 at a tertiary clinical centre in Lithuania. A total of 48 patients out of 102 underwent combined procedures of transbronchial forceps biopsy (TBFB) and TBCB. Diagnostic values and safety outcomes of TBFB and TBCB were analysed. The sensitivity, specificity, positive predictive value (PPV), negative predictive value (NPV) and accuracy were 72.9%, 100%, 100%, 7.7%, and 88.0% for TBFB, 85.1%, 100%, 100%, 12.5%, and 93% for TBCB, as well as 91.5%, 100%, 100%, 20.0% and 96.7% for the combined procedures, respectively, with a significantly higher accuracy for cryobiopsies compared to forceps biopsies (p < 0.05). The diagnostic values for transbronchial cryobiopsies were similar, irrespective of the radial mini probe endobronchial ultrasound (RP-EBUS) position, lesion size or bronchus sign, however, the sensitivity of the combined procedures in cases with RP-EBUS adjacent to the target was significantly higher compared to TBFB (86.2% vs. 64.3%, p = 0.016). Samples of cryobiopsies were significantly larger than forceps biopsies (34.62 mm2 vs. 4.4 mm2, p = 0.001). The cumulative diagnostic yield of transbronchial cryobiopsy was 80.0% after the second biopsy and reached a plateau of 84.1% after four biopsies. No severe bleeding, pneumothorax, respiratory failure or death was registered in our study. TBCB is a potentially safe procedure, which increases diagnostic values in diagnosing peripheral lung lesions compared to TBFB.

Short-Term Continuous Positive Air Pressure Treatment: Effects on Quality of Life and Sleep in Patients with Obstructive Sleep Apnea.

Background and Objectives: The aim of this study was to evaluate short-term continuous positive air pressure (CPAP) treatment for health-related quality of life (HRQL) in patients with obstructive sleep apnea. Materials and Methods: Our subjects were 18−65 years old, diagnosed with moderate-to-severe obstructive sleep apnea and treated with CPAP between January 2020 and June 2021 in Hospital of Lithuanian University of Health Sciences Kaunas clinics. All the patients completed the Epworth Sleepiness Scale (ESS), the 36-Item Short Form Health Survey (SF-36), the and Pittsburgh Sleep Quality Index (PSQI) before and after 3 months of treatment. Polysomnography was also repeated. Statistical analyses were performed using SPSS 27.0 software. The value of p < 0.05 was considered as statistically significant. Results: The active-treatment group comprised 17 subjects with a mean age of 51.9 ± 8.9 years. The total SF-36 questionnaire score improved from 499.8 ± 122.3 to 589.6 ± 124.7 (p = 0.012). The SF-36 role limitations due to emotional problems (p = 0.021), energy (fatigue) (p = 0.035), and general health (p = 0.042) domains score significantly improved after CPAP treatment for 3 months. The PSQI mean score at baseline was 12.6 ± 2.9 and in the post-treatment group, it was −5.5 ± 2.3 (p = 0.001). The ESS also changed significantly from a pretreatment mean score of 10.9 ± 5.7 to −5.3 ± 3.2 (p = 0.002) after 3 months. Conclusions: Improvement in HRQL is seen even after a short treatment period with CPAP. Questionnaires are a good tool to evaluate CPAP treatment efficacy.

Effective Initial Treatment of Diffuse Pulmonary Lymphangiomatosis with Sirolimus and Propranolol: A Case Report.

Diffuse pulmonary lymphangiomatosis (DPL), an exceptionally rare disease, mainly occurs in children and young adults of both sexes. Even though DPL is considered to be a benign disease, its prognosis is relatively poor. Because of its rarity, little guidance on diagnosis and treatment is available, which makes working with patients with DPL challenging for clinicians. We present here a case of a young man with DPL in whom treatment with sirolimus and propranolol rapidly achieved positive radiological and clinical effects.

