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Objectives: While segmentectomy is considered a viable option for small peripheral non-small-cell lung cancer, its efficacy for central lesions remains uncertain. This study aimed to assess the oncological outcomes of segmentectomy for central lesions compared to peripheral ones., Methods: We retrospectively examined 338 clinical stage IA non-small-cell lung cancer patients who underwent thoracoscopic anatomical segmentectomy at our institution from January 2013 to December 2021. Patients were divided into 2 groups based on intrapulmonary tumour location: inner two-thirds (central group, n = 82) and outer one-third (peripheral group, n = 256)., Results: The gender, body mass index, performance score, smoking, comorbidities and preoperative pulmonary function were similar in both groups. On computed tomography images, tumour diameter and consolidation-to-tumour ratio were comparable between the groups. The central group had significantly greater tumour-to-pleura distances [mm, 23 (18-27) vs 11 (8-14); P < 0.001], shorter margin distances [mm, 20 (15-20) vs 20 (20-20); P < 0.001] and larger resected lung volumes based on subsegment count [4 (3-6) vs 3 (3-5); P = 0.004] than the peripheral group. Surgery duration, bleeding, hospitalization or drainage period, mortality, readmission and pathological stage were equivalent between the groups. The central group showed significantly more postoperative pleural effusions (5% vs 1%; P = 0.03) than the peripheral group, with no adverse impact on postoperative pulmonary functions. During the follow-up period, local-only recurrence rates were 0% and 8% in the respective groups (Gray test P = 0.07), and total recurrence rates were 6% and 11% (Gray test P = 0.70), with no significant differences. Moreover, no significant inter-group difference in overall survival rates was observed (82% vs 93%; P = 0.15)., Conclusions: Segmentectomy may be a promising therapeutic option for early-stage non-small-cell lung cancer located in the inner two-thirds of the parenchyma., (© The Author(s) 2024. Published by Oxford University Press on behalf of the European Association for Cardio-Thoracic Surgery. All rights reserved.)

Background: CD8 + tumor infiltrating lymphocytes (TILs) are often observed in non-small cell lung cancers (NSCLC). However, the characteristics of CD8 + TILs, especially T-cell populations specific for tumor antigens, remain poorly understood., Methods: High throughput single-cell RNA sequencing and single-cell T-cell receptor (TCR) sequencing were performed on CD8 + TILs from three surgically-resected lung cancer specimens. Dimensional reduction for clustering was performed using Uniform Manifold Approximation and Projection. CD8 + TIL TCR specific for the cancer/testis antigen KK-LC-1 and for predicted neoantigens were investigated. Differentially-expressed gene analysis, Gene Set Enrichment Analysis (GSEA) and single sample GSEA was performed to characterize antigen-specific T cells., Results: A total of 6998 CD8 + T cells was analyzed, divided into 10 clusters according to their gene expression profile. An exhausted T-cell (exhausted T (Tex)) cluster characterized by the expression of ENTPD1 (CD39), TOX , PDCD1 (PD1), HAVCR2 (TIM3) and other genes, and by T-cell oligoclonality, was identified. The Tex TCR repertoire (Tex-TCRs) contained nine different TCR clonotypes recognizing five tumor antigens including a KK-LC-1 antigen and four neoantigens. By re-clustering the tumor antigen-specific T cells (n=140), it could be seen that the individual T-cell clonotypes were present on cells at different stages of differentiation and functional states even within the same Tex cluster. Stimulating these T cells with predicted cognate peptide indicated that TCR signal strength and subsequent T-cell proliferation and cytokine production was variable but always higher for neoantigens than KK-LC-1., Conclusions: Our approach focusing on T cells with an exhausted phenotype among CD8 + TILs may facilitate the identification of tumor antigens and clarify the nature of the antigen-specific T cells to specify the promising immunotherapeutic targets in patients with NSCLC., Competing Interests: Competing interests: This study was partly funded by NEC Corporation., (© Author(s) (or their employer(s)) 2023. Re-use permitted under CC BY-NC. No commercial re-use. See rights and permissions. Published by BMJ.)

