Objective: To evaluate the feasibility and perioperative safety of anterior mediastinal tumor resection using a flexible single-port robotic system (SR-ENS-600) via a single subxiphoid approach. Methods: This prospective single-center feasibility study included the first 4 consecutive patients undergoing anterior mediastinal tumor resection with the SR-ENS-600 system. The primary end point was successful completion of resection without conversion or major device malfunction. Secondary end points included operative metrics, intraoperative safety, and 30-day postoperative outcomes. Results: All procedures were completed via a single subxiphoid approach without conversion or device malfunction (technical success rate: 100%). Robotic manipulation time ranged from 62 to 116 minutes, and total operative time ranged from 89 to 131 minutes. Docking time decreased from 6 minutes in the first case to 2 to 3 minutes in subsequent cases. No intraoperative complications occurred. No Clavien-Dindo grade III or greater complications, reoperations, or 30-day readmissions were observed. Conclusions: Early clinical experience suggests that flexible single-port robotic resection of anterior mediastinal tumors via a subxiphoid approach is feasible and perioperatively safe in selected patients. Further evaluation in larger cohorts is warranted.

To prove the concept of conversion surgery after induction therapy in initially unresectable stage III non-small-cell lung cancer (NSCLC), we conducted this single-arm, open label, prospective study. In this proof-of-concept prospective study, patients with initially unresectable stage III NSCLC who had received induction therapy and evaluated radically resectable were included and underwent surgery. The primary outcome was perioperative morbidity. Bulk-RNA sequencing of baseline and post-treatment samples from patients receiving immunochemotherapy (ICT) as induction therapy was conducted to explore the transcriptomic characteristics of therapeutic response. This study was registered with ClinicalTrials.gov, NCT04945928. From August 2021 to January 2024, 30 patients were enrolled. The R0 resection rate was 93.3

Background:Robotic-assisted bronchoscopy is an effective platform for transbronchial localization of pulmonary nodules before sublobar resection. However, access to this specialized technology and expertise is often limited to tertiary centers, creating geographic disparities in care. This case report describes the first clinical application of fifth-generation (5G)-assisted remote robotic bronchoscopy for preoperative dye marking, aiming to address this gap in surgical access and resource distribution. Case Description:A 53-year-old asymptomatic male with two persistent ground-glass nodules [14 mm in the right upper lobe (RUL) and 7 mm in the right lower lobe (RLL)] was scheduled for resection. His medical history was unremarkable. Preoperative localization was performed using an artificial intelligence-enhanced robotic bronchoscopy system (PolarisTM). The surgeon, operating from a remote console, successfully navigated to both lesions and injected indocyanine green at each site, with stable network latency of 21-24 milliseconds. Subsequent uniportal video-assisted thoracic surgery (VATS) wedge resection, guided by fluorescence imaging, was completed within 30 minutes with negligible estimated blood loss. Final pathology confirmed that the nodule in the RUL was atypical adenomatous hyperplasia (AAH), while that in the RLL was predominantly bronchiolar adenoma with a focal 2-mm non-mucinous adenocarcinoma in situ (AIS) component. The patient had an uneventful recovery and was discharged on postoperative day (POD) three. Conclusions:This initial case suggests the technical feasibility of 5G remote-controlled robotic bronchoscopy for preoperative localization. The ultra-low latency 5G network ensured real-time and precise control. This approach potentially expands access to specialized thoracic surgical expertise across geographical barriers. Its broader safety, efficacy, and clinical utility require validation in larger, prospective studies.

Background The prognostic relevance of type 2 diabetes in esophageal cancer patients undergoing neoadjuvant therapy followed by surgery remains unclear. This study assessed whether type 2 diabetes influences perioperative outcomes and long-term survival. Methods A total of 1099 patients who received neoadjuvant therapy followed by surgery at three high-volume institution in China from 2013 to 2024 were included. The diagnosis of type 2 diabetes was based on American Diabetes Association criteria. A 1:4 propensity score matching was performed using the R software. Baseline characteristics, perioperative outcomes, overall survival and progression-free survival were compared. Results After 1:4 matching, 114 patients in the diabetic group and 456 patients in the non-diabetic group were compared. No significant differences were found between non-diabetic and diabetic group regarding length of stay (9 days vs 9 days, P = 0.856), re-operation (2.2% vs 0.9%, P = 0.594), re-admission (1.5% vs 1.8%, P > 0.990), total complications (45.0% vs 51.8%, P = 0.231), or specific complications. At a median follow-up of 1086 days, the 2-year overall survival between non-diabetic and diabetic group was 73.9% vs 77.2%, and the 3-year overall survival was 62.4% vs 67.8% [hazard ratio: 0.840, 95% CI: 0.570–1.220, P = 0.356]. After a median follow-up of 927 days, the 2-year progression-free survival of the two groups was 73.2% vs 65.1%, and the 3-year progression-free survival was 65.2% vs 62.4% [hazard ratio: 1.130, 95% CI: 0.780–1.630, P = 0.529]. Conclusions Type 2 diabetes does not adversely affect perioperative outcomes or long-term survival in esophageal cancer patients undergoing neoadjuvant therapy and surgery.