Is analysis of inflammatory biomarkers and lymphocyte subpopulations useful in prediction of tuberculosis treatment outcomes?

Analysis of inflammatory biomarkers and lymphocytes during the treatment of tuberculosis (TB) could yield findings that influence the routine clinical practice and use of new anti-TB drugs. This study aimed to evaluate whether the selected biomarkers-soluble intercellular adhesion molecule type 1, soluble urokinase-type plasminogen activator receptor (suPAR), and C-reactive protein (CRP)-and T-cell subpopulations are useful for predicting culture conversion, treatment outcomes, and the extent of radiological lesions (calculated using X-ray score) in patients with drug-sensitive pulmonary TB. This study included 62 patients with drug-sensitive pulmonary TB. CRP and suPAR levels significantly decreased after 1 month of treatment. Before treatment initiation, CRP and suPAR levels were significantly higher in patients without culture conversion; however, none of the selected host biomarkers appeared to significantly influence the conversion status or treatment outcomes. Some lymphocyte subpopulations were correlated with X-ray scores before TB treatment initiation, but lung destruction, as determined using X-ray scores, showed the highest correlation with the baseline CRP value. We conclude that selected host biomarkers have a very limited role in predicting TB treatment outcomes and culture conversion and do not appear to be superior to CRP in monitoring TB treatment.

Post COVID-19 Organizing Pneumonia: The Right Time to Interfere.

The COVID-19 pandemic dramatically changed medical care. Healthcare professionals are faced with new issues. Patients who survived COVID-19 have plenty of different continuing symptoms, of which the most common are fatigue and breathlessness. It is not well known how to care for patients with persistent or worsening respiratory symptoms and changes on chest X-ray following COVID-19 pneumonia. In this article, we talk about a subgroup of patients with organizing pneumonia following COVID-19 pneumonia that could be effectively treated with systemic glucocorticoids. It is important that patients with COVID-19 pneumonia be followed-up at least three weeks after diagnosis, in order to recognize early lung damage. We are providing a management algorithm for early diagnosis of lung diseases after COVID-19 pneumonia.

Care of patients with non-small-cell lung cancer stage III - the Central European real-world experience.

Background Management of non-small-cell lung cancer (NSCLC) is affected by regional specificities. The present study aimed at determining diagnostic and therapeutic procedures including outcome of patients with NSCLC stage III in the real-world setting in Central European countries to define areas for improvements. Patients and methods This multicentre, prospective and non-interventional study collected data of patients with NSCLC stage III in a web-based registry and analysed them centrally. Results Between March 2014 and March 2017, patients (n=583) with the following characteristics were entered: 32% females, 7% never-smokers; ECOG performance status (PS) 0, 1, 2 and 3 in 25%, 58%, 12% and 5%, respectively; 21% prior weight loss; 53% squamous carcinoma, 38% adenocarcinoma; 10% EGFR mutations. Staging procedures included chest X-ray (97% of patients), chest CT (96%), PET-CT (27%), brain imaging (20%), bronchoscopy (89%), endobronchial ultrasound (EBUS) (13%) and CT-guided biopsy (9%). Stages IIIA/IIIB were diagnosed in 55%/45% of patients, respectively. N2/N3 nodes were diagnosed in 60%/23% and pathologically confirmed in 29% of patients. Most patients (56%) were treated by combined modalities. Surgery plus chemotherapy was administered to 20%, definitive chemoradiotherapy to 34%, chemotherapy only to 26%, radiotherapy only to 12% and best supportive care (BSC) to 5% of patients. Median survival and progression-free survival times were 16.8 (15.3;18.5) and 11.2 (10.2;12.2) months, respectively. Stage IIIA, female gender, no weight loss, pathological mediastinal lymph node verification, surgery and combined modality therapy were associated with longer survival. Conclusions The real-world study demonstrated a broad heterogeneity in the management o f stage III NSCLC in Central European countries and suggested to increase the rates of PET-CT imaging, brain imaging and invasive mediastinal staging.

