MAIT cells are associated with responsiveness to neoadjuvant immunotherapy in COPD-associated NSCLC.

BACKGROUND: Patients with non-small cell lung cancer (NSCLC) and chronic obstructive pulmonary disease (COPD) experience worse clinical outcomes but respond better to immunotherapy than patients with NSCLC without COPD. Mucosal-associated invariant T (MAIT) cells, a versatile population of innate immune T lymphocytes, have a crucial function in the response to infection and tumors. This study investigated the distribution of MAIT cells in COPD-associated NSCLC and their involvement in the immune response. METHODS: Flow cytometry, immunohistochemistry, and immunofluorescence were performed on tissue samples of patients with NSCLC, with or without COPD, treated with or without anti-programmed death 1 (PD1) immunotherapy. MAIT cells were stimulated with 5-OP-RU using a mouse subcutaneous tumor model. RESULTS: Tumors contained significantly more MAIT cells than paraneoplastic tissues, and CD8+ MAIT cells accounted for more than 90% of these cells. Patients with NSCLC and COPD had higher CD8+ MAIT cell counts than those with NSCLC without COPD. Additionally, patients with NSCLC and COPD displayed reduced expression of the activation marker, CD69, and functional markers, granzyme B (GZMB) and interferon γ (IFNγ), and higher expression of the immune exhaustion marker, PD1. Among patients who received immunotherapy, the proportion with a complete or partial response was higher in those with COPD than in those without COPD. In patients with NSCLC and COPD, the major pathologic response (MPR) group had higher MAIT levels than those in the no major pathologic response (NPR) group. In the mouse subcutaneous tumor model stimulation of MAIT cells using 5-OP-RU enhanced the antitumor effects of anti-PD1. CONCLUSIONS: In patients with NSCLC and COPD, response to immunotherapy is associated with accumulation of CD8+ MAIT cells showing immune exhaustion. These findings may contribute to innovative approaches for immunotherapy targeting CD8+ MAIT cells.

Pulmonary Function Recovery and Displacement Patterns After Anatomic Segmentectomy vs Lobectomy.

BACKGROUND: The functional benefit of segmentectomy compared with lobectomy remains controversial. This ambispective study characterizes the changes in pulmonary function as correlated to displacement patterns of residual lung after segmentectomies vs lobectomies. METHODS: Patients with normal preoperative pulmonary function and undergoing segmentectomy or lobectomy between 2017 and 2021 were considered. Pulmonary function testing was scheduled preoperatively and at least 3 months postoperatively. Differences in the proportions of the median forced expiratory volume in 1 second (FEV1) reduction between segmentectomy and lobectomy were calculated. Covariance analysis was used to estimate the adjusted postoperative FEV1 (apoFEV1) and compare the difference value (DV) in apoFEV1 between segmentectomy and lobectomy. RESULTS: The study enrolled 634 patients (334 lobectomies and 300 segmentectomies). Median difference in the proportions of the FEV1 reduction between segmentectomy and lobectomy was 4.58%, with maximal difference observed in right S6 (9.08%) and minimal difference in left S1+2+3 (2.80%). For resections involving the upper lobe, apoFEV1 was significantly higher after segmentectomy than after lobectomy (DV, 0.15-0.22 L), except for left S3 and S1+2+3 segmentectomies (DV, 0.08 L and 0.06 L, respectively). Compared with a lower lobe lobectomy, S6 segmentectomy conferred a higher apoFEV1, whereas S7+8 and S9+10 had a similar apoFEV1 (DV, 0.16-0.18 L, 0.07 L, and 0.00-0.06 L, respectively). Functional recovery after segmentectomy was associated with the number of intersegment planes (P < .01) and the presence of an adjacent nonoperated on lobe (P = .03). CONCLUSIONS: Basilar and left S3 segmentectomies did not preserve more pulmonary function compared with their corresponding lobectomies, possibly due to the presence of multiple intersegmental resection planes.

Surgical strategies for benign acquired tracheoesophageal fistula.

