The performance of detecting Mycobacterium tuberculosis complex in lung biopsy tissue by metagenomic next-generation sequencing.

BACKGROUND: Tuberculosis (TB) is a chronic infectious disease caused by the Mycobacterium tuberculosis complex (MTBC), which is the leading cause of death from infectious diseases. The rapid and accurate microbiological detection of the MTBC is crucial for the diagnosis and treatment of TB. Metagenomic next-generation sequencing (mNGS) has been shown to be a promising and satisfying application of detection in infectious diseases. However, relevant research about the difference in MTBC detection by mNGS between bronchoalveolar lavage fluid (BALF) and lung biopsy tissue specimens remains scarce. METHODS: We used mNGS to detect pathogens in BALF and lung biopsy tissue obtained by CT-guide percutaneous lung puncture (CPLP) or radial endobronchial ultrasound transbronchial lung biopsy (R-EBUS-TBLB) from 443 hospitalized patients in mainland China suspected of pulmonary infections between May 1, 2019 and October 31, 2021. Aim to evaluate the diagnostic performance of mNGS for detecting MTBC and explore differences in the microbial composition in the 2 specimen types. RESULTS: Among the 443 patients, 46 patients finally were diagnosed with TB, of which 36 patients were detected as MTBC positive by mNGS (8.93%). Striking differences were noticed in the higher detection efficiency of lung biopsy tissue compared with BALF (P = 0.004). There were no significant differences between the 2 specimen types in the relative abundance among the 27 pathogens detected by mNGS from the 36 patients. CONCLUSIONS: This study demonstrates that mNGS could offer an effective detection method of MTBC in BALF or lung tissue biopsy samples in patients suspected of TB infections. When it comes to the situations that BALF samples have limited value to catch pathogens for special lesion sites or the patients have contraindications to bronchoalveolar lavage (BAL) procedures, lung biopsy tissue is an optional specimen for MTBC detection by mNGS. However, whether lung tissue-mNGS is superior to BALF-mNGS in patients with MTBC infection requires further prospective multicenter randomized controlled studies with more cases.

Neoadjuvant Savolitinib targeted therapy stage IIIA-N2 primary lung adenocarcinoma harboring MET Exon 14 skipping mutation: A case report.

MET exon 14 skipping mutation (METex14m) is rare and occurs in approximately 1-4% of all non-small cell lung cancer (NSCLC) patients and approximately 2.8% of resected stage I-III NSCLC patients. Savolitinib is an oral, potent and highly selective type Ib MET inhibitor, which has been shown to be promising activity and acceptable safety profile in patients with advanced NSCLC harboring METex14m. Most recently, many studies have been probing into the feasibility and efficacy of target therapy for perioperative application in NSCLC. Interestingly, there are very few recorded cases of such treatments. Here, we presented that systemic treatment with the MET inhibitor savolitinib before surgery could provide the potential to prolong overall survival (OS) of patients with locally advanced potentially resectable NSCLC. A 49-year-old woman was diagnosed with stage IIIA (T2bN2M0) primary lung adenocarcinoma exhibiting a METex14m by real-time quantitative polymerase chain reaction (RT-qPCR). Given that the tumor load and the size of lymph nodes experienced a significant downstaging after the neoadjuvant treatment of savolitinib with 600mg once a day for 5 weeks, left lower lobectomy and systemic lymphadenectomy were successfully performed. The pathological response was 50% and the final postoperative pathological staging was pT1cN0M0, IA3 (AJCC, 8th edition). The case provides empirical basis for the neoadjuvant treatment with savolitinib in METex14m-positive locally advanced primary lung adenocarcinoma, which will offer some innovative insights and clinical evidence for more effective clinical treatment of neoadjuvant targeted therapy for METex14m-positive NSCLC.

Comparison of epidermal growth factor receptor mutations between primary tumors and lymph nodes in non-small cell lung cancer: a review and meta-analysis of published data.

BACKGROUND: Epidermal growth factor receptor (EGFR) mutations in non-small cell lung cancer (NSCLC) can predict the clinical response to tyrosine kinase inhibitor (TKI) therapy. However, EGFR mutations may be different in primary tumors (PT) and metastatic lymph nodes (MLN). The aim of this study was to compare EGFR mutations between PT and the corresponding MLN in NSCLC patients, and provide some guidelines for clinical treatment using TKI therapy. MATERIALS AND METHODS: A systematic review and meta-analysis was performed with several research databases. Relative risk (RR) with the 95% confidence interval (CI) were used to investigate the EGFR mutation status between PT and the corresponding MLN. A random-effects model was used. RESULTS: 9 publications involving 707 patients were included in the analysis. It was found that activation of EGFR mutations identified in PT and the corresponding MLN was 26.4% (187/707) and 19.9% (141/707), respectively. The overall discordance rate in our meta-analysis was 12.2% (86/707). The relative risk (RR) for EGFR mutation in PT relative to MLN was 1.33 (95%CI: 1.10-1.60; random-effects model). There was no significant heterogeneity between the studies (I2=5%, p=0.003). CONCLUSIONS: There exists a considerable degree of EGFR mutation discrepancy in NSCLC between PT and corresponding MLN, suggesting that tumor heterogeneity might arise at the molecular level during the process of metastasis.