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Background: The treatment of pulmonary malignancies remains a challenge. The efficacy and safety of bronchoscopic radiofrequency ablation (RFA) for the treatment of lung cancer are not well elucidated. Objective: This study aimed to evaluate the feasibility and safety of RFA guided by bronchoscopic transparenchymal nodule access (BTPNA) in vivo. Methods: In an attempt to determine the parameters of RFA, we first performed RFA in conjunction with automatic saline microperfusion in the lung in vitro with various ablation energy (10, 15, 20, 25, and 30 W) and ablation times (3, 5, 8, and 10 min). The correlation between ablated area and RFA parameter was recorded and analyzed. Further, we conducted a canine study with RFA by BTPNA in vivo, observing the ablation effect and morphological changes in the lung assessed by chest CT and histopathologic examination at various follow-up time points (1 day, n = 3; 30 days, n = 4; 90 days, n = 4). The related complications were also observed and recorded. Results: More ablation energy, but not ablation time, induced a greater range of ablation area in the lung. Ablation energy applied with 15 W for 3 min served as the appropriate setting for pulmonary lesions ≤1 cm. RFA guided by BTPNA was performed in 11 canines with 100% success rate. Inflammation, congestion, and coagulation necrosis were observed after ablation, which could be repaired within 7 days; subsequently, granulation and fibrotic scar tissue developed after 30 days. No procedure-related complication occurred during the operation or in the follow-up periods. Conclusion: The novel RFA system and catheter in conjunction with automatic saline microperfusion present a safe and feasible modality in pulmonary parenchyma. RFA guided by BTPNA appears to be well established with an acceptable tolerance; it might further provide therapeutic benefit in pulmonary malignancies. [ABSTRACT FROM AUTHOR]

Monosubsegmentectomy (MSS) involves removal of less lung parenchyma than monosegmentectomy (MS) does. However, the clinical efficacy of MSS in lung cancer treatment remains unclear, with concerns regarding insufficient surgical margins and increased complications. Between February 2015 and December 2019, patients who underwent thoracoscopic MSS (n = 126) or MS (n = 678) for small ground-glass opacity (GGO) dominant lung cancer were examined. The primary endpoints were the procedure success rate (defined as resection with a surgical margin ≥2 cm or tumor size) and surgical margin. There were no significant differences in age, sex, smoking history, or comorbidities between the groups. Both groups achieved a success rate of 100%. No significant group differences were observed in the number of lymph nodes removed (p = 0.060), overall complications (p = 0.147), or major complications (p = 0.450). The MSS group had a smaller surgical margin (median, 17 vs. 21mm, p < 0.001) and longer operative time (median, 138 vs. 130 min, p = 0.005) than the MS group did. Propensity score-matched analysis of 122 pairs of patients revealed consistent results. Surgical margins were further compared based on the number of resected subsegments. The 1 subsegment group had the smallest median surgical margin, followed by the 2 and 3 subsegments groups (17, 20, and 23 mm, p < 0.001). Thoracoscopic MSS is an acceptable option for treating patients with small-sized GGO-dominant lung cancer. However, the close surgical margins and prolonged operative time should be considered. • The procedure success and postoperative complication rates of thoracoscopic monosubsegmentectomy were comparable to those of thoracoscopic monosegmentectomy. • Monosubsegmentectomy was associated with significantly smaller surgical margins compared to monosegmentectomy. • Relative to thoracoscopic monosegmentectomy, thoracoscopic monosubsegmentectomy may be more technically demanding. [ABSTRACT FROM AUTHOR]

Background: The present study analyzed the relationship between clinical features and the T790M mutation in non-small cell lung cancer (NSCLC) patients resistant to epidermal growth factor receptor tyrosine kinase inhibitors (EGFR-TKIs) treatment. Methods: NSCLC patients with resistance to first-generation EGFR-TKIs in which the disease control time was more than 6 months after initial TKI treatment were enrolled. T790M mutation analysis was performed using one of the following methods according to each manufacturer's protocols: Cobas EGFR mutation test (41/105, 39.0%), digital PCR (42/105, 40.0%) or Scorpion amplification refractory mutation system (ARMS) (22/105, 21.0%). Sample type of T790M was from tissue only (53/105, 50.5%), plasma only (46/105, 43.8%), tissue and plasma (6/105, 5.7%). Results: Of 105 patients, 57 were T790M-positive and 48 were T790M-negative. T790M-positive patients had longer progression-free survival (PFS) after initial EGFR-TKI treatment (p = 0.019). T790M positivity was more frequent in patients treated with gefitinib than in those treated with icotinib (65% vs 40.54%, p = 0.018). The rate of T790M positivity was lower in patients with EGFR L858R (44.44%, 12/27) before TKI treatment than in those with EGFR 19del (72.0%, 36/50, p = 0.036). Patients who achieved PR after initial EGFR-TKI treatment had a higher rate of T790M positivity than those with SD (75.76% vs 50%, p = 0.023). There was no relationship between T790M status and age, gender, primary site, metastasis site, or treatment before TKI. Conclusion: Progression-free survival (PFS), drug type, response to initial EGFR-TKI treatment, and EGFR status before initial EGFR treatment were associated with the frequency of T790M mutation. [ABSTRACT FROM AUTHOR]