OBJECTIVES: Tracheoesophageal fistula (TEF) is characterized by abnormal connectivity between the posterior wall of the trachea or bronchus and the adjacent anterior wall of the oesophagus. Benign TEF can result in serious complications; however, there is currently no uniform standard to determine the appropriate surgical approach for repairing TEF. METHODS: The PubMed database was used to search English literature associated with TEF from 1975 to October 2023. We employed Boolean operators and relevant keywords: 'tracheoesophageal fistula', 'tracheal resection', 'fistula suture', 'fistula repair', 'fistula closure', 'flap', 'patch', 'bioabsorbable material', 'bioprosthetic material', 'acellular dermal matrix', 'AlloDerm', 'double patch', 'oesophageal exclusion', 'oesophageal diversion' to search literature. The evidence level of the literature was assessed based on the GRADE classification. RESULTS: Nutritional support, no severe pulmonary infection and weaning from mechanical ventilation were the 3 determinants for timing of operation. TEFs were classified into 3 levels: small TEF (<1 cm), moderate TEF (≥1 but <5 cm) and large TEF (≥5 cm). Fistula repair or tracheal segmental resection was used for the small TEF with normal tracheal status. If the anastomosis cannot be finished directly after tracheal segmental resection, special types of tracheal resection, such as slide tracheoplasty, oblique resection and reconstruction, and autologous tissue flaps were preferred depending upon the site and size of the fistula. Oesophageal exclusion was applicable to refractory TEF or patients with poor conditions. CONCLUSIONS: The review primarily summarizes the main surgical techniques employed to repair various acquired TEF, to provide references that may contribute to the treatment of TEF.

Proteogenomic characterization of small cell lung cancer identifies biological insights and subtype-specific therapeutic strategies.

We performed comprehensive proteogenomic characterization of small cell lung cancer (SCLC) using paired tumors and adjacent lung tissues from 112 treatment-naive patients who underwent surgical resection. Integrated multi-omics analysis illustrated cancer biology downstream of genetic aberrations and highlighted oncogenic roles of FAT1 mutation, RB1 deletion, and chromosome 5q loss. Two prognostic biomarkers, HMGB3 and CASP10, were identified. Overexpression of HMGB3 promoted SCLC cell migration via transcriptional regulation of cell junction-related genes. Immune landscape characterization revealed an association between ZFHX3 mutation and high immune infiltration and underscored a potential immunosuppressive role of elevated DNA damage response activity via inhibition of the cGAS-STING pathway. Multi-omics clustering identified four subtypes with subtype-specific therapeutic vulnerabilities. Cell line and patient-derived xenograft-based drug tests validated the specific therapeutic responses predicted by multi-omics subtyping. This study provides a valuable resource as well as insights to better understand SCLC biology and improve clinical practice.

Surgery for bronchiectasis-destroyed lung: feasibility of video-assisted thoracoscopic surgery, and surgical outcomes.

OBJECTIVES: To provide the experience of surgical treatment for bronchiectasis-destroyed lung (BDL) and evaluate the feasibility of video-assisted thoracoscopic surgery (VATS). METHODS: BDL patients underwent surgical treatment between January 2013 and June 2018 were included. Logistic regression was performed to assess factors for major complications, and Cox's regression was performed to assess factors affected symptomatic outcome. RESULTS: Totally, 143 patients were treated by VATS (n = 64) and thoracotomy (n = 79). Nine (14.1%) cases scheduled for VATS were converted to thoracotomy for dense adhesions (n = 6) and frozen hilum (n = 3). The VATS group had a median chest tube duration, hospitalization and a time of returning to full activity of 4 days, 5 days and 1.5 months, respectively. Major complications occurred in 28 (19.6%) of all patients, 50.0% after pneumonectomy and 13.4% after lobectomy/extensive lobectomy. Multivariable analysis identified pneumonectomy [odds ratio, 3.64; 95% confidence interval (CI), 1.18-11.21] as a significant predictor for major complications. Overall, 141 (98.6%) patients benefitted from surgery (completely asymptomatic, n = 109; acceptable alleviation, n = 32). Thirty-four patients experienced relapse of the disease, including 13 with productive cough, 11 with haemoptysis and 10 with recurrent infections. Pseudomonas aeruginosa infection [hazard ratio (HR), 3.07; 95% CI, 1.38-6.83] and extent of remanent bronchiectatic areas (HR, 1.03; 95% CI, 1.00-1.05) were independent risk factors for shorter relapse free interval. CONCLUSIONS: VATS for BDL is feasible in well-selected patients. Pneumonectomy increased the risk of postoperative major complications. Removing all BDL lesions contributed to satisfactory prognosis.