Diagnostic Yield of Endobronchial Ultrasound-Guided Transbronchial Needle Aspiration Cytological Smears and Cell Blocks: A Single-Institution Experience.

Background and Objective: Endobronchial ultrasound (EBUS) is a minimally invasive endobronchial technique, which uses ultrasound along with a bronchoscope to visualize the airway wall and structures that are adjacent to it. Indications for endobronchial ultrasound-guided transbronchial needle aspiration (EBUS-TBNA) are samplings of mediastinal, hilar lymph nodes, and tumors adjacent to airway walls. EBUS-TBNA has been used in our clinic since 2009. The aim of the study is to evaluate the sensitivity, specificity, positive and negative predictive value, and diagnostic accuracy of cytological and histological specimens, and the safety of EBUS-TBNA in an unselected patient population that has been referred to our hospital. Materials and Methods: We have retrospectively analyzed the medical documentation of 215 patients who had EBUS-TBNA performed in our clinic from April 2009 to February 2014. Results: There were 215 patients who underwent EBUS-TBNA. A total of 296 lymph nodes were sampled. EBUS-TBNA was diagnostic in 176 (81.9%) cases of cytological, 147 (68.4%) cases of histological, and 191 (88.9%) cases of the combined evaluation. In the lung cancer patients, EBUS-TBNA cytology had a sensitivity of 72.9% and histology of 72.9%, and in the sarcoidosis group, it had a cytology of 55.8% and histology of 64.5%. As all positive cytology and histology specimens were assumed to be true positive, specificity and positive predictive value (PPV) were 100%. The sensitivity and diagnostic accuracy was significantly higher when cytology and histology specimens were combined, compared with cytology or histology results evaluated separately (p < 0.05) (for lung cancer 84.1% and for sarcoidosis 78.8%). The sensitivity and diagnostic accuracy of EBUS-TBNA procedures increased significantly over time, with increased experience. There were no complications with EBUS-TBNA in our clinical practice. Conclusions: EBUS-TBNA had a high diagnostic yield and was safe in the diagnosis of lung cancer and sarcoidosis. It was most informative when cytology and histology were combined. The informative value of EBUS-TBNA histology increased with our experience.

Distribution of M1 and M2 macrophages in tumor islets and stroma in relation to prognosis of non-small cell lung cancer.

BACKGROUND: Non-small cell lung cancer (NSCLC) remains the most common cause of cancer related death worldwide. Tumor-infiltrating macrophages are believed to play an important role in growth, progression, and metastasis of tumors. In NSCLC, the role of macrophages remains controversial; therefore, we aimed to evaluate the distribution of macrophages (M1 and M2) in tumor islets and stroma and to analyze their relations to patients' survival. METHODS: Lung tissue specimens from 80 NSCLC patients who underwent surgical resection for NSCLC (pathological stage I-III) and 16 control group subjects who underwent surgery because of recurrent spontaneous pneumothorax were analyzed. Immunohistochemical double staining of CD68/iNOS (markers for M1 macrophages) and CD68/CD163 (markers for M2 macrophages) was performed and evaluated in a blinded manner. The numbers of M1 and M2 macrophages in tumor islets and stroma were counted manually. RESULTS: Predominant infiltration of M1 and M2 macrophages was observed in the tumor stroma compared with the tumor islets. M2 macrophages predominated over M1 macrophages in the tumor tissue. Tumor islets-infiltrating M1 macrophages and the number of total tumor-infiltrating M2 macrophages were independent predictors of patients survival: high infiltration of M1 macrophages in tumor islets was associated with increased overall survival in NSCLC (P < 0.05); high infiltration of total M2 macrophages in tumor (islets and stroma) was associated with reduced overall survival in NSCLC (P < 0.05). CONCLUSIONS: This study demonstrated that high infiltration of M1 macrophages in the tumor islets and low infiltration of total tumor-infiltrating M2 macrophages were associated with improved NSCLC patients' survival. TRIAL REGISTRATION: ClinicalTrials.gov NCT01955343 , registered on September 27, 2013.

