ObjectiveTo explore the risk factors for lymph node metastasis in patients with T2 stage non-small cell lung cancer.MethodsThe clinical data of 271 patients with non-small cell lung cancer who underwent surgical treatment in our hospital from 2014 to 2017 were collected, including 179 males and 92 females, with an average age of 62.73±0.58 years. The patients were divided into N0, N1, and N2 groups according to the lymph node metastasis status. The clinical data of the patients in different groups were compared.ResultsThe body mass index (BMI, P=0.043), preoperative lymph node enlargement (P<0.001), and tumor diameter (P<0.001) were significantly different among groups. The BMI (OR=1.131, 95%CI 1.001-1.277, P=0.048) and preoperative lymph node enlargement (OR=3.498, 95%CI 1.666-7.342, P=0.001) were independent risk factors for N2 lymph node metastasis, and tumor diameter was an independent risk factor for both N1 (OR=1.538, 95%CI 1.067-2.218, P=0.021) and N2 (OR=1.814, 95%CI 1.196-2.752, P=0.005) lymph node metastasis.ConclusionPatients with high BMI or enlarged lymph nodes before surgery have a high risk for N2 lymph node metastasis, and those with large tumor diameter have a high risk for both N1 and N2 lymph node metastasis.
Abstract： Objective To evaluate the safety, feasibility, and clinical outcome of complete video-assisted thoracoscopic surgery （VATS） lobectomy for patients with early-stage non-small cell lung cancer （NSCLC）. Methods We retrospectively analyzed the clinical data of 160 consecutive patients（the VATS group, 83 males and 77 females with average age at 60.8 years）with early-stage NSCLC who underwent complete VATS lobectomy between January 2005 andDecember 2008 in Zhongshan Hospital of Fudan University，and compared them with 357 patients（the thoracotomy group, 222 males and 135 females with average age at 59.5 years）who underwent open thoracotomy in the same period. Results The conversion rate of the VATS group was 5.0%（8/160）. The operation time of the VATS group was significantly shorter than that of the thoracotomy group（113.0 min vs.125.0 min, P=0.039）. Length of postoperative hospital stay was not statistically different between the two groups（10.3±4.3 d vs.9.1±4.6 d，P=0.425）. The postoperative morbidity of the VATS lobectomy group and the thoracotomy group was 9.4%（15/160）and 10.1% （36/357） respectively，and the postoperative mortality of the two groups was 0.6%（1/160）and 2.0%（7/357）respectively. There was no statistical difference in the mean group of lymph node dissection （2.4±1.5 groups vs.2.4±1.7 groups，P=0.743） and the mean number of lymph node dissection （9.8±6.3 vs.10.1±6.4，P=0.626） between the two groups. The overall 5-year survival rate of the VATS group was significantly higher than that of the thoracotomy group （81.5% vs.67.8%, P=0.001）. Subgroup analysis showed that the 5-year survival rate of pⅠa stage, pⅠb stage, and pⅢa stage was 86.0%, 84.5%, and 58.8% respectively in the VATS group, and 92.9%, 76.4%, and 25.3% respectively in the thoracotomy group. Conclusion Complete VATS lobectomy is technically safe and feasible for patients with early-stage NSCLC. The lymph node dissection extension of complete VATS lobectomy is similar to that of open thoracotomy, and long-term outcome of complete VATS lobectomy is superior to that of open thoracotomy. Randomized controlled trials of large sample size are further needed to demonstrate superiority.