Background:Emerging evidence highlights defects in DNA damage repair as critical modulators of tumor immunogenicity, yet the mechanistic interplay between repair pathway dynamics and immune checkpoint inhibitor efficacy remains elusive. This study aims to investigate the role of exonuclease 1 (EXO1), a dual-function nuclease involved in homologous recombination (HR) and mismatch repair (MMR), in immunogenomic regulation and immunotherapy response in lung adenocarcinoma (LUAD). Methods:An integrated multi-omics analysis was performed using LUAD cohorts from The Cancer Genome Atlas (TCGA) to assess EXO1 expression, genomic instability, and prognosis. Functional studies were conducted in syngeneic murine models to evaluate the effects of Exo1 ablation on DNA repair pathway kinetics, mutation burden, tumor evolution, and immune cell infiltration. The response to anti-programmed death receptor-1 (PD-1) therapy was assessed in Exo1-deficient versus control tumors. Results:EXO1 overexpression was strongly associated with genomic instability and poor prognosis in LUAD (hazard ratio =1.047, P =3.72×10-8). In murine models, Exo1 ablation induced a "controlled genomic chaos" state, delaying HR‑mediated fidelity (P<0.0001) while accelerating error‑prone non‑homologous end joining (P<0.01), thereby amplifying clonal mutation burden and tumor evolution. This was accompanied by enrichment of tumor‑specific cytotoxic CD8+ T cells (CD39+ Granzyme B+; P<0.0001). Exo1‑deficient tumors exhibited a 100% objective response to anti‑PD‑1 therapy versus 40% in controls (P<0.001), with a synergistic reduction of tumor mass (77.3% versus 21.2%, P<0.01). Crucially, Exo1 suppression spared MMR functionality while preferentially engaging non‑homologous end joining‑driven immunoediting. Conclusions:This work deciphers DNA damage repair‑immune crosstalk governed by biased repair kinetics, and nominates EXO1 abrogation as a transformative strategy to overcome immune checkpoint inhibitor resistance in genomically stable tumors.

Objective This study aims to present the initial clinical experience and evaluate the feasibility and safety of an artificial intelligence agent-based robotic-assisted bronchoscopy system for preoperative dye localization of pulmonary nodules before video-assisted thoracoscopic surgery. Methods This single-center, retrospective study analyzed 15 patients with peripheral pulmonary nodules who underwent preoperative dye localization using the artificial intelligence agent-based robotic-assisted bronchoscopy system (Polaris, LungHealth MedTech Company). Procedural efficacy was assessed by navigation success rate, localization time, and resection success rate. Safety was evaluated based on the incidence of complications. Results All 15 nodules (mean diameter: 1.03 ± 0.28 cm) were successfully navigated (100% navigation success). Dye localization was successful in 14 cases (93.3%), with 1 nodule resected anatomically. The median localization time was 10.0 minutes (interquartile range, 7.0-12.5). All nodules were completely resected with negative margins. No procedural complications, such as pneumothorax or hemorrhage, occurred. Conclusions The artificial intelligence agent-based robotic-assisted bronchoscopy–assisted dye localization technique demonstrates high precision and safety for guiding video-assisted thoracoscopic surgery resection of peripheral pulmonary nodules. These promising results support its potential as a viable alternative to existing localization methods and warrant further validation in larger randomized trials to establish its clinical value.