Background: Among anatomical sublobar resection techniques for non-small cell lung cancer (NSCLC), the clinical benefit of subsegmentectomy remains unclear. We investigated whether anatomical sublobar resection including subsegmentectomy-segmental resection with subsegmental additional resection or subsegmental resection alone-is an effective and feasible surgical procedure for NSCLC., Methods: We retrospectively reviewed data of 285 patients with clinical stage I NSCLC who underwent anatomical sublobar resection at our institution from January 2013 to March 2021 and compared surgical outcomes between patients who underwent anatomical sublobar resection including (IS; n = 50) and excluding (ES; n = 235) subsegmentectomy., Results: No significant intergroup differences were noted in terms of age, sex, smoking, comorbidities, tumor size or location, consolidation tumor ratio, and preoperative pulmonary function. The IS group had more preoperative computed tomography-guided markings (34 vs. 15%; p = .004) and smaller resected lung volumes converted to the total subsegment number [3 (2-4) vs. 3 (3-6); p = .02] than the ES group. No significant differences in margin distance [mm, 20 (15-20) vs. 20 (20-20); p = .93], readmission rate (2% vs. 3%; p > .99), and intraoperative (8% vs. 7%; p = .77) or postoperative (8% vs. 10%; p = .80) complication rates were observed, and the 5-year local recurrence-free survival (91% vs. 90%; p = .92) or postoperative pulmonary function change were comparable between both groups., Conclusions: Although further investigations are required, anatomical sublobar resection including subsegmentectomy for clinical stage I NSCLC could be an acceptable therapeutic option., (© 2023. The Author(s) under exclusive licence to Société Internationale de Chirurgie.)

Introduction: The differences in biological characteristics among different genotypes of classical EGFR mutations have not been clarified. This study aimed to clarify the clinical and biological differences between L858R and 19 deletion in NSCLC., Methods: We analyzed a cohort of 191 consecutive cases of surgically resected NSCLC harboring EGFR driver mutations (L858R or 19 deletion) in which curative resection was performed in Aichi Cancer Center Hospital, Nagoya, Japan, from January 2006 to September 2021 and in which recurrence subsequently developed. We also subjected 61 surgically resected NSCLC specimens harboring EGFR driver mutations (L858R or 19 deletion) to an RNA sequencing analysis., Results: In patients with stage I disease, the median time to recurrence did not differ to a statistically significant extent between the types of EGFR mutations; however, among those with stage II and III disease, the median time to recurrence in patients with the L858R genotype tended to be shorter in comparison to those with 19 deletion (log-rank test, p = 0.47 and 0.46, respectively). In comparison to 19 deletion tumors, L858R tumors had higher cytological malignancy (e.g., mitotic ability) and showed stronger immunogenicity., Conclusion: L858R and 19 deletion tumors are likely to have a slight difference in the time to recurrence. They suggest that even in EGFR driver tumors, which are treated as the same disease category, the biological characteristics of the tumors are different, which may leave room for innovations in postoperative treatment and treatment at recurrence., (© 2022 S. Karger AG, Basel.)

Objectives: We retrospectively analysed the surgical prognosis of patients with pathological stage I non-small-cell lung cancer (NSCLC) who after complete resection underwent low-dose computed tomography (LDCT) or conventional CT as postoperative surveillance., Methods: We investigated 416 patients who underwent lobectomy or segmentectomy between January 2013 and December 2016. We compared the prognosis between the LDCT and conventional CT groups using the propensity score-matched analysis., Results: The median follow-up period was 57 months. Cancer recurrence occurred in 47 patients (11.3%). In the entire cohort (n = 416), recurrence-free survival (RFS) and overall survival (OS) were better in the LDCT group (P = 0.001 and 0.002, respectively). Both intrathoracic recurrence and distant metastasis were higher in the conventional group (P = 0.015 and 0.009, respectively). However, there was no statistical difference in the factors leading to recurrence detection (routine radiological examination, symptoms and elevated tumour markers: all P > 0.05). Both groups were matched using a ratio of 1:1. The area under the receiver operating characteristic curve was 0.788. A total of 226 patients were successfully matched. After matching, there was no statistical difference between the 2 groups for RFS and OS (P = 0.263 and 0.226). There were also no statistical differences in recurrence rate, the factors leading to recurrence detection or recurrence site (all P > 0.05)., Conclusions: After using propensity score matched, RFS and OS did not differ significantly between LDCT and conventional CT groups. Retrospective comparisons suggest no disadvantages of using LDCT for postoperative surveillance of pathological stage I NSCLC. Further validation will be needed in the future., (© The Author(s) 2022. Published by Oxford University Press on behalf of the European Association for Cardio-Thoracic Surgery. All rights reserved.)