Objective To compare the perioperative results between uniportal and three-portal thoracoscopic lobectomy for non-small cell lung cancer (NSCLC). Methods Electronic databases including PubMed, Web of Science, EMbase, CNKI, Wanfang were systematically searched from the establishment of each database until April 2022. Literature screening, data extraction and bias risk assessment were independently conducted by two researchers. All combined results were performed by RevMan 5.3 and Stata 16.0. The quality of the literature and the risk of bias were evaluated using the Cochrane Bias Risk Assessment Tool. Results Eighteen eligible randomized controlled trials (1 597 patients) were identified eventually, including 800 patients undergoing uniportal thoracoscopic lobectomy and 797 patients undergoing three-portal thoracoscopic lobectomy. Meta-analysis results showed that compared to the three-portal approach, uniportal lobectomy took longer operation time (WMD=7.63, 95%CI 2.36 to 12.91, P=0.005) with less intraoperative blood loss (WMD=–28.81, 95%CI –42.54 to –15.08, P<0.001). Furthermore, patients undergoing uniportal lobectomy achieved lower visual analogue score within 24 hours after the operation (WMD=–1.60, 95%CI –2.26 to –0.94, P<0.001), less volume of drainage after the operation (WMD=–25.30, 95%CI –46.22 to –4.37, P=0.020), as well as shorter drainage duration (WMD=–0.36, 95%CI –0.72 to –0.01, P=0.040). Besides, patients undergoing uniportal lobectomy were also observed with shorter length of hospital stay (WMD=–2.28, 95%CI –2.68 to –1.88, P<0.001) and lower incidence of postoperative complications (RR=0.49, 95%CI 0.38 to 0.63, P<0.001). However, the number of lymph nodes harvested during the operation (WMD=–0.01, 95%CI –0.24 to 0.21, P=0.930) was similar between the two groups. Conclusion Both uniportal and three-portal thoracoscopic lobectomy for NSCLC are safe and feasible. The uniportal approach is superior in reducing short-term postoperative pain, postoperative complications and shortening the length of hospital stay.
Objective To investigate the prognostic value of ERBB2 Exon20ins (Exon20ins) in advanced non-small cell lung cancer (NSCLC) patients receiving first-line chemotherapy combined with immunotherapy. Methods A retrospective analysis was conducted on clinical data from ERBB2-mutant stage IV NSCLC patients who received first-line chemotherapy combined with immunotherapy at West China Hospital of Sichuan University between 2020 and 2024. ERBB2 wild-type patients were matched using propensity score matching. Clinical pathological characteristics, distant metastatic sites, and treatment outcomes were compared among patients with different mutation statuses. The primary endpoint was progression-free survival (PFS), and Kaplan-Meier method was used to plot survival curves. Cox regression analysis was performed to adjust for confounding factors. Results This study included 41 ERBB2-mutant stage IV NSCLC patients, of whom 22 had Exon20ins mutations, and 19 had other ERBB2 mutations. Forty-one ERBB2 wild-type patients were matched for comparison. The mean age of all patients was 60.0±9.3 years, with 61 males (74.4%). A total of 67 patients (81.7%) received chemotherapy combined with immunotherapy, and 15 patients (18.3%) received chemotherapy combined with immunotherapy and anti-angiogenesis therapy. The Exon20ins group showed a higher incidence of lymph node metastasis compared with the ERBB2 other mutation group and the wild-type group (36.4% vs. 15.8% vs. 9.8%, P=0.045). The median PFS in the Exon20ins group was significantly shorter than in the other mutation group (5.8 months vs. 10.3 months, P=0.025) and the wild-type group (5.8 months vs. 8.3 months, P=0.023). Univariate Cox regression analysis indicated that the ERBB2 Exon20ins mutation was an adverse prognostic factor (Exon20ins vs. other ERBB2 mutations, HR=2.9, 95%CI 1.18 - 7.1, P=0.014; Exon20ins vs. wild-type, HR=2.6, 95%CI 1.25 - 5.6, P=0.014). The combination with anti-angiogenesis therapy did not significantly affect the prognosis of PFS (HR=0.66, 95%CI 0.28 - 1.6, P=0.363). Multivariate Cox regression analysis revealed that the ERBB2 Exon20ins mutation was an independent adverse prognostic factor for PFS (Exon20ins vs. other ERBB2 mutations, HR=3.3, 95%CI 1.27 - 8.3, P=0.015; Exon20ins vs. wild-type, HR=2.7, 95%CI 1.2 - 5.88, P=0.014). For the 67 patients receiving chemotherapy combined with immunotherapy, Cox regression analysis showed that the ERBB2 Exon20ins mutation was still associated with poor prognosis in advanced NSCLC (Exon20ins vs. other ERBB2 mutations, HR=3.2, 95%CI 1.12 - 9.1, P=0.030; Exon20ins vs. wild-type, HR=2.5, 95%CI 1 - 5.88, P=0.040). Conclusions Advanced NSCLC patients with ERBB2 Exon20ins mutation have a worse prognosis compared with those with other ERBB2 mutation subtypes or ERBB2 wild-type when treated with first-line chemotherapy combined with immunotherapy. This suggests that ERBB2 Exon20ins mutation, as a particularly refractory mutation, requires the exploration of new combination strategies based on molecular subtyping to improve survival outcomes.