Background: The relationships between coagulation factors and non‐small cell lung cancer (NSCLC) prognosis have been intensively studied. However, no previous study has investigated the combined effects of preoperative platelet (PLT), fibrinogen (FIB), and D‐dimer (D‐D) levels on the prognosis of NSCLC. Methods: A multicenter prospective study was conducted over seven hospitals. A total of 395 patients diagnosed with operable NSCLC for the first time were included and followed‐up until disease progression or the end of the study. Baseline demographic and clinicopathological information, and preoperative coagulation test results were collected for each patient. Univariate and multilevel survival analyses were conducted using Cox regression and shared frailty models. Results: Multilevel analyses revealed that there was a marginally significant association between elevated PLT level (> 215 × 109/L) and unfavorable progression‐free survival (PFS) (hazard ratio 2.42, P = 0.05), whereas preoperative FIB and D‐D were not significant prognostic factors for PFS (P = 0.31 and 0.30, respectively). Compared to patients with one elevation of the three coagulation factors, patients with at least two elevations of the three factors had a significantly higher risk of cancer progression (hazard ratio 4.62, P = 0.02). Conclusion: The number of elevated preoperative coagulation factors may have a significant effect on PFS and could be used to predict the prognosis of NSCLC patients after surgery. Future studies are warranted to further investigate the interactions between these three coagulation factors. [ABSTRACT FROM AUTHOR]

Whether segmentectomy could yield similar oncological outcomes with lobectomy for cT1a-bN0M0 non-small cell lung cancer (NSCLC) in the deep lung parenchyma remained unclear. This study aimed to compare the long-term prognosis of segmentectomy and lobectomy for deep NSCLC. We retrospectively screened cT1a-bN0M0 NSCLC patients who underwent segmentectomy or lobectomy between 2012 and 2019. The 3D multiplanar reconstruction software was used to determine the tumor location. Log-rank test, Cox hazard proportional regression, and propensity score matching analyses were adopted for prognostic evaluation. In total, 321 patients with segmentectomy and 239 subjects undergoing lobectomy with a median follow-up time of 48.2 months remained. All the patients had a R0 resection, and no 30-day or 90-day mortality was observed. The 5-year overall survival and disease-free survival were 99.0% and 96.6% for patients undergoing segmentectomy. No significant survival differences existed between segmentectomy and lobectomy after adjusting other factors (disease-free survival, DFS: HR = 1.20, 95%CI: 0.49–2.99, P = 0.688; overall survival, OS: HR = 1.09, 95%CI: 0.30–3.95, P = 0.892). After propensity score matching, patients with segmentectomy (n = 128) had a similar OS (P = 0.870) and DFS (P = 0.900) with those receiving lobectomy (n = 128). To further evaluate the outcomes of segmentectomy for deep lung cancer, 557 peripheral lung cancer patients who underwent segmentectomy at the same period were taken as the reference. As expected, segmentectomy for deep lesions achieved equivalent OS (P = 0.610) and DFS (P = 0.580) with the peripheral lesions. Segmentectomy could achieve comparable long-term outcomes with lobectomy for deep cT1a-bN0M0 NSCLC with careful preoperative design and 3D navigation. [ABSTRACT FROM AUTHOR]

This paper analyzed the results of a modified and simpler technique for distinguishing the intersegmental border during lung segmentectomy surgery. From January 2013 to December 2015, 539 patients with screening‐detected lung nodules <2 cm in maximum diameter underwent anatomic segmentectomy. With the guidance of preoperative three‐dimensional computed tomography bronchography and angiography, the bronchus, artery, and intrasegmental vein of the targeted segment could be precisely dissected under unilateral differential ventilation, and then intersegmental demarcation was confirmed by the modified inflation‐deflation method. The demarcation presented by this method was highly coincident with the real intersegmental border. Dissection along the border between the collapsed and inflated segments using either electrocautery or staples was safe, with almost no air leak or bleeding. This technique is a simple and effective alternative to previously described intersegmental border marking methods. [ABSTRACT FROM AUTHOR]

Segmentectomy is a widely adopted surgical procedure, however, experiences of tailoring the intersegmental border have rarely been reported. This paper investigates the strategy and results of tailoring complex demarcation during lung segmentectomy surgery. Because intersegmental demarcation can be divided into plane or curved types according to the location and stereo shape of a segment, a one‐size‐fits‐all method for tailoring the intersegmental demarcation is obviously unreasonable. For tailoring a complex segmentectomy with two or more curved borders, tips including good exposure of the intersegmental demarcation, sharp‐blunt combined dissection skill, "work‐plane" extension, and "gate" opening techniques all contribute to an accurate segmentectomy. This technique, based on anatomical characteristics, can provide a cutting surface with a greater physiological shape and less curling of the edge, and should be recommended as a general standard method for tailoring complex demarcation. [ABSTRACT FROM AUTHOR]

Tumor survival is significantly correlated with the immune response of patients. IFNG plays an important role in the tumor host response and decreased IFNG expression is often observed in lung cancer. Studies have shown that CpG island hypermethylation plays a critical role in transcriptional silencing of IFNG gene expression. However, there is limited understanding regarding the molecular mechanisms of altered methylation, and whether the tumor microenvironment has any effect on DNA methylation and IFNG production. In the current study, we demonstrate that plasma and intra-cellular IFNG levels are significantly lower in lung cancer patients. Hypermethylation of the IFNG promoter in CD4+ T cells and plasma IFNG was negatively correlated. CD4+ T cells from healthy individuals co-cultured with SPC-A1 cells generated lower levels of IFNG after activation, elevated expression of DNA methyltransferases (DNMTs), and exhibited hypermethylation of the IFNG promoter. In conclusion, decreased IFNG expression of CD4+ T cells co-cultured with lung cancer cell is associated with IFNG promoter hypermethylation. Our study suggests that interaction between lung cancer cells and CD4+ T cells induces DNMT expression and IFNG promoter hypermethylation in CD4+ T cell, which may serve as an important mechanism of tumor-induced immunosuppression. [ABSTRACT FROM AUTHOR]