Background Hepatocellular carcinoma (HCC) is a global health challenge with high mortality rates, particularly in patients with advanced disease and lung metastasis. T-cell receptor (TCR)-T cell therapy based on specific neoantigens, is an emerging treatment with potential for HCC. However, the prognosis of patients remains poor, underscoring the need for novel targets and strategies.Methods We conducted a comprehensive study to investigate the role of C7orf50 and its neoantigens in HCC. We evaluated the functional impact on HCC progression and metastasis in vitro and in vivo, and further explored the mechanism by which C7orf50 promotes cancer metastasis and remodels tumor immune environment. Using exome and transcriptome sequencing, we identified neoantigens associated with C7orf50 and assessed their potential in TCR-T therapy.Results Our in vitro experiments revealed that C7orf50 overexpression enhances HCC cell proliferation, migration, and invasion, while knockdown inhibits these processes. In vivo, C7orf50 promoted tumor growth and lung metastasis, with a significant correlation between C7orf50 expression and poor clinical outcomes in patients with HCC. We further demonstrated that C7orf50 activates the NF-κB/PAI-1 pathway by binding to AEG-1 and facilitating its nuclear translocation, thereby promoting tumor-associated macrophage recruitment. Meanwhile, we found that TCR-T from C7orf50-related neoantigen could obviously realize the killing effect on HCC cells, revealing its great role in cell therapy.Conclusion C7orf50 is a critical mediator of HCC progression and lung metastasis, acting through the NF-κB/PAI-1 pathway and AEG-1. Its expression levels, along with those of PAI-1 and CD68, serve as independent prognostic markers. And C7orf50-related neoantigen shows great application potential in TCR-T therapy. These findings provide a foundation for developing C7orf50-targeted therapies and highlight its potential in precision medicine and immunotherapy for HCC.

Purpose:The comparative efficacy of neoadjuvant chemoimmunotherapy (NCIT) vs neoadjuvant chemoradiotherapy (NCRT) for locally advanced esophageal squamous cell carcinoma (LA-ESCC) remains controversial. Methods and materials:This multicenter retrospective cohort study included patients with LA-ESCC who received NCIT or NCRT followed by esophagectomy across 7 Chinese medical centers between January 2012 and January 2024. The primary outcomes were disease-free survival (DFS) and overall survival (OS). Propensity score matching (PSM) was utilized to balance baseline covariates. Results:Among 2535 enrolled patients, 1414 received NCIT and 1121 received NCRT. After 1:1 PSM, 1258 patients (629 per group) were evaluated. With a median follow-up of 32.7 months, no significant differences were observed between the NCIT and NCRT groups in DFS (hazard ratio [HR], 1.14; 95% CI, 0.94-1.38; P = .20) or OS (HR, 0.98; 95% CI, 0.77-1.25; P = .89). The 2-year DFS rates were 68.7% (NCIT) vs 72.0% (NCRT), and 2-year OS rates were 81.3% vs 83.7%, respectively. NCIT showed a trend toward improved distant metastasis-free survival (DMFS) (HR, 0.87; 95% CI, 0.69-1.11; P = .27), whereas NCRT was associated with a trend toward improved locoregional recurrence-free survival (LRFS) (HR, 1.22; 95% CI, 0.96-1.56; P = .11). Conclusions:NCIT and NCRT demonstrated comparable DFS and OS. These findings suggest that both modalities are valid neoadjuvant strategies, possessing differing strengths in local vs systemic tumor control. These observations await confirmation in prospective trials.

CASE PRESENTATION:A 68-year-old man presented to our thoracic surgery department for evaluation of a left upper-lobe pulmonary nodule detected on chest CT scan. The oncologic history extended over 7 years. In December 2014, the patient was diagnosed with colorectal adenocarcinoma (ileocecal junction) by colonoscopy, and he underwent a laparoscopic right hemicolectomy and lymph node dissection. Postoperative pathological examination revealed a grade II-III adenocarcinoma of the ileocecal region (ulcerative type), infiltrating into the muscularis. Surgical margins were free of tumor. No metastasis was identified in the examined lymph nodes, including paracolic (19), paracolic (7), intermediate mesenteric (23), and central vascular (2) lymph nodes, corresponding to a pathologic stage of pT2N0M0. The patient recovered well and was placed on regular follow-up.