Medical studies have found that tumor mutation burden (TMB) is positively correlated with the efficacy of immunotherapy for non-small cell lung cancer (NSCLC), and TMB value can be used to predict the efficacy of targeted therapy and chemotherapy. However, the calculation of TMB value mainly depends on the whole exon sequencing (WES) technology, which usually costs too much time and expenses. To deal with above problem, this paper studies the correlation between TMB and slice images by taking advantage of digital pathological slices commonly used in clinic and then predicts the patient TMB level accordingly. This paper proposes a deep learning model (RCA-MSAG) based on residual coordinate attention (RCA) structure and combined with multi-scale attention guidance (MSAG) module. The model takes ResNet-50 as the basic model and integrates coordinate attention (CA) into bottleneck module to capture the direction-aware and position-sensitive information, which makes the model able to locate and identify the interesting positions more accurately. And then, MSAG module is embedded into the network, which makes the model able to extract the deep features of lung cancer pathological sections and the interactive information between channels. The cancer genome map (TCGA) open dataset is adopted in the experiment, which consists of 200 pathological sections of lung adenocarcinoma, including 80 data samples with high TMB value, 77 data samples with medium TMB value and 43 data samples with low TMB value. Experimental results demonstrate that the accuracy, precision, recall and F1 score of the proposed model are 96.2%, 96.4%, 96.2% and 96.3%, respectively, which are superior to the existing mainstream deep learning models. The model proposed in this paper can promote clinical auxiliary diagnosis and has certain theoretical guiding significance for TMB prediction.
Objective To investigate the expression and clinical significance of S100A4 protein in tumorstroma of nonsmall cell lung cancer（NSCLC） to study its correlation with invasion, metastasis and prognosis. Methods Immunohistochemical staining（SP method）for S100A4 protein expression was performed in tissue sections from 130 patients with NSCLC operated and to analyze association of S100A4 protein with clinicopathological parameters in lung cancer and prognosis. Results The total positive expression rates of S100A4 protein in stroma of NSCLC was 72.3%. The positive expression rates of S100A4 protein in stroma of squamous cell carcinoma, adenocarcinoma, adenosquamous carcinoma and large cell lung cancer were 84.3%，59.6%，70.0% and 75% respectively.The expression of S100A4 protein was significantly associated with lymph node metastasis (χ2=18.91, P=0.000), distant metastasis(χ2=5.51, P=0.019) and TNM stage (χ2=21.54, P=0.000). The 3 years survival rates of patients whose tumourstroma stained positive for S100A4 was lower than that of patients whose tumourstroma stained negative (36.2% vs. 63.9%, P=0.003). Cox’ risk ratio model analysis indicated that age ≤50 years (OR=1.866), lymph node metastasis(OR=1.826), distant metastasis(OR=6.224), lower histology differentiation and undifferentiation (OR=1.793), TNM stage Ⅲ-Ⅳ (OR=2.573) and positive expression of S100A4 protein in stroma of NSCLC(OR=1.776) were significantly independent prognostic factors which affected survival. Conclusion Expression of S100A4 protein in stroma of NSCLC is significantly associated with invasion, metastasis, TNM stage and prognosis. S100A4 protein might become a marker for prediction of tumor progression of disease and clinical therapy.
In order to study the variation of complex impedance and characteristic parameters on human normal and tumor lung tissue during the extracorporeal time, we established a real part-imaginary part chart of complex impedance on lung tissue which provided the basic theory and the reference data for research on elementary medicine and clinical diagnosis of lung cancer and meanwhile provided prior information for electrical impedance tomography (EIT) research. In the experiment carried out in our laboratory, when operation was finished, we kept the lung cancer tissue and normal tissue neatly separated into the cylindrical testing cavities and kept the temperature and humidity at expected values. Then the measurements of complex impedance property are performed at frequency from 1 000 Hz to 30 MHz using 4294A impedance analyzer of Aglient Company. With time changing, the results showed that there was a significant change occurring on the complex impedance of human normal and tumor lung tissue. However, the impedance of normal lung tissue is greater than that of tumor lung tissue. We consider that this change should be related to the change in extracellular fluid, intracellular fluid and cell membrane.
