Journal of thoracic disease最新文献

Background: In recent years, the number of treatment options for locally advanced non-small cell lung cancer (NSCLC) has increased, including neoadjuvant therapy. Accurate preoperative evaluation of malignancy can assist in planning of therapeutic strategies for NSCLC. We evaluated whether the maximum standardized uptake value (SUVmax) could serve as a predictive prognostic factor for locally advanced clinical stage IB to IIIB NSCLC.

Methods: We enrolled 396 patients with clinical stage IB-IIIB NSCLC who underwent lobectomy at the Kanagawa Cancer Center between January 2012 and December 2021. All patients underwent preoperative positron-emission tomography/computed tomography at our institution. The SUVmax cutoff value was determined using a receiver operating characteristic curve. Recurrence-free survival (RFS) and overall survival (OS) were analyzed using Kaplan-Meier curves and were compared using log-rank tests. Factors associated with RFS and OS were determined using a Cox proportional hazards model.

Results: Multivariate analysis demonstrated that the SUVmax of the primary tumor was independently associated with RFS and OS in clinical stage IB to IIIB NSCLC patients. SUVmax could stratify both the RFS and OS of patients, particularly from clinical stage IB to IIB. Furthermore, the rates of pathological upstaging and distant recurrence were higher in patients with resected clinical stage IB to IIIB NSCLC with a high SUVmax (>6.0) than in those with a low SUVmax (≤6.0).

Conclusions: The SUVmax of the primary tumor is an important preoperative predictor of prognosis in clinical stage IB to IIIB NSCLC.

Background: Spontaneous oesophageal perforation (Boerhaave's syndrome) is a life-threatening emergency with significant morbidity and mortality. Surgical repair remains a key component of management for selected patients; however, many high-risk patients are unsuitable for operative management. This article discusses how, in these high-risk individuals, minimally invasive strategies such as the use of covered self-expanding metal stents (SEMS) offer a valuable alternative to surgery. Stent therapy aims to achieve rapid control of oesophageal leakage, limit mediastinal contamination, and facilitate early sepsis control. When applied in appropriately selected patients, this approach may reduce procedural morbidity while providing effective source control.

Methods: This retrospective cohort study analysed all patients diagnosed with spontaneous oesophageal perforation between 2012 and 2024 at a tertiary referral centre. Patients deemed unfit for surgical intervention following comprehensive clinical assessment and acute multidisciplinary team (MDT) discussion-incorporating physiological status, comorbidities, Charlson Comorbidity Index (CCI), Pittsburgh score, markers of infection, and end-organ function-were managed with covered SEMS. Clinical, biochemical, and outcome data were reviewed.

Results: Of 102 patients with oesophageal perforation, 69 were diagnosed with Boerhaave's syndrome. Twenty-two high-risk patients underwent endoscopic stenting with covered SEMS. The in-hospital mortality rate was 45%, predominantly from sepsis and multiorgan failure, while no deaths were directly stent-related. The 1-year survival rate was 50%.

Conclusions: Endoscopic stenting offers a feasible and effective salvage option for high-risk Boerhaave's syndrome patients unsuitable for surgery. SEMS likely prevent otherwise inevitable fatalities in this cohort.

Background: Lung cancer is a leading cause of cancer deaths. Epidermal growth factor receptor-tyrosine kinase inhibitors (EGFR-TKIs) have improved outcomes for EGFR-mutant non-small cell lung cancer (NSCLC), but acquired resistance remains a major challenge. Third-generation EGFR-TKIs like aumolertinib show efficacy, yet their molecular mechanisms and sensitivity optimization need further exploration. The aim of this study is to enhance the efficacy of aumolertinib in the treatment of NSCLC.

Methods: In vitro experiments using PC-9 cells included Cell Counting Kit-8 (CCK-8) assays (cell viability), wound healing assays (migration), flow cytometry (apoptosis/cell cycle), RNA sequencing (RNA-seq), public transcriptome datasets (GSE193258, GSE178975) were analyzed to compare ETS variant transcription factor 4 (ETV4) expression across EGFR-TKIs (aumolertinib, osimertinib, and gefitinib). Small interfering RNA (siRNA) mediated knockdown of ETV4 was verified through quantitative real-time polymerase chain reaction (qRT-PCR) and Western blot analysis. In vivo validation employed BALB/C nude mouse xenograft models treated with aumolertinib, ETV4 siRNA (siETV4), or their combination.

Results: Aumolertinib time- and dose-dependently inhibited PC-9 viability, inducing G2/M arrest, apoptosis, and migration suppression. RNA-seq and cross-dataset analysis identified ETV4 as a conserved differentially expressed gene (DEG) across EGFR-TKI generations. ETV4 knockdown enhanced aumolertinib-induced apoptosis/G2/M arrest in vitro and synergistically suppressed tumor growth in vivo.

