Observational cross-sectional study of 5279 bronchoscopy results for the practical effectiveness of various biopsy techniques in the diagnosis of lung diseases with particular emphasis on lung cancer.

INTRODUCTION: Bronchoscopy is the main method in the diagnosis of various lung diseases. Endobronchial ultrasound-guided transbronchial needle aspiration (EBUS-TBNA) is the most modern bronchoscopic technique useful in diagnosis and staging of lung cancer (LC). OBJECTIVE: The aim of the study was to assess the yield of bronchoscopy in patients with suspected various respiratory diseases including LC. In particular, we examined the efficiency of different biopsy techniques in the diagnosis of LC in correlation with its localisation and pathomorphological type. PATIENTS AND METHODS: The results of pathomorphological examinations from 5279 bronchoscopies performed in 2016-2018 were analysed. The material was collected with EBUS-TBNA, endoscopic ultrasound-guided fine needle aspiration (EUS-FNA) and endobronchial forceps biopsy. Clinical and demographic factors were analysed using the Fisher χ2 test. RESULTS: 5279 patients were diagnosed due to various respiratory symptoms. LC was confirmed in 36.42% of patients. 40.81% of patients had no definitive pathomorphological diagnosis. Among patients with LC, the most frequent diagnosis was non-small cell LC: squamous cell lung cancer (SCC)-32.07% and adenocarcinoma (AC)-30.61%, then small cell LC-25.83% and not otherwise specified non-small cell lung cancer (NSCLC-NOS)-11.49%. Diagnosis of SCC was obtained significantly more often (χ2=43.143, p<0.000001) by forceps biopsy (41.09%) than by EBUS-TBNA/EUS-FNA (26.62%). On the contrary, diagnosis of AC or NSCLC-NOS was significantly more often (χ2=20.394, p<0.000007, and χ2=3.902, p<0.05, respectively) observed in EBUS-TBNA/EUS-FNA (34.31% and 12.6%) than in endobronchial biopsies (24.52% and 9.64%). CONCLUSIONS: The use of bronchoscopy in the diagnosis of various lung diseases is vital but also has many limitations. Effectiveness of EBUS-TBNA and endobronchial forceps biopsy in the diagnosis of lung cancer is strongly affected by tumour localisation and type of cancer.

Impact of copy number variant and single nucleotide polymorphism of the programmed death-ligand 1 gene, programmed death-ligand 1 protein expression and therapy regimens on overall survival in a large group of Caucasian patients with non-small cell lung carcinoma.

Anti-programmed death-1 or anti-programmed death-ligand 1 (PD-L1) blockade may be ineffective in some patients with non-small cell lung cancer (NSCLC) with high percentage of tumor cells with PD-L1 expression. In addition, immunotherapy may provide great benefits in patients without PD-L1 expression. The present study assessed PD-L1 protein expression by immunohistochemistry, copy number variation (CNV) of PD-L1 and two single nucleotide polymorphisms (SNPs), rs822335 and rs822336, in the promoter of PD-L1 by quantitative PCR in 673 patients with NSCLC. Overall survival time of patients with NSCLC depending on the assessed predictive factors (PD-L1 CNV or SNP) and the treatment methods (immunotherapy in first/second line of treatment or chemotherapy) was analyzed. The present study revealed significantly higher PD-L1 copies number in patients with ≥10% and ≥50% of tumor cells with PD-L1 expression compared to patients with lower percentage of PD-L1-positive tumor cells (P=0.02 and P=0.0002, respectively). There was a significant positive correlation (R=0.2; P=0.01) between number of PD-L1 copies and percentage of tumor cells with PD-L1 protein expression. Percentage of tumor cells with PD-L1 expression was lower in patients with TT genotype of the rs822335 polymorphism compared to those with CC genotype (P=0.03). The present study observed significantly higher risk of death in patients treated with chemotherapy compared to those treated with immunotherapy (P<0.0001; hazard ratio=2.4768; 95% confidence interval, 2.0120-3.0490). The present study demonstrated a close relationship between PD-L1 copies number, genotype of rs822335 PD-L1 polymorphism and PD-L1 protein expression on tumor cells. However, the impact of CNV and SNPs of PD-L1 on overall survival of patients with NSCLC requires further investigation.

Cytology smears as diagnostic material for EGFR gene testing in non-small cell lung cancer.