Cisplatin-induced sudden cardiac death with hemodynamic collapse: a severe adverse drug reaction: Case report.

RATIONALE: Cisplatin is responsible for a significant percentage of adverse drug reactions (ADRs) in oncology setting. A great proportion of cisplatin-induced severe adverse events are difficult to foresee, and giving premedication does not always prevent the occurrence of such events. PATIENT CONCERNS: A 53-year-old woman with progressive T4 N0 M0 stage IV pleural mesothelioma experienced cardiac arrest with hemodynamic collapse after cisplatin and pemetrexed chemotherapy administration. DIAGNOSES: Progressive pleural T4 N0 M0 stage IV mesothelioma of the right lung, primary arterial hypertension, and cardiac arrest with hemodynamic collapse. INTERVENTIONS: The cisplatin and pemetrexed chemotherapy was administered intravenously for progressive pleural T4 N0 M0 stage IV mesothelioma of the right lung. During infusion of cisplatin the patient developed cardiac arrest, and cardiopulmonary resuscitation was initiated. OUTCOMES: The patient was treated in intensive care unit and recovered successfully. Further chemotherapy with cisplatin and pemetrexed was withheld due to this severe adverse reaction to cisplatin. LESSONS: Cisplatin therapy should be thoroughly monitored including electrolyte, especially magnesium levels. Absence of previous ADRs to cisplatin and premedication should not give false sense of security.

Factors associated with sputum culture conversion in patients with pulmonary tuberculosis.

OBJECTIVE: The aim of this study was to determine what factors are associated with sputum culture conversion after 1 month of tuberculosis (TB) treatment. MATERIALS AND METHODS: A total of 52 patients with new drug susceptible pulmonary TB were included in the study. Patients completed St. George respiratory questionnaire (SGRQ), they were asked about smoking, alcohol use, living conditions and education. Body mass index (BMI) measurements, laboratory tests (C reactive protein [CRP], vitamin D, albumin) were performed, and chest X-ray was done. After 1 month of treatment sputum culture was repeated. RESULTS: Culture conversion after 1 month of treatment was found in 38.5% cases. None of investigated social factors appeared to have an effect on conversion, but worse overall health status (as reported in SGRQ) and longer duration of tobacco smoking were detected in the "no conversion" group. Concentrations of albumin, CRP, X-ray score and the time it took Mycobacterium tuberculosis culture to grow also differed. Patients who scored 30 or more on SGRQ were more than 7 times as likely to have no conversion. However, the most important factor predicting sputum culture conversion was sputum smear grade at the beginning of treatment: patients with grade of 2+ or more had more than 20-fold higher relative risk for no conversion. Using receiver operating characteristic curve analysis, we also developed a risk score for no conversion. CONCLUSIONS: The most important factors in predicting sputum culture conversion after 1 month of treatment were grades of acid-fast bacilli in sputum smears at time of diagnosis and scores of SGRQ.

Multidrug-resistant tuberculosis in Lithuania - Still a long way ahead.

Despite the recent advances in the diagnosis of tuberculosis, treatment of the disease, for the most part, remains the same as it was half a century ago. In recent years only two new anti-tuberculosis drugs have been approved by the European Medicines Agency and Food and Drug Administration. Though the prevalence of this disease is slowly decreasing all over Europe, new challenges appear. One of them is multidrug-resistant tuberculosis (MDR-TB). This problem is especially prominent in Lithuania, which is one of the 27 high MDR-TB burden countries in the world and falls behind neighboring countries in terms of the prevalence of the disease. The objective of this paper was to review the situation of tuberculosis and MDR-TB in Lithuania, and current available methods of treatment, control and diagnosis of this disease.