Background: This study assessed the clinicopathological background of early-stage KRAS-mutated non-small-cell lung cancer and analyzed the biological process of KRAS-mutated tumor using an RNA sequencing procedure., Patients and Methods: We used a cohort of consecutive series of 179 surgically resected early-stage non-small-cell lung cancers harboring KRAS mutations and analyzed the clinicopathological features, including the KRAS genotypes, affecting the recurrence-free survival and prognosis. Consequently, we performed RNA sequencing to determine the gene expression profiles of nineteen KRAS-mutated non-small-cell cancers., Results: The most common KRAS genotype was p.G12C (57; 31.8%). A high p-stage (hazard ratio [HR], 4.181; P < 0.0001) and solid predominant adenocarcinoma histology (HR, 2.343; P = 0.0076) were significant independent prognostic factors for the recurrence-free survival. A high p-stage (HR, 3.793; P < 0.0001), solid predominant adenocarcinoma histology (HR, 2.373; P = 0.0147), and KRAS p.G12V genotype (HR, 1.975; P = 0.0407) were significant independent prognostic factors for the overall survival. A gene expression analysis of the two factors revealed the p.G12V genotype to be closer to those of stem cells, and the traits of e an enhanced fatty acid and amino acid metabolism. as well as And a solid predominant phenotype were shown to an acquired a trait that can withstand hypoxia and the effect of prostaglandin-endoperoxide synthase., Conclusion: The KRAS p.G12V genotype and solid predominant adenocarcinoma phenotype may be independent predictive factors of a poor clinical course in resected early-stage non-small-cell lung cancers, possibly due to the differentiation tendency observed in stem cells, the trait of an enhanced fatty acid and amino acid metabolism, and the effect of prostaglandin-endoperoxide synthase., (Copyright © 2022. Published by Elsevier Inc.)

Concurrent EGFR mutation and ROS1 rearrangement is a rare event in early-stage non-small-cell lung cancer. In addition, a co-occurring de novo EGFR T790M mutation in such a case is extremely rare. We encountered a 72-year-old woman who developed 3 early-stage lung lesions synchronously, one each harboring EGFR L858R, ROS1 rearrangement, and EGFR L858R and de novo T790M. These three nodules were pathologically time-matched lepidic predominant adenocarcinoma with small invasive lesions, which may reflect the concept of field cancerization with driver mutations., (Copyright © 2022. Published by Elsevier Inc.)

Background: A better understanding of the tumor immune microenvironment (TIME) will facilitate the development of prognostic biomarkers and more effective therapeutic strategies in patients with lung cancer. However, little has been reported on the comprehensive evaluation of complex interactions among cancer cells, immune cells, and local immunosuppressive elements in the TIME., Methods: Whole-exome sequencing and RNA sequencing were carried out on 113 lung cancers. We performed single sample gene set enrichment analysis on TIME-related gene sets to develop a new scoring system (TIME score), consisting of T-score ( t umor proliferation), I-score (antitumor i mmunity) and S-score (immuno s uppression). Lung cancers were classified according to a combination of high or low T-score, I-score, and S-scores (eight groups; G1-8). Clinical and genomic features, and immune landscape were investigated among eight groups. The external data sets of 990 lung cancers from The Cancer Genome Atlas and 76 melanomas treated with immune checkpoint inhibitors (ICI) were utilized to evaluate TIME scoring and explore prognostic and predictive accuracy., Results: The representative histological type including adenocarcinoma and squamous cell carcinoma, and driver mutations such as epidermal growth factor receptor and TP53 mutations were different according to the T-score. The numbers of somatic mutations and predicted neoantigens were higher in T hi (G5-8) than T lo (G1-4) tumors. Immune selection pressure against neoantigen expression occurred only in T hi and was dampened in T hi /I lo (G5-6), possibly due to a reduced number of T cells with a high proportion of tumor specific but exhausted cells. T hi /I lo /S hi (G5) displayed the lowest immune responses by additional immune suppressive mechanisms. The T-score, I-score and S-scores were independent prognostic factors, with survival curves well separated into eight groups with G5 displaying the worst overall survival, while the opposite group T lo /I hi /S lo (G4) had the best prognosis. Several oncogenic signaling pathways influenced on T-score and I-scores but not S-score, and PI3K pathway alteration correlated with poor prognosis in accordance with higher T-score and lower I-score. Moreover, the TIME score predicted the efficacy of ICI in patients with melanoma., Conclusion: The TIME score capturing complex interactions among tumor proliferation, antitumor immunity and immunosuppression could be useful for prognostic predictions or selection of treatment strategies in patients with lung cancer., Competing Interests: Competing interests: None declared., (© Author(s) (or their employer(s)) 2022. Re-use permitted under CC BY-NC. No commercial re-use. See rights and permissions. Published by BMJ.)