Abstract Topic Esophageal Cancer: Surgical Treatment of Esophageal Cancer – early outcomes and complications Background The prognostic impact of type 2 diabetes in esophageal cancer patients receiving neoadjuvant therapy followed by surgery remains unclear. We evaluated its association with perioperative outcomes and long-term survival. Methods We retrospectively analyzed 1,099 patients who underwent neoadjuvant therapy followed by surgery between 2013 and 2024 across three high-volume centers. Type 2 diabetes was defined according to American Diabetes Association criteria. A 1:4 propensity score matching analysis was performed to minimize baseline imbalance. Perioperative outcomes, overall survival (OS), and progression-free survival (PFS) were compared between diabetic and non-diabetic patients. Results After matching, 114 diabetic patients were compared with 456 non-diabetic patients. No significant differences were observed in length of hospital stay, re-operation, re-admission, total complications, or specific postoperative morbidities. After a median follow-up of 1,086 days, 2- and 3-year OS rates were 73.9% vs 77.2% and 62.4% vs 67.8%, respectively (HR 0.84, 95% CI 0.57–1.22, P=0.356). After a median follow-up of 927 days, 2- and 3-year PFS rates were 73.2% vs 65.1% and 65.2% vs 62.4%, respectively (HR 1.13, 95% CI 0.78–1.63, P=0.529). Type 2 diabetes was not associated with inferior survival outcomes. Conclusion Type 2 diabetes was not associated with increased perioperative morbidity or impaired long-term survival following neoadjuvant therapy and surgery.

Insufficient T-cell infiltration is a major barrier to the efficacy of immune checkpoint inhibitors (ICIs) in lung adenocarcinoma (LUAD). We aimed to investigate how the tumor-intrinsic m5C methyltransferase NSUN2 shapes the immune landscape of LUAD. Nsun2 conditional knockout mice and syngeneic mice models were employed. Single-cell RNA sequencing (scRNA-seq) and m5C sequencing were performed to elucidate the downstream pathway regulated by NSUN2. LUAD specimens from patients receiving neoadjuvant immunotherapy were used to assess the correlation between NSUN2 expression and immune infiltration. Elevated tumoral NSUN2 expression was correlated with a marked lack of CD8+ T-cell infiltration and immunotherapy resistance. Mechanistically, NSUN2 enhances the translation of histone deacetylase HDAC8 in an m⁵C-YBX1-dependent manner, which in turn directly represses the transcription of the chemoattractant CCL5, thereby impairing CD8+ T-cell recruitment into the tumor. NSUN2 depletion reversed this immunosuppressive axis and converted immunologically “cold” tumors into “hot”. Tumor-targeted liposomes loaded with the NSUN2 inhibitor synergized with anti-PD-1 therapy to induce significant tumor regression. Our findings identify NSUN2 as a critical orchestrator of T-cell exclusion in LUAD. It serves as both a candidate predictive biomarker for ICI failure and a promising druggable target. Targeting NSUN2 offers a potential strategy to overcome immunotherapy resistance and improve clinical outcomes in LUAD patients.

Background:Synchronous double primary lung adenocarcinoma (sDPLA) is a distinct subtype of lung adenocarcinoma characterized by the co-existence of two independent lesions in the same patient. We conducted the first comprehensive analysis of the immune microenvironment of sDPLA lesions with different degrees of invasiveness to examine immune evolution during early lung adenocarcinoma progression. Methods:In total, 10 sDPLA patients undergoing synchronous surgical resection were enrolled in the study. The minimally invasive adenocarcinoma (MIA) and invasive adenocarcinoma (IAC) lesions were analyzed by next-generation sequencing (NGS) or single-cell RNA sequencing (scRNA-seq), focusing on T/natural killer (NK) cell subsets. The key cell subsets and signaling pathways were identified using Mfuzz clustering, CellChat, and Monocle, and validated by multiplex immunofluorescence and flow cytometry. Results:We identified 11 T/NK cell subsets, among which the CD4+ exhausted T (Tex) cell CXCL13 population was significantly enriched in the IAC lesions. These cells exhibited high expression of PD-1 and TIM-3, enhanced interactions with epithelial cells, and enrichment of the JAK-STAT and PI3K-AKT pathways, suggesting a central role in immune suppression. Validation confirmed the preferential accumulation of this subset of cells in the IAC tissues. Conclusions:This study found significant immune heterogeneity between sDPLA lesions with different degrees of invasiveness and identified CD4+ Tex CXCL13 cells as key drivers of tumor immune progression. Our findings provide new insights into early immune evolution and may inform precision immunotherapy strategies.