Conclusions: These findings revealed that ETV4 enhanced the therapeutic efficacy of aumolertinib in vitro and in vivo, indicating that ETV4 is a potential therapeutic co-target, serving as a treatment strategy to prevent the acquired resistance induced by aumolertinib.

Background: Pleural infections pose significant clinical challenges due to diagnostic delays, poor culture yield, and rising regional incidence. Local microbial data is vital to inform empirical therapy, particularly given geographical variation and low pleural fluid culture positivity. We aim to describe the microbiological profile of pleural infections in Singapore and identify factors associated with culture positivity and mortality.

Methods: A retrospective study was conducted on patients diagnosed with pleural infections at Tan Tock Seng Hospital between July 2016 and March 2024. Clinical, biochemical, and microbiological data of community and hospital-acquired pleural infections were analysed and compared. Logistic regression identified predictors for pleural fluid culture positivity and mortality.

Results: A total of 561 patients had pleural infections. Culture positivity was 29.2%, with Streptococcus anginosus, Klebsiella pneumoniae, and anaerobes being most common organisms isolated. There was a predominance of gram-positive organisms for community-acquired infections, while gram-negative organisms being more prevalent in hospital-acquired infections. Patients with hospital-acquired infections had higher mortality (in-hospital: 26.1% vs. 7.2%, P<0.001). Culture positivity was associated with higher comorbidity index, neutrophil-to-lymphocyte ratio, hospital-acquired infection, and elevated lactate dehydrogenase (LDH). Age, comorbidity burden and hospital-acquired infection were independent predictors of mortality, while there was no pathogen-specific effect on outcomes.

Conclusions: The bacteriology of local pleural infections differs from that previously published of the region. Reasons for these may include an older population, the impact of vaccinations, and high burden of comorbidities such as diabetes and relatively high incidence of lung cancer in the region. The low culture positivity indicates the limitations of conventional culture methods and underscores the need for efforts to improve microbiological detection.

Background: Acute lung injury (ALI) is characterized by alveolar epithelial barrier dysfunction, largely driven by excessive inflammation. This study aimed to elucidate the specific role and mechanism of macrophage pyroptosis in sepsis-induced epithelial injury.

Methods: We established an in vitro sepsis model using lipopolysaccharide (LPS)-stimulated macrophages, employing the NLRP3 inhibitor MCC950. Activation of the NLRP3 pathway and pyroptosis markers was assessed. The functional impact on the alveolar epithelial barrier was then evaluated by treating epithelial cells with conditioned medium (CM) from these macrophages. The protective effect of MCC950 was further verified in a murine model of LPS-induced septic ALI.

Results: LPS stimulation potently activated the NLRP3 inflammasome in macrophages, leading to robust pyroptosis, as indicated by a significant increase in caspase-1 activity, lactate dehydrogenase (LDH) release, and the secretion of interleukin-1 β (IL-1β) and IL-18. Pre-treatment with MCC950 completely abolished this activation. CM from LPS-activated macrophages (LPS-CM) induced severe epithelial barrier injury, manifesting as a significant increase in epithelial cell death and monolayer permeability, and a marked downregulation of tight junction proteins zonula occludens-1 (ZO-1) and occludin. Crucially, all these aforementioned effects were significantly attenuated when epithelial cells were incubated with CM from macrophages pre-treated with MCC950, demonstrating that inhibiting macrophage pyroptosis preserves epithelial barrier integrity. In vivo, MCC950 administration markedly alleviated LPS-induced lung injury, reducing pulmonary edema and alveolar-capillary barrier leakage.

Conclusions: Macrophage pyroptosis, activated via the LPS/NLRP3 pathway, is a pivotal mechanism in sepsis-induced alveolar epithelial barrier dysfunction. Pharmacological inhibition of this pathway represents a promising therapeutic strategy for ALI.

Background: The optimal duration of adjuvant immunotherapy following neoadjuvant chemoimmunotherapy and surgery for resectable non-small cell lung cancer (NSCLC) remains unclear. This systematic review and meta-analysis aimed to compare the efficacy of 12/13-cycle versus 6/8-cycle adjuvant programmed cell death 1/programmed death-ligand 1 (PD-1/PD-L1) inhibitor therapy in this clinical setting.

Methods: A systematic search of PubMed, Embase, the Cochrane Library, and major oncology conferences was performed from database inception to July 31, 2024. Eligible studies were phase II/III randomized controlled trials evaluating perioperative PD-1/PD-L1 inhibitor plus neoadjuvant chemotherapy compared with neoadjuvant chemotherapy alone. Hazard ratios (HRs) for survival outcomes were synthesized using the inverse-variance method. Indirect comparisons between the 12/13-cycle and 6/8-cycle adjuvant immunotherapy were performed using frequentist methods, with chemotherapy as a common comparator. The primary outcome was event-free survival (EFS).