Background and Objectives: Panel-based next-generation sequencing (NGS) has been carried out in daily clinical settings for the diagnosis and treatment guidance of patients with non-small cell lung cancer (NSCLC). The success of genomic tests including NGS depends in large part on preparing better-quality DNA or RNA; however, there are no established operating methods for preparing genomic DNA and RNA samples. Materials and Methods: We compared the following two quantitative methods, the QubitTM and NanoDropTM, using 585 surgical specimens, 278 biopsy specimens, and 82 cell block specimens of lung cancer that were used for genetic tests, including NGS. We analyzed the success rate of the genomic tests, including NGS, which were performed with DNA and RNA with concentrations that were outliers for the Qubit Fluorometer. Results: The absolute value for DNA concentrations had a tendency to be higher when measured with NanoDropTM regardless of the type of specimen; however, this was not the case for RNA. The success rate of DNA-based genomic tests using specimens with a concentration below the lower limit of QubitTM detection was as high as approximately 96%. At less than 60%, the success rate of RNA-based genomic tests, including RT-PCR, was not as satisfactory. The success rates of the AmpliSeqTM DNA panel sequencing and RNA panel sequencing were 77.8% and 91.5%, respectively. If at least one PCR amplification product could be obtained, then all RNA-based sequencing was performed successfully. Conclusions: The concentration measurements with NanoDropTM are reliable. The success rate of NGS with samples at concentrations below the limit of detection of QubitTM was relatively higher than expected, and it is worth performing PCR-based panel sequencing, especially in cases where re-biopsy cannot be performed.

Background and Objectives : Lobe-specific nodal dissection (L-SND) is currently acceptable for the dissection of early-stage non-small cell lung cancer (NSCLC) but not for cancers of more advanced clinical stages. We aimed to assess the efficacy of L-SND, compared to systemic nodal dissection (SND). Materials and Methods : We retrospectively collected the clinical data of patients with carcinoembryonic antigen (CEA) abnormality who underwent complete resection of NSCLC via lobectomy or more in addition to either SND or L-SND at two cancer-specific institutions from January 2006 to December 2017. Results : A total of 799 patients, including 265 patients who underwent SND and 534 patients who underwent L-SND, were included. On multivariate analysis, thoracotomy, more than lobectomy, cN1-2, advanced pathological stage, adjuvant treatment, and EGFR or ALK were strongly associated with SND. No significant differences were found in overall survival, disease-free survival, and overtime survival after propensity adjustment ( p = 0.09, p = 0.11, and p = 0.50, respectively). There were no significant differences in local ( p = 0.16), regional ( p = 0.72), or distant ( p = 0.39) tumor recurrence between the two groups. Conclusions : SND did not improve the prognosis of NSCLC patients with CEA abnormality. Complete pulmonary resection via L-SND seems useful for NSCLC patients with CEA abnormality.

Background/aim: Circulating tumor cells (CTCs) is one of the promising markers that predict dissemination and metastases. This study aimed to identify the relationship between CTCs in pulmonary vein (PuV) and spread through air space (STAS) in non-small cell lung cancers., Materials and Methods: We applied a cytology-based microfluidic platform for rare cell isolation. Twenty-four patients were enrolled., Results: The rate of CTC detection in PuV was 79.2%, and STAS was observed in 54.2% of the samples. When the definitive cut-off value was 1 CTC/1 ml, of the 14 CTC-PuV-high cases, 11 (78.6%) were STAS-positive, whereas 2 of the 10 (20.0%) CTC-PuV-low cases were STAS-positive, and the difference between the two groups was statistically significant (p=0.02). CTC-PuV-high exhibited a significantly poorer survival (p<0.01)., Conclusion: The higher frequency of STAS is significantly associated with a higher number of CTCs in PuV, and the combination of STAS and CTC was significantly associated with poor prognosis., (Copyright © 2021 International Institute of Anticancer Research (Dr. George J. Delinasios), All rights reserved.)

Objectives: This study aims to assess the feasibility and impact on long-term pulmonary function of chest drain removal on the operation day following thoracoscopic right upper lobectomy for clinical stage I non-small cell lung cancer., Methods: We retrospectively evaluated the data of 116 patients between May 2013 and March 2019. We evaluated the correlations of clinical parameters of chest drain removal and medium- and long-term pulmonary function by comparing removal on operation day (R group) and retainment (D group)., Results: The R group comprised 64 patients, and the D group had 52 patients. Fifty patients (96.2%) in the D group had chest drain removed within 3 postoperative days. Since February 2016, chest drain removal on operation day was performed in 64 of 74 patients (86.5%) according to our chest drain removal protocol. Removal of chest drains on operation day was associated with shorter postoperative hospitalization (p < 0.01) and lower postoperative complications ≧ grade II of the Clavien-Dindo classification (p = 0.026). Only one patient in the R group needed reinsertion. The R group had greater spirometry results at 3- and 12-postoperative months (POM). R group patients had statistically improved pulmonary functions from 3 to 12POM, while those in the D Group were stagnated at 6POM., Conclusions: Removal of chest drains on operation day using our protocol is safe and feasible for thoracoscopic right upper lobectomy. This protocol was statistically associated with slightly better long-term pulmonary function, which could not bring clinically meaningful medium- and long-term benefit.