Recurrence prediction of lung adenocarcinoma using an immune gene expression and clinical data trained and validated support vector machine classifier.

Background: Immune microenvironment plays a critical role in cancer from onset to relapse. Machine learning (ML) algorithm can facilitate the analysis of lab and clinical data to predict lung cancer recurrence. Prompt detection and intervention are crucial for long-term survival in lung cancer relapse. Our study aimed to evaluate the clinical and genomic prognosticators for lung cancer recurrence by comparing the predictive accuracy of four ML models. Methods: A total of 41 early-stage lung cancer patients who underwent surgery between June 2007 and October 2014 at New York University Langone Medical Center were included (with recurrence, n=16; without recurrence, n=25). All patients had tumor tissue and buffy coat collected at the time of resection. The CIBERSORT algorithm quantified tumor-infiltrating immune cells (TIICs). Protein-protein interaction (PPI) network and Kyoto Encyclopedia of Genes and Genomes (KEGG) pathway analysis were conducted to unearth potential molecular drivers of tumor progression. The data was split into training (75%) and validation sets (25%). Ensemble linear kernel support vector machine (SVM) ML models were developed using optimized clinical and genomic features to predict tumor recurrence. Results: Activated natural killer (NK) cells, M0 macrophages, and M1 macrophages showed a positive correlation with progression. Conversely, T CD4+ memory resting cells were negatively correlated. In the PPI network, TNF and IL6 emerged as prominent hub genes. Prediction models integrating clinicopathological prognostic factors, tumor gene expression (45 genes), and buffy coat gene expression (47 genes) yielded varying receiver operating characteristic (ROC)-area under the curves (AUCs): 62.7%, 65.4%, and 59.7% in the training set, 58.3%, 83.3%, and 75.0% in the validation set, respectively. Notably, merging gene expression with clinical data in a linear SVM model led to a significant accuracy boost, with an AUC of 92.0% in training and 91.7% in validation. Conclusions: Using ML algorithm, immune gene expression data from tumor tissue and buffy coat may enhance the precision of lung cancer recurrence prediction.

Use of an autologous dermal flap and rib cartilage graft in the repair of a large tracheoesophageal fistula with tracheal stenosis.

Management of large tracheoesophageal fistulas complicated by tracheal stenosis remains challenging as it requires an ideal replacement for the membranous defect as well as a permanent buttress to reconstruct the stenotic segment. We present the successful use of an autologous free dermal flap reinforced with a pedicled pectoralis major muscle to repair the tracheal membranous wall and a rib cartilage graft to enlarge the tracheal lumen.

Neoadjuvant Afatinib for stage III EGFR-mutant non-small cell lung cancer: a phase II study.

Afatinib, an irreversible ErbB-family blocker, could improve the survival of advanced epidermal growth factor receptor (EGFR)-mutant non-small cell lung cancer patients (NSCLCm+). This phase II trial (NCT04201756) aimed to assess the feasibility of neoadjuvant Afatinib treatment for stage III NSCLCm+. Forty-seven patients received neoadjuvant Afatinib treatment (40 mg daily). The primary endpoint was objective response rate (ORR). Secondary endpoints included pathological complete response (pCR) rate, pathological downstaging rate, margin-free resection (R0) rate, event-free survival, disease-free survival, progression-free survival, overall survival, treatment-related adverse events (TRAEs). The ORR was 70.2% (95% CI: 56.5% to 84.0%), meeting the pre-specified endpoint. The major pathological response (MPR), pCR, pathological downstaging, and R0 rates were 9.1%, 3.0%, 57.6%, and 87.9%, respectively. The median survivals were not reached. The most common TRAEs were diarrhea (78.7%) and rash (78.7%). Only three patients experienced grade 3/4 TRAEs. Biomarker analysis and tumor microenvironment dynamics by bulk RNA sequencing were included as predefined exploratory endpoints. CISH expression was a promising marker for Afatinib response (AUC = 0.918). In responders, compared to baseline samples, increasing T-cell- and B-cell-related features were observed in post-treatment tumor and lymph-node samples, respectively. Neoadjuvant Afatinib is feasible for stage III NSCLC+ patients and leads to dynamic changes in the tumor microenvironment.

Prognostic factors and role of postoperative radiotherapy in surgically resected thymomas.