Results: Four trials involving 12/13-cycle adjuvant immunotherapy and two trials with 6/8-cycle regimens, totaling 3,003 patients, were included. Direct meta-analysis demonstrated significant improvements in EFS for chemoimmunotherapy compared with chemotherapy alone in both 12/13-cycle and 6/8-cycle adjuvant groups. In the indirect comparison, 12/13 cycles of adjuvant immunotherapy did not significantly improve EFS (HR, 1.05; 95% confidence interval: 0.77-1.45) compared with the 6/8-cycle regimen. However, a trend favoring 12/13 cycles of adjuvant therapy was observed in the PD-L1 expression ≥50% subgroup (P for interaction =0.02).

Conclusions: Adjuvant immunotherapy with 6-8 cycles may be sufficient for patients with resectable NSCLC who have already received neoadjuvant chemoimmunotherapy. Further clinical trials are needed to determine the optimal duration of adjuvant therapy, particularly for patients with PD-L1 ≥50%.

Background: Chest tube placement after pulmonary resection has been conventionally recommended, yet the associated patient discomfort can hinder postoperative recovery. In previous work, we demonstrated that catheter drainage is a safe alternative to conventional chest tube following wedge resection and provides superior pain relief. This study aims to evaluate whether a complete tubeless strategy offers further advantages compared to catheter drainage.

Methods: We conducted a retrospective cohort study and enrolled patients who underwent video-assisted thoracoscopic surgery (VATS) pulmonary wedge resection at our institution between September 2020 and November 2024. Participants were categorized into a catheter drainage group or a tubeless group based on the absence of postoperative thoracic drainage. Propensity score matching (PSM) was applied in a 1:1 ratio to balance baseline characteristics. Univariate analysis was then used to compare operative outcomes and perioperative complications between the matched groups.

Results: Of the 460 initially eligible patients, 133 matched pairs were generated after PSM. The tubeless group demonstrated a significantly shorter operative duration (57.00 vs. 80.00 min, P<0.001) and lower postoperative pain scores [Numerical Rating Scale (NRS): 0.00 vs. 2.00, P<0.001] than the catheter group. No significant differences were observed in the incidence of postoperative complications, rates of reintubation, or length of postoperative hospital stay.

Conclusions: Omitting thoracic drainage entirely is a feasible and advantageous approach for a highly selected subset of patients undergoing pulmonary wedge resection. In this selected cohort, the tubeless strategy is associated with diminished postoperative pain and enhanced patient satisfaction, without increasing perioperative risks. The observed reduction in operative time is likely confounded by patient selection factors and should not be interpreted as a direct benefit of the technique. These findings support its consideration in patients intraoperatively assessed as low-risk; however, the observed benefits should be interpreted in the context of the stringent selection criteria applied, which may limit generalizability.

Background and objective: Lung transplantation (LTx) serves as the only definitive therapy for end-stage lung disease, yet, its clinical success is chronically constrained by the severe shortage of donor organs and the high incidence of postoperative complications such as primary graft dysfunction (PGD) and chronic rejection. As a transformative technology, artificial intelligence (AI) demonstrates substantial potential to address these systemic challenges and reshape the entire transplantation clinical pathway. The primary purpose of this article is to consolidate existing research findings to comprehensively assess the current status, technical mechanisms, and future ecosystem of AI applications in various stages of LTx, with a focus on its profound implications for organ allocation optimization, surgical assistance, complication prediction, and personalized medication management.

Methods: A systematic search was performed in PubMed from inception to September 30, 2025, using a combination of Medical Subject Headings (MeSH) terms and keywords related to "artificial intelligence" (e.g., machine learning, deep learning) and "lung transplantation". Inclusion criteria focused on English-language original research, reviews, and landmark case reports.

Key content and findings: In the pre-transplant phase, AI optimizes organ allocation by shifting focus from "urgency" to "utility" and enhances donor assessment and matching via computer vision. Intraoperatively, AI integrates with robotic platforms to enable augmented reality navigation and real-time risk warnings. Post-transplant applications, currently the most mature area, utilize machine learning to accurately predict complications like PGD and chronic lung allograft dysfunction (CLAD), enabling non-invasive monitoring (e.g., electronic nose) and personalized immunosuppressant dosing through deep learning analysis of time-series data.

Conclusions: AI has demonstrated distinct advantages in improving decision-making precision, optimizing resource allocation, and improving patient prognosis. However, the heterogeneity of data quality, model interpretability, and the complexity of clinical integration remain major barriers to its widespread adoption. Future efforts need to construct a data ecosystem based on FAIR (Findable, Accessible, Interoperable, and Reusable) principles and strengthen human-machine collaboration mechanisms to ensure that algorithmic precision translates into substantive improvements in patient survival and quality of life.