Distribution of CD4(+) and CD8(+) T cells in tumor islets and stroma from patients with non-small cell lung cancer in association with COPD and smoking.

BACKGROUND AND OBJECTIVE: The immune system plays an important role in non-small cell lung cancer (NSCLC) and chronic obstructive pulmonary disease (COPD). The aim of this study was to evaluate the infiltration patterns of CD4(+) and CD8(+) T cells in NSCLC and to analyze their relation to COPD, smoking status and other clinicopathologic variables. MATERIALS AND METHODS: Lung tissue specimens from 50 patients who underwent surgery for NSCLC (stages I-III) and 10 control group subjects were analyzed immunohistochemically. RESULTS: NSCLC patients had a greater number of CD4(+) and CD8(+) T cells infiltrating the lung tissue than the control group (P=0.001) with predominant infiltration in the tumor stroma. We found a significant association between the number of total and tumor stroma-infiltrating CD4(+) and CD8(+) T cells, and smoking status (P<0.05). There were more CD8(+) T cells in the tumor stroma and fewer in the tumor islets in NSCLC patients with COPD as compared to NSCLC patients without COPD (P<0.05). However, there was no such association between CD4(+) T cells and COPD status. A high level of CD8(+) T cell infiltration in the tumor stroma was independently associated with the coexistence of COPD in multivariate analysis (P<0.05). CONCLUSIONS: According to our data, COPD but not smoking seems to be associated with higher infiltration of CD8(+) T cells in the tumor stroma of patients with NSCLC. It allows us to hypothesize that NSCLC patients with coexisting COPD may have a more favorable outcome due to anticancer properties of stromal CD8(+) T cells.

The prognostic influence of tumor infiltrating Foxp3(+)CD4(+), CD4(+) and CD8(+) T cells in resected non-small cell lung cancer.

BACKGROUND: Different subsets of tumor infiltrating T lymphocytes are believed to play essential role in the immune response to cancer cells. The data of these cells in NSCLC are relatively rare and controversial therefore we aimed to evaluate the infiltration patterns of Foxp3 + CD4+, CD4+ and CD8+ T cells in NSCLC and to analyze their relations to survival. METHODS: Lung tissue specimens from 80 newly diagnosed and untreated patients who underwent surgery for NSCLC (stages I-III), and 16 control group subjects, who underwent surgery due to recurrent spontaneous pneumothorax, were analyzed. Foxp3 + CD4+, CD4+ and CD8+ T cells in tumor stroma and islets were evaluated immunohistochemically. All statistical analyses were performed using the Statistical Package for the Social Sciences (SPSS), version 20.0. RESULTS: Tumor infiltrating CD4+, CD8+ T cells were associated with neither overall survival nor disease-free survival. The presence of high tumor stroma infiltrating Foxp3 + CD4+ T cells was independently associated with improved NSCLC patients overall survival (P < 0.05). CONCLUSIONS: Our study demonstrated that tumor infiltrating Foxp3 + CD4+ T cells are associated with improved NSCLC patients' survival. In addition our findings highlight a tendency of high CD4+/CD8+ and CD8+/Foxp3 + CD4+ T cells ratio in prolonged NSCLC patients' survival.

Local and systemic neutrophilic inflammation in patients with lung cancer and chronic obstructive pulmonary disease.