Programmed death-ligand 1 (PD-L1) expression is a predictor of immune checkpoint inhibitor (ICI) treatment efficacy. The clinical efficacy of ICIs for non-small-cell lung cancer (NSCLC) patients harboring major mutations, such as EGFR or ALK mutations, is limited. We genotyped 190 patients with advanced lung adenocarcinomas who received nivolumab or pembrolizumab monotherapy, and examined the efficacy in NSCLC patients with or without major mutations. Among the patients enrolled in the genotyping study, 47 patients harbored EGFR mutations, 25 patients had KRAS mutations, 5 patients had a HER2 mutation, 6 patients had a BRAF mutation, and 7 patients had ALK rearrangement. The status of PD-L1 expression was evaluated in 151 patients, and the rate of high PD-L1 expression (≥50%) was significantly higher in patients with ALK mutations. The progression-free survival was 0.6 (95% CI: 0.2-2.1) months for ALK -positive patients and 1.8 (95% CI: 1.2-2.1) months for EGFR -positive patients. All patients with ALK rearrangement showed disease progression within three months from the initiation of anti-PD-1 treatment. Our data suggested that ICI treatment was significantly less efficacious in patients with ALK rearrangement than in patients with EGFR mutations, and PD-L1 expression was not a critical biomarker for ICI treatment for patients with one of these mutations.

One in four non-small cell lung cancer (NSCLC) patients are diagnosed at an early-stage. Following the results of the National Lung Screening Trial that demonstrated a survival benefit for low-dose computed tomography screening in high-risk patients, the incidence of early-stage NSCLC is expected to increase. Use of 18F-fluorodeoxyglucose positron emission tomography/computed tomography during initial diagnosis of these early-stage lesions has been increasing. Traditionally, positron emission tomography/computed tomography scans have been utilized for mediastinal nodal staging and to rule out distant metastases in suspected early-stage NSCLC. In clinically node-negative NSCLC, the use of sublobar resection and selective lymph node dissection has been increasing as a therapeutic option. The higher rate of locoregional recurrences after limited resection and the significant incidence of occult lymph node metastases underscores the need to further stratify clinically node-negative NSCLC in order to select patients for limited resection versus lobectomy with complete mediastinal lymph node dissection. In this report, we review the published data, and discuss the significance and potential role of 18F-fluorodeoxyglucose positron emission tomography/computed tomography evaluation for clinically node-negative NSCLC. Consequently, the literature review demonstrates that maximum standardized uptake value is a predictive factor for occult nodal metastasis with an accuracy of 55-77%. In addition, maximum standardized uptake value is a predictor for worse overall, as well as disease-free, survival., (© 2019 The Authors. Thoracic Cancer published by China Lung Oncology Group and John Wiley & Sons Australia, Ltd.)

Recent improvement of outcomes for resected non-small cell lung cancer (NSCLC) has been contributed not only by increased detection of early-stage disease and improvement of preoperative diagnosis/perioperative management but also by improvement of multimodality treatment. The introduction of newly developed systemic therapies including molecular targeted agents and immune checkpoint inhibitors dramatically changed clinical outcomes of advanced NSCLC. Accordingly, the role of surgery during the multimodality treatment will be changed more than ever. In this article, we overviewed the current status of the multimodality treatment for clinical stageⅢ (N2)disease and postoperative adjuvant therapy and discussed the role of surgery during these situations. We also discussed the future perspectives of the role of surgery during the multimodality treatment for advanced NSCLC.