With the increasing incidence of lung cancer in the elderly, how to improve the quality and speed of postoperative recovery on the basis of ensuring the therapeutic effect has become an important issue in surgical management. The postoperative recovery process of elderly patients with lung cancer shows higher complexity and challenge due to their unique frailty, comorbidity burden and treatment response. This article will focus on the postoperative rehabilitation strategy, systematically sort out the physiological, pathological and treatment response characteristics of postoperative recovery in elderly patients with lung cancer, propose five postoperative rehabilitation intervention modules based on the enhanced recovery after surgery concept, and further integrate the three challenges of insufficient compliance, research heterogeneity and health economic barriers, and propose a breakthrough method with precise rehabilitation and digital management as the core, providing theoretical support and practical guidance for the optimization and implementation of postoperative rehabilitation programs for elderly patients with lung cancer.
Objective To investigate the regulatory effects of SHP2 inhibition on the secretion of macrophage-associated inflammatory factors in KRAS-mutant lung cancer cells and to elucidate the underlying mechanisms by which this inhibition remodels the tumor immune microenvironment. Methods Three KRAS-mutant lung cancer cell lines were treated with the SHP2 inhibitor SHP099. The levels of phosphorylated SHP2 and ERK were assessed by Western blot. The expression levels of related inflammatory factors were analyzed using Luminex assay and qRT-PCR assay. Transcriptome sequencing was performed to identify differentially expressed genes and conduct KEGG pathway enrichment analysis. The expression of CXCL8 was validated by flow cytometry and Western blot. Survival analysis and gene set correlation analysis were conducted based on the TCGA database. Results SHP099 significantly inhibited the expression of p-SHP2 and p-ERK proteins, and reduced the secretion of multiple macrophage-related inflammatory factors. qRT-PCR confirmed a decrease in CXCL8 mRNA levels. Transcriptome analysis revealed significant enrichment of the rheumatoid arthritis pathway. Flow cytometry and Western blot validated a significant reduction in CXCL8 protein expression. Survival analysis showed that patients with KRAS-mutant lung adenocarcinoma and high CXCL8 expression had a shorter overall survival, and CXCL8 was positively correlated with M2 macrophage marker genes. Conclusion Targeted inhibition of SHP2 can suppress the expression of some macrophage-related inflammatory factors in KRAS-mutant lung cancer cells, with the most significant inhibition of CXCL8 expression. The mechanism may involve SHP2 regulating the transcription factor AP-1.
Surgical resection is the only radical method for the treatment of early-stage non-small cell lung cancer. Intraoperative frozen section (FS) has the advantages of high accuracy, wide applicability, few complications and real-time diagnosis of pulmonary nodules. It is one of the main means to guide surgical strategies for pulmonary nodules. Therefore, we searched PubMed, Web of Science, CNKI, Wanfang and other databases for nearly 30 years of relevant literature and research data, held 3 conferences, and formulated this consensus by using the Delphi method. A total of 6 consensus contents were proposed: (1) Rapid intraoperative FS diagnosis of benign and malignant diseases; (2) Diagnosis of lung cancer types including adenocarcinoma, squamous cell carcinoma, others, etc; (3) Diagnosis of lung adenocarcinoma infiltration degree; (4) Histological subtype diagnosis of invasive adenocarcinoma; (5) The treatment strategy of lung adenocarcinoma with inconsistent diagnosis on degree of invasion between intraoperative FS and postoperative paraffin diagnosis; (6) Intraoperative FS diagnosis of tumor spread through air space, visceral pleural invasion and lymphovascular invasion. Finally, we gave 11 recommendations in the above 6 consensus contents to provide a reference for diagnosis of pulmonary nodules and guiding surgical decision-making for peripheral non-small cell lung cancer using FS, and to further improve the level of individualized and precise diagnosis and treatment of early-stage lung cancer.