BACKGROUND: Recent investigations suggest that neutrophils play an important role in the immune response to lung cancer as well as chronic obstructive pulmonary disease (COPD). The aim of this study was to evaluate the amount of neutrophils and markers of their activity in lung cancer and COPD and in coexistence of these two diseases. METHODS: In total, 267 persons were included in the study: 139 patients with lung cancer, 55 patients with lung cancer and COPD, 40 patients with COPD, and 33 healthy subjects. Peripheral blood and BAL fluid samples were obtained for cell count analysis and determination of NE, MPO levels and ROS production. NE and MPO levels in the serum and BAL fluid were determined by ELISA. ROS production was analyzed by flow cytometer. RESULTS: The percentage, cell count of neutrophils and neutrophil to lymphocyte ratio in the peripheral blood were significantly higher in lung cancer patients with or without COPD compared to COPD patients or healthy individuals (P < 0.05). The percentage and cell count of neutrophils in BAL fluid were significantly lower in patients with lung cancer with or without COPD than in patients with COPD (P < 0.05). However, BAL fluid and serum levels of both NE and MPO were significantly higher in patients with lung cancer than COPD patients or healthy individuals (P < 0.05). Neutrophils produced higher amounts of ROS in patients with lung cancer with or without COPD compared with COPD patients or healthy individuals (P < 0.05). CONCLUSIONS: The results from this study demonstrate higher degree of local and systemic neutrophilic inflammation in patients with lung cancer (with or without COPD) than in patients with COPD.

The role of mutation status of the epidermal growth factor receptor gene in advanced non-small cell lung cancer.

OBJECTIVE: The aim of this study was to examine the prevalence of epidermal growth factor receptor (EGFR) gene mutations among patients with advanced nonsquamous non-small cell lung cancer (NSCLC) treated in our institution and to evaluate the associations between EGFR mutations and clinicopathological characteristics. MATERIALS AND METHODS: A total of 103 patients with NSCLC were examined from April 2010 to September 2011. The patients were screened for EGFR mutations in exons 19 and 21 using sequence analysis. RESULTS: EGFR mutations were detected in 10 patients (9.71%): 23.1% of women and 5.2% of men (P<0.05), 31.8% of never-smokers and 4.7% of smokers (P<0.05), and 12.3% of patients with adenocarcinomas and 6.25% of patients with large cell carcinomas (P>0.05). Eight mutations (80.0%) were found in exon 21: 7 patients had the L858R mutation and 1 patient had the L861G mutation. Two mutations (20.0%) were found in exon 19: 1 patient had the L747-A748 deletion and 1 patient had the L747-A750insE deletion. The overall response rate was significantly greater in the EGFR mutation-positive group than in the EGFR mutation-negative or control groups (P<0.05). The median progression-free survival in the EGFR mutation-negative group and the control group that received systemic standard chemotherapy was 5.6 months (95% CI, 4.3 to 7.0) and 5.3 months (95% CI, 4.9 to 5.7), respectively, but it was not achieved in the EGFR mutation-positive group that received EGFR tyrosine kinase inhibitors (P<0.05). CONCLUSIONS: The frequency of EGFR mutations in our patients with nonsquamous NSCLC was found to be similar to that reported in Europe. EGFR mutations were more frequent in women and never-smokers.

Pseudoaneurysm of brachiocephalic artery mimicking the mediastinal tumor.

58 year-old male admitted to the Hospital of Lithuanian University of Health Sciences due to suspicion of mediastinal tumor for diagnostic endobronchial ultrasound procedure (EBUS). The main patient's complain was progressive dyspnea. Objective investigation revealed no major findings: normal breath sounds, heart rate - 96 bpm, blood pressure - 120/80 mmHg. Chest CT scan showed the mediastinal tumor of 3.8 × 3.5 cm. During bronchoscopy smooth intratracheal nodule of 5 mm was found. Superficial biopsy showed normal airway mucosa. During EBUS procedure no clear lymph node structure or blood flow was detected. It was decided to observe the patient clinically. One month later massive hemoptysis started. Urgent bronchoscopy revealed large right-sided mass and intratracheal wall dislocation due to the possible mediastinal tumor in the same location as the polyp in the previous investigation. Repeated chest CT scan showed increasing tumor of size 4.0 × 3.2 × 4.0 cm in the mediastinum and pseudoaneurysm of brachiocephalic artery was suspected. The diagnosis was later confirmed by aortography. The patient underwent successful aneurysmectomy.