AIMS AND BACKGROUND: Cytology smears can be effectively used for EGFR mutation testing in the qualification of NSCLC patients for EGFR tyrosine kinase inhibitor therapy. However, tissue specimens are preferred for EGFR mutation analysis. The aim of this study was to estimate the effectiveness of the real-time PCR method for EGFR testing in histology and cytology materials obtained simultaneously from NSCLC patients. METHODS: Fourteen adenocarcinoma patients with EGFR-mutation-positive primary tumor tissues were included in the study. Corresponding cytological smears of metastatic lymph nodes obtained by EBUS-TBNA were examined. EGFR Mutation Analysis Kit (EntroGen, USA) and real-time PCR (m2000rt system, Abbott, USA) were used for EGFR mutation analysis in both types of material. RESULTS: In primary tumor tissues, 12 deletions in exon 19 and 2 substitutions in exon 21 (L858R mutation) of the EGFR gene were found. Except for 1 deletion in exon 19, the same EGFR gene mutations were detected in all corresponding cytology samples. The percentage of tumor cells, DNA concentration, percentage of mutated DNA as well as ΔCt values were similar in cytology slides and histology material. In both types of materials, no significant correlations were found between the percentage of tumor cells and the percentage of mutated DNA nor between the DNA concentration and the percentage of mutated DNA. CONCLUSIONS: We demonstrated the high effectiveness of a sensitive real-time PCR method in EGFR gene mutation detection in cytology smears.

Immunotherapy of lung adenocarcinoma patient with Peptide-pulsed dendritic cells: a case report.

Immunotherapy with ex vivo generated dendritic cells (DCs) is reported to be of low toxicity and of diverse effectiveness in cancer treatment. The synthetic antigens are frequently used for immunotherapy especially for patients with stable disease after prior treatment. We described the effect of peptide-loaded DCs-based immunotherapy on patient with recurrent surgically resected adenocarcinoma with bronchoalveolar feature with co-existing of Takayasu arteritis and chronic hepatitis B. In January 2010, 61-year-old patient received subcutaneously four bi-weekly vaccinations of DCs loaded with MUC1 and MAGE-3 epitopes. Additionally, he received three bi-weekly booster vaccinations after 7 months from the first course of immunotherapy. Delayed-type hypersensitivity test was positive only for MAGE-3 antigen. The evidence expansion of MAGE-3-specific CD8(+) cells after first vaccination and after third vaccination during boosters injections was observed (from 0.08% before vaccination to 0.5% after first vaccination; from 0.05% before booster vaccination to 0.24% after third injection). Computed tomography scans performed after first course and after booster course of vaccination until April 2011 did not shown any presence of lung tumour or metastases. Based on clinical factors (no completed wedge-resection and recurrent character of cancer) as well as on the presence of the tumour-antigen-specific immunological response, we could speculated that immunotherapy prolonged disease free-survival in our patient. Over 16 months from first vaccination, the patient remains without symptoms of cancer.

[Effect of topotecan as a second line treatment in small cell lung cancer patients. Preliminary report]. / Ocena wartosci topotekanu w drugiej linii leczenia drobnokomórkowego raka ptuca. Doniesienie wstepne.

INTRODUCTION: Small cell lung cancer (SCLC) is an aggressive malignancy with high propensity for early regional and distant metastases. Response rate to first-line chemotherapy is high but typically short-therm. All patients with extensive disease and majority with limited disease have recurrence of disease. The choice of second-line chemotherapy in case of progression depends on many factors, including type of first-line chemotherapy, response to treatment, progression-free survival and patients' performance status. No standard second-line treatment has been established until recently. Monotherapy with topotecan is widely used in second-line treatment especially in patients in poor performance status. MATERIAL AND METHODS: The aim of the study was to evaluate the results of monotherapy with topotecan. We also determined the predictive markers which could affect the therapeutic effect of topotecan. The examined group consisted of 42 patients with extensive stage of SCLC. Cox regression model was used to establish adverse factors, which were prognostic for overall survival of our patients divided into two groups according to administrated chemotherapy: 21 topotecan-treated and 21 standard chemotherapy-treated. Six variables that gave a maximum hazard ratio (HR) were used in the final model, e.g.: the age above 65 (HR = 2.35), anemia (HR = 1.83) and poor performance status (HR = 1.51). These variables scored the points according to their prognostic significance and HR. RESULTS: In Kaplan-Meier analysis, in the group of patients treated with topotecan, the higher survival probability was noted for patients scored below 10 points than for patients scored above 10 points. The prognostic scale was not useful for patients with other scheme of chemotherapy. Five partial responses (24%) in topotecan-treated patients were noted. CONCLUSIONS: Precise qualification of patients to topotecan monotherapy in second-line treatment may be effective to prolong survival and increase the percentage of SCLC patients with objective response.

Blood myeloid and lymphoid dendritic cells reflect Th1/Th2 balance in sarcoidosis and extrinsic allergic alveolitis.

Dendritic cells play a specific regulatory role in the immune system. In this paper, the significance of myeloid and lymphoid dendritic cells in sarcoidosis and extrinsic allergic alveolitis (EAA) was evaluated. Myeloid dendritic cells are connected with Th1 type of immunological response, whereas lymphoid ones--with Th2 type. The latest findings indicate that both diseases are characterized by serious disturbances of Th1/Th2 response to Th1 dominance. Our studies seem to confirm these suggestions. In the peripheral blood of patients with sarcoidosis as well as with EAA, myeloid dendritic cells outnumbered lymphoid ones.