Background/Objectives: Perioperative chemoimmunotherapy has become an important curative-intent strategy for selected patients with resectable non-small cell lung cancer (NSCLC). However, most pivotal trials evaluate neoadjuvant therapy, surgery, and postoperative immune checkpoint inhibitor (ICI) treatment as an integrated regimen. Whether continued postoperative immunotherapy provides independent incremental benefit for all patients after effective neoadjuvant chemoimmunotherapy and complete resection remains unresolved. This review focuses on the adjuvant-phase dilemma and discusses how postoperative treatment may be refined according to response and residual risk. Methods: We performed a narrative review of major neoadjuvant and perioperative chemoimmunotherapy trials, indirect comparative analyses, pathological-response studies, circulating tumor DNA (ctDNA)-based molecular residual disease (MRD) evidence, immune biomarker studies, and emerging data in driver-positive and real-world populations. Particular attention was given to evidence informing postoperative continuation, de-escalation, or intensification after neoadjuvant chemoimmunotherapy. Results: Current phase III perioperative trials demonstrate clinically meaningful activity but do not isolate the independent contribution of the adjuvant ICI phase. Pathological response provides the most accessible postoperative risk signal: pathologic complete response identifies the deepest-response group, major pathologic response represents an intermediate state, and non-major pathologic response or persistent nodal disease suggests higher relapse risk. ctDNA-based MRD offers dynamic risk refinement and may help identify patients with residual systemic disease, although prospective validation is required before it can guide routine treatment omission or escalation. Programmed death-ligand 1 (PD-L1), tumor mutational burden, tertiary lymphoid structures, B-cell signatures, radiomics, and pathomics may provide complementary information but are not sufficient as standalone decision tools. Driver-positive disease requires molecularly stratified perioperative strategies rather than unselected extrapolation from epidermal growth factor receptor (EGFR)/anaplastic lymphoma kinase (ALK)-negative trials. Conclusions: The key question in resectable NSCLC is shifting from whether perioperative immunotherapy is active to which patients truly require postoperative immunotherapy. Future trials should prospectively test response-guided strategies integrating pathological response, ctDNA-based MRD, immune contexture, baseline risk, and treatment feasibility.

Background Global clinical programs based on TIGIT (T cell immunoglobulin and ITIM domain) blockade have been terminated due to inadequate clinical efficacy. New approaches are needed to increase the antitumor activity of anti-TIGIT-based immunotherapy.Methods Multiomics analyses, including single-cell RNA sequencing (scRNA-seq), single-cell TCR sequencing (scTCR-seq), and The Cancer Genome Atlas bulk RNA-seq, were performed to profile TIGIT and the costimulator CD226 expression and assess intratumoral regulatory T cells (Tregs) clonality, with validation by flow cytometry in murine and patient-derived tumor-infiltrating lymphocytes. The therapeutic efficacy of anti-TIGIT antibodies (αTIGIT), including αTIGIT-IgG1-wild-type (WT), αTIGIT-IgG1-WT with enhanced antibody-dependent cellular cytotoxicity (ADCC) activity (αTIGIT-IgG1-ADCC), αTIGIT-IgG4-WT, and tiragolumab, was evaluated in MC38 tumors-inoculated humanized TIGIT knock-in mice (Tigith/h, Tigith/m). Tumor microenvironment alterations were analyzed using flow cytometry and scRNA/TCR-seq. Antibody binding affinity and ADCC activity were assessed via biolayer interferometry and in vitro ADCC assays. Safety profiles were examined in a murine immune-related adverse events model through growth monitoring, survival analysis, and histopathological evaluation.Results Using mouse models and clinical sample analysis, we identified a population of TIGIThigh CD226− clonally expanded intratumoral Tregs as a major barrier limiting the ability of TIGIT blockade to enhance effector cell function. αTIGIT-IgG1-ADCC specifically targeted and eliminated the TIGIThigh CD226− clonally expanded Treg subset, resulting in a marked improvement in antitumor efficacy compared with WT and clinically unsuccessful αTIGIT. Mechanistically, removal of these Tregs through αTIGIT-IgG1-ADCC relieved their suppression of stem-like CD4+ T cells, facilitating their differentiation into T helper cell 1 (Th1) effector cells. Th1-derived interferon-gamma (IFN-γ) further enhanced the functionality of tumor-infiltrating CD8+ T cells. Importantly, the presence of clonally expanded intratumoral Tregs and the suppression of stem-like CD4+ T cells correlated with poor immunotherapy response in patients with non-small cell lung cancer.Conclusions Targeted elimination of clonally expanded intratumoral Tregs is essential to unlock the full therapeutic potential of αTIGIT. These novel findings provide a key rationale and strategic direction for overcoming the limitations of current αTIGIT-based cancer immunotherapy.