Objective: To investigate the prognostic factors in and role of postoperative radiotherapy (PORT) for surgically resected thymomas. Methods: A total of 1540 patients with pathologically confirmed thymomas undergoing resection between 2000 and 2018 were identified retrospectively from the SEER (Surveillance, Epidemiology, and End Results) database. Tumors were restaged as local (limited to thymus), regional (invasion to mediastinal fat and other neighboring structures), or distant stage. Disease-specific survival (DSS) and overall survival (OS) were estimated by the Kaplan-Meier method and the log-rank test. Adjusted hazard ratios (HRs) with 95% CIs were calculated by Cox proportional hazards modeling. Results: Tumor stage and histology were independent predictors of both DSS (regional: HR, 3.711; 95% CI, 2.006-6.864; distant: HR, 7.920; 95% CI, 4.061-15.446; type B2/B3: HR, 1.435; 95% CI, 1.008-2.044) and OS (regional: HR, 1.461; 95% CI, 1.139-1.875; distant: HR, 2.551; 95% CI, 1.855-3.509; type B2/B3: HR, 1.409; 95% CI, 1.153-1.723). For patients with regional stage and type B2/B3 thymomas, PORT was associated with better DSS after thymectomy/thymomectomy (HR, 0.268; 95% CI, 0.099-0.727), but the association was not significant after extended thymectomy (HR, 1.514; 95% CI, 0.516-4.44). Among patients with lymph node metastases, those who received PORT (HR, 0.372; 95% CI, 0.146-0.949), chemotherapy (HR, 0.843; 95% CI, 0.303-2.346), or both (HR, 0.296, 95% CI, 0.071-1.236) had a better OS. Conclusions: The extent of invasion and tumor histology were independent predictors of worse survival following surgical resection of thymoma. Patients with regional invasion and type B2/B3 thymoma who undergo thymectomy/thymomectomy may benefit from PORT, while patients with nodal metastases may benefit from multimodal therapy, including PORT and chemotherapy.

Multiparametric MRI for evaluation of pathological response to the neoadjuvant chemo-immunotherapy in resectable non-small-cell lung cancer.

OBJECTIVES: This study aimed to explore the predictive value of intravoxel incoherent motion diffusion-weighted imaging (IVIM-DWI) and diffusion kurtosis imaging (DKI) quantitative parameters for the response to neoadjuvant chemo-immunotherapy (NCIT) in resectable non-small-cell lung cancer (NSCLC) patients, so as to provide a basis for clinical individualized precision treatment. METHODS: Treatment naive locally advanced NSCLC patients who enrolled in 3 prospective, open-label, and single-arm clinical trials and received NCIT were retrospectively analyzed in this study. Functional MRI imaging was performed at baseline and following 3 weeks of treatment as an exploratory endpoint to evaluate treatment efficacy. Univariate and multivariate logistic regressions were used to identify independent predictive parameters for NCIT response. Prediction models were built with statistically significant quantitative parameters and their combinations. RESULTS: In total of 32 patients, 13 were classified as complete pathological response (pCR) and 19 were non-pCR. Post-NCIT ADC, ΔADC, and ΔD values in the pCR group were significantly higher than those in the non-pCR group, while the pre-NCIT D, post-NCIT Kapp, and ΔKapp were significantly lower than those in non-pCR group. Multivariate logistic regression analysis demonstrated that pre-NCIT D and post-NCIT Kapp values were independent predictors for NCIT response. The combined predictive model, which consisted of IVIM-DWI and DKI, showed the best prediction performance with AUC of 0.889. CONCLUSIONS: The pre-NCIT D, post-NCIT parameters (ADC and Kapp) and Δ parameters (ΔADC, ΔD, and ΔKapp) were effective biomarkers for predicting pathologic response, and pre-NCIT D and post-NCIT Kapp values were independent predictors of NCIT response for NSCLC patients. CLINICAL RELEVANCE STATEMENT: This exploratory study indicated that IVIM-DWI and DKI MRI imaging would predict pathologic response of neoadjuvant chemo-immunotherapy in locally advanced NSCLC patients at initial state and early treatment, which could help make clinical individualized treatment strategies. KEY POINTS: • Effective NCIT treatment resulted in increased ADC and D values for NSCLC patients. • The residual tumors in non-pCR group tend to have higher microstructural complexity and heterogeneity, as measured by Kapp. • Pre-NCIT D and post-NCIT Kapp values were independent predictors of NCIT response.

The Prognostic Impact of Epidermal Growth Factor Receptor Mutation in Clinical Stage I Lung Adenocarcinoma.

BACKGROUND: This study investigated the prognostic impact of epidermal growth factor receptor (EGFR) mutation in clinical stage I lung adenocarcinoma patients. METHODS: Data for 952 patients who received surgical resection and underwent detection of oncogenic driver mutations were retrospectively collected. Recurrence-free survival (RFS) and overall survival (OS) were estimated by the Kaplan-Meier method and compared using the log-rank test. The adjusted hazard ratio (aHR) with 95% CI of the prognosticator was calculated by Cox proportional hazards model, and cumulative incidence function was measured by competing risk regression model. RESULTS: EGFR mutation was detected in 581 patients (61.0%) and was more frequent in women (63.9%), nonsmokers (85.5%), and those with ground-glass nodules (GGNs; 56.6%). EGFR mutation was not associated with recurrence and death in the entire cohort or GGN cohort. However, for patients with radiologic pure-solid appearance, EGFR mutation was an independent risk factor for RFS (aHR, 1.623; 95% CI, 1.192-2.210) and distant recurrence (aHR, 1.863; 95% CI, 1.311-2.650), but not OS. Subsequently, subgroup analysis based on EGFR mutation subtypes, including exon 19 deletions (19-Del), exon 21 L858R substitution (L858R), and rare mutations in patients with radiologic pure-solid appearance, revealed that all 3 subtypes have poorer RFS (19-Del: aHR, 1.424; 95% CI, 0.991-2.047; L858R: aHR, 1.708; 95% CI, 1.172-2.490; rare mutations: aHR, 2.500; 95% CI, 1.400-4.465) and higher prevalent distant recurrence (19-Del: aHR, 1.595; 95% CI, 1.061-2.400; L858R: aHR, 2.073; 95% CI, 1.371-3.140; rare mutations: aHR, 2.657; 95% CI, 1.397-5.050) compared with wild-type. CONCLUSIONS: In clinical stage I lung adenocarcinoma, EGFR mutation was associated with worse RFS and higher prevalent distant recurrence in patients with radiologic pure-solid appearance but not in patients with GGN.

Rivaroxaban versus nadroparin for thromboprophylaxis following thoracic surgery for lung cancer: A randomized, noninferiority trial.

The benefit of rivaroxaban in thromboprophylaxis after oncologic lung surgery remains unknown. To evaluate the efficacy and safety of rivaroxaban, patients who underwent thoracic surgery for lung cancer were enrolled, and randomly assigned to rivaroxaban or nadroparin groups in a 1:1 ratio; anticoagulants were initiated 12-24 h after surgery and continued until discharge. Four hundred participants were required according to a noninferiority margin of 2%, assuming venous thromboembolism (VTE) occurrence rates of 6.0% and 12.6% for patients in the rivaroxaban and nadroparin groups, respectively. The primary efficacy outcome was any VTE during the treatment and 30-day follow-up periods. The safety outcome was any on-treatment bleeding event. Finally, 403 patients were randomized (intention-to-treat [ITT] population), with 381 included in per-protocol (PP) population. The primary efficacy outcomes occurred in 12.5% (25/200) of the rivaroxaban group and 17.7% (36/203) of the nadroparin group (absolute risk reduction, -5.2%; 95% confidence interval [CI], [-12.2-1.7]), indicating the noninferiority of rivaroxaban in ITT population. Sensitivity analysis was performed in the PP population and yielded similar results, confirming the noninferiority of rivaroxaban. In the safety analysis population, the incidence of any on-treatment bleeding events did not differ significantly between the groups (12.2% for rivaroxaban vs. 7.0% for nadroparin; relative risk [RR], 1.9; 95% CI, [0.9-3.7]; p = .08), including major bleeding (9.7% vs. 6.5%; RR, 1.6 [95% CI, 0.9-3.7]; p = .24), and nonmajor bleeding (2.6% vs. 0.5%; RR, 5.2 [95% CI, 0.6-45.2]; p = .13). Rivaroxaban for thromboprophylaxis after oncologic lung surgery was shown to be noninferior to nadroparin.

Single- versus multi-port video-assisted thoracic surgery for pulmonary aspergilloma: a propensity-matched study.

OBJECTIVES: The utilization of single-port video-assisted thoracic surgery for pulmonary aspergilloma (PA) has not been well studied. The study was performed to evaluate the safety and feasibility of it for PA compared with multi-port video thoracic-assisted surgery. METHODS: From August 2007 to December 2019, consecutive PA patients receiving surgeries at Shanghai Pulmonary Hospital were enrolled retrospectively. Propensity score matching based on preoperative clinical variables was utilized to compare perioperative and long-term outcomes. RESULTS: In all 358 patients, a total of 63 patients underwent single-port video-assisted thoracic surgery, and 63 out of 145 patients for multi-port surgeries were paired with the single-port video-assisted thoracic surgery recipients. The median follow-up period was 40 months (range, 2-140 months). Patients receiving single-port video-assisted thoracic surgery showed a similar operation time, intraoperative blood loss, drainage duration and drainage volume to those of multi-port video-assisted thoracic surgery recipients (P > 0.05). Patients undergoing lobectomy by single-port approach experienced a shorter postoperative hospital stay {4.9 [standard deviation (SD): 2.0] vs 5.9 (SD: 2.3), P = 0.014}. The average postoperative pain scores [day 0: 2.6 (SD: 0.7) vs 3.1 (SD: 0.8), day 3: 4.0 (SD: 0.9) vs 4.8 (SD: 3.9), day 7: 2.2 (SD: 0.5) vs 3.1 (SD: 0.8), P < 0.001] and the number of days that patients required analgesic agents [3.0 (SD: 2.2) vs 4.8 (SD: 2.1), P < 0.001] were also decreased in the single-port video-assisted thoracic surgery group. CONCLUSIONS: Single-port video-assisted thoracic surgery is a safe and feasible alternative to multi-port video-assisted thoracic surgery for simple PA and selected complex ones, with a potential advantage of reduced postoperative pain.

Subcarinal lymph node dissection facilitated by applying suture passer in uniportal video-assisted thoracoscopic surgery.

With the advancement of surgical skills and instrumentation, uniportal video-assisted thoracoscopic surgery (UniVATS) has become a popular option for the treatment of early stage lung cancer surgery. However, performing subcarinal lymph node dissection remains technically challenging under UniVATS view. We introduce a novel technique that utilized a suture passer to improve the exposure of the subcarinal area and simplify lymph node dissection, which has the potential for widespread adoption in clinical practice. There were 13 lung cancer patients who underwent UniVATS lobectomy with mediastinal lymphadenectomy in our institution from July to August 2022. Clinical data of the patients were documented and reviewed. The study population consisted of nine females and four males, with an average age of 57.5 ± 9.1 years. UniVATS lobectomy with mediastinal lymphadectomy was successfully performed in all patients without conversion to open surgery. The mean operation time was 90.7 ± 36.0 min (53-178 min), intraoperative blood loss was 73.1 ± 43.8 mL (50-200 mL), and postoperative hospital stay was 2.9 ± 0.3 days (2-3 days). No complications related to lymph node dissection, such as chylothorax, occurred. Our novel method of using a suture passer could simplify the procedure of subcarinal lymph node dissection during UniVATS in initial clinical practice. Further comparative studies are warranted in the future.

Differentiation-related genes in tumor-associated macrophages as potential prognostic biomarkers in non-small cell lung cancer.

Background: The purpose of this study was to evaluate the role of differentiation-related genes (DRGs) in tumor-associated macrophages (TAMs) in non-small cell lung cancer (NSCLC). Methods: Single cell RNA-seq (scRNA-seq) data from GEO and bulk RNA-seq data from TCGA were analyzed to identify DRGs using trajectory method. Functional gene analysis was carried out by GO/KEGG enrichment analysis. The mRNA and protein expression in human tissue were analyzed by HPA and GEPIA databases. To investigate the prognostic value of these genes, three risk score (RS) models in different pathological types of NSCLC were generated and predicted NSCLC prognosis in datasets from TCGA, UCSC and GEO databases. Results: 1,738 DRGs were identified through trajectory analysis. GO/KEGG analysis showed that these genes were predominantly related to myeloid leukocyte activation and leukocyte migration. 13 DRGs (C1QB, CCL4, CD14, CD84, FGL2, MS4A6A, NLRP3, PLEK, RNASE6, SAMSN1, SPN, TMEM176B, ZEB2) related to prognosis were obtained through univariate Cox analysis and Lasso regression. C1QB, CD84, FGL2, MS4A6A, NLRP3, PLEK, SAMSN1, SPN, and ZEB2 were downregulated in NSCLC compared to non-cancer tissue. The mRNA of 13 genes were significantly expressed in pulmonary macrophages with strong cell specificity. Meanwhile, immunohistochemical staining showed that C1QB, CCL4, SPN, CD14, NLRP3, SAMSN1, MS4A6A, TMEM176B were expressed in different degrees in lung cancer tissues. ZEB2 (HR=1.4, P<0.05) and CD14 (HR=1.6, P<0.05) expression were associated with a worse prognosis in lung squamous cell carcinoma; ZEB2 (HR=0.64, P<0.05), CD84 (HR=0.65, P<0.05), PLEK (HR=0.71, P<0.05) and FGL2 (HR=0.61, P<0.05) expression were associated with a better prognosis in lung adenocarcinoma. Three RS models based on 13 DRGs both showed that the high RS was significantly associated with poor prognosis in different pathological types of NSCLC. Conclusions: This study highlights the prognostic value of DRGs in TAMs in NSCLC patients, providing novel insights for the development of therapeutic and prognostic targets based on TAM functional differences.

Tumor microenvironment remodeling after neoadjuvant immunotherapy in non-small cell lung cancer revealed by single-cell RNA sequencing.

BACKGROUND: Immunotherapy has revolutionized cancer treatment, but most patients are refractory to immunotherapy or acquire resistance, with the underlying mechanisms remaining to be explored. METHODS: We characterized the transcriptomes of ~92,000 single cells from 3 pre-treatment and 12 post-treatment patients with non-small cell lung cancer (NSCLC) who received neoadjuvant PD-1 blockade combined with chemotherapy. The 12 post-treatment samples were categorized into two groups based on pathologic response: major pathologic response (MPR; n = 4) and non-MPR (NMPR; n = 8). RESULTS: Distinct therapy-induced cancer cell transcriptomes were associated with clinical response. Cancer cells from MPR patients exhibited a signature of activated antigen presentation via major histocompatibility complex class II (MHC-II). Further, the transcriptional signatures of FCRL4+FCRL5+ memory B cells and CD16+CX3CR1+ monocytes were enriched in MPR patients and are predictors of immunotherapy response. Cancer cells from NMPR patients exhibited overexpression of estrogen metabolism enzymes and elevated serum estradiol. In all patients, therapy promoted expansion and activation of cytotoxic T cells and CD16+ NK cells, reduction of immunosuppressive Tregs, and activation of memory CD8+T cells into an effector phenotype. Tissue-resident macrophages were expanded after therapy, and tumor-associated macrophages (TAMs) were remodeled into a neutral instead of an anti-tumor phenotype. We revealed the heterogeneity of neutrophils during immunotherapy and identified an aged CCL3+ neutrophil subset was decreased in MPR patients. The aged CCL3+ neutrophils were predicted to interact with SPP1+ TAMs through a positive feedback loop to contribute to a poor therapy response. CONCLUSIONS: Neoadjuvant PD-1 blockade combined with chemotherapy led to distinct NSCLC tumor microenvironment transcriptomes that correlated with therapy response. Although limited by a small patient sample size subjected to combination therapy, this study provides novel biomarkers to predict therapy response and suggests potential strategies to overcome immunotherapy resistance.

Hybrid uniportal robotic-assisted thoracoscopic surgery using video-assisted thoracoscopic surgery staplers: technical aspects and results.

Background: The clinical efficacy of robot-assisted thoracic surgeries has been explored by numerous recent studies. Nonetheless, since current standard robotic systems (da Vinci Xi system) were intended for multiportal surgical processes and robotic staplers were still unavailable in the developing world, obstacles still remain concerning the feasibility of uniportal robotic surgeries. Methods: A hybrid uniportal robotic-assisted thoracoscopic surgery (RATS) modality utilizing video-assisted thoracoscopic surgery (VATS) staplers was investigated in Shanghai Pulmonary Hospital. Clinicopathological characteristics and perioperative outcomes concerning patients receiving hybrid uniportal RATS between August 2022 and September 2022 were collected. Results: A total of 40 patients were included in this study. Most of the patients (23/40, 57.5%) received hybrid uniportal RATS lobectomies. One conversion from uniportal RATS to biportal process was encountered due to extensive adhesions discovered intraoperatively. The median procedural duration was 76 min [interquartile range (IQR), 61-99 min], and the median blood loss volume was 50 mL (IQR, 50-50 mL). A median stay length of three days (IQR, 2-4 days) was recorded. Eleven patients (27.5%) developed Clavien-Dindo grade I-II postoperative complications, while no grade III-IV complications were observed. Aside from this, none of the patients were readmitted or died within 30 days post-surgery. Conclusions: The feasibility of hybrid uniportal RATS procedures using VATS staplers has been preliminarily validated. For early-stage non-small cell lung cancer patients, such a procedure might clinical efficacy comparable to that of uniportal RATS utilizing robotic staplers.

The efficacy and safety of wedge resection for peripheral stage IA lung adenocarcinoma: a real-world study based on a single center.

Background: The effectiveness of segmentectomy for stage IA lung adenocarcinoma (IA-LUAD) has been well-documented. However, the efficacy and safety of wedge resection for peripheral IA-LUAD remains controversial. This study evaluated the feasibility of wedge resection in patients with peripheral IA-LUAD. Methods: Patients with peripheral IA-LUAD who underwent wedge resection by video-assisted thoracoscopic surgery (VATS) at Shanghai Pulmonary Hospital were reviewed. Cox proportional hazards modeling was performed to identify predictors of recurrence. Receiver operating characteristic (ROC) curve analysis was used to calculate the optimal cutoffs of identified predictors. Results: A total of 186 patients (female/male, 115/71; mean age, 59.9 years) were included. Mean maximum dimension of consolidation component (MCD) was 5.6 mm, consolidation-to-tumor ratio (CTR) was 37%, and mean computed tomography value of tumor (CTVt) was -285.4 HU. With a median follow-up of 67 months (interquartile range, 52-72 months), the 5-year recurrence rate was 4.84%. Ten patients occurred recurrence postoperatively. No recurrence was observed adjacent to the surgical margin. Increasing MCD, CTR, and CTVt were associated with a higher risk of recurrence, with corresponding hazard ratios (HRs) of 1.212 [95% confidence interval (CI): 1.120-1.311], 1.054 (95% CI: 1.018-1.092), and 1.012 (95% CI: 1.004-1.019) with optimal cutoffs for predicting recurrence of 10 mm, 60%, and -220 HU, respectively. When a tumor had characteristics under these respective cutoffs, no recurrence was observed. Conclusions: Wedge resection can be considered to be a safe and efficacious management strategy for patients with peripheral IA-LUAD, especially for MCD less than 10 mm, CTR less than 60% and CTVt less than -220 HU.

A novel drainage strategy using chest tube plus pleural catheter in uniportal upper lobectomy: A randomized controlled trial.

BACKGROUND: In this study we explored whether one pleural catheter plus single chest tube drainage could achieve a noninferior drainage effect when compared with the traditional two chest tubes in uniportal video-assisted thoracoscopic surgery (VATS) for an upper pulmonary lobectomy. METHODS: Patients that underwent an upper pulmonary lobectomy from January to November 2020 were enrolled in this single-center, randomized, open-label, noninferiority trial. Prior to closure, patients were randomized to an intervention group who received an improved drainage strategy involving one pleural catheter with one chest tube (24 Fr), while traditional double chest tube drainage was applied for the control group. RESULTS: A total of 390 patients entered the study, although 190 were excluded for changing nonuniportal surgical approaches or opting for nonlobectomy resections. Finally, 200 patients were randomized (100 in the intervention group and 100 in the control group). The baseline demographic and clinical characteristics were comparable between the groups. The incidence of pneumothorax in the intervention and control groups was similar on postoperative Day 1 (noninferiority, 10% vs. 13%, p = 0.658). In addition, there were no significant differences in secondary outcomes such as incidence of pneumothorax by Day 30, postoperative chest tube/pleural catheter removal time, amount of drainage on Day 1, total amount of drainage after operation, or postoperative hospitalization. A significantly lower pain score was observed in the intervention group (3.33 ± 0.68 vs. 3.68 ± 0.94, p = 0.003). CONCLUSIONS: The new strategy is noninferior to double chest tube drainage after an upper pulmonary lobectomy offers superior pain control, and is recommended for an upper lobectomy by uniportal VATS.