Background and Objective: Long-term pulmonary function which might include compensatory response (CR) significantly influences quality of life of long-term survivor after major lung resection. We investigated long-term pulmonary function after major lung resection., Methods: A total of 137 patients who had undergone lobar resection for non-small cell lung cancer (NSCLC) from May 2013 to June 2014 had spirometry at 10-14 months after surgery. Actual post-operative forced expiratory volume in 1 s (FEV 1 ) (FEV 1apo )/predicted post-operative FEV 1 (FEV 1ppo ), actual post-operative forced vital capacity (FVC) (FVC apo )/predicted post-operative FVC (FVC ppo ), its relationship with clinicopathological factors and immunohistochemistry for pro-surfactant protein C (pro-SPC), thyroid transcription factor-1 (TTF-1) and vascular endothelial growth factor receptor 2 (VEGFR2) were investigated., Results: FEV 1apo /FEV 1ppo showed strong correlation with FVC apo /FVC ppo (r = 0.628; P < 0.001). We defined greater CR as both FEV 1apo /FEV 1ppo and FVC apo /FVC ppo were >120%. Greater CR was significantly associated with decreased smoking index (P < 0.001) and greater resected subsegments (P = 0.037). The never-smoker group revealed significantly greater CR compared with the smoker group in both FEV 1apo /FEV 1ppo (119.9 ± 12.5% vs 107.5 ± 14.2%; P = 0.030) and FVC apo /FVC ppo (117.9 ± 9.98% vs 107.2 ± 13.1%; P = 0.046) in case-matched comparison. The expression of pro-SPC, TTF-1 and VEGFR2 in the normal lung parenchyma of greater CR group was significantly higher than those of lesser CR group (P < 0.001 for each). In addition, pro-SPC, TTF-1 and VEGFR2 expressions showed a significant correlation to the degree of CR especially in the smoker group (r = 0.631, 0.705 and 0.732, respectively; P < 0.001 for each)., Conclusion: Our data suggest that smokers may develop lesser long-term CR after major lung resection. Decreased expression of pro-SPC, TTF-1 and VEGFR2 may indicate decreased capacity of CR, especially in patients who smoke., (© 2016 Asian Pacific Society of Respirology.)

Objective: A precise preoperative diagnosis of in situ or minimally invasive carcinoma may identify patients who can be treated by limited resection. Although some clinical trials of limited resection for lung cancer have started, it will take a long time before the results will be published. We have already reported a large-scale study of limited resection. We herein report the data for a subclass analysis according to differences in pathology., Methods: Data from multiple institutions were collected on 1710 patients who had undergone limited resection (segmentectomy or wedge resection) for cT1N0M0 non-small cell carcinoma. The disease-free survival (DFS) and recurrence-free proportion (RFP) were analyzed. Small cell carcinomas and carcinoid tumors were excluded from this analysis. Adenocarcinomas were sub-classified into four groups using two factors, the ratio of consolidation to the tumor diameter (C/T) and the tumor diameter alone., Results: The median patient age was 64 (20-75) years old. The mean maximal diameter of the tumors was 1.5 ± 0.5 cm. The DFS and RFP at 5 years based on the pathology were 92.2 and 94.7 % in adenocarcinoma (n = 1575), 76.3 and 82.4 % in squamous cell carcinoma (SqCC) (n = 100), and 73.6 and 75.9 % in patients with other tumors (n = 35). The prognosis of adenocarcinoma in both groups A (C/T ≤0.25 and tumor diameter ≤2.0 cm) and B (C/T ≤0.25 and tumor diameter >2.0 cm) was good. In SqCC, only segmentectomy was a favorable prognostic factor. In the groups with other pathologies, large cell carcinomas were worse in prognosis (the both DFS and RFP: 46.3 %)., Conclusion: Knowing the pathological diagnosis is important to determine the indications for limited resection. Measurement of the tumor diameter and C/T was useful to determine the indications for limited resection for adenocarcinoma. Limited resection for adenocarcinomas is similar with a larger resection, while the technique should be performed with caution in squamous cell carcinoma and other pathologies.

Objectives: In 2015, we reported the outcomes of patients undergoing intentional limited resection (ILR) for non-small-cell lung cancer (NSCLC) from a retrospective, multi-institutional large database in Japan. Here, we analyse the clinicopathological characteristics of the patients extracted from this database with late recurrence and compare them with those with early recurrence., Methods: Of 1538 patients in the database with cT1aN0M0 NSCLC, 92 (6%) had recurrence. In this study, early recurrence was defined as recurrence within 5 years and late recurrence as recurrence beyond 5 years after surgery. We compared the clinicopathological characteristics and post-recurrence survival (PRS) between patients with early and late recurrence., Results: Of the 92 patients with recurrence, 21 (23%) had late recurrence. Compared with the early recurrence group, there were significantly more adenocarcinomas and local recurrences in the late recurrence group (P = 0.04 for both). The 3- and 5-year PRS rates were 53 and 24%, respectively, and the median PRS period was 38 months. There were no significant differences in the PRS curves between patients with early and late recurrence (P = 0.12). Only 3 patients (0.2%) had recurrence more than 10 years after ILR. Of the 21 late-recurrence patients, 17 (81%) had tumours with a consolidation/tumour ratio (CTR) >0.25., Conclusions: Late recurrence occurred in 21 (23%) of 92 patients with recurrence after ILR for cT1aN0M0 NSCLC. Late recurrence was more likely to involve adenocarcinoma and local recurrence. It is thus considered reasonable to follow patients with a CTR >0.25 for 10 years after ILR., (© The Author 2016. Published by Oxford University Press on behalf of the European Association for Cardio-Thoracic Surgery. All rights reserved.)

Background: The immune system has been shown to play an important role in preventing cancer progression. The neutrophil-lymphocyte ratio (NLR) has been proposed to be an indicator of a systemic inflammatory response. We investigated the prognostic significance of NLR in patients with completely resected stage I non-small lung cancer (NSCLC)., Methods: A series of 343 pathological stage I NSCLC patients, completely resected between 2000 and 2008 at a single institution, were evaluated retrospectively. Perioperative clinical and laboratory data were collected, and the cohort was divided into two groups according to preoperative NLR. We examined the correlation between NLR and clinicopathological parameters and determined the prognostic significance., Results: High NLR was significantly correlated with patients of older age (p = 0.045), preoperative hypoalbuminemia (p = 0.030), and nonadenocarcinoma histology (p = 0.045). Upon univariate analysis, the high NLR group had significantly lower 5-year recurrence-free survival (81.2 vs. 59.9 %, p < 0.001) and 5-year overall survival (89.2 vs. 72.8 %, p < 0.001) than the low NLR group. Multivariate analysis showed that NLR was an independent prognostic factor (hazard ratio 2.141, 95 % confidence interval; 1.306-3.515, p = 0.003). In terms of initial recurrent sites, the proportion of patients who developed distant metastasis was significantly higher in the high NLR group than in the low NLR group (p < 0.001)., Conclusions: Preoperative high NLR is a significant predictor of poor prognosis and is associated with more frequent distant metastasis in patients with completely resected stage I NSCLC. This readily available and simply calculated ratio provides useful information for the clinician to consider in terms of perioperative management.

Background: Early detection of non-small-cell lung cancer (NSCLC) and accurate prognostic risk assessment could improve patient outcome. We examined the significance of urinary N(1), N(12)-diacetylspermine (DiAcSpm) in the detection and prognostic stratification of NSCLC patients., Methods: A DiAcSpm/cutoff ratio (DASr) was established for 260 NSCLC patients, 99 benign lung disease patients, and 140 healthy volunteers, using colloidal gold aggregation methods. The DASr was compared between patients and healthy controls, and the prognostic significance of DASr was examined., Results: The median urinary DASr of NSCLC patients was significantly higher than that of healthy controls (0.810 vs 0.534, P<0.001). The DASr was higher in squamous cell carcinoma (SqCC) patients than in adenocarcinoma patients (1.18 vs 0.756, respectively, P=0.039). An increased urinary DASr value was significantly associated with pathological stage, other histological invasive factors and unfavourable outcomes in patients with completely resected NSCLC. Multivariate Cox regression analysis showed that increased urinary DASr was an independent prognostic factor (hazard ratio=4.652, 95% confidence interval (CI), 2.092-10.35; P<0.001)., Conclusions: Urinary DASr was significantly increased in NSCLC, especially in SqCC. Urinary DASr was an independent poor prognostic indicator in patients with completely resected NSCLC. The DASr could be a useful biomarker for detecting malignancies and predicting prognosis.

Objectives: Despite recent progress in diagnostic technology and therapeutic approaches to non-small-cell lung cancer (NSCLC), 30-75% of patients develop tumour recurrence after resection. However, the details of post-recurrence survival (PRS) are not well understood. We aimed to investigate the predictors of PRS in patients with NSCLC initially completely resected., Methods: A series of 568 NSCLC patients who had undergone complete resection between 2000 and 2009 were evaluated retrospectively. Patients who had developed recurrent NSCLC after complete resection were subjected to the current analysis. We examined PRS using the Kaplan-Meier method and multivariate Cox regression analyses., Results: Of the 568 patients, 138 (24.3%) were identified as having disease recurrence. The 2-year and 5-year PRS rates were 44.6 and 25.9%, respectively, while the median PRS time was 22.5 months. Non-adenocarcinoma histology [hazard ratio (HR) = 2.825, 95% confidence interval (CI): 1.825-4.367, P < 0.001], serum carcinoembryonic antigen (CEA) at recurrence ≥5.0 mg/dl (HR = 2.205, 95% CI: 1.453-3.344, P < 0.001) and no systemic chemotherapy (HR = 2.137, 95% CI: 1.304-3.247, P = 0.002) were independent prognostic factors for PRS., Conclusions: The current results showed that non-adenocarcinoma histology, elevated serum CEA at recurrence and no systemic chemotherapy were independent unfavourable post-recurrence prognostic factors. The current data can be informative for patient follow-up after complete resection and further clinical investigation may give us more information about PRS and accurate treatment strategy for recurrent NSCLC after initial complete resection., (© The Author 2015. Published by Oxford University Press on behalf of the European Association for Cardio-Thoracic Surgery. All rights reserved.)

Background: To select optimal candidates for limited lung resection, it is necessary to accurately differentiate the non-invasive tumors from other small-sized lung cancer. Urinary N(1), N(12)-diacetylspermine (DiAcSpm) has been reported to be a useful tumor marker for various cancers. We aimed to examine the correlation between preoperative urinary DiAcSpm levels and specific clinicopathological characteristics such as the histological tumor invasiveness in patients with clinical stage IA non-small cell lung cancer (NSCLC)., Methods: We defined non-invasive tumors as NSCLC showing no vascular invasion, lymphatic permeation, pleural invasion, or lymph node metastasis. Preoperative urine samples were obtained from 516 consecutive patients with NSCLC resected at our institution between April 2008 and January 2013. Urinary DiAcSpm values were determined for all preoperative urine samples using the colloid gold aggregation procedure. Among these patients, 171 patients with clinical stage IA NSCLC met the criteria of our study cohort. Finally, we investigated the correlation between non-invasive tumor and urinary DiAcSpm levels., Results: The median urine DiAcSpm for males was 147.2 nmol/g creatinine and 161.8 nmol/g creatinine in females. These median values were set as the cut-off values for each gender. Patients with higher urinary DiAcSpm levels frequently had significantly elevated serum CEA (p = 0.023) and greater lymph node metastasis (p = 0.048), lymphatic permeation (p = 0.046), and vascular invasion (p = 0.010). Compared with patients with non-invasive tumors, patients with invasive tumors had a tumor size >2.0 cm (p = 0.001), serum CEA >5.0 mg/dL (p < 0.001), high urinary DiAcSpm (p = 0.002), and a tumor disappearance rate (TDR) <0.75 (p < 0.001). Multivariate analysis revealed that a tumor size < 2.0 cm (RR = 2.901, 95% CI; 1.372-6.136, p = 0.005), high urinary DiAcSpm (RR = 3.374, 95% CI; 1.547-7.361, p = 0.002), and TDR < 0.75 (RR = 4.673, 95% CI; 2.178-10.027, p < 0.001) were independent predictors for invasive tumors., Conclusions: We successfully showed that there was a significant correlation between urinary DiAcSpm levels and pathological tumor invasiveness in patients with clinical stage IA NSCLC. Further research would elucidate the clinical usefulness of DiAcSpm levels as a predictor of tumor invasiveness.

Objectives: A precise preoperative diagnosis of 'very early' lung carcinoma may identify patients who can undergo curative surgery with limited resections., Methods: Data from a multi-institutional project were collected on 1737 patients who had undergone limited resections (segmentectomy or wedge resection) for T1N0M0 non-small-cell carcinomas. As it was expected, this study was predominantly including ground glass nodules. Computed tomography was used to obtain the ratio of consolidation to the maximal tumour diameter to determine invasive potential of the tumours. Overall and disease-free survivals and recurrence-free proportions were analysed., Results: Median age was 64 years. Mean maximal diameter of the tumours was 1.4±0.5 cm. Overall and recurrence-free survivals after limited lung resection were 94.0 and 91.1% at 5 years, respectively. Recurrence-free proportions were 93.7% at 5 years. Unfavourable prognostic factors in overall survival were lymph node metastasis, interstitial pneumonia, male gender, older age, comorbidities (cardiac disease, diabetes etc.) and consolidation/tumour ratio (C/T)≤0.25. C/T≤0.25 predicted good outcomes especially in cT1aN0M0 disease. In a subclass analysis of cT1N0M0 squamous cell carcinomas, wedge resection was the only unfavourable prognostic factor in both overall and disease-free survivals., Conclusions: If the patient was 75 years old or younger and was judged fit for lobectomy, limited resection for cStage I non-small-cell lung cancer (NSCLC) showed excellent outcomes and was not inferior to the reported results of lobectomy for small-sized NSCLC. The carcinomas with C/T≤0.25 rarely recur and are especially good candidates for limited resection., (© The Author 2014. Published by Oxford University Press on behalf of the European Association for Cardio-Thoracic Surgery. All